bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation studies of self-focusing carbon nanotube field emitter
Authors: Liao Ko Pin , Hu Yuan , Lin Tsang-Lang , Lan Yung-Chiang
Published: April 2007

It has been shown that carbon nanotubes exhibit good electron field emission properties, therefore have potential application in field emission displays as electron field emitters. In this study, the authors propose a new coplanar printed carbon nanotube (CNT) field emitter design that possesses symmetrical self-focusing properties without adding a focusing gate. A cylindrical gate electrode is located at the center and surrounded by the cathode. CNT paste can be applied to the cathode surface near or on the corner. A two-dimensional, particle-in-cell computer simulation code MAGIC was used to investigate the field emission characteristics of this new type of field emitter. Simulations were carried out for different gate voltages to investigate the effects on the emission current and beam divergence. Typical simulation parameters are anode voltage of 1000V, cathode voltage of 0V, and an anode-cathode distance of 95μm. It was found that there is an optimum gate voltage that gives the best focusing effect. The optimum gate voltages are different for different CNT paste locations. For CNT paste located on the round corner, with a radius of curvature of 0.5μm, an optimum negative gate voltage of about −15V is needed to push the overfocused emitted electrons to a focused spot having a current-weighted beam radius of 2.1μm. For a ring of CNT paste with 1μm width located on the flat surface next to the corner of the cathode, it would require an optimum gate voltage of about 45V to attract the emitted electrons to fall on a single spot on the anode having a current-weighted beam radius of 1.6μm. The electron emission can be turned off on individual emitter by applying a large negative gate voltage. This study shows the proposed simple field emitter design can produce well-focused electron beams for high resolution display applications.
Field emission from metal-coated nanocrystalline graphitic films
Authors: Deng Jicai , Zhang Lan , Zhang Binglin , Yao Ning , Fang Lili
Published: April 2007

Nanocrystalline graphitic films were synthesized directly on stainless-steel plates by microwave-plasma chemical-vapor deposition. Surface treatment of the samples, coated with a thin layer of titanium, was performed by pulsed-laser-deposition technique. Field-emission measurements were carried out using a diode structure. The experimental results indicate that the field-emission properties of the films coated with titanium metal were improved in comparison with those of untreated film. The possible reasons for the improvement of field-emission properties for the sample are discussed.
Role of Cu on the electrical properties of CdTe∕CdS solar cells: A cross-sectional conductive atomic force microscopy study
Authors: Moutinho H. R. , Dhere R. G. , Jiang C.-S. , Gessert T. , Duda A. , Young M. , Metzger W. K. , Al-Jassim M. M.
Published: April 2007

The authors have studied the electrical properties of CdTe∕CdS solar cells using conductive atomic force microscopy (C-AFM) applied to cross sections of the device. This novel technique uses the sharp tip of an atomic force microscope to contact the sample and apply an electrical potential, allowing the study of device properties with spatial resolution second to none. The CdTe∕CdS∕SnO2/substrate structures were treated with CdCl2 and etched with bromine/methanol or nitric/phosphoric acid solution. Finally, a Cu-containing back contact was applied to the surface of the device. The C-AFM analysis showed the existence of high-conductivity regions in CdTe close to the film surface, while the regions close to the junction with CdS remain resistive. The width of the conductive area in general varied laterally and, occasionally, reached the junction in some spots, causing microshunts in the devices. By analyzing the fracture of the cross sections, they observed that the conductive areas are concentrated at grain-boundary regions, whereas the interior of the grains is resistive. Analysis of samples without a Cu-containing back contact revealed that the conductive areas are caused by the diffusion of Cu from the back contact into the CdTe. The conductive layers directly affect the current transport in the device and impose a minimum CdTe thickness to prevent short-circuit problems.
Field emission properties of bare and gold-coated nickel nanowires grown in polymer ion-track membranes
Authors: Dangwal A. , Müller G. , Maurer F. , Brötz J. , Fuess H.
Published: April 2007

The authors have measured the field emission properties of freestanding bare and Au-coated Ni nanowires randomly distributed on thin metallic substrates. The nanowires of uniform length and diameter were grown in the etched ion-tracked pores of polycarbonate membranes by electrochemical deposition. While bare Ni samples yielded only 1.6×104emitters∕cm2 at 10V∕μm, Au coating of the Ni nanowires improved the emission site density to 1.4×105∕cm2 at 5V∕μm and about 1.6×106emitters∕cm2 at 18V∕μm. Average field enhancement factors β of 331 for bare Ni and 302 for Au-coated Ni nanowires correspond well to their cylindrical shape in the scanning electron microscope images. Stable Fowler-Nordheim-like emission was obtained on average up to currents of about 0.4 and 8μA for bare and Au-coated Ni nanowires, respectively. Locally measured I-V curves, maximum current Imax, and derived β values hint for the clustering of nanowires.
Characterization and field emission properties of lanthanum monosulfide nanoprotrusion arrays obtained by pulsed laser deposition on self-assembled nanoporous alumina templates
Authors: Cahay M. , Garre K. , Fraser J. W. , Lockwood D. J. , Semet V. , Thien Binh Vu , Bandyopadhyay S. , Pramanik S. , Kanchibotla B. , Fairchild S. , Grazulis L.
Published: April 2007

Three distinct types of nanostructures—nanodomes, nanodots, and nanowires—have been simultaneously self-assembled by pulsed laser deposition of lanthanum monosulfide on anodic alumina films containing hexagonal arrays of pores about 50nm wide and 500nm deep. The nanostructures have been characterized by x-ray diffraction, atomic force microscopy (AFM), and field emission scanning electron microscopy (FE-SEM). Nanodomes preferentially grow on the boundary separating regions (grains) of the alumina template that have near perfect pore ordering, and their density is ∼109∕cm2. The diameter of a nanodome at the base is about 100nm and their aspect ratio (height/diameter at the base) is between 1 and 3. Additionally, nanodots nucleate on top of the alumina walls that separate adjacent pores. They have a diameter of ∼50nm, a density equal to the pore density (1010∕cm2), and an aspect ratio less than 1. Finally, cross sectional FE-SEM images of the templates indicate that LaS nanowires grow inside the pores with a density of 1010∕cm2. They have a diameter of 50nm and a maximum length equal to the length of the pores (∼500nm). The field emission properties of the LaS nanodomes and nanodots have been analyzed via the scanning anode field emission microscopy technique (SAFEM). For a fixed SAFEM probe to cathode distance, the applied voltage necessary to extract the same FE current is found to be ∼3.5 times less for a LaS thin film deposited on alumina templates compared to the value recorded for LaS thin films deposited on Silicon substrates. Assuming a LaS work function of ∼1eV (as recorded for LaS thin films grown on silicon substrates), a field enhancement factor of ∼5.8 is extracted for the nanoscale emitters from Fowler-Nordheim plots of the FE data. The field enhancement effect accrues from the concentration of electric field lines at the tip of the nanodome and nanodot emitters. The value of 5.8 can be correlated to an aspect ratio of 2.7 for the dominant emitter, which is in good agreement with the aspect ratio of the tallest nanodomes observed in AFM measurements.
Field emission of individual carbon nanotubes on tungsten tips
Authors: Bai Xin , Wang Mingsheng , Zhang Gengmin , Yu Jie , Zhang Zhaoxiang , Guo Dengzhu , Zhao Xingyu , Xue Zengquan
Published: April 2007

Individual multiwalled carbon nanotubes (MWCNTs) were assembled onto tungsten tips in a transmission-electron microscope. Then they were transferred into a field-emission microscope for the measurement of field-emission properties. Stable field emission was established after repeated heat treatment and extraction of field-emission current, which are believed to have cleaned and blunted the MWCNT ends. Even under high voltages and large currents, most of the emitted electrons that hit the screen were found to be still restricted within an ∼10−2 solid angle, indicating the possible availability of a high brightness.
Field emission characteristics of surface-reconstructed heavily phosphorus-doped homoepitaxial diamond
Authors: Yamada Takatoshi , Yamaguchi Hisato , Kudo Yuki , Okano Ken , Shikata Shin-ichi , Nebel Christoph E.
Published: April 2007

The authors report about field emission from reconstructed phosphorus-doped diamond surfaces. Field emission from reconstructed surfaces is compared with that of hydrogen plasma treated and wet chemical oxidized surfaces. The threshold field of reconstructed surface is 16V∕μm, while 28 and 44V∕μm are required for oxidized and H-terminated surfaces, respectively. Field emission models are introduced to discuss the data by taking into account the electron affinities of diamond surfaces. For the first time, the authors also show field emission stabilities for reconstructed, oxidized, and H-terminated diamonds.
Anisotropic fluorocarbon plasma etching of Si∕SiGe heterostructures
Authors: Ding R. , Klein L. J. , Eriksson M. A. , Wendt A. E.
Published: April 2007

Fluorocarbon plasma etching of Si∕SiGe heterostructures is demonstrated as a method for fabrication of quantum devices with vertical sidewalls. The heterostructures consist of layers of Si and SiGe, and anisotropic etching of the heterostructures using plasmas to isolate device elements is an attractive approach to fabricating devices. A challenge that has limited the use of fluorocarbon etching is the difference in Si and SiGe etch rates under comparative conditions. Preferential etching of SiGe can lead to undercutting beneath the top Si layer, causing a reduction in critical device dimensions of unknown magnitude. By using fluorocarbon etch gases with high carbon content, fluorocarbon sidewall passivation improves the anisotropy of etched feature profiles by preventing lateral etching of SiGe. Etch results with a C4F8∕Ar∕N2 gas mixture show a straight sidewall profile through the layers of the heterostructure.
Fast neutron irradiation effects in n-GaN
Authors: Polyakov A. Y. , Smirnov N. B. , Govorkov A. V. , Markov A. V. , Pearton S. J. , Kolin N. G. , Merkurisov D. I. , Boiko V. M. , Lee Cheul-Ro , Lee In-Hwan
Published: April 2007

The electrical properties and deep level spectra in undoped n-GaN films irradiated by fast neutrons are reported. The electron removal rate was ∼5cm−1, and the dominant deep states introduced by neutron damage were electron traps with activation energy of 0.75eV. For high doses of 1.7×1017–1018cm−2 the material becomes semi-insulating n-type with the Fermi level pinned near Ec−0.85eV. Deep level spectra are dominated by electron traps with activation energy of 0.75eV, close to the energy of the Fermi level pinning in heavily irradiated material. Neutron irradiation also introduces a high density of centers giving rise to strong persistent photocapacitance. The observed phenomena are explained under the assumption that the dominant defects in neutron irradiated GaN are disordered regions produced by high-energy recoil atoms.
Space charge effects on the I-V characteristics of field emission arrays
Authors: Lin Ming-Chieh
Published: April 2007

Field emission arrays (FEAs) are good candidates for the use as field emitters. The field emission due to quantum mechanical tunneling is described by the well-known Fowler-Nordheim (FN) equation. The FN plots are widely employed to fit the experimental data. In recent experiments of field emission arrays, the results show that the FN plots become nonlinear and are apart from the prediction of the conventional FN theory. In this work, space charge effects on the I-V characteristics of the FEAs that may be operated at high current density are investigated. Within the framework of the effective work function approximation, a good fit to the I-V characteristics of FEAs can be generated by solving the FN equation and Poisson’s equation for planar space-charge-limited field emission self-consistently. This solution has been verified by the finite-difference time-domain particle-in-cell simulation. The theoretical results also show good agreement in comparison with some experimental results. This indicates that the space charge effects play an important role in the saturation behavior of field emission arrays.
High-current-density field emission from multiwalled carbon nanotubes by chemical-vapor deposition with effective aging treatment
Authors: Mu Hui , Zhang Xiaobing , Lei Wei , Lou Chaogang , Wang Qilong , Yin Xiaowei
Published: April 2007

Carbon nanotubes have been grown on silicon substrates coated with nickel-catalyst films by chemical-vapor deposition using mixtures of acetylene and nitrogen. An effective aging treatment was carried out before the field-emission measurement of carbon-nanotube samples. The results show that the turn-on field is 1.8V∕μm at 2μA emission current and that the highest emission current of 13mA at the electrical field of 23V∕μm. This corresponds to the field-emission current density of 414mA∕cm2. Some discussions about the long growing time of carbon nanotubes, the aging process, and high-current field emission are given.
Functional Quantum Nodes for Entanglement Distribution over Scalable Quantum Networks
Authors: Chou Chin-Wen , Laurat Julien , Deng Hui , Choi Kyung Soo , de Riedmatten Hugues , Felinto Daniel , Kimble H. Jeff
Published: April 2007

We demonstrated entanglement distribution between two remote quantum nodes located 3 meters apart. This distribution involves the asynchronous preparation of two pairs of atomic memories and the coherent mapping of stored atomic states into light fields in an effective state of near-maximum polarization entanglement. Entanglement is verified by way of the measured violation of a Bell inequality, and it can be used for communication protocols such as quantum cryptography. The demonstrated quantum nodes and channels can be used as segments of a quantum repeater, providing an essential tool for robust long-distance quantum communication.
Genes Required for Mitotic Spindle Assembly in
Drosophila
S2 Cells
Authors: Goshima Gohta , Wollman Roy , Goodwin Sarah S. , Zhang Nan , Scholey Jonathan M. , Vale Ronald D. , Stuurman Nico
Published: April 2007

The formation of a metaphase spindle, a bipolar microtubule array with centrally aligned chromosomes, is a prerequisite for the faithful segregation of a cell's genetic material. Using a full-genome RNA interference screen of
Drosophila
S2 cells, we identified about 200 genes that contribute to spindle assembly, more than half of which were unexpected. The screen, in combination with a variety of secondary assays, led to new insights into how spindle microtubules are generated; how centrosomes are positioned; and how centrioles, centrosomes, and kinetochores are assembled.
Comparative proteomic analysis for the detection of biomarkers in pancreatic ductal adenocarcinomas
Authors: Qi T , Han J , Cui Y , Zong M , Liu X , Zhu B
Published: April 2007

Aims:

To search for novel potential protein biomarkers for the early detection and better intervention of pancreatic ductal adenocarcinoma (PDAC).

Methods:

Eight pairs of matched PDAC and non-cancerous pancreas tissues were profiled with two-dimensional electrophoresis; differentially expressed proteins were identified by mass spectrometry. Expression patterns of TBX4 (T-box transcription factor TBX4) and HSP60 (60 KDa heat shock protein) were studied with immunohistochemistry using tissue microarrays.

Results:

A total of 48 differentially expressed proteins were identified; 30 of them are novel potential biomarkers. Immunohistochemistry showed that TBX4 expression could be seen in both centroacinar cells and small ducts in normal pancreas and tumour cells in 5/5 (100%) well differentiated, 35/38 (92.1%) moderately differentiated, and 11/18 (61.1%) poorly differentiated PDAC tissues with different staining intensity. However, in normal acinar cells and tumour cells in the other 3/38 (7.9%) moderately differentiated and 7/18 (38.9%) poorly differentiated PDAC tissues, there was no visible TBX4 expression. The expression difference of TBX4 between moderately differentiated and poorly differentiated PDAC tissues was statistically significant (p<0.01). In addition, there was obvious morphology difference between TBX4 negatively stained and positively stained tumour cells, which suggests different cellular origins. Strong expression of HSP60 could be seen in both acinar cells and small ducts in normal pancreas tissues and tumour cells in PDAC tissues except for islets and tumour stoma; no correlation was found between HSP60 expression and differentiation of PDAC tissues.

Conclusions:

30 novel potential biomarkers differentially expressed in PDAC tissues were identified. TBX4 may be a differentiation related protein; its prognostic value for PDAC deserves further study.
Comparing subjective and digital image analysis HER2/neu expression scores with conventional and modified FISH scores in breast cancer
Authors: Skaland I , Øvestad I , Janssen E A M , Klos J , Kjellevold K H , Helliesen T , Baak J P A
Published: April 2007

Background:

HER2/neu expression and fluorescence in situ hybridisation (FISH) amplification have therapeutic significance.

Aims:

To compare subjective HER2/neu expression scores with digital image analysis (DIA) and conventional and modified FISH scores in breast cancer.

Methods:

Sixty HercepTest-immunostained breast carcinomas, prospectively scored as consensus 2+ and 3+ (DAKO protocol) by two observers, were analysed with DIA, and conventional (Vysis) and modified FISH scoring protocols.

Results:

With consensus scoring, 23 (38%) of the 60 cases were 2+ and 37 (62%) were 3+. Agreement with DIA scores was 100%. With conventional FISH scoring, 4 of the 3+ cases did not show amplification, but all of those negative cases had high HER2/neu copy numbers. With the modified FISH scoring protocol, all HercepTest immunohistochemical 3+ cases were amplified. Of the 2+ cases, 3 were amplified with the modified FISH protocol and 4 with the conventional FISH protocol.

Conclusions:

Modified FISH scores were better correlated with HercepTest 3+ consensus and DIA scores than were conventional FISH scores. HER2/neu DIA scoring is a cost-effective supplementary tool in surgical pathology.
Antigenicity testing by immunohistochemistry after tissue oxidation
Authors: Blind C , Koepenik A , Pacyna-Gengelbach M , Fernahl G , Deutschmann N , Dietel M , Krenn V , Petersen I
Published: April 2007

Aims:

Archived tissue blocks preserve the antigenicity of samples for a long time under normal storage conditions, whereas tissue sections may show a diminished immunoreactivity over time. Little is known about the processes responsible for antigenicity loss and how tissue sections should be conserved for extended storage. Oxidation and drying are presumed mechanisms of antigenicity loss. To prove this, degradation of immunoreactivity was provoked by chemical oxidation, photo-oxidation and artificial drying.

Methods:

First, paraffin sections of an oestrogen receptor (ER) positive breast carcinoma were subjected for variable time periods to H2O2, ultraviolet A (UVA) irradiation and dry heat (56°C) prior to ER immunohistochemistry. Second, using heat and UVA irradiation several other antigens (ER, PR, HER-2neu, p53, p63, p16, PSA, CK5/6, CK7, CK20, SMA, Fli-1, c-kit, CD20 and EGFR) were tested, using internal control tissue microarray sections.

Results:

While H2O2had no effect on the ER-staining intensity, extended drying showed a detectable decrease in staining after 10 days, and UVA irradiation induced a decrease after 3 days. Entire antigenicity loss was not observed. Except for HER-2neu, PSA and Fli-1, all antigens showed some diminution in antigenicity, but no entire antigenicity loss, after heating and UVA irradiation.

Conclusions:

This study confirms that photo-oxidation and drying have an influence on immunohistochemistry outcome, and protocols for testing the stability of specific antigens are provided.
POLYGON DECOMPOSITION AND THE ORTHOGONAL ART GALLERY PROBLEM
Authors: WORMAN CHRIS , KEIL J. MARK
Published: April 2007

A decomposition of a polygon P is a set of polygons whose geometric union is exactly P. We study a polygon decomposition problem that is equivalent to the Orthogonal Art Gallery problem. Two points are r-visible if the orthogonal bounding rectangle for p and q lies within P. A polygon P is an r-star if there exists a point k ∈ P such that for each point q ∈ P, q is r-visible from k. In this problem we seek a minimum cardinality decomposition of a polygon into r-stars. We show how to compute the minimum r-star cover of an orthogonal polygon in polynomial time.
AN APPROXIMATE ARRANGEMENT ALGORITHM FOR SEMI-ALGEBRAIC CURVES
Authors: MILENKOVIC VICTOR , SACKS ELISHA
Published: April 2007

We present an arrangement algorithm for plane curves. The inputs are (1) continuous, compact, x-monotone curves and (2) a module that computes approximate crossing points of these curves. There are no general position requirements. We assume that the crossing module output is ∊ accurate, but allow it to be inconsistent, meaning that three curves are in cyclic y order over an x interval. The curves are swept with a vertical line using the crossing module to compute and process sweep events. When the sweep detects an inconsistency, the algorithm breaks the cycle to obtain a linear order. We prove correctness in a realistic computational model of the crossing module. The number of vertices in the output is V = 2n + N + min (3kn,n2/2) and the running time is O (V log n) for n curves with N crossings and k inconsistencies. The output arrangement is realizable by curves that are O (∊ + kn∊) close to the input curves, except in kn∊ neighborhoods of the curve tails. The accuracy can be guaranteed everywhere by adding tiny horizontal extensions to the segment tails, but without the running time bound. An implementation is described for semi-algebraic curves based on a numerical equation solver. Experiments show that the extensions only slightly increase the running time and have little effect on the error. On challenging data sets, the number of inconsistencies is at most 3N, the output accuracy is close to ∊, and the running time is close to that of the standard, non-robust floating point sweep.
Human cecal bile acids: concentration and spectrum
Authors: Hamilton James P. , Xie Guofeng , Raufman Jean-Pierre , Hogan Susan , Griffin Terrance L. , Packard Christine A. , Chatfield Dale A. , Hagey Lee R. , Steinbach Joseph H. , Hofmann Alan F.
Published: April 2007

To obtain information on the concentration and spectrum of bile acids in human cecal content, samples were obtained from 19 persons who had died an unnatural death from causes such as trauma, homicide, suicide, or drug overdose. Bile acid concentration was measured via an enzymatic assay for 3α-hydroxy bile acids; bile acid classes were determined by electrospray ionization mass spectrometry and individual bile acids by gas chromatography mass spectrometry and liquid chromatography mass spectrometry. The 3α-hydroxy bile acid concentration (μmol bile acid/ml cecal content) was 0.4 ± 0.2 mM (mean ± SD); the total 3-hydroxy bile acid concentration was 0.6 ± 0.3 mM. The aqueous concentration of bile acids (supernatant after centrifugation) was identical, indicating that most bile acids were in solution. By liquid chromatography mass spectrometry, bile acids were mostly in unconjugated form (90 ± 9%, mean ± SD); sulfated, nonamidated bile acids were 7 ± 5%, and nonsulfated amidated bile acids (glycine or taurine conjugates) were 3 ± 7%. By gas chromatography mass spectrometry, 10 bile acids were identified: deoxycholic (34 ± 16%), lithocholic (26 ± 10%), and ursodeoxycholic (6 ± 9), as well as their primary bile acid precursors cholic (6 ± 9%) and chenodeoxycholic acid (7 ± 8%). In addition, 3β-hydroxy derivatives of some or all of these bile acids were present and averaged 27 ± 18% of total bile acids, indicating that 3β-hydroxy bile acids are normal constituents of cecal content. In the human cecum, deconjugation and dehydroxylation of bile acids are nearly complete, resulting in most bile acids being in unconjugated form at submicellar and subsecretory concentrations.
Human organic anion transporter 1B1 and 1B3 function as bidirectional carriers and do not mediate GSH-bile acid cotransport
Authors: Mahagita Chitrawina , Grassl Steven M. , Piyachaturawat Pawinee , Ballatori Nazzareno
Published: April 2007

Organic anion transporting polypeptides (OATP/ SLCO) are generally believed to function as electroneutral anion exchangers, but direct evidence for this contention has only been provided for one member of this large family of genes, rat Oatp1a1/Oatp1 ( Slco1a1). In contrast, a recent study has indicated that human OATP1B3/OATP-8 ( SLCO1B3) functions as a GSH-bile acid cotransporter. The present study examined the transport mechanism and possible GSH requirement of the two members of this protein family that are expressed in relatively high levels in the human liver, OATP1B3/OATP-8 and OATP1B1/OATP-C ( SLCO1B1). Uptake of taurocholate in Xenopus laevis oocytes expressing either OATP1B1/OATP-C, OATP1B3/OATP-8, or polymorphic forms of OATP1B3/OATP-8 (namely, S112A and/or M233I) was cis-inhibited by taurocholate and estrone sulfate but was unaffected by GSH. Likewise, taurocholate and estrone sulfate transport were trans-stimulated by estrone sulfate and taurocholate but were unaffected by GSH. OATP1B3/OATP-8 also did not mediate GSH efflux or GSH-taurocholate cotransport out of cells, indicating that GSH is not required for transport activity. In addition, estrone sulfate uptake in oocytes microinjected with OATP1B3/OATP-8 or OATP1B1/OATP-C cRNA was unaffected by depolarization of the membrane potential or by changes in pH, suggesting an electroneutral transport mechanism. Overall, these results indicate that OATP1B3/OATP-8 and OATP1B1/OATP-C most likely function as bidirectional facilitated diffusion transporters and that GSH is not a substrate or activator of their transport activity.
Differential regulation of cyclin D1 and cell death by bile acids in primary rat hepatocytes
Authors: Castro Rui E. , Amaral Joana D. , Solá Susana , Kren Betsy T. , Steer Clifford J. , Rodrigues Cecília M. P.
Published: April 2007

Ursodeoxycholic (UDCA) and tauroursodeoxycholic (TUDCA) acids modulate apoptosis and regulate cell-cycle effectors, including cyclin D1. In contrast, deoxycholic acid (DCA) induces cell death and cyclin D1. In this study, we explored the role of cyclin D1 in DCA-induced toxicity and further elucidated the antiapoptotic function of UDCA and TUDCA in primary rat hepatocytes. Cells were incubated with DCA and with or without UDCA or TUDCA for 8–30 h. In addition, hepatocytes were transfected with either an adenovirus expressing cyclin D1 or with a cyclin D1 reporter plasmid with or without bile acids. Finally, cells were cotransfected with short interfering RNA targeting p53. Unlike DCA, both UDCA and TUDCA reduced cyclin D1 expression and transcriptional activation, confirming our previous DNA microarray data. Furthermore, UDCA and TUDCA prevented DCA-induced cyclin D1 and cell death. Cyclin D1 overexpression increased DCA-induced Bax translocation, cytochrome c release, and apoptosis. However, UDCA and TUDCA were less efficient at decreasing cyclin D1 levels as well as DCA-induced changes with overexpression. Finally, after p53 silencing, the effects of cyclin D1 overexpression were almost completely abrogated, whereas UDCA and TUDCA cytoprotective potential was reestablished. In conclusion, cyclin D1 is a relevant player in modulating apoptosis by bile acids, in part through a p53-dependent mechanism.
Consequences of postural changes and removal of vestibular inputs on the movement of air in and out of the lungs of conscious felines
Authors: Arshian M. , Holtje R. J. , Cotter L. A. , Rice C. D. , Cass S. P. , Yates B. J.
Published: April 2007

A variety of experimental approaches in human subjects and animal models established that the vestibular system contributes to regulation of respiration. In cats, the surgical elimination of labyrinthine signals produced changes in the spontaneous activity and posturally related responses of a number of respiratory muscles. However, these effects were complex and sometimes varied between muscle compartments, such that the physiological role of vestibulo-respiratory responses is unclear. The present study determined the functional significance of vestibulo-respiratory influences by examining the consequences of a bilateral labyrinthectomy on breathing rate and the pressure, volume, and flow rate of air exchanged during inspiration and expiration as body orientation with respect to gravity was altered. Data were collected from conscious adult cats acclimated to breathing through a facemask connected to a pneuomotach during 60° head-up pitch and ear-down roll body rotations. Removal of vestibular inputs resulted in a 15% reduction in breathing rate, a 13% decrease in minute ventilation, a 16% decrease in maximal inspiratory airflow rate, and a 14% decrease in the maximal expiratory airflow rate measured when the animals were in the prone position. However, the lesions did not appreciably affect phasic changes in airflow parameters related to alterations in posture. These results suggest that the role of the vestibular system in the control of breathing is to modify baseline respiratory parameters in proportion to the general intensity of ongoing movements, and not to rapidly alter ventilation in accordance with body position.
The biphasic force-velocity relationship in whole rat skeletal muscle in situ
Authors: Devrome A. N. , MacIntosh B. R.
Published: April 2007

Edman has reported that the force-velocity relationship (FVR) departs from Hill's classic hyperbola near 0.80 of measured isometric force ( J Physiol 404: 301–321, 1988). The purpose of this study was to investigate the biphasic nature of the FVR in the rested state and after some recovery from fatigue in the rat medial gastrocnemius muscle in situ. Force-velocity characteristics were determined before and during recovery from fatigue induced by intermittent stimulation at 170 Hz for 100 ms each second for 6 min. Force-velocity data were obtained for isotonic contractions with 100 ms of 200-Hz stimulation, including several measurements with loads above 0.80 of measured isometric force. The force-velocity data obtained in this study were fit well by a double-hyperbolic equation. A departure from Hill's classic hyperbola was found at 0.88 ± 0.01 of measured isometric force, which is higher than the ∼0.80 reported by Edman et al. for isolated frog fibers. After 45 min of recovery, maximum shortening velocity was 86 ± 2% of prefatigue, but neither curvature nor predicted isometric force was significantly different from prefatigue. The location of the departure from Hill's classic hyperbola was not different after this recovery from the fatiguing contractions. Including an isometric point in the data set will not yield the same values for maximal velocity and the degree of curvature as would be obtained using the double hyperbola approach. Data up to 0.88 of measured isometric force can be used to fit data to the Hill equation.
Protection of muscle membrane excitability during prolonged cycle exercise with glucose supplementation
Authors: Stewart R. D. , Duhamel T. A. , Foley K. P. , Ouyang J. , Smith I. C. , Green H. J.
Published: April 2007

To determine if exercise-induced depressions in neuromuscular function are altered with oral glucose supplementation, 15 untrained participants (V̇o2 peak = 45 ± 2 ml·kg−1·min−1, mean ± SE) performed prolonged cycle exercise at ∼60% V̇o2 peak on two occasions: without glucose supplementation (NG) and with oral glucose supplementation (G). The oral G began at 30 min of exercise and was administered every 15 min (total ingested = 1.23 ± 0.11 g carbohydrate/kg body mass). Quadriceps isometric properties and membrane excitability were assessed prior to exercise, after 90 min of exercise, and at fatigue. Cycle time to fatigue was greater ( P < 0.05) in G compared with NG (137 ± 7 vs. 115 ± 6 min). Progressive reductions ( P < 0.05) in maximal voluntary contraction (MVC, N) were observed for NG at 90 min (441 ± 29) and at fatigue (344 ± 33) compared with pre-exercise (666 ± 30). At fatigue in G, the reduction in MVC was not as pronounced ( P < 0.05) as in NG. Motor unit activation assessed with the interpolated twitch technique during an MVC following exercise was not different between conditions. During cycling, the G condition also resulted in a higher ( P < 0.05) muscle compound potential (M-wave) amplitude (mV) at both 90 min (+50%) and at fatigue (+87%) compared with NG. Similar effects were also found M-wave area (mV/ms). These results suggest that the ergogenic effect of glucose supplementation occurs not as a result of decreased neural activation but to improved muscle function, possibly as a consequence of protection of muscle membrane excitability.
Quantitative trait loci associated with maximal exercise endurance in mice
Authors: Lightfoot J. Timothy , Turner Michael J. , Knab Amy Kleinfehn , Jedlicka Anne E. , Oshimura Tomohiro , Marzec Jacqui , Gladwell Wesley , Leamy Larry J. , Kleeberger Steven R.
Published: April 2007

The role of genetics in the determination of maximal exercise endurance is unclear. Six- to nine-week-old F2mice ( n = 99; 60 female, 39 male), derived from an intercross of two inbred strains that had previously been phenotyped as having high maximal exercise endurance (Balb/cJ) and low maximal exercise endurance (DBA/2J), were treadmill tested to estimate exercise endurance. Selective genotyping of the F2cohort ( n = 12 high exercise endurance; n = 12 low exercise endurance) identified a significant quantitative trait locus (QTL) on chromosome X (53.7 cM, DXMit121) in the entire cohort and a suggestive QTL on chromosome 8 (36.1 cM, D8Mit359) in the female mice. Fine mapping with the entire F2cohort and additional informative markers confirmed and narrowed the QTLs. The chromosome 8 QTL ( EE8F) is homologous with two suggestive human QTLs and one significant rat QTL previously linked with exercise endurance. No effect of sex ( P = 0.33) or body weight ( P = 0.79) on exercise endurance was found in the F2cohort. These data indicate that genetic factors in distinct chromosomal regions may affect maximal exercise endurance in the inbred mouse. Whereas multiple genes are located in the identified QTL that could functionally affect exercise endurance, this study serves as a foundation for further investigations delineating the identity of genetic factors influencing maximum exercise endurance.
Lifetime Weight History and Endometrial Cancer Risk by Type of Menopausal Hormone Use in the NIH-AARP Diet and Health Study
Authors: Chang Shih-Chen , Lacey James V. , Brinton Louise A. , Hartge Patricia , Adams Kenneth , Mouw Traci , Carroll Leslie , Hollenbeck Albert , Schatzkin Arthur , Leitzmann Michael F.
Published: April 2007

Obesity and menopausal estrogen therapy are established risk factors for endometrial cancer. However, the joint effects of obesity and menopausal hormone therapy on endometrial cancer risk are incompletely understood. We addressed this issue in a cohort of 103,882 women ages 50 to 71 years at baseline in 1995 to 1996. During a median of 4.6 years, which contributed to a total of 455,304 person-years of follow-up through 2000, 677 cases of endometrial cancer were ascertained. Both baseline body mass index (BMI) and adult weight gain were associated with increased endometrial cancer risk. The multivariate relative risk (RR) comparing obese with normal weight women (BMI >30 versus <25 kg/m2) was 3.03 [95% confidence interval (95% CI), 2.50-3.68]. Compared with women with stable weight (gained or lost <5 kg) between age 18 and baseline, women who gained ≥20 kg had a RR of 2.75 (95% CI, 1.96-3.86). Menopausal hormone therapy significantly modified the relations of BMI (Pinteraction < 0.001) and adult weight gain (Pinteraction = 0.004) to endometrial cancer risk. Compared with normal weight, the RRs for obesity were 5.41 (95% CI, 4.01-7.29) among women who never used menopausal hormone therapy, 2.53 (95% CI, 1.21-5.30) among former menopausal hormone therapy users, and 1.44 (95% CI, 1.00-2.05) among current users. Compared with a stable weight between age 18 and baseline, the RRs for weight gain of ≥20 kg among never users and ever users of menopausal hormone therapy were 5.35 (95% CI, 3.01-9.52) and 1.43 (95% CI, 0.96-2.15), respectively. We conclude that both current adiposity and adult weight gain are associated with substantial increases in the risk of endometrial cancer, with relations particularly evident among never users of menopausal hormone therapy. (Cancer Epidemiol Biomarkers Prev 2007;16(4):723–30)
The UDP-Glucuronosyltransferase 2B17 Gene Deletion Polymorphism: Sex-Specific Association with Urinary 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol Glucuronidation Phenotype and Risk for Lung Cancer
Authors: Gallagher Carla J. , Muscat Joshua E. , Hicks Amy N. , Zheng Yan , Dyer Anne-Marie , Chase Gary A. , Richie John , Lazarus Philip
Published: April 2007

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone is a potent and abundant procarcinogen found in tobacco smoke, and glucuronidation of its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), by UDP-glucuronosyltransferases (UGT) including UGT2B17 is an important mechanism for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone detoxification. Both copies of the UGT2B17 gene are deleted in ∼10% of Whites and the deletion is associated with a reduction in NNAL glucuronidation activity in vitro. In this study, we examined the effects of the UGT2B17 deletion (0/0) on NNAL glucuronidation rates in a sample of 82 healthy cigarette smokers and further examined its effects on lung cancer risk in a separate case-control study. In the healthy smokers study, a lower urinary ratio of NNAL-glucuronide to NNAL was observed in women with the UGT2B17 deletion (0/0) as compared with women with either the wild-type or heterozygous genotypes (P = 0.058). There were no significant differences in this ratio by genotype in men (P = 0.597). In the case-control study of 398 lung cancer patients and 697 community controls, the UGT2B17 deletion (0/0) was associated with a significant increase in risk of lung cancer in women (odds ratio, 2.0; 95% confidence interval, 1.01-4.0). The risk for the subset of women with lung adenocarcinoma was 2.8 (95% confidence interval, 1.2-6.3). The deletion was not associated with other lung histologic types in women and was not associated with the risk for any lung histologic types in men. The association of the UGT2B17 deletion with increased lung adenocarcinoma in women is consistent with its association with decreased NNAL glucuronidation rates in women and with studies showing that NNAL is a selective inducer of lung adenocarcinoma in experimental animals. (Cancer Epidemiol Biomarkers Prev 2007;16(4):823–8)
Grilled Meat Consumption and PhIP-DNA Adducts in Prostate Carcinogenesis
Authors: Tang Deliang , Liu Jason J. , Rundle Andrew , Neslund-Dudas Christine , Savera Adnan T. , Bock Cathryn H. , Nock Nora L. , Yang James J. , Rybicki Benjamin A.
Published: April 2007

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the major heterocyclic amine generated from cooking meats at high temperatures, and dietary exposures have been shown to induce prostate cancer in rats. PhIP derives its carcinogenic potential through the formation of PhIP-DNA adducts. The purpose of this study was to examine whether self-reported consumption and preparation doneness of grilled meats were associated with PhIP-DNA adduct levels in prostate epithelial cells. The study population consisted of 268 African-American and Caucasian men who underwent radical prostatectomy for prostate cancer. PhIP-DNA adducts in tumor and adjacent nontumor cells were measured using immunohistochemical methods, and dietary meat intake information was based on food frequency questionnaires. Data were analyzed using multivariate linear regression models. After adjusting for age at prostatectomy and race, grilled meat consumption (P = 0.002) was significantly associated with higher adduct levels in tumor cells, but this association seemed to be primarily due to consumption of grilled red meats (P = 0.001) as opposed to grilled white meat consumption (P = 0.15). Among the specific food items, grilled hamburger consumption had the most significant association with adduct level in tumor cells (P = 0.002). Similar trends in positive associations with grilled meat consumption and adduct levels were observed in nontumor cells, but none of these associations reached statistical significance. Our results suggest that dietary interventions targeted at lower consumption of grilled red meats may reduce prostate cancer risk via the PhIP prostate carcinogenic pathway. (Cancer Epidemiol Biomarkers Prev 2007;16(4):803–8)
Plasma 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D and Risk of Incident Ovarian Cancer
Authors: Tworoger Shelley S. , Lee I-Min , Buring Julie E. , Rosner Bernard , Hollis Bruce W. , Hankinson Susan E.
Published: April 2007

Few modifiable factors are known to reduce ovarian cancer risk. Ecologic studies and experimental data suggest that vitamin D may reduce ovarian cancer risk. Therefore, we examined whether plasma concentrations of 25-hydroxyvitamin D (a measure of overall vitamin D status) and 1,25-dihydroxyvitamin D (biologically active form) were associated with risk of epithelial ovarian cancer in a nested-case control study using data from three prospective cohorts: the Nurses' Health Study (NHS), NHSII, and the Women's Health Study (WHS). The analysis had 224 cases (161 from NHS/NHSII and 63 from WHS) and 603 controls (matching ratio, 1:3 for NHS/NHSII and 1:2 for WHS). Women ranged in age from 34 to 73 years (mean, 56 years). We did not observe significant associations between 25-hydroxyvitamin D [top versus bottom quartile: relative risk (RR), 0.83; 95% confidence interval (95% CI), 0.49-1.39; Ptrend = 0.57] or 1,25-dihydroxyvitamin D levels (RR, 1.14; 95% CI, 0.70-1.85, Ptrend = 0.93) and ovarian cancer risk. Study-specific associations were not statistically significant and no statistical heterogeneity existed between studies (P = 0.66, 25-hydroxyvitamin D; P = 0.40, 1,25-dihydroxyvitamin D). However, there was a significant inverse association among overweight and obese women for 25-hydroxyvitamin D levels (RR, 0.39; 95% CI, 0.16-0.93; Ptrend = 0.04). Further, those with adequate (≥32 ng/mL) versus inadequate 25-hydroxyvitamin D levels had a modestly decreased risk of serous ovarian cancer (RR, 0.64; 95% CI, 0.39-1.05). Overall, our results do not suggest that plasma vitamin D levels are associated with risk of ovarian cancer. However, we observed significant associations in some subgroups, which should be evaluated further in other studies because increasing vitamin D intake is an easy preventive measure to adopt. (Cancer Epidemiol Biomarkers Prev 2007;16(4):783–8)
Interaction of α9β1 Integrin With Thrombospondin-1 Promotes Angiogenesis
Authors: Staniszewska Izabela , Zaveri Shachi , Valle Luis Del , Oliva Isabela , Rothman Vicki L. , Croul Sidney E. , Roberts David D. , Mosher Deane F. , Tuszynski George P. , Marcinkiewicz Cezary
Published: April 2007

Thrombospondin-1 is a multifunctional protein interacting with several cell surface receptors including integrins. We found that it is a ligand for α9β1 integrin, and has an integrin binding site within its N-terminal domain (NoC1). Interaction of thrombospondin-1 and its recombinant NoC1 domain with α9β1 integrin was confirmed in ELISA and cell adhesion assays. Binding of NoC1 to cells expressing α9β1 integrin activated signaling proteins such as Erk1/2 and paxillin. Blocking of this integrin by monoclonal antibody and the met-leu-asp-disintegrin inhibited dermal human microvascular endothelial cell proliferation and NoC1-induced migration of these cells. Immunohistochemical studies revealed that α9β1 is expressed on microvascular endothelium in several organs including skin, lung, heart and brain. NoC1 induced neovascularization in an experimental quail chorioallantoic membrane system and Matrigel plug formation assay in mice. This proangiogenic activity of NoC1 in vivo was inhibited by α9β1 inhibitors. In summary, our results revealed that α9β1 integrin expressed on microvascular endothelial cells interacts with thrombospondin-1, and this interaction is involved in modulation of angiogenesis.
A Role for the Aryl Hydrocarbon Receptor in Regulation of Ischemia-Induced Angiogenesis
Authors: Ichihara Sahoko , Yamada Yoshiji , Ichihara Gaku , Nakajima Tamie , Li Ping , Kondo Takahisa , Gonzalez Frank J. , Murohara Toyoaki
Published: April 2007

Objective—

The aryl hydrocarbon receptor (AHR) is a transcription factor that binds to DNA as a heterodimer with the AHR nuclear translocator (ARNT) after interaction with ligands such as polycyclic and halogenated aromatic hydrocarbons found in tobacco smoke and the environment. We have investigated the interaction between AHR and hypoxia signaling pathways in regulation of angiogenesis with the use of a surgical model of ischemia.

Methods and Results—

Ischemia was induced by femoral artery occlusion in wild-type and AHR-null mice. Ischemia-induced angiogenesis was markedly enhanced in AHR-null mice compared with that in wild-type animals. Ischemia-induced upregulation of the expression of hypoxia-inducible factor–1α (HIF-1α) and ARNT as well as that of target genes for these transcription factors, such as that for vascular endothelial growth factor (VEGF), were also enhanced in AHR-null mice. Furthermore, the DNA binding activity of the HIF-1α–ARNT complex as well as the association of HIF-1α and ARNT with the VEGF gene promoter were increased by ischemia to a greater extent in AHR-null mice than in wild-type animals.

Conclusions—

Ablation of AHR resulted in enhancement of ischemia-induced angiogenesis. This effect was likely attributable in part to the associated enhancement of ischemia-induced VEGF expression, which in turn may be caused by an increased abundance and activity of the HIF-1α–ARNT heterodimer.