bluuebunny/crossref_metadata_2025 huggingface dataset:
Propagation of two longitudinal waves in human cancellous bone: An in vitro study
Authors: Mizuno Katsunori , Matsukawa Mami , Otani Takahiko , Laugier Pascal , Padilla Frédéric
Published: May 2009

The ultrasonic wave propagation of fast and slow waves was investigated in vitro in 35 cubic cancellous bone specimens extracted from human femoral heads. Measurements were performed in three orthogonal directions using home-made PVDF transducers excited by a single sinusoidal wave at 1 MHz. The apparent density of the specimens was measured. Two separated fast and slow waves were clearly observed in 16 specimens, mainly in the main load direction. The waveforms and the sound speeds of fast and slow waves were similar to the reported data in bovine bone. The group of specimens in which the two waves were observed did not exhibit statistically higher apparent density than the rest of the specimens, but did exhibit statistically higher acoustic anisotropy ratio. The speeds in the main load direction were higher than those in the other direction. The fast and slow wave speeds were in good agreement with Biot’s model, showing an increase with bone volume fraction (BV/TV). The ratio of peak amplitudes of the fast and slow waves nonlinearly increased as a function of BV/TV. These results open interesting perspective for acoustic assessment of cancellous bone micro-architecture and especially anisotropy that might lead to an improved assessment of bone strength.
Numerical study on source-distance dependency of head-related transfer functions
Authors: Otani Makoto , Hirahara Tatsuya , Ise Shiro
Published: May 2009

This paper investigates the source-distance dependency of head-related transfer functions (HRTFs) on the horizontal and median sagittal planes using the boundary-element method and a dummy head scanned with laser and computer tomography scanners. First, the HRTF spectra are compared among various source positions in a head-centered coordinate system, confirming that the major HRTF spectral features vary with source distance as stated in previous works. Furthermore, the HRTF spectra are compared in an ear-centered coordinate system, revealing how the outer ear angle of incidence affects the source-distance dependency of the HRTFs. Next, the comparison across coordinate systems reveals that the source-distance dependency of the ipsilateral HRTFs on the horizontal plane is mainly attributable to the outer ear angle of incidence, whereas the contralateral HRTFs vary with the source distance mainly due to the head’s presence. Finally, results also show that, in an ear-centered coordinate system, the ipsilateral HRTFs do not depend strongly on a source distance greater than 0.2m from the center of the head, whereas the contralateral HRTFs depend on source distance less than 1.8m. Results also show that HRTFs on the median sagittal plane depend on a source distance of less than 0.4m.
The pitch levels of female speech in two Chinese villages
Authors: Deutsch Diana , Le Jinghong , Shen Jing , Henthorn Trevor
Published: May 2009

The pitch levels of female speech in two villages situated in a relatively remote area of China were compared. The dialects spoken in the two villages are similar to Standard Mandarin, and all subjects had learned to read and speak Standard Mandarin at school. Subjects read out a passage of roughly 3.25min in Standard Mandarin, and pitch values were obtained at 5-ms intervals. The overall pitch levels in the two villages differed significantly, supporting the conjecture that pitch levels of speech are influenced by a mental representation acquired through long-term exposure to the speech of others.
Experimental investigation of bottom target detection by single channel iterative time reversal.
Authors: Ying Yingzi , Guo Shengming , Sun Bingwen , Ma Li , Cai Zhenghua , Fu Huamin , Hu Bing
Published: May 2009

Iterative time reversal process will gradually lead echo waves to converge to a dominant narrowband resonant mode of the target and enhance the return level in noisy and reverberant environment. This technique is used in bottom target detection and an experiment has been performed in the Yellow Sea, China. The experiment is in a monostatic configuration, and the target, which is a 53 cm external diameter and 260 cm long stainless steel cylindrical shell with concrete interior, is resting on the seafloor, and the directional transceiver, which is a transmitter and receiver couple, is located right above the target. First, a broadband interrogation pulse is launched, and the echo is measured and a bandpass filter is applied to avoid transceiver response peak, then the signal is time reversed and retransmitted, and repeat above procedures iteratively. The bottom reverberation will gradually be suppressed, and the center frequency of converged signal corresponds to a target resonance frequency, which is different from inhomogeneous bottom response in no target case. The existence of target is determined by this important acoustic signature, and the results illustrate the feasibility of this method. [Work partially supported by the CAS Innovation Fund.]
Numerical simulation of fluctuated ultrasound wave propagation through random medium.
Authors: Nomura Hideyuki , Kamakura Tomoo
Published: May 2009

Multiply scattered ultrasound wave propagation in a random medium is numerically simulated to consider the relationship between the physical properties of the random medium and wave fluctuations propagating through that medium. The medium is assumed to be randomly distributed scatters, which are characterized by the means and variances of number, size, density, and volume elasticity of scatters in a host medium. The ultrasound propagation is simulated using a finite-difference time-domain method. To evaluate the fluctuation of propagating ultrasound wave, the ratio of coherent intensity to incoherent and the ratio of the average wave energy to difference wave are statistically estimated. Numerical experiments show that the ratios of intensities and average and difference wave energies decrease with increasing the randomness and number density (scattering cross-sectional area) of scatters. This result suggests that the statistical estimation of wave pulse propagation is useful for measurements of physical properties of distributed particles in a solution. It is our expectation that the proposed numerical model will provide fundamental understandings on multiple scattering of ultrasound in a random medium.
Sonar simulation toolset modeling for underwater acoustic communications and networking.
Authors: Hsieh Julia B. , Rouseff Daniel , Song Aijun , Badiey Mohsen
Published: May 2009

The sonar simulation toolset (SST) is a ray-based propagation model capable of generating time series realizations with stochastic spreading of acoustic sequences. The model supports varying environments and geometries including moving sources and/or receivers. The simulated data were compared with experimental data collected at the Pacific Missile Range Facility, Kauai, Hawaii in 2003 (KauaiEx2003) and 2008 (KAM08). Models generated with appropriate sound speed profiles and wind speeds are shown to have similar channel impulse response functions to those observed during the experiments. The high-frequency communications sequences simulated from those models have been demodulated to demonstrate analogous results. These results suggest that underwater acoustic communications and networking can be effectively simulated with sonar simulation toolset to aid in experiment planning and data analysis. [Work supported by the Office of Naval Research.]
Recent advances in the design, synthesis and study of covalent conjugated oligomer–C60 ensembles
Authors: Bazaco Raúl Blanco , Segura José L. , Seoane Carlos
Published: May 2009

This review presents an overview of the most recent results in the field of conjugated oligomer covalently attached to the C60 sphere focusing mainly on donor–conjugated oligomer–C60 triads and conjugated oligomer–multifullerene materials. Well-defined monodisperse oligomers as new materials that exhibit interesting optoelectronic properties have been the subject of intense study during the last decade. In this regard, a huge amount of work has been devoted to the development of new synthetic strategies toward the synthesis of conjugated oligomeric materials with precise length and constitution and to their chemical functionalization in order to incorporate them into more complex molecular and supramolecular architectures. An important area of research in the field of conjugated oligomers involves the design and synthesis of donor–acceptor ensembles by combination of monodisperse π-conjugated oligomeric systems with C60 fullerene. Such hybrid systems have shown excited-state interactions making them excellent candidates for fundamental photophysical studies. In addition, these materials have found applications in the field of photovoltaic devices. A review with 70 references.
Cancer mortality and congenital anomalies in a region of Italy with intense environmental pressure due to waste
Authors: Martuzzi M , Mitis F , Bianchi F , Minichilli F , Comba P , Fazzo L
Published: May 2009

Objectives:

Waste management in the Campania region has been characterised, since the 1980s, by widespread uncontrolled and illegal practices of waste dumping, generating concerns over the health implications. The objective of this study was to evaluate possible adverse health effects of such environmental pressure.

Methods:

The health effects of waste-related environmental exposures in Campania were assessed in a correlation study on nine causes of death (for the years 1994–2001) and 12 types of congenital anomaly (CA) (1996–2002) in 196 municipalities of the provinces of Naples and Caserta. Poisson regression was used to analyse the association between health outcomes and environmental contamination due to waste, as measured through a composite index, adjusting for deprivation.

Results:

Statistically significant excess relative risks (ERR, %) in high-index compared with low-index (unexposed) municipalities were found for all-cause mortality (9.2 (95% CI 6.5 to 11.9) in men and 12.4 (9.5 to 15.4) in women and liver cancer (19.3 (1.4 to 40.3) in men and 29.1 (7.6 to 54.8) in women). Increased risks were also found for all cancer mortality (both sexes), stomach and lung cancer (in men). Statistically significant ERRs were found for CAs of the internal urogenital system (82.7 (25.6 to 155.7)) and of the central nervous system (83.5 (24.7 to 169.9)).

Conclusion:

Although the causal nature of the association is uncertain, findings support the hypothesis that waste-related environmental exposures in Campania produce increased risks of mortality and, to a lesser extent, CAs.
THEORY OF THE PROTON TRANSFER IN HYDROGEN-BONDED FERROELECTRICS
Authors: CHENG YUAN-FA , HUANG LIANG
Published: May 2009

We investigate dynamics properties of proton transfer in hydrogen-bonded ferroelectrics with asymmetric double-well potential, in an externally applied field, based on a two-component model. We obtain the equations of motion and their soliton solution. The soliton velocity and conductivity are found; this expression shows that the phase-transition critical index is equal to unity, and this value coincides quite well with the experimental result.
THE CONSENSUS IN MULTI-AGENT SYSTEM WITH SPEED-OPTIMIZED NETWORK
Authors: WU ZHENGPING , WANG RENMING
Published: May 2009

In this paper, we mainly investigate the character of consensus convergence speed of Multi-Agent Systems (MAS) with small-world communication network and the method of devising a speed-optimized small-world communication network in consensus problem based on genetic-algorithm (GA). It is found that, for a small-world communication network, the time to reach a consensus changes rapidly with the change of the number of long-range communication links and the agents which the long-range links connect. The convergence speed of consensus of MAS increases rapidly with the number of long-range links increasing. As we construct a small-world communication network for MAS with a smaller network size and fixed long-range links, we can optimize the long-range link configuration using GA methodology to obtain a small-world communication network with faster consensus speed for MAS.
SYNTHESIS AND CHARACTERIZATION OF α–Fe2O3 NANORODS BY A SIMPLE REACTION OF IRON AND WATER
Authors: SHAH M. A. , ASIRI A. M.
Published: May 2009

A soft approach has been described for the formation of α– Fe 2 O 3 nanorods by simple reaction of iron with water at a very low temperature range of 100–300°C. It is shown that the nanorods have diameters ranging from 50–80 nm, and their typical lengths are in the range of 5–10 μm. The chemical composition and crystalline structure of nanorods were investigated by various characterization techniques. The initial formation and subsequent growth of α– Fe 2 O 3 nanostructures may be explained by the iron metal corrosion mechanism.
THE INFLUENCES OF TEMPERATURE AND CHAIN–CHAIN INTERACTION ON FEATURES OF SOLITONS EXCITED IN α-HELIX PROTEIN MOLECULES WITH THREE CHANNELS
Authors: PANG XIAO-FENG , LIU MEI-JIE
Published: May 2009

The dynamic features of soliton transporting the bio-energy in the α-helix protein molecules with three channels under influences of temperature of systems and chain–chain interaction among these channels have been numerically studied by using the dynamic equations in a new model and the fourth-order Runge–Kutta method. This result obtained shows that the chain–chain interaction depresses the stability of the soliton due to the dispersed effect, but the stability of the soliton in the case of simultaneous motivation of three channels by an initial conditions is better than that in another initial condition. We also find from this investigation that the new soliton can transport steadily over 1000 amino acid residues in the cases of motion of long time of 120 ps, and retain their shapes and energies to travel towards the protein molecules after mutual collision of the solitons at the biological temperatures of 300 K. Therefore the soliton is very robust against the thermal perturbation of the α-helix protein molecules at 300 K. From the investigation of changes of features of the soliton with increasing temperature, we find that the amplitudes and velocities of the solitons decrease with increasing temperature of proteins, but the soliton disperses in the cases of higher temperature of 325 K and larger structure disorders. Thus we find that the critical temperature of the soliton occurring in the α-helix protein molecules is about 320 K. Therefore we can conclude that the soliton in the new model can play an important role in the bio-energy transport in the α-helix protein molecules with three channels at biological temperature, and the new model is possibly a candidate for the mechanism of this transport.
越洋寻求空间：
Authors: 王赓武
Published: May 2009

本文从历史角度， 论析长期以来， "陆地思维" 如何限制中国的发展， 如何影响中国处理与海洋的关系；中国又为何需要经历漫长时间才逐渐突破这种限制，这一过程中它怎样改进与越洋移民者、尤其是东南亚华人的关系，怎样影响海外华人。另一方面，在不同阶段海外华人的不同群体，如何回应不断改变态度的中国，又如何通过其自身独特的历史、文化条件和某些个别事件的影响来适应所在地的社会。最后，作者也关心对海洋发展的日益重视将如何影响中国对海外华人、对侨居传统以及对外籍公民文化自主的政策。
PPARγ inhibits NF-κB-dependent transcriptional activation in skeletal muscle
Authors: Remels A. H. V. , Langen R. C. J. , Gosker H. R. , Russell A. P. , Spaapen F. , Voncken J. W. , Schrauwen P. , Schols A. M. W. J.
Published: May 2009

Skeletal muscle pathology associated with a chronic inflammatory disease state (e.g., skeletal muscle atrophy and insulin resistance) is a potential consequence of chronic activation of NF-κB. It has been demonstrated that peroxisome proliferator-activated receptors (PPARs) can exert anti-inflammatory effects by interfering with transcriptional regulation of inflammatory responses. The goal of the present study, therefore, was to evaluate whether PPAR activation affects cytokine-induced NF-κB activity in skeletal muscle. Using C2C12 myotubes as an in vitro model of myofibers, we demonstrate that PPAR, and specifically PPARγ, activation potently inhibits inflammatory mediator-induced NF-κB transcriptional activity in a time- and dose-dependent manner. Furthermore, PPARγ activation by rosiglitazone strongly suppresses cytokine-induced transcript levels of the NF-κB-dependent genes intracellular adhesion molecule 1 (ICAM-1) and CXCL1 (KC), the murine homolog of IL-8, in myotubes. To verify whether muscular NF-κB activity in human subjects is suppressed by PPARγ activation, we examined the effect of 8 wk of rosiglitazone treatment on muscular gene expression of ICAM-1 and IL-8 in type 2 diabetes mellitus patients. In these subjects, we observed a trend toward decreased basal expression of ICAM-1 mRNA levels. Subsequent analyses in cultured myotubes revealed that the anti-inflammatory effect of PPARγ activation is not due to decreased RelA translocation to the nucleus or reduced RelA DNA binding. These findings demonstrate that muscle-specific inhibition of NF-κB activation may be an interesting therapeutic avenue for treatment of several inflammation-associated skeletal muscle abnormalities.
Decreased whole body lipolysis as a mechanism of the lipid-lowering effect of pioglitazone in type 2 diabetic patients
Authors: Gastaldelli Amalia , Casolaro Arturo , Ciociaro Demetrio , Frascerra Silvia , Nannipieri Monica , Buzzigoli Emma , Ferrannini Ele
Published: May 2009

Pioglitazone has been shown to reduce fasting triglyceride levels. The mechanisms of this effect have not been fully elucidated, but decreased lipolysis may contribute to blunt the hypertriglyceridemic response to a meal. To test this hypothesis, we studied 27 type 2 diabetes mellitus (T2DM) patients and 7 sex-, age-, and body mass index-matched nondiabetic controls. Patients were randomized to pioglitazone (45 mg/day) or placebo for 16 wk. Whole body lipolysis was measured [as the [2H5]glycerol rate of appearance (Ra)] in the fasting state and for 6 h following a mixed meal. Compared with controls, T2DM had higher postprandial profiles of plasma triglycerides, free fatty acid (FFA), and β-hydroxybutyrate, and a decreased suppression of glycerol Ra( P < 0.04) despite higher insulin levels [268 (156) vs. 190 (123) pmol/l, median (interquartile range)]. Following pioglitazone, triglycerides and FFA were reduced ( P = 0.05 and P < 0.04, respectively), and glycerol Rawas more suppressed [−40 (137) vs. +7 (202) μmol/min of placebo, P < 0.05] despite a greater fall in insulin [−85 (176) vs. −20 (58) pmol/l, P = 0.05]. We conclude that, in well-controlled T2DM patients, whole body lipolysis is insulin resistant, and pioglitazone improves the insulin sensitivity of lipolysis.
Sex differences in the resistive and elastic work of breathing during exercise in endurance-trained athletes
Authors: Guenette Jordan A. , Querido Jordan S. , Eves Neil D. , Chua Romeo , Sheel A. William
Published: May 2009

It is not known whether the high total work of breathing (WOB) in exercising women is higher due to differences in the resistive or elastic WOB. Accordingly, the purpose of this study was to determine which factors contribute to the higher total WOB during exercise in women. We performed a comprehensive analysis of previous data from 16 endurance-trained subjects (8 men and 8 women) that underwent a progressive cycle exercise test to exhaustion. Esophageal pressure, lung volumes, and ventilatory parameters were continuously monitored throughout exercise. Modified Campbell diagrams were used to partition the esophageal-pressure volume data into inspiratory and expiratory resistive and elastic components at 50, 75, 100 l/min and maximal ventilations and also at three standardized submaximal work rates (3.0, 3.5, and 4.0 W/kg). The total WOB was also compared between sexes at relative submaximal ventilations (25, 50, and 75% of maximal ventilation). The inspiratory resistive WOB at 50, 75, and 100 l/min was 67, 89, and 109% higher in women, respectively ( P < 0.05). The expiratory resistive WOB was 131% higher in women at 75 l/min ( P < 0.05) with no differences at 50 or 100 l/min. There were no significant sex differences in the inspiratory or expiratory elastic WOB across any absolute minute ventilation. However, the total WOB was 120, 60, 50, and 45% higher in men at 25, 50, 75, and 100% of maximal exercise ventilation, respectively ( P < 0.05). This was due in large part to their much higher tidal volumes and thus higher inspiratory elastic WOB. When standardized for a given work rate to body mass ratio, the total WOB was significantly higher in women at 3.5 W/kg (239 ± 31 vs. 173 ± 12 J/min, P < 0.05) and 4 W/kg (387 ± 53 vs. 243 ± 36 J/min, P < 0.05), and this was due exclusively to a significantly higher inspiratory and expiratory resistive WOB rather than differences in the elastic WOB. The higher total WOB in women at absolute ventilations and for a given work rate to body mass ratio is due to a substantially higher resistive WOB, and this is likely due to smaller female airways relative to males and a breathing pattern that favors a higher breathing frequency.
Breath-to-breath hypercapnic response in neonatal rats: temperature dependency of the chemoreflexes and potential implications for breathing stability
Authors: Cummings Kevin J. , Frappell Peter B.
Published: May 2009

The breathing of newborns is destabilized by warm temperatures. We hypothesized that in unanesthetized, intact newborn rats, body temperature (TB) influences the peripheral chemoreflex response (PCR response) to hypercapnia. To test this, we delivered square-wave challenges of 8% CO2 in air to postnatal day 4–5 (P4–P5) rats held at a TB of 30°C (Cold group, n = 11), 33°C (Cool group, n = 10), and 35°C thermoneutral zone group [thermoneutral zone (TNZ) group, n = 11], while measuring ventilation (V̇e) directly with a pneumotach and mask. Cool animals were challenged with 8% CO2 balanced in either air or hyperoxia ( n = 10) to identify the PCR response. Breath-to-breath analysis was performed on 30 room air breaths and every breath of the 1-min CO2 challenge. As expected, warmer TB was associated with an unstable breathing pattern in room air: TNZ animals had a coefficient of variation in V̇e (V̇e CV%) that was double that of animals held at cooler TB ( P < 0.001). Hyperoxia markedly suppressed the hypercapnic ventilatory response over the first 10 breaths (or ∼4 s), suggesting that this domain is dominated by the PCR response. The PCR response ( P = 0.03) and total response ( P = 0.04) were significantly greater in TNZ animals compared with hypothermic animals. The total response had a significant, negative relationship with V̇co2 ( R2 = 0.53; P < 0.001). Breathing stability was positively related to the total response ( R2 = 0.36; P < 0.001) and to a lesser extent, the PCR response ( R2 = 0.19; P = 0.01) and was negatively related to V̇co2 ( R2 = 0.34; P < 0.001). ANCOVA confirmed a significant effect of TB alone on breathing stability ( P < 0.01), with no independent effects of V̇co2 ( P = 0.41), the PCR response ( P = 0.82), or the total V̇e response ( P = 0.08). Our data suggest that in early postnatal life, the chemoreflex responses to CO2 are highly influenced by TB, and while related to breathing stability, are not predictors of stability after accounting for the independent effect of TB.
Niacin ameliorates oxidative stress, inflammation, proteinuria, and hypertension in rats with chronic renal failure
Authors: Cho Kyu-hyang , Kim Hyun-ju , Rodriguez-Iturbe Bernardo , Vaziri Nosratola D.
Published: May 2009

Significant reduction of renal mass causes progressive deterioration of renal function and structure which is mediated by systemic and glomerular hypertension, hyperfiltration, oxidative stress, inflammation, and dyslipidemia. Niacin is known to improve lipid metabolism and exert antioxidant/anti-inflammatory actions. Therefore, we considered that niacin supplementation may attenuate oxidative stress, inflammation, and tissue injury in the remnant kidney. To this end, [Formula: see text] nephrectomized [chronic kidney disease (CKD)] rats were randomly assigned to niacin-treated (50 mg·kg−1·day−1 in the drinking water for 12 wk) and untreated groups. Sham-operated rats served as controls. The untreated CKD rats exhibited azotemia, hypertension, hypertriglyceridemia, proteinuria, glomerulosclerosis, tubulointerstitial damage, upregulation of MCP-1, plasminogen activator inhibitor-1 (PAI-1), transforming growth factor (TGF)-β, cyclooxygenase (COX)-1, COX-2, and NAD(P)H oxidase (NOX-4, gp91phox, p47phox and p22phox subunits) and activation of NF-κB (IκB phosphorylation). Niacin administration reduced MCP-1, PAI-1, TGF-β, p47phox, p22phox, COX-1, and NF-κB activation, ameliorated hypertension, proteinuria, glomerulosclerosis, and tubulointerstitial injury. Although niacin lowered serum creatinine and raised creatinine clearance, the differences did not reach statistical significance. Thus niacin supplementation helps to attenuate histological injury and mitigate upregulation of oxidative and inflammatory systems in the remnant kidney.
Effects of nitroglycerin or pentaerithrityl tetranitrate treatment on the gene expression in rat hearts: evidence for cardiotoxic and cardioprotective effects
Authors: Pautz Andrea , Rauschkolb Peter , Schmidt Nadine , Art Julia , Oelze Matthias , Wenzel Philip , Förstermann Ulrich , Daiber Andreas , Kleinert Hartmut
Published: May 2009

Nitroglycerin (NTG) and pentaerithrityl tetranitrate (PETN) are organic nitrates used in the treatment of angina pectoris, myocardial infarction, and congestive heart failure. Recent data show marked differences in the effects of NTG and PETN on the generation of reactive oxygen species. These differences are attributed to different effects of NTG and PETN on the expression of antioxidative proteins like the heme oxygenase-I. To analyze the expressional effects of NTG and PETN in a more comprehensive manner we performed whole genome expression profiling experiments using cardiac total RNA from NTG- or PETN-treated rats and DNA microarrays containing oligonucleotides representing 27,044 rat gene transcripts. The data obtained show that NTG and PETN together significantly modify the expression of >1,600 genes (NTG 532, PETN 1212). However, the expression of only a small group of these genes ( 68 ) was modified by both treatments, indicating marked differences in the expressional effects of NTG and PETN. NTG treatment resulted in the enhanced expression of genes that are believed to be markers for cardiotoxic processes. In addition, NTG treatment reduced the expression of genes described to code for cardioprotective proteins. In sharp contrast, PETN treatment enhanced the expression of cardioprotective genes and reduced the expression of genes believed to perform cardiotoxic effects. In conclusion, our data suggest that NTG treatment results in the induction of cardiotoxic gene expression networks leading to an activation of mechanisms that result in pathological changes in cardiomyocytes. In contrast, PETN treatment seems to activate gene expression networks that result in cardioprotective effects.
Potential Benefits of Dynamic Beam Synthesis to Mobile Satellite Communication, Using the Inmarsat 4 Antenna Architecture as a Test Example
Authors: Guy R. F. E.
Published: May 2009

Present mobile satellite communication systems use large antennas to provide multiple high-gain beams. Each beam covers a fixed geographic cell on the earth. Spatial frequency reuse is provided by synthesising beams with low-power levels over all cells operating at the same frequency. The performance needs for future systems are steadily increasing, leading to higher-gain requirements, which are met by using larger antennas with narrower beams. So the antenna pointing errors become a significant loss factor. An alternative approach is to abandon the use of fixed beams and dynamically synthesise the beams to optimise the antenna performance in real time. This both increases user gain and lowers cofrequency interference whilst also reducing the effects of pointing errors. Simulations, using the Inmarsat 4 antenna architecture as a test example, show that the spatial isolation performance can be significantly improved by using Dynamic Beam Synthesis.
Spatial Heterogeneity and Imperfect Mixing in Chemical Reactions: Visualization of Density‐Driven Pattern Formation
Authors: Sobel Sabrina G. , Hastings Harold M. , Testa Matthew
Published: May 2009

Imperfect mixing is a concern in industrial processes, everyday processes (mixing paint, bread machines), and in understanding salt water‐fresh water mixing in ecosystems. The effects of imperfect mixing become evident in the unstirred ferroin‐catalyzed Belousov‐Zhabotinsky reaction, the prototype for chemical pattern formation. Over time, waves of oxidation (high ferriin concentration, blue) propagate into a background of low ferriin concentration (red); their structure reflects in part the history of mixing in the reaction vessel. However, it may be difficult to separate mixing effects from reaction effects. We describe a simpler model system for visualizing density‐driven pattern formation in an essentially unmixed chemical system: the reaction of pale yellow Fe3+ with colorless SCN− to form the blood‐red Fe(SCN) 2+ complex ion in aqueous solution. Careful addition of one drop of Fe to KSCN yields striped patterns after several minutes. The patterns appear reminiscent of Rayleigh‐Taylor instabilities and convection rolls, arguing that pattern formation is caused by density‐driven mixing.
Clinical Efficacy and Toxicity of Anti-EGFR Therapy in Common Cancers
Authors: Harandi Amir , Zaidi Aisha S. , Stocker Abigail M. , Laber Damian A.
Published: May 2009

Epidermal growth factor receptor (EGFR) is a cell surface molecule and member of the ErbB family of receptor tyrosine kinases. Its activation leads to proliferation, antiapoptosis, and metastatic spread, making inhibition of this pathway a compelling target. In recent years, an increasing number of clinical trials in the management of solid malignancies have become available indicating the clinical efficacy of anti-EGFR monoclonal antibodies and oral small molecule tyrosine kinase inhibitors (TKIs). This review addresses frequently used EGFR inhibitors, summarizes clinical efficacy data of these new therapeutic agents, and discusses their associated toxicity and management.
Chaos Synchronization between Two Different Fractional Systems of Lorenz Family
Authors: Matouk A. E.
Published: May 2009

This work investigates chaos synchronization between two different fractional order chaotic systems of Lorenz family. The fractional order Lü system is controlled to be the fractional order Chen system, and the fractional order Chen system is controlled to be the fractional order Lorenz‐like system. The analytical conditions for the synchronization of these pairs of different fractional order chaotic systems are derived by utilizing Laplace transform. Numerical simulations are used to verify the theoretical analysis using different values of the fractional order parameter.
Selective Vulnerability of the Cochlear Basal Turn to Acrylonitrile and Noise
Authors: Pouyatos B. , Gearhart C. A. , Nelson-Miller A. , Fulton S. , Fechter L. D.
Published: May 2009

Exposure to acrylonitrile, a high-production industrial chemical, can promote noise-induced hearing loss (NIHL) in the rat even though this agent does not itself produce permanent hearing loss. The mechanism by which acrylonitrile promotes NIHL includes oxidative stress as antioxidant drugs can partially protect the cochlea fromacrylonitrile+noise. Acrylonitrile depletes glutathione levels while noise can increase the formation of reactive oxygen species. It was previously noted that the high-frequency or basal turn of the cochlea was particularly vulnerable to the combined effects of acrylonitrile and noise when the octave band noise (OBN) was centered at 8 kHz. Normally, such a noise would be expected to yield damage at a more apical region of the cochlea. The present study was designed to determine whether the basal cochlea is selectively sensitive to acrylonitrile or whether, by adjusting the frequency of the noise band, it would be possible to control the region of the auditory impairment. Rats were exposed to one of three different OBNs centered at different frequencies (4 kHz, 110 dB and 8 or 16 kHz at 97 dB) for 5 days, with and without administration of acrylonitrile (50 mg/kg/day). The noise was set to cause limited NIHL by itself. Auditory function was monitored by recording distortion products, by compound action potentials, and by performing cochlear histology. While the ACN-only and noise-only exposures induced no or little permanent auditory loss, the three exposures toacrylonitrile+noiseproduced similar auditory and cochlear impairments above 16 kHz, despite the fact that the noise exposures covered 2 octaves. These observations show that the basal cochlea is much more sensitive toacrylonitrile+noisethan the apical partition. They provide an initial basis for distinguishing the pattern of cochlear injury that results from noise exposure from that which occurs due to the combined effects of noise and a chemical contaminant.
Valuation of Game Options in Jump-Diffusion Model and with Applications to Convertible Bonds
Authors: Wang Lei , Jin Zhiming
Published: May 2009

Game option is an American-type option with added feature that the writer can exercise the option at any time before maturity. In this paper, we consider some type of game options and obtain explicit expressions through solving Stefan(free boundary) problems under condition that the stock price is driven by some jump-diffusion process. Finally, we give a simple application about convertible bonds.
Interaction of E-cadherin and PTEN Regulates Morphogenesis and Growth Arrest in Human Mammary Epithelial Cells
Authors: Fournier Marcia V. , Fata Jimmie E. , Martin Katherine J. , Yaswen Paul , Bissell Mina J.
Published: May 2009

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a dual-function phosphatase with tumor suppressor function compromised in a wide spectrum of cancers. Because tissue polarity and architecture are crucial modulators of normal and malignant behavior, we postulated that PTEN may play a role in maintenance of tissue integrity. We used two nonmalignant human mammary epithelial cell lines that form polarized, growth-arrested structures (acini) when cultured in three-dimensional laminin-rich extracellular matrix gels (lrECM). As acini begin to form, PTEN accumulates both in the cytoplasm and at cell-cell contacts where it colocalizes with the E-cadherin/β-catenin complex. Reduction of PTEN levels by shRNA in lrECM prevents formation of organized breast acini and disrupts growth arrest. Importantly, disruption of acinar polarity and cell-cell contact by E-cadherin function–blocking antibodies reduces endogenous PTEN protein levels and inhibits its accumulation at cell-cell contacts. Conversely, in Skbr-3 breast cancer cells lacking endogenous E-cadherin expression, exogenous introduction of E-cadherin gene causes induction of PTEN expression and its accumulation at sites of cell interactions. These studies provide evidence that E-cadherin regulates both the PTEN protein levels and its recruitment to cell-cell junctions in three-dimensional lrECM, indicating a dynamic reciprocity between architectural integrity and the levels and localization of PTEN. This interaction thus seems to be a critical integrator of proliferative and morphogenetic signaling in breast epithelial cells. [Cancer Res 2009;69(10):4545–52]
Epithelial-to-Mesenchymal Transition and Resistance to Ingenol 3-Angelate, a Novel Protein Kinase C Modulator, in Colon Cancer Cells
Authors: Ghoul Aïda , Serova Maria , Astorgues-Xerri Lucile , Bieche Ivan , Bousquet Guilhem , Varna Mariana , Vidaud Michel , Phillips Edelmira , Weill Sophie , Benhadji Karim A. , Lokiec François , Cvitkovic Esteban , Faivre Sandrine , Raymond Eric
Published: May 2009

Acquired resistance to protein kinase C (PKC) modulators may explain the failure of clinical trials in patients with cancer. Herein, we established a human colon cancer cell line resistant to PEP005, a drug that inhibits PKCα and activates PKCδ. Colo205-R cells, selected by stepwise exposure to PEP005, were >300-fold more resistant to PEP005 than parental Colo205-S cells and were cross-resistant to phorbol 12-myristate 13-acetate, bryostatin, bistratene A, and staurosporine. No PKCα or PKCδ mutation was detected in Colo205-S and Colo205-R cells. Changes in Colo205-R cells were reminiscent of the epithelial-to-mesenchymal transition (EMT) phenotype. Accordingly, Colo205-R cells were more invasive than Colo205-S in Matrigel assays and in mouse xenografts. We also found an increased mRNA expression of several EMT genes, such as those encoding for transforming growth factor-β and vimentin, along with a decreased mRNA expression of genes involved in epithelial differentiation, such as CDH1 (E-cadherin), CLDN4 (claudin 4), S100A4, and MUC1, in Colo205-R compared with Colo205-S cells in vitro and in vivo. Interestingly, high expression of ET-1 was shown in Colo205-R cells and correlated with low sensitivity to PEP005 and staurosporine in a panel of 10 human cancer cell lines. Inhibition of the ET-1 receptor ETR-A with bosentan restored the antiproliferative effects of PEP005 in Colo205-R cells and decreased the invasive properties of this cell line. Exogenous exposure to ET-1 and silencing ET-1 expression using small interfering RNA modulated cell signaling in Colo205-S and Colo205-R. In summary, acquired resistance to PEP005 was associated with expression of EMT markers and activates the ET-1/ETR-A cell signaling. [Cancer Res 2009;69(10):4260–69]
The Role of ATF4 Stabilization and Autophagy in Resistance of Breast Cancer Cells Treated with Bortezomib
Authors: Milani Manuela , Rzymski Tomasz , Mellor Howard R. , Pike Luke , Bottini Alberto , Generali Daniele , Harris Adrian L.
Published: May 2009

The ubiquitin-proteasome system plays a key regulatory role in cellular homeostasis. The inhibition of the 26S proteasome by Bortezomib leads to the accumulation of misfolded proteins, resulting in endoplasmic reticulum stress followed by a coordinated cellular response called unfolded protein response (UPR). Endoplasmic reticulum stress is also a potent inducer of macroautophagy. Bortezomib is a selective and potent inhibitor of the 26S proteasome and is approved for the treatment of multiple myeloma. Clinical trials with Bortezomib have shown promising results for some types of cancers, but not for some others, including those of the breast. In this study, we show that Bortezomib induces the UPR and autophagy in MCF7 breast cancer cells. Surprisingly, Bortezomib did not induce phosphorylation of PERK, a key initial step of the UPR. We show that induction of autophagy by Bortezomib is dependent on the proteasomal stabilisation of ATF4 and up-regulation of LC3B by ATF4. We show that ATF4 and LC3B play a critical role in activating autophagy and protecting cells from Bortezomib-induced cell death. Our experiments also reveal that HDAC6 knockdown results in decreased LC3B protein and reduced autophagy. Our work shows that the induction of autophagy through ATF4 may be an important resistance mechanism to Bortezomib treatment in breast cancer, and targeting autophagy may represent a novel approach to sensitize breast cancers to Bortezomib. [Cancer Res 2009;69(10):4415–23]
RETRACTED: A New Class of Quinoline-Based DNA Hypomethylating Agents Reactivates Tumor Suppressor Genes by Blocking DNA Methyltransferase 1 Activity and Inducing Its Degradation
Authors: Datta Jharna , Ghoshal Kalpana , Denny William A. , Gamage Swarna A. , Brooke Darby G. , Phiasivongsa Pasit , Redkar Sanjeev , Jacob Samson T.
Published: May 2009

Reactivation of silenced tumor suppressor genes by 5-azacytidine (Vidaza) and its congener 5-aza-2′-deoxycytidine (decitabine) has provided an alternate approach to cancer therapy. We have shown previously that these drugs selectively and rapidly induce degradation of the maintenance DNA methyltransferase (DNMT) 1 by a proteasomal pathway. Because the toxicity of these compounds is largely due to their incorporation into DNA, it is critical to explore novel, nonnucleoside compounds that can effectively reactivate the silenced genes. Here, we report that a quinoline-based compound, designated SGI-1027, inhibits the activity of DNMT1, DNMT3A, and DNMT3B as well M. SssI with comparable IC50 (6-13 μmol/L) by competing with S-adenosylmethionine in the methylation reaction. Treatment of different cancer cell lines with SGI-1027 resulted in selective degradation of DNMT1 with minimal or no effects on DNMT3A and DNMT3B. At a concentration of 2.5 to 5 μmol/L (similar to that of decitabine), complete degradation of DNMT1 protein was achieved within 24 h without significantly affecting its mRNA level. MG132 blocked SGI-1027–induced depletion of DNMT1, indicating the involvement of proteasomal pathway. Prolonged treatment of RKO cells with SGI-1027 led to demethylation and reexpression of the silenced tumor suppressor genes P16, MLH1, and TIMP3. Further, this compound did not exhibit significant toxicity in a rat hepatoma (H4IIE) cell line. This study provides a novel class of DNA hypomethylating agents that have the potential for use in epigenetic cancer therapy. [Cancer Res 2009;69(10):4277–85]
A Novel Technology for the Imaging of Acidic Prostate Tumors by Positron Emission Tomography
Authors: Vāvere Amy L. , Biddlecombe Gráinne B. , Spees William M. , Garbow Joel R. , Wijesinghe Dayanjali , Andreev Oleg A. , Engelman Donald M. , Reshetnyak Yana K. , Lewis Jason S.
Published: May 2009

Solid tumors often develop an acidic environment due to the Warburg effect. The effectiveness of diagnosis and therapy may therefore be enhanced by the design and use of pH-sensitive agents that target acidic tumors. Recently, a novel technology was introduced to target acidic tumors using pH low insertion peptide (pHLIP), a peptide that inserts across cell membranes as an α-helix when the extracellular pH (pHe) is acidic. In this study, we expanded the application of the pHLIP technology to include positron emission tomography imaging of the acidic environment in prostate tumors using 64Cu conjugated to the pHLIP (64Cu-DOTA-pHLIP). Studies showed that this construct avidly accumulated in LNCaP and PC-3 tumors, with higher uptake and retention in the LNCaP tumors. Uptake correlated with differences in the bulk pHe of PC-3 and LNCaP tumors measured in magnetic resonance spectroscopy experiments by the 31P chemical shift of the pHe marker 3-aminopropylphosphonate. This article introduces a novel class of noninvasive pH-selective positron emission tomography imaging agents and opens new research directions in the diagnosis of acidic solid tumors. [Cancer Res 2009;69(10):4510–6]
Association between Rectal Optical Signatures and Colonic Neoplasia: Potential Applications for Screening
Authors: Roy Hemant K. , Turzhitsky Vladimir , Kim Young , Goldberg Michael J. , Watson Patrice , Rogers Jeremy D. , Gomes Andrew J. , Kromine Alexey , Brand Randall E. , Jameel Mohammed , Bogovejic Andrej , Pradhan Prabhakar , Backman Vadim
Published: May 2009

Field carcinogenesis detection represents a promising means for colorectal cancer (CRC) screening, although current techniques (e.g., flexible sigmoidoscopy) lack the requisite sensitivity. The novel optical technology low-coherence enhanced backscattering (LEBS) spectroscopy, allows identification of microscale architectural consequences of the field carcinogenesis in preclinical CRC models with unprecedented accuracy. To investigate the potential clinical translatability of this approach, we obtained biopsies from the normal-appearing rectal mucosa from patients undergoing colonoscopy (n = 219). LEBS signals were recorded through a bench-top instrument. Four parameters characterizing LEBS signal were linearly combined into a single marker. We found that LEBS signal parameters generally mirrored neoplasia progression from patients with no neoplasia, to 5 to 9 mm adenoma and to advanced adenomas. The composite LEBS marker calculated from the LEBS signal paralleled this risk status (ANOVA P < 0.001). Moreover, this was independent of CRC risk factors, benign colonic findings, or clinically unimportant lesions (diminutive adenomas, hyperplastic polyps). For advanced adenomas, the LEBS marker had a sensitivity of 100%, specificity of 80%, and area under the receiver operator characteristic curve of 0.895. Leave-one-out cross-validation and an independent data set (n = 51) supported the robustness of these findings. In conclusion, we provide the first demonstration that LEBS-detectable alterations in the endoscopically normal rectum were associated with the presence of neoplasia located elsewhere in the colon. This study provides the proof of concept that rectal LEBS analysis may potentially provide a minimally intrusive CRC screening technique. Further studies with an endoscopically compatible fiber optic probe are under way for multicenter clinical validation. [Cancer Res 2009;69(10):4476–83]
From Chronic Feed-Induced Intestinal Inflammation to Adenocarcinoma with Metastases in Salmonid Fish
Authors: Dale Ole B. , Tørud Brit , Kvellestad Agnar , Koppang Hanna S. , Koppang Erling O.
Published: May 2009

Neoplasms in fish normally show poor abilities for metastasis, and there are no reports on intestinal cancer with metastasis to other organs. In aquaculture production, carnivorous salmonids in Northern Europe receive commercial feeds with plant ingredients. Such contents have been shown to cause chronic intestinal inflammation. Inflammation provokes carcinogenesis in the human gut, and here, we report a similar pathologic progression in salmonids. Nine commercially farmed groups of Atlantic salmon and rainbow trout (n = 39,160) and one experimental positive group (n = 789) fed the same commercial feed and two negative control groups (n = 3009) were investigated for the occurrence of intestinal tumors and metastases. Exposure period, gender, and sexual maturation were registered. Autopsy revealed an overall intestinal tumor occurrence of 10.62%, of which liver metastasis varied from 0% to 11.35% between the groups. Intestinal cancer prevalence increased from 0.50% to 14.81% during 4 months of feeding in the experimental group. A significant gender effect was registered in the commercially farmed groups but not in the experimental group. Histologic examination showed adenocarcinomas evolving through progressive epithelial dysplasia associated with severe chronic inflammation. One intestinal tumor was registered in one individual in the negative control groups. This is the first report on feed-induced intestinal carcinogenesis and metastasizing adenocarcinomas in fish fed an approved commercial diet. The pathogenesis was associated with a certain commercial diet provoking the inflammation-dysplasia-carcinoma sequence. The histologic progression was analogous to that of human colorectal cancer associated with inflammatory bowel disease. [Cancer Res 2009;69(10):4355–62]