bluuebunny/crossref_metadata_2025 huggingface dataset:
Doping of Silicon Quantum Dots Embedded in Nitride Matrix for All-Silicon Tandem Cells
Authors: Huang Shujuan , So Yong Heng , Conibeer Gavin , Green Martin
Published: October 2012

Boron (B)- and antimony (Sb)-doped Si quantum dots (QDs) in Si3N4films were fabricated using the co-sputtering method with a post-deposition anneal. The effect of B and Sb on Si QDs films was investigated in terms of structural, optical and electrical properties. It is found that a low dopant concentration induced negligible structural changes in the Si QD films. The PL intensity decreases with increasing B or Sb content. This could result from the non-radiative recombination processes attributed to defects associated with the dopants and Auger processes due to successful doping of Si QDs. For the B-doped sample the conductivity increases about 100 times, which could be attributed to an increase in carrier concentration. For the Sb-doped sample, a significant increase (six orders of magnitude) in conductivity suggests an effective Sb doping. The charge transport mechanism in the Sb-doped Si QD films matches well with the percolation-hopping model in low temperature region. Both B- and Sb-doped samples show thermally activated hopping conduction characteristics in the range of 220–320 K.
Carbazole Dyes with Ether Groups for Dye-Sensitized Solar Cells: Effect of Negative Charges in Dye Molecules on Electron Lifetime
Authors: Uemura Yu , Mori Shogo , Hara Kohjiro , Koumura Nagatoshi
Published: October 2012

In order to examine the effect of partial charges of dye molecules on charge recombination in dye-sensitized solar cells, we synthesized carbazole-based dyes with ether chains on a π-conjugated oligothiophene linker. The addition of negatively charged oxygen atoms on ether chains resulted in a decrease of electron lifetime, suggesting that partial charges on the dye increased I3
- concentration at the surface of TiO2.
Indoline Dye-Coupled Polyviologen: Its Electrochemical Property and Electropolymerization
Authors: Sano Naoki , Suzuki Miu , Tomita Wataru , Oyaizu Kenichi , Nishide Hiroyuki
Published: October 2012

An indoline dye-coupled polyviologen was designed as a possible photoanode material for organic photovoltaic cells. A new donor–acceptor (D–A) coupled molecule (CVD131) was immobilized on a current collector by the reductive electropolymerization of its two cyanopyridinium moieties. The formed polyviologen could efficiently accept an excited electron from the indoline dye moiety.
Improvement on the Long-Term Stability of Dye-Sensitized Solar Module by Structural Alternation
Authors: Seo Hyunwoong , Son Min-Kyu , Kim Hee-Je , Shiratani Masaharu
Published: October 2012

Dye-sensitized solar cell (DSC) module still lacks the long-term stability because of a volatile electrolyte. In this work, structural alternation of DSC parallel modules was proposed for high performance and stability. In the conventional module, the adhesion with the photo/counter electrodes was not stable with only one layer of sealant so that the stability was poor. On the other hand, buried grid module proposed in this work is possible to be stably sealed with only one layer of sealant. In this structure, grid electrodes are leveled with the same height of transparent conductive oxides (TCOs) because grid electrodes are inserted under furrows of etched TCOs. Consequently, the buried grid module had better long-term stability than conventional module. Additionally, the photo-current and efficiency were improved by the sonicated grid and the light scattering layer.
Photoelectrochemical Properties of Nanocrystalline Sb6O13, MgSb2O6, and ZnSb2O6-Based Electrodes for Dye-Sensitized Solar Cells
Authors: Jang Jiyeon , Kim Seung-Joo
Published: October 2012

Three kinds of antimony compounds – Sb6O13, MgSb2O6 and ZnSb2O6 – were prepared in the form of nanocrystalline film and their photo-electrochemical properties were investigated. The preparation of Sb6O13 was based on thermolysis of a colloidal Sb2O5·4H2O suspension. MgSb2O6 and ZnSb2O6 were prepared via low-temperature hydrothermal methods. All the compounds exhibited semiconducting properties applicable to dye-sensitized solar cell (DSSC). The energy band gaps were estimated to be 3.39 eV for Sb6O13, 3.60 eV for MgSb2O6, and 3.31 eV for ZnSb2O6, respectively. After sensitization with a conventional ruthenium-dye (N719), Sb6O13-based solar cell exhibited the highest open circuit voltage (V
oc = 0.76 V) whereas the V
oc values (0.44–0.46 V) of MgSb2O6 and ZnSb2O6 are relatively low. The V
oc values were proven to be related to the flat band potentials of the antimony compounds. The overall solar-to-electric energy conversion efficiencies were in the range of 0.7–1.0% under AM 1.5, 100 mW/cm2 illumination.
Influence of Thermal Annealing on the Carrier Extraction in Ge/Si Quantum Dot Solar Cells
Authors: Tayagaki Takeshi , Usami Noritaka , Kanemitsu Yoshihiko
Published: October 2012

Ge quantum dot (QD) layers inserted in an intrinsic region of a Si p–i–n diode cause additional photon absorption at longer wavelengths of the solar spectrum. We studied the mechanism of carrier extraction in Ge/Si QD solar cells using photocurrent, capacitance, and photoluminescence measurements. Our findings show that the photon absorption and carrier extraction in Ge/Si QD solar cells depend strongly on the thermal annealing process to form the p–i–n diode. Control of Ge–Si interdiffusion at the Ge/Si interface during thermal annealing is critical for the increase in the conversion efficiency of Ge/Si QD solar cells.
Energy Level Alignment of C60/Ca Interface with Bathocuproine as an Interlayer Studied by Ultraviolet Photoelectron Spectroscopy
Authors: Wang Shenghao , Sakurai Takeaki , Kuroda Ryusuke , Akimoto Katsuhiro
Published: October 2012

The energy level alignment of C60/bathocuproine (BCP)/Ca interfaces as a function of BCP layer thickness has been studied by ultraviolet photoelectron spectroscopy. The results show that the energy level alignment is very sensitive to the BCP layer thickness. The energy levels of the lowest unoccupied molecular orbital of C60 and BCP were found to be almost the same when the thickness of BCP interlayer is less than 1.6 nm. Such energy level alignment, which is favorable to the carrier transport, may be caused by an interaction between C60 and Ca, where Ca passed through the BCP interlayer and diffused to the C60 layer. The role and optimum design for BCP interlayer were discussed.
Epidemiological Analysis of Degradation in Silicon Photovoltaic Modules
Authors: Sakamoto Sadao , Kobayashi Tomonao , Nonomura Shuichi
Published: October 2012

We have studied the power reduction rate and degradation modes of crystalline-silicon photovoltaic modules, which had been operated in an outdoor field for about 10 years. We measured the electric parameters of the modules before and after 10-year operation, and classified our photovoltaic modules into four groups that were manufactured by four manufacturers. Analyzing the age-related decreases in electric parameters of the modules, we found two dominant degradation modes by correlation analysis of the electric parameters. In addition, we found delamination mode degradation by visual inspection. We have recognized a degradation rate in terms of the statistical distribution of the module power reduction. The power reduction rate was found to be an average of 4.7% for ten years.
Estimation of Energy and Analysis of Time-Related Degradation Using Contour Map of Photovoltaic Module Performance
Authors: Yoshida Shota , Minemoto Takashi , Takei Ryosuke , Takakura Hideyuki
Published: October 2012

The output energies of multicrystalline and amorphous silicon/microcrystalline silicon photovoltaic (PV) modules were estimated using the performance contour map as a function of module temperature and solar spectral irradiance distribution taking into consideration time-related degradation. Generally, the performance of outdoor PV modules degrades yearly. When degradation is not considered, the error of the estimated output energy tends to increase yearly. To estimate the precise output energy, the degradation rates of the performance of the PV modules was considered. The yearly degradation rates were estimated using the measurement data from the years 2005–2009 by linear approximation, and the performance contour map in 2010 was estimated. The estimated contour maps were similar to the actual ones, and the errors between the estimated and actual maps were decreased. The error between the estimated and actual energies was within 2.5% in the PV modules. The results indicated that the method of using the contour map taking into account the yearly degradation is useful for estimating the output energy of the PV modules after outdoor exposure.
Diode-Side-Pumped Q-Switched Intracavity Frequency-Doubled Nd:Gd3Ga5O12/LiB3O5 Laser at 555 nm
Authors: Shen Hongbin , Wang Qingpu , Zhang Xingyu , Liu Zhaojun , Bai Fen , Chen Xiaohan , Cong Zhenhua , Gao Liang , Lan Weixia
Published: October 2012

A frequency-doubled laser emitting at 555 nm within a diode-side-pumped acousto optically Q-switched Nd:Gd3Ga5O12 laser is demonstrated for the first time. A simple straight cavity scheme is employed to achieve a compact configuration and all the coatings are specially designed. A 25.5 W 1110 nm laser continuous wave output is achieved under the incident pump power of 168 W. A LiB3O5 crystal is used for second-harmonic generation of the laser. When the pump power is 168 W, the average output power at 555 nm of 6.6 W is obtained, corresponding to the optical conversion efficiency of 3.9%. The minimum pulse width (FWHM) is 176 ns with the pulse repetition rate of 10 kHz. The M
2 factors are measured to be 19.6 and 21.3 in the horizontal and vertical directions, respectively.
Structures and Dielectric Properties of Pb(Fe1/2Nb1/2)1-xTixO3Single Crystals
Authors: Liu Kui , Zhang Xinyi , Wei Shiqiang , Oyanagi Hiroyuki , Xiao Jingzhong
Published: October 2012

The structures and dielectric properties of Pb(Fe1/2Nb1/2)1-xTixO3(PFNT,x= 0.07 and 0.48) single crystals were investigated using a combination of temperature-dependent dielectric, X-ray diffraction (XRD), Raman, and X-ray absorption fine structure (XAFS) spectra. Detailed structure analyses reveal that the crystal structure of PFNT (x= 0.48) is single-phase tetragonal perovskite, whereas that of PFNT (x= 0.07) is a mixture of rhombohedral and tetragonal phases. The structural differences are found to have significant connections with the dielectric properties in the temperature range of 90–300 K. Both samples exhibit a frequency-dependent dielectric anomaly, arising primarily from the 3d electrons hopping between Fe2+and Fe3+. The second dielectric anomaly, which is a weak frequency dispersion and observable only for PFNT (x= 0.07), was probably caused by a dipole glass behavior near the morphotropic phase boundary.
The novel growth factor, progranulin, stimulates mouse cholangiocyte proliferation via sirtuin-1-mediated inactivation of FOXO1
Authors: Frampton Gabriel , Ueno Yoshiyuki , Quinn Matthew , McMillin Matthew , Pae Hae Yong , Galindo Cheryl , Leyva-Illades Dinorah , DeMorrow Sharon
Published: October 2012

Progranulin (PGRN), a secreted growth factor, regulates the proliferation of various epithelial cells. Its mechanism of action is largely unknown. Sirtuin 1 (Sirt1) is a protein deacetylase that is known to regulate the transcriptional activity of the forkhead receptor FOXO1, thereby modulating the balance between proapoptotic and cell cycle-arresting genes. We have shown that PGRN is overexpressed in cholangiocarcinoma and stimulates proliferation. However, its effects on hyperplastic cholangiocyte proliferation are unknown. In the present study, the expression of PGRN and its downstream targets was determined after bile duct ligation (BDL) in mice and in a mouse cholangiocyte cell line after stimulation with PGRN. The effects of PGRN on cholangiocyte proliferation were assessed in sham-operated (sham) and BDL mice treated with PGRN or by specifically knocking down endogenous PGRN expression using Vivo-Morpholinos or short hairpin RNA. PGRN expression and secretion were upregulated in proliferating cholangiocytes isolated after BDL. Treatment of mice with PGRN increased biliary mass and cholangiocyte proliferation in vivo and in vitro and enhanced cholangiocyte proliferation observed after BDL. PGRN treatment decreased Sirt1 expression and increased the acetylation of FOXO1, resulting in the cytoplasmic accumulation of FOXO1 in cholangiocytes. Overexpression of Sirt1 in vitro prevented the proliferative effects of PGRN. Conversely, knocking down PGRN expression in vitro or in vivo inhibited cholangiocyte proliferation. In conclusion, these data suggest that the upregulation of PGRN may be a key feature stimulating cholangiocyte proliferation. Modulating PGRN levels may be a viable technique for regulating the balance between ductal proliferation and ductopenia observed in a variety of cholangiopathies.
Xenin-25 increases cytosolic free calcium levels and acetylcholine release from a subset of myenteric neurons
Authors: Zhang Sheng , Hyrc Krzysztof , Wang Songyan , Wice Burton M.
Published: October 2012

Xenin-25 (Xen) is a 25 amino acid neurotensin-related peptide reportedly produced with glucose-dependent insulinotropic polypeptide (GIP) by a subset of K cells in the proximal gut. We previously showed exogenously administered Xen, with GIP but not alone, increases insulin secretion in humans and mice. In mice, this effect is indirectly mediated via a central nervous system-independent cholinergic relay in the periphery. Xen also delays gastric emptying, reduces food intake, induces gall bladder contractions, and increases gut motility and secretion from the exocrine pancreas, suggesting that some effects of Xen could be mediated by myenteric neurons (MENs). To determine whether Xen activates these neurons, MENs were isolated from guinea pig proximal small intestines. Cells expressed neuronal markers and exhibited typical neuron-like morphology with extensive outgrowths emanating from cell bodies. Cytosolic free Ca2+levels ([Ca2+]i) were measured using Fura-2. ATP/UTP, KCl, and forskolin increased [Ca2+]iin 99.6%, 92%, and 23% of the MENs imaged, respectively, indicating that they are functional and activated by nucleotide receptor signaling, direct depolarization, and cAMP. [Ca2+]iincreased in only 12.7% of MENs treated with Xen. This rise was blocked by pretreatment with EGTA, diazoxide, SR48692, and neurotensin. Thus the Xen-mediated increase in [Ca2+]iinvolves influx of extracellular Ca2+and activation of neurotensin receptor-1 (NTSR1). Xen also increased acetylcholine release from MENs. Amylin, produced by β-and enteroendocrine cells, delays gastric emptying and increased [Ca2+]ialmost exclusively in Xen-responsive MENs. Immunohistochemistry demonstrated NTSR1 expression in human duodenal MENs. Thus myenteric rather than central neurons could mediate some effects of Xen and amylin.
Lactobacillus acidophilus upregulates intestinal NHE3 expression and function
Authors: Singh Varsha , Raheja Geetu , Borthakur Alip , Kumar Anoop , Gill Ravinder K. , Alakkam Anas , Malakooti Jaleh , Dudeja Pradeep K.
Published: October 2012

A major mechanism of electroneutral NaCl absorption in the human ileum and colon involves coupling of Na+/H+ and Cl−/HCO3− exchangers. Disturbances in these mechanisms have been implicated in diarrheal conditions. Probiotics such as Lactobacillus have been indicated to be beneficial in the management of gastrointestinal disorders, including diarrhea. However, the molecular mechanisms underlying antidiarrheal effects of probiotics have not been fully understood. We have previously demonstrated Lactobacillus acidophilus (LA) to stimulate Cl−/HCO3− exchange activity via an increase in the surface levels and expression of the Cl−/HCO3− exchanger DRA in vitro and in vivo. However, the effects of LA on NHE3, the Na+/H+ exchanger involved in the coupled electroneutral NaCl absorption, are not known. Current studies were, therefore, undertaken to investigate the effects of LA on the function and expression of NHE3 and to determine the mechanisms involved. Treatment of Caco2 cells with LA or its conditioned culture supernatant (CS) for 8–24 h resulted in a significant increase in Na+/H+ exchange activity, mRNA, and protein levels of NHE3. LA-CS upregulation of NHE3 function and expression was also observed in SK-CO15 cells, a human colonic adenocarcinoma cell line. Additionally, LA treatment increased NHE3 promoter activity, suggesting involvement of transcriptional mechanisms. In vivo, mice gavaged with live LA showed significant increase in NHE3 mRNA and protein expression in the ileum and colonic regions. In conclusion, LA-induced increase in NHE3 expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of probiotics.
The scanning ion conductance microscope for cellular physiology
Authors: Lab Max J. , Bhargava Anamika , Wright Peter T. , Gorelik Julia
Published: October 2012

The quest for nonoptical imaging methods that can surmount light diffraction limits resulted in the development of scanning probe microscopes. However, most of the existing methods are not quite suitable for studying biological samples. The scanning ion conductance microscope (SICM) bridges the gap between the resolution capabilities of atomic force microscope and scanning electron microscope and functional capabilities of conventional light microscope. A nanopipette mounted on a three-axis piezo-actuator, scans a sample of interest and ion current is measured between the pipette tip and the sample. The feedback control system always keeps a certain distance between the sample and the pipette so the pipette never touches the sample. At the same time pipette movement is recorded and this generates a three-dimensional topographical image of the sample surface. SICM represents an alternative to conventional high-resolution microscopy, especially in imaging topography of live biological samples. In addition, the nanopipette probe provides a host of added modalities, for example using the same pipette and feedback control for efficient approach and seal with the cell membrane for ion channel recording. SICM can be combined in one instrument with optical and fluorescent methods and allows drawing structure-function correlations. It can also be used for precise mechanical force measurements as well as vehicle to apply pressure with precision. This can be done on living cells and tissues for prolonged periods of time without them loosing viability. The SICM is a multifunctional instrument, and it is maturing rapidly and will open even more possibilities in the near future.
Passive limb movement: evidence of mechanoreflex sex specificity
Authors: Ives Stephen J. , McDaniel John , Witman Melissa A. H. , Richardson Russell S.
Published: October 2012

Previous studies have determined that premenopausal women exhibit an attenuated metaboreflex; however, little is known about sex specificity of the mechanoreflex. Thus, we sought to determine if sex differences exist in the central and peripheral hemodynamic responses to passive limb movement. Second-by-second measurements of heart rate, stroke volume, cardiac output (CO), mean arterial pressure, and femoral artery blood flow (FBF) were recorded during 3 min of supine passive knee extension in 24 young healthy subjects (12 women and 12 men). Normalization of CO and stroke volume to body surface area, expressed as cardiac index and stroke index, eliminated differences in baseline central hemodynamics, whereas, peripherally, basal FBF and femoral vascular conductance were similar between the sexes. In response to passive limb movement, women displayed significantly attenuated peak central hemodynamic responses compared with men (heart rate: 9.0 ± 1 vs. 14.8 ± 2% change, stroke index: 4.5 ± 0.6 vs. 7.8 ± 1.2% change, cardiac index: 9.6 ± 1 vs. 17.2 ± 2% change, all P < 0.05), whereas movement induced similar increases in peak FBF (167 ± 32 vs. 193 ± 17% change) and femoral vascular conductance (172 ± 31 vs. 203 ± 16% change) in both sexes (women vs. men, respectively). Additionally, there was a significant positive relationship between individual peak FBF and peak CO response to passive movement in men but not in women. Thus, although both sexes exhibited similar movement-induced hyperemia and peripheral vasodilatory function, the central hemodynamic response was blunted in women, implying an attenuated mechanoreflex. Therefore, this study reveals that, as already recognized with the metaboreflex, there is likely a sex-specific attenuation of the mechanoreflex in women.
Ventricular tachyarrhythmias in rats with acute myocardial infarction involves activation of small-conductance Ca2+-activated K+channels
Authors: Gui Le , Bao Zhiwei , Jia Yinyu , Qin Xiaotong , (Jack) Cheng Zixi , Zhu Jianhua , Chen Qing-Hui
Published: October 2012

In vitro experiments have shown that the upregulation of small-conductance Ca2+-activated K+(SK) channels in ventricular epicardial myocytes is responsible for spontaneous ventricular fibrillation (VF) in failing ventricles. However, the role of SK channels in regulating VF has not yet been described in in vivo acute myocardial infarction (AMI) animals. The present study determined the role of SK channels in regulating spontaneous sustained ventricular tachycardia (SVT) and VF, the inducibility of ventricular tachyarrhythmias, and the effect of inhibition of SK channels on spontaneous SVT/VF and electrical ventricular instability in AMI rats. AMI was induced by ligation of the left anterior descending coronary artery in anesthetized rats. Spontaneous SVT/VF was analyzed, and programmed electrical stimulation was performed to evaluate the inducibility of ventricular tachyarrhythmias, ventricular effective refractory period (VERP), and VF threshold (VFT). In AMI, the duration and episodes of spontaneous SVT/VF were increased, and the inducibility of ventricular tachyarrhythmias was elevated. Pretreatment in the AMI group with the SK channel blocker apamin or UCL-1684 significantly reduced SVT/VF and inducibility of ventricular tachyarrhythmias ( P < 0.05). Various doses of apamin (7.5, 22.5, 37.5, and 75.0 μg/kg iv) inhibited SVT/VF and the inducibility of ventricular tachyarrhythmias in a dose-dependent manner. Notably, no effects were observed in sham-operated controls. Additionally, VERP was shortened in AMI animals. Pretreatment in AMI animals with the SK channel blocker significantly prolonged VERP ( P < 0.05). No effects were observed in sham-operated controls. Furthermore, VFT was reduced in AMI animals, and block of SK channels increased VFT in AMI animals, but, again, this was without effect in sham-operated controls. Finally, the monophasic action potential duration at 90% repolarization (MAPD90) was examined in the myocardial infarcted (MI) and nonmyocardial infarcted areas (NMI) of the left ventricular epicardium. Electrophysiology recordings showed that MAPD90in the MI area was shortened in AMI animals, and pretreatment with SK channel blocker apamin or UCL-1684 significantly prolonged MAPD90( P < 0.05) in the MI area but was without effect in the NMI area or in sham-operated controls. We conclude that the activation of SK channels may underlie the mechanisms of spontaneous SVT/VF and suseptibility to ventricular tachyarrhythmias in AMI. Inhibition of SK channels normalized the shortening of MAPD90in the MI area, which may contribute to the inhibitory effect on spontaneous SVT/VF and inducibility of ventricular tachyarrhythmias in AMI.
Site-specific dynamics of CD11b+and CD103+dendritic cell accumulations following ozone exposure
Authors: Brand Jeffrey D. , Ballinger Carol A. , Tuggle Katherine L. , Fanucchi Michelle V. , Schwiebert Lisa M. , Postlethwait Edward M.
Published: October 2012

Pulmonary dendritic cells (DCs) are among the first responders to inhaled environmental stimuli such as ozone (O3), which has been shown to activate these cells. O3reacts with epithelial lining fluid (ELF) components in an anatomically site-specific manner dictated by O3concentration, airway flow patterns, and ELF substrate concentration. Accordingly, the anatomical distribution of ELF reaction products and airway injury are hypothesized to produce selective DC maturation differentially within the airways. To investigate how O3affects regional airway DC populations, we utilized a model of O3-induced pulmonary inflammation, wherein C57BL/6 mice were exposed to 0.8 ppm O38 h/day for 1, 3, and 5 days. This model induced mild inflammation and no remarkable epithelial injury. Tracheal, but not more distant airway sites, and mediastinal lymph node (MLN) DC numbers were increased significantly after the third exposure day. The largest increase in each tissue was of the CD103+DC phenotype. After 3 days of exposure, fewer DCs expressed CD80, CD40, and CCR7, and, at this same time point, total MLN T cell numbers increased. Together, these data demonstrate that O3exposure induced site-specific and phenotype changes in the pulmonary and regional lymph node DC populations. Possibly contributing to ozone-mediated asthma perturbation, the phenotypic changes to DCs within pulmonary regions may alter responses to antigenic stimuli. Decreased costimulatory molecule expression within the MLN suggests induction of tolerance mechanisms; increased tracheal DC number may raise the potential for allergic sensitization and asthmatic exacerbation, thus overcoming O3-induced decrements in costimulatory molecule expression.
Insufficient autophagy in idiopathic pulmonary fibrosis
Authors: Araya Jun , Kojima Jun , Takasaka Naoki , Ito Saburo , Fujii Satoko , Hara Hiromichi , Yanagisawa Haruhiko , Kobayashi Kenji , Tsurushige Chikako , Kawaishi Makoto , Kamiya Noriki , Hirano Jun , Odaka Makoto , Morikawa Toshiaki , Nishimura Stephen L. , Kawabata Yoshinori , Hano Hiroshi , Nakayama Katsutoshi , Kuwano Kazuyoshi
Published: October 2012

Autophagy, a process that helps maintain homeostatic balance between the synthesis, degradation, and recycling of organelles and proteins to meet metabolic demands, plays an important regulatory role in cellular senescence and differentiation. Here we examine the regulatory role of autophagy in idiopathic pulmonary fibrosis (IPF) pathogenesis. We test the hypothesis that epithelial cell senescence and myofibroblast differentiation are consequences of insufficient autophagy. Using biochemical evaluation of in vitro models, we find that autophagy inhibition is sufficient to induce acceleration of epithelial cell senescence and myofibroblast differentiation in lung fibroblasts. Immunohistochemical evaluation of human IPF biospecimens reveals that epithelial cells show increased cellular senescence, and both overlaying epithelial cells and fibroblasts in fibroblastic foci (FF) express both ubiquitinated proteins and p62. These findings suggest that insufficient autophagy is an underlying mechanism of both accelerated cellular senescence and myofibroblast differentiation in a cell-type-specific manner and is a promising clue for understanding the pathogenesis of IPF.
High pulsatility flow stimulates smooth muscle cell hypertrophy and contractile protein expression
Authors: Scott Devon , Tan Yan , Shandas Robin , Stenmark Kurt R. , Tan Wei
Published: October 2012

Proximal arterial stiffening is an important predictor of events in systemic and pulmonary hypertension, partly through its contribution to downstream vascular abnormalities. However, much remains undetermined regarding the mechanisms involved in the vascular changes induced by arterial stiffening. We therefore addressed the hypothesis that high pulsatility flow, caused by proximal arterial stiffening, induces downstream pulmonary artery endothelial cell (EC) dysfunction that in turn leads to phenotypic change of smooth muscle cells (SMCs). To test the hypothesis, we employed a model pulmonary circulation in which upstream compliance regulates the pulsatility of flow waves imposed onto a downstream vascular mimetic coculture composed of pulmonary ECs and SMCs. The effects of high pulsatility flow on SMCs were determined both in the presence and absence of ECs. In the presence of ECs, high pulsatility flow increased SMC size and expression of the contractile proteins, smooth muscle α-actin (SMA) and smooth muscle myosin heavy chain (SM-MHC), without affecting proliferation. In the absence of ECs, high pulsatility flow decreased SMC expression of SMA and SM-MHC, without affecting SMC size or proliferation. To identify the molecular signals involved in the EC-mediated SMC responses, mRNA and/or protein expression of vasoconstrictors [angiotensin-converting enzyme (ACE) and endothelin (ET)-1], vasodilator (eNOS), and growth factor (TGF-β1) in EC were examined. Results showed high pulsatility flow decreased eNOS and increased ACE, ET-1, and TGF-β1 expression. ACE inhibition with ramiprilat, ET-1 receptor inhibition with bosentan, and treatment with the vasodilator bradykinin prevented flow-induced, EC-dependent SMC changes. In conclusion, high pulsatility flow stimulated SMC hypertrophy and contractile protein expression by altering EC production of vasoactive mediators and cytokines, supporting the idea of a coupling between proximal vascular stiffening, flow pulsatility, and downstream vascular function.
Reduced motor unit discharge rates of maximal velocity dynamic contractions in response to a submaximal dynamic fatigue protocol
Authors: Harwood B. , Choi I. , Rice C. L.
Published: October 2012

Fatigability is highly task dependent wherein motor unit (MU) discharge rates and recruitment thresholds are affected differently depending on whether contractions are performed at maximal or submaximal intensities. Although much is described for isometric tasks, the behavior of MU properties during the production of maximal velocity dynamic contractions following submaximal fatiguing contractions is unknown. In seven young men, we evaluated changes in MU recruitment thresholds and MU discharge rates of the anconeus muscle during both submaximal and maximal dynamic elbow extensions following a submaximal dynamic fatiguing protocol of moderate intensity to velocity task failure. Velocity and power of the maximal dynamic contractions declined ∼45 and ∼55%, respectively, but these variables were unchanged for the submaximal target velocity contractions. Discharge rates of the 12 MUs at task failure were unchanged for submaximal dynamic contractions, but were decreased ∼20% for maximal dynamic and ballistic isometric contractions at task failure. MU recruitment thresholds of submaximal dynamic contractions decreased 52% at task failure, but were similar throughout the fatiguing protocol for maximal contractions. These findings support the concept of a common neural mechanism responsible for the relative declines in MU discharge rate associated with submaximal fatigability in both isometric and dynamic contractions.
Role of autophagy in COPD skeletal muscle dysfunction
Authors: Hussain Sabah N. A. , Sandri Marco
Published: October 2012

Chronic obstructive pulmonary disease (COPD) is a debilitating disease caused by parenchymal damage and irreversible airflow limitation. In addition to lung dysfunction, patients with COPD develop weight loss, malnutrition, poor exercise performance, and skeletal muscle atrophy. The latter has been attributed to an imbalance between muscle protein synthesis and protein degradation. Several reports have confirmed that enhanced protein degradation and atrophy of limb muscles of COPD patient is mediated in part through activation of the ubiquitin-proteasome pathway and that this activation is triggered by enhanced production of reactive oxygen species. Until recently, the importance of the autophagy-lysosome pathway in protein degradation of skeletal muscles has been largely ignored, however, recent evidence suggests that this pathway is actively involved in recycling of cytosolic proteins, organelles, and protein aggregates in normal skeletal muscles. The protective role of autophagy in the regulation of muscle mass has recently been uncovered in mice with muscle-specific suppression of autophagy. These mice develop severe muscle weakness, atrophy, and decreased muscle contractility. No information is yet available about the involvement of the autophagy in the regulation of skeletal muscle mass in COPD patients. Pilot experiments on vastus lateralis muscle samples suggest that the autophagy-lysosome system is induced in COPD patients compared with control subjects. In this review, we summarize recent progress related to molecular structure, regulation, and roles of the autophagy-lysosome pathway in normal and diseased skeletal muscles. We also speculate about regulation and functional importance of this system in skeletal muscle dysfunction in COPD patients.
Functional classification of skeletal muscle networks. I. Normal physiology
Authors: Wang Yu , Winters Jack , Subramaniam Shankar
Published: October 2012

Extensive measurements of the parts list of human skeletal muscle through transcriptomics and other phenotypic assays offer the opportunity to reconstruct detailed functional models. Through integration of vast amounts of data present in databases and extant knowledge of muscle function combined with robust analyses that include a clustering approach, we present both a protein parts list and network models for skeletal muscle function. The model comprises the four key functional family networks that coexist within a functional space; namely, excitation-activation family (forward pathways that transmit a motoneuronal command signal into the spatial volume of the cell and then use Ca2+fluxes to bind Ca2+to troponin C sites on F-actin filaments, plus transmembrane pumps that maintain transmission capacity); mechanical transmission family (a sophisticated three-dimensional mechanical apparatus that bidirectionally couples the millions of actin-myosin nanomotors with external axial tensile forces at insertion sites); metabolic and bioenergetics family (pathways that supply energy for the skeletal muscle function under widely varying demands and provide for other cellular processes); and signaling-production family (which represents various sensing, signal transduction, and nuclear infrastructure that controls the turn over and structural integrity and regulates the maintenance, regeneration, and remodeling of the muscle). Within each family, we identify subfamilies that function as a unit through analysis of large-scale transcription profiles of muscle and other tissues. This comprehensive network model provides a framework for exploring functional mechanisms of the skeletal muscle in normal and pathophysiology, as well as for quantitative modeling.
Functional classification of skeletal muscle networks. II. Applications to pathophysiology
Authors: Wang Yu , Winters Jack , Subramaniam Shankar
Published: October 2012

In our preceding companion paper (Wang Y, Winters J, Subramaniam S. J Appl Physiol. doi: 10.1152/japplphysiol.01514.2011), we used extensive expression profile data on normal human subjects, in combination with legacy knowledge to classify skeletal muscle function into four models, namely excitation-activation, mechanical, metabolic, and signaling-production model families. In this paper, we demonstrate how this classification can be applied to study two well-characterized myopathies: amyotrophic lateral sclerosis (ALS) and Duchenne muscular dystrophy (DMD). Using skeletal muscle profile data from ALS and DMD patients compared with that from normal subjects, normal young in the case of DMD, we delineate molecular mechanisms that are causative and consequential to skeletal muscle dysfunction. In ALS, our analysis establishes the metabolic role and specifically identifies the mechanisms of calcium dysregulation and defects in mitochondrial transport of materials as important for muscle dysfunction. In DMD, we illustrate how impaired mechanical function is strongly coordinated with other three functional networks, resulting in transformation of the skeletal muscle into hybrid forms as a compensatory mechanism. Our functional models also provide, in exquisite detail, the mechanistic role of myriad proteins in these four families in normal and disease function.
A Nonclassical Radau Collocation Method for Nonlinear Initial‐Value Problems with Applications to Lane‐Emden Type Equations
Authors: Maleki Mohammad , Tavassoli Kajani M. , Hashim I. , Kilicman A. , Atan K. A. M.
Published: October 2012

We propose a numerical method for solving nonlinear
initial‐value problems of Lane‐Emden type. The method is based upon
nonclassical Gauss‐Radau collocation points, and weighted interpolation.
Nonclassical orthogonal polynomials, nonclassical Radau points
and weighted interpolation are introduced on arbitrary intervals. Then
they are utilized to reduce the computation of nonlinear initial‐value
problems to a system of nonlinear algebraic equations. We also present
the comparison of this work with some well‐known results and show
that the present solution is very accurate.
On Impulsive Boundary Value Problems of Fractional Differential Equations with Irregular Boundary Conditions
Authors: Wang Guotao , Ahmad Bashir , Zhang Lihong
Published: October 2012

We study nonlinear impulsive differential equations of fractional order with irregular boundary conditions. Some existence and uniqueness results are obtained by applying standard fixed‐point theorems. For illustration of the results, some examples are discussed.
Digital Augmented Reality Audio Headset
Authors: Rämö Jussi , Välimäki Vesa
Published: October 2012

Augmented reality audio (ARA) combines virtual sound sources with the real sonic environment of the user. An ARA system can be realized with a headset containing binaural microphones. Ideally, the ARA headset should be acoustically transparent, that is, it should not cause audible modification to the surrounding sound. A practical implementation of an ARA mixer requires a low‐latency headphone reproduction system with additional equalization to compensate for the attenuation and the modified ear canal resonances caused by the headphones. This paper proposes digital IIR filters to realize the required equalization and evaluates a real‐time prototype ARA system. Measurements show that the throughput latency of the digital prototype ARA system can be less than 1.4 ms, which is sufficiently small in practice. When the direct and processed sounds are combined in the ear, a comb filtering effect is brought about and appears as notches in the frequency response. The comb filter effect in speech and music signals was studied in a listening test and it was found to be inaudible when the attenuation is 20 dB. Insert ARA headphones have a sufficient attenuation at frequencies above about 1 kHz. The proposed digital ARA system enables several immersive audio applications, such as a virtual audio tourist guide and audio teleconferencing.
Systemic and Urinary Neutrophil Gelatinase-Associated Lipocalins Are Poor Predictors of Acute Kidney Injury in Unselected Critically Ill Patients
Authors: Royakkers Annick A. , Bouman Catherine S. , Stassen Pauline M. , Korevaar Joke C. , Binnekade Jan M. , van de Hoek Willem , Kuiper Michael A. , Spronk Peter E. , Schultz Marcus J.
Published: October 2012

Background. Neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine have been suggested as potential early predictive biological markers of acute kidney injury (AKI) in selected critically ill patients.Methods. We performed a secondary analysis of a multicenter prospective observational cohort study of unselected critically ill patients.Results. The analysis included 140 patients, including 57 patients who did not develop AKI, 31 patients who developed AKI, and 52 patients with AKI on admission to the ICU. Levels of sNGAL and uNGAL on non-AKI days were significantly lower compared to levels of sNGAL on RIFLERISKdays, RIFLEINJURYdays, and RIFLEFAILUREdays. The AUC of sNGAL for predicting AKI was low: 0.45 (95% confidence interval (CI) 0.27–0.63) and 0.53 (CI 0.38–0.67), 2 days and 1 day before development of AKI, respectively. The AUC of uNGAL for predicting AKI was also low: 0.48 (CI 0.33–0.62) and 0.48 (CI 0.33–0.62), 2 days and 1 day before development of AKI, respectively. AUC of sNGAL and uNGAL for the prediction of renal replacement therapy requirement was 0.47 (CI 0.37–0.58) and 0.26 (CI 0.03–0.50).Conclusions. In unselected critically ill patients, sNGAL and uNGAL are poor predictors of AKI or RRT.
Radiographically Negative, Asymptomatic, Sentinel Lymph Node Positive Cutaneous T-Cell Lymphoma in a 3-Year-Old Male: A Case Report
Authors: Carson Jeffrey , Bedrnicek Jiri , Abdessalam Shahab
Published: October 2012

We present a case of a 3-year-old male originally diagnosed with a CD30+ anaplastic cutaneous T-cell lymphoma with no evidence of systemic disease after CT scan, PET scan, and bone marrow aspiration. Sentinel lymph node biopsy (SLNB) was performed as an additional step in the workup and showed microscopic disease. Current management/recommendations for cutaneous T-cell lymphoma do not include SLNB. Medical and surgical management of cutaneous malignancies is dramatically different for local versus advanced disease. Therefore adequate evaluation is necessary to properly stage patients for specific treatment. Such distinction in extent of disease suggests more extensive therapy including locoregional radiation and systemic chemotherapy versus local excision only. Two international case reports have described SLNB in cutaneous T-cell lymphoma with one demonstrating evidence of node positive microscopic disease despite a negative metastatic disease workup. This case is being presented as a novel case in a child with implications including lymphoscintigraphy and SLNB as a routine procedure for evaluation and staging of cutaneous T-cell lymphoma if the patient does not demonstrate evidence of metastatic disease on routine workup.
Dynamic Properties of a Forest Fire Model
Authors: Min Na , Zhang Hongyang , Qu Zhilin
Published: October 2012

The reaction‐diffusion equations have been widely used in physics, chemistry, and other areas. Forest fire can also be described by such equations. We here propose a fighting forest fire model. By using the normal form approach theory and center manifold theory, we analyze the stability of the trivial solution and Hopf bifurcation of this model. Finally, we give the numerical simulations to illustrate the effectiveness of our results.
Determination of the Ionization Constants of Some Benzoyl Thiourea Derivatives in Dioxane‐Water Mixture
Authors: Binzet Gun , Zeybek Bülent , Kılıç Esma , Külcü Nevzat , Arslan Hakan
Published: October 2012

The stoichiometric ionization constants of N,N‐dialkyl‐N′‐(4‐substituted benzoyl) thiourea (Substitutes: H, Cl, and Br; alkyl groups: ethyl, n‐propyl, n‐butyl, and phenyl) derivatives have been determined potentiometrically in dioxane‐water (v:v, 50:50) mixture at ionic strength of 0.1 M and 25.0 ± 0.1°C. The ionization constants were calculated with the BEST computer program and the formation curves using the data obtained from the potentiometric titrations. The effects of substituents and alkyl groups on the ionization constants of the benzoyl thiourea derivatives have been investigated. A comparison of the basicities of ethyl, n‐propyl, and n‐butyl thiourea derivatives (−C2H5 < −C3H7 < −C4H9) shows that the n‐butyl group is a more powerful electron‐releasing group than the other groups in 50% dioxane‐50% water mixture (v:v). So, the acidity of benzoyl thiourea derivative compounds decreases, while the length of alkyl chain increases. The orders of pKa values for all thiourea derivatives are as expected in the light of steric, resonance and inductive effects of substituents. Furthermore, when the basicities of halogen derivatives of the same substitution pattern are compared, orders obtained (4‐Br <4‐Cl <4‐H) can be explained by considering the total electronic substituent effect (electron‐withdrawing and electron‐donating effects) except the 4‐Br_Ph derivative.
Al‐MCM‐41: An Efficient and Recyclable Heterogeneous Catalyst for the Synthesis of β‐Hydroxy Thiocyanates in Water
Authors: Sayyahi Soheil , Menati Saied , Karamipour Mehri
Published: October 2012

An efficient and green procedure has been developed for the synthesis of β‐hydroxy thiocyanate by the regioselective ring opening of epoxides with NH4SCN. The reaction was carried out in water without any organic solvent at 40°C, using Al‐MCM‐41 (a mesoporous aluminosilicate) as catalyst. In this method, several types of epoxides carrying electron‐donating or withdrawing groups were rapidly converted to the corresponding β‐hydroxy thiocyanates in good from excellent yields. Various advantages associated with this protocol include simple workup procedure, short reaction times, high product yields, greater regioselectivity, and easy recovery and reusability of the catalyst.
Targeting CD4+ T-Helper Cells Improves the Induction of Antitumor Responses in Dendritic Cell–Based Vaccination
Authors: Aarntzen Erik H.J.G. , De Vries I. Jolanda M. , Lesterhuis W. Joost , Schuurhuis Danita , Jacobs Joannes F.M. , Bol Kalijn , Schreibelt Gerty , Mus Roel , De Wilt Johannes H.W. , Haanen John B.A.G. , Schadendorf Dirk , Croockewit Alexandra , Blokx Willeke A.M. , Van Rossum Michelle M. , Kwok William W. , Adema Gosse J. , Punt Cornelis J.A. , Figdor Carl G.
Published: October 2012

To evaluate the relevance of directing antigen-specific CD4+ T helper cells as part of effective anticancer immunotherapy, we investigated the immunologic and clinical responses to vaccination with dendritic cells (DC) pulsed with either MHC class I (MHC-I)–restricted epitopes alone or both MHC class I and II (MHC-I/II)–restricted epitopes. We enrolled 33 stage III and IV HLA-A*02:01–positive patients with melanoma in this study, of whom 29 were evaluable for immunologic response. Patients received intranodal vaccinations with cytokine-matured DCs loaded with keyhole limpet hemocyanin and MHC-I alone or MHC-I/II–restricted tumor-associated antigens (TAA) of tyrosinase and gp100, depending on their HLA-DR4 status. In 4 of 15 patients vaccinated with MHC-I/II–loaded DCs and 1 of 14 patients vaccinated with MHC-I–loaded DCs, we detected TAA-specific CD8+ T cells with maintained IFN-γ production in skin test infiltrating lymphocyte (SKIL) cultures and circulating TAA-specific CD8+ T cells. If TAA-specific CD4+ T-cell responses were detected in SKIL cultures, it coincided with TAA-specific CD8+ T-cell responses. In 3 of 13 patients tested, we detected TAA-specific CD4+CD25+FoxP3− T cells with high proliferative capacity and IFN-γ production, indicating that these were not regulatory T cells. Vaccination with MHC-I/II–loaded DCs resulted in improved clinical outcome compared with matched control patients treated with dacarbazine (DTIC), median overall survival of 15.0 versus 8.3 months (P = 0.089), and median progression-free survival of 5.0 versus 2.8 months (P = 0.0089). In conclusion, coactivating TAA-specific CD4+ T-helper cells with DCs pulsed with both MHC class I and II–restricted epitopes augments TAA-specific CD8+ T-cell responses, contributing to improved clinical responses. Cancer Res; 73(1); 19–29. ©2012 AACR.