bluuebunny/crossref_metadata_2025 huggingface dataset:
NOISE IN SWAPPING BETWEEN TWO PAIRS OF NON-ORTHOGONAL ENTANGLED COHERENT STATES
Authors: KUMAR SHIVANI A. , PRAKASH H. , CHANDRA N. , PRAKASH R.
Published: December 2012

We consider a scheme of swapping between two pairs of non-orthogonal entangled coherent states with our suggested modification [H. Prakash, N. Chandra, R. Prakash and Shivani, Int. J. Mod. Phys. B 23(8) (2009) 2083] and discuss effect of decoherence on fidelity in swapping. We find that for odd photon counts, MAF (minimum of the fidelity for any arbitrary information) decreases with increase in |α|2 for low noise but in case of high noise, it increases, attains a maximum value and then decreases with |α|2. However, for nonzero even photon counts, the case is reversed. For this case, MAF decreases with increase in |α|2 for high noise but in case of low noise, it increases, attains a maximum value and then decreases with |α|2. We discuss the variation of average fidelity with |α|2 and show that it depends appreciably on the information for low values of |α|2 only.
CONFINEMENT OF A DIRAC PARTICLE TO A HARD-WALL CONFINING POTENTIAL INDUCED BY NONINERTIAL EFFECTS
Authors: BAKKE K.
Published: December 2012

In this contribution, we discuss the influence of noninertial effects on a Dirac particle in the Minkowski spacetime by showing that the geometry of the manifold can play the role of a hard-wall confining potential. Thus, we discuss a limit case where the relativistic bound states can be achieved in analogous way to having a Dirac particle confined to a quantum dot. We discuss the application of this mathematical model in studies of noninertial effects on condensed matter systems described by the Dirac equation, and compare the nonrelativistic limit of the energy levels with the spectrum of energy of a spin-½ particle confined to a quantum dot [E. Tsitsishvili et al., Phys. Rev. B70 (2004) 115316].
DESIGN OF NOVEL COMPOSITE BEAM SPLITTER WITH DIRECTIONAL COUPLERS AND RING RESONATORS USING PHOTONIC CRYSTAL
Authors: LIAO QINGHUA , GUO HAO , YU TIANBAO , HUANG YONGZHEN
Published: December 2012

We propose and analyze a novel multiway high efficiency composite beam splitter based on propagation properties of the light waves in directional coupler (DC) and ring resonator. The spectral transmittance and splitting properties of the beam splitter have been numerically simulated and analyzed using the plane wave expansion (PWE) method and finite difference time domain (FDTD) method. By simply adjusting the symmetrical coupling rods in the ring resonators, inducing the redistribution of the power of the optical field, equipartition or free distribution of the light field energy can be achieved. It was shown that the novel composite beam splitter has a large separating angle, a high beam transmittance, and high flexibility. Furthermore, this beam splitter can be easily extended to the structure with more light output channels. These features of the proposed composite beam splitter make it a promising candidate in optical communication applications.
AN EFFECTIVE DISTRIBUTED MODEL FOR XMLISED POWER SYSTEM DATA GENERATION
Authors: VENUGOPAL GOMATHI , PALANIMUTHU ANBALAGAN , MOSES BALASINGH
Published: December 2012

One of the outcomes of the continuous research on the evolution of distributed computing is the Web services. The aim of this paper is to represent Power System data effectively in XML in order to improve the interoperability and to develop an enhanced distributed model for unique XMLised Power System Data generation for solving various Power System applications in heterogeneous environment. Power System industries are now increasingly becoming privatized and hence the system data is becoming increasingly distributed, with more constrained and complex operational and control requirements. Because of the complex physical connectivity of the power systems, all levels of industry like generation, transmission, distribution and market need proper operational and equipmental data. As expected, the data to be shared between different power system applications is huge and hence it is vital to have an efficient and reliable data generation model to reduce more human efforts and to have the data in a secure and compatible form. The developed JAX-RPC-based model has the capability to generate the data dynamically in XML, fetching the power system data from various sources such as database, text file, etc. The standards such as XML and SOAP enable software design based on loose coupling which reduces restriction and eliminates similarity requirement between coordinating applications.
PRECISING COMPLEX-COMPENSATED CURRENT REFERENCE BASED ON DIFFERENTIAL MODE OF CURRENTS
Authors: SHI L. F. , ZHAO Y. , JIA W. G. , CHENG L. Y. , LAI X. Q.
Published: December 2012

A current reference with complex compensation using negative temperature coefficient of multiple currents is proposed. The principle of compensation is introduced in detail. This work generates two different compensated currents in the whole temperature range, which is different from the traditional curvature-compensated circuit. The compensation is achieved by using difference of the negative temperature coefficients. Piecewise curvature-compensation and higher order nonlinear temperature compensation are applied at the same time. The proposed circuit is simple and easy to implement. Results of simulation with HSPICE show that the achieved temperature coefficient is only 34.2 ppm/°C compared with 364 ppm/°C under 1 μm BCD process, which is unnecessary to compensate in the range of -25°C ∼ 125°C at 5 V supply voltage.
CYLINDRICAL SOLUTIONS IN MODIFIED f(T) GRAVITY
Authors: HOUNDJO M. J. S. , MOMENI D. , MYRZAKULOV R.
Published: December 2012

We investigate static cylindrically symmetric vacuum solutions in Weyl coordinates in the framework of f(T) theory of gravity, where T is the torsion scalar. The set of modified Einstein equations is presented and the forthcoming equations are established. Specific physical expressions are assumed for the algebraic function f(T) and solutions are obtained. Moreover, general solution is obtained with finite values of u(r) on the axis r = 0 and this leads to a constant torsion scalar. Cosmological constant is also introduced and its relation to Linet–Tian solution in GR is commented.
THERMAL RADIATION FROM AN EVOLVING VISCOUS QUARK GLUON PLASMA
Authors: MITRA SUKANYA , MOHANTY PAYAL , SARKAR SOURAV , ALAM JAN-E
Published: December 2012

The effects of viscosity on the space-time evolution of quark gluon plasma produced in nuclear collisions at relativistic heavy ion collider energies have been studied. The entropy generated due to the viscous motion of the fluid has been taken into account in constraining the initial temperature by the final multiplicity (measured at the freeze-out point). The viscous effects on the photon spectra has been introduced consistently through the evolution dynamics and phase space factors of all the participating partons/hadrons in the production process. In contrast to some of the recent calculations the present work includes the contribution from the hadronic phase. A small change in the transverse momentum (pT) distribution of photons is observed due to viscous effects.
ALTERNATIVE METHOD FOR DETERMINING INDUSTRIAL BOND RATINGS: THEORY AND EMPIRICAL EVIDENCE
Authors: KAO LIE-JANE , LEE CHENG-FEW
Published: December 2012

The financial-ratio-based credit-scoring model for bond rating system requires the maximization of two conflicting objectives (i.e., the explanatory and discriminatory power, simultaneously), which had not been directly addressed in literature. The main purpose of this study is to develop a hybrid multivariate credit-scoring model that combines the principle component analysis and Fisher's discriminant analysis using the MINIMAX goal programming technique so that the maximization of the two conflicting objectives can be compromised. The performance of alternative credit-scoring models is analyzed and compared using dataset from previous studies. We find that the proposed hybrid credit-scoring model outperforms other alternative models in both explanatory and discriminatory powers.
External Ba2+ block of Kv4.2 channels is enhanced in the closed-inactivated state
Authors: Kehl Steven J. , Fedida David , Wang Zhuren
Published: December 2012

The effect of external barium ions on rat Kv4.2 channels expressed in HEK293 cells was investigated using whole cell, voltage-clamp recordings to determine its mechanism of action as well as its usefulness as a tool to probe the permeation pathway. Ba2+ caused a concentration-dependent inhibition of current that was antagonized by increasing the external concentration of K+ ([K+]o), and the concentration and time dependence of the inhibition were well fitted by a model involving two binding sites aligned in series. Recovery from current inhibition was enhanced by increasing the intensity, duration, or frequency of depolarizing steps or by increasing [K+]o. These properties are consistent with the conclusion that Ba2+ is a permeant ion that, by virtue of a stable interaction with a deep pore site, is able to block conduction. This blocking action was subsequently exploited to gain insights into the pore configuration in different channel states. In addition to blocking one or more states populated by brief depolarizing pulses to 80 mV, Ba2+ blocked closed channels [the membrane voltage ( Vm) = −80 mV] and closed-inactivated channels ( Vm = −40 mV). Interestingly, the block of closed-inactivated channels was faster and more complete than for closed channels, which we interpret to mean that conformational changes underlying closed-state inactivation (CSI) enhance Ba2+ binding and that the outer pore mouth remains patent during CSI. This provides the first direct evidence that an inactivation process involving a constriction of the outer pore mouth does not account for CSI in Kv4.2.
Lipoprotein remodeling generates lipid-poor apolipoprotein A-I particles in human interstitial fluid
Authors: Miller Norman E. , Olszewski Waldemar L. , Hattori Hiroaki , Miller Irina P. , Kujiraoka Takeshi , Oka Tomoichiro , Iwasaki Tadao , Nanjee M. Nazeem
Published: December 2012

Although much is known about the remodeling of high density lipoproteins (HDLs) in blood, there is no information on that in interstitial fluid, where it might have a major impact on the transport of cholesterol from cells. We incubated plasma and afferent (prenodal) peripheral lymph from 10 healthy men at 37°C in vitro and followed the changes in HDL subclasses by nondenaturing two-dimensional crossed immunoelectrophoresis and size-exclusion chromatography. In plasma, there was always initially a net conversion of small pre-β-HDLs to cholesteryl ester (CE)-rich α-HDLs. By contrast, in lymph, there was only net production of pre-β-HDLs from α-HDLs. Endogenous cholesterol esterification rate, cholesteryl ester transfer protein (CETP) concentration, CE transfer activity, phospholipid transfer protein (PLTP) concentration, and phospholipid transfer activity in lymph averaged 5.0, 10.4, 8.2, 25.0, and 82.0% of those in plasma, respectively (all P < 0.02). Lymph PLTP concentration, but not phospholipid transfer activity, was positively correlated with that in plasma ( r = +0.63, P = 0.05). Mean PLTP-specific activity was 3.5-fold greater in lymph, reflecting a greater proportion of the high-activity form of PLTP. These findings suggest that cholesterol esterification rate and PLTP specific activity are differentially regulated in the two matrices in accordance with the requirements of reverse cholesterol transport, generating lipid-poor pre-β-HDLs in the extracellular matrix for cholesterol uptake from neighboring cells and converting pre-β-HDLs to α-HDLs in plasma for the delivery of cell-derived CEs to the liver.
Exercise pressor response and arterial baroreflex unloading during exercise in chronic kidney disease
Authors: Park Jeanie , Quyyumi Arshed A. , Middlekauff Holly R.
Published: December 2012

Patients with chronic kidney disease (CKD) have poor exercise capacity, which contributes to cardiovascular risk. We sought to determine whether patients with stage 2 or stage 3 CKD have an augmented blood pressure (BP) response during exercise, and if so, whether overactivation of the sympathetic nervous system (SNS) during exercise might play a role. In 13 patients with CKD and hypertension and 13 controls with hypertension, we measured hemodynamics and muscle sympathetic nerve activity (MSNA) during the following maneuvers: low-level rhythmic handgrip (RHG 20%), which primarily stimulates mechanoreceptors, and moderate static handgrip exercise (SHG 30%) followed by posthandgrip circulatory arrest (PHGCA), which isolates metaboreceptors. During baseline studies, patients with CKD had significantly greater increases in mean arterial pressure (MAP) during SHG 30% ( P = 0.045), RHG 20% ( P = 0.031), and PHGCA ( P = 0.043); however, the MSNA response was not augmented in patients with CKD compared with controls. We hypothesized that an augmented SNS response during exercise might be revealed in CKD if arterial baroreflex constraint was equalized using nitroprusside (NTP). These exercise maneuvers were repeated in patients with CKD during NTP infusion to equalize the BP response between groups, thereby relieving baroreflex-mediated suppression of SNS activity. With NTP infusion, patients with CKD had significantly increased MSNA responses during SHG 30% ( P = 0.0044), and RHG 20% ( P = 0.0064), but not during PHGCA ( P > 0.05), suggesting increased reflex activation of the SNS during exercise, which may be mediated by mechanoreceptors but not metaboreceptors. Patients with CKD have an exaggerated BP response during rhythmic and static exercise with underlying SNS overactivation that is revealed during arterial baroreflex unloading during exercise.
Gluconeogenesis and hepatic glycogenolysis during exercise at the lactate threshold
Authors: Emhoff Chi-An W. , Messonnier Laurent A. , Horning Michael A. , Fattor Jill A. , Carlson Thomas J. , Brooks George A.
Published: December 2012

Because the maintenance of glycemia is essential during prolonged exercise, we examined the effects of endurance training, exercise intensity, and plasma lactate concentration ([lactate]) on gluconeogenesis (GNG) and hepatic glycogenolysis (GLY) in fasted men exercising at, and just below, the lactate threshold (LT), where GNG precursor lactate availability is high. Twelve healthy men (6 untrained, 6 trained) completed 60 min of constant-load exercise at power outputs corresponding to their individual LT. Trained subjects completed two additional 60-min sessions of constant-load exercise: one at 10% below the LT workload (LT-10%), and the other with a lactate clamp (LT-10%+LC) to match the [lactate] of the LT trial. Flux rates were determined by primed continuous infusion of [6,6-2H2]glucose, [3-13C]lactate, and [13C]bicarbonate tracers during 90 min of rest and 60 min of cycling. Exercise at LT corresponded to 67.6 ± 1.3 and 74.8 ± 1.7% peak O2consumption in the untrained and trained subjects, respectively ( P < 0.05). Relative exercise intensity was matched between the untrained group at LT and the trained group at LT-10%, and [lactate] during exercise was matched in the LT and LT-10%+LC trials via exogenous lactate infusion. Glucose kinetics (rate of appearance, rate of disposal, and metabolic clearance rate) were augmented with the lactate clamp. GNG was decreased in the trained subjects exercising at LT and LT-10% compared with the untrained subjects, but increasing [lactate] in the LT-10%+LC trial significantly increased GNG (4.4 ± 0.9 mg·kg−1·min−1) compared with its corresponding control (1.7 ± 0.4 mg·kg−1·min−1, P < 0.05). Hepatic GLY was higher in the trained than untrained subjects, but not significantly different across conditions. We conclude that GNG plays an essential role in maintaining total glucose production during exercise in fasted men, regardless of training state. However, endurance training increases the ability to achieve a higher relative exercise intensity and absolute power output at the LT without a significant decrease in GNG. Furthermore, raising systemic precursor substrate availability increases GNG during exercise, but not at rest.
Electromagnetic fields enhance chondrogenesis of human adipose-derived stem cells in a chondrogenic microenvironment in vitro
Authors: Chen Chung-Hwan , Lin Yi-Shan , Fu Yin-Chih , Wang Chih-Kuang , Wu Shun-Cheng , Wang Gwo-Jaw , Eswaramoorthy Rajalakshmanan , Wang Yan-Hsiung , Wang Chau-Zen , Wang Yao-Hsien , Lin Sung-Yen , Chang Je-Ken , Ho Mei-Ling
Published: December 2012

We tested the hypothesis that electromagnetic field (EMF) stimulation enhances chondrogenesis in human adipose-derived stem cells (ADSCs) in a chondrogenic microenvironment. A two-dimensional hyaluronan (HA)-coated well (2D-HA) and a three-dimensional pellet culture system (3D-pellet) were used as chondrogenic microenvironments. The ADSCs were cultured in 2D-HA or 3D-pellet, and then treated with clinical-use pulse electromagnetic field (PEMF) or the innovative single-pulse electromagnetic field (SPEMF) stimulation. The cytotoxicity, cell viability, and chondrogenic and osteogenic differentiations were analyzed after PEMF or SPEMF treatment. The modules of PEMF and SPEMF stimulations used in this study did not cause cytotoxicity or alter cell viability in ADSCs. Both PEMF and SPEMF enhanced the chondrogenic gene expression (SOX-9, collagen type II, and aggrecan) of ADSCs cultured in 2D-HA and 3D-pellet. The expressions of bone matrix genes (osteocalcin and collagen type I) of ADSCs were not changed after SPEMF treatment in 2D-HA and 3D-pellet; however, they were enhanced by PEMF treatment. Both PEMF and SPEMF increased the cartilaginous matrix (sulfated glycosaminoglycan) deposition of ADSCs. However, PEMF treatment also increased mineralization of ADSCs, but SPEMF treatment did not. Both PEMF and SPEMF enhanced chondrogenic differentiation of ADSCs cultured in a chondrogenic microenvironment. SPEMF treatment enhanced ADSC chondrogenesis, but not osteogenesis, when the cells were cultured in a chondrogenic microenvironment. However, PEMF enhanced both osteogenesis and chondrogenesis under the same conditions. Thus the combination of a chondrogenic microenvironment with SPEMF stimulation can promote chondrogenic differentiation of ADSCs and may be applicable to articular cartilage tissue engineering.
Pulmonary Mucormycosis: An Emerging Infection
Authors: Muqeetadnan Mohammed , Rahman Ambreen , Amer Syed , Nusrat Salman , Hassan Syed , Hashmi Syed
Published: December 2012

Mucormycosis is a rare, but emerging, life-threatening, rapidly progressive, angioinvasive fungal infection that usually occurs in immunocompromised patients. We present a case of pulmonary mucormycosis in a diabetic patient who was on chronic steroid therapy for ulcerative colitis. Early recognition of this diagnosis, along with aggressive management, is critical to effective therapy and patient survival. The delay in diagnosis of this rapidly progressive infection can result in mortality.
Atomistic Modeling of Gas Adsorption in Nanocarbons
Authors: Zollo G. , Gala F.
Published: December 2012

Carbon nanostructures are currently under investigation as possible ideal media for gas storage and mesoporous materials for gas sensors. The recent scientific literature concerning gas adsorption in nanocarbons, however, is affected by a significant variation in the experimental data, mainly due to the different characteristics of the investigated samples arising from the variety of the synthesis techniques used and their reproducibility. Atomistic simulations have turned out to be sometimes crucial to study the properties of these systems in order to support the experiments, to indicate the physical limits inherent in the investigated structures, and to suggest possible new routes for application purposes. In consideration of the extent of the theme, we have chosen to treat in this paper the results obtained within some of the most popular atomistic theoretical frameworks without any purpose of completeness. A significant part of this paper is dedicated to the hydrogen adsorption on C‐based nanostructures for its obvious importance and the exceptional efforts devoted to it by the scientific community.
Reversal of the Symptoms of Diabetic Neuropathy through Correction of Vitamin D Deficiency in a Type 1 Diabetic Patient
Authors: Bell David S. H.
Published: December 2012

Vitamin D deficiency has been associated with both type 1 and type 2 diabetes as well as both the microvascular and macrovascular complications of diabetes. Vitamin D deficiency has been shown to be more common in diabetic patients who have symptoms of distal symmetrical polyneuropathy. In addition, vitamin D deficiency has been associated with a lower pain threshold which increases when vitamin D deficiency is corrected. Herein, I describe a type 1 diabetic patient with neuropathic symptoms so severe that he could not work and for which he needed narcotics for pain management and whose symptoms improved dramatically with correction of the vitamin D deficiency. To my knowledge, this is the first report of an improvement in severe symptoms of diabetic neuropathy with correction of vitamin D deficiency in a single patient.
Endodontic Management of a Maxillary First Molar with Two Palatal Canals and a Single Buccal Canal: A Case Report
Authors: Atash biz Yeganeh Leila , Adel Mamak , Vahedi Reza , Tofangchiha Maryam
Published: December 2012

Thorough knowledge of root canal morphology is essential for the endodontic therapy. There are rare variations in canal number and configuration in maxillary molars, which could affect treatment outcome. This paper presents the endodontic management of a maxillary first molar with two palatal canals in one root (Vertucci type IV) and a single buccal canal. In this paper cone-beam computed tomography was made to asses this morphology. This paper is intended to reinforce clinician’s awareness of the rare morphology of root canals.
Quantifying Serum Level of Glycochenodeoxycholic Acid Using High Performance Liquid Chromatography in Obstructive Jaundice Patients
Authors: Lalisang Toar J. M. , Sari Wiria Metta Sinta , Sutikno Vivian , Louisa Melva , Estuningtyas Arie
Published: December 2012

Introduction.Accumulation of glycochenodeoxycholic acid (GCDC) in serum has a clinical significance as an inductor of pathological hepatocyte apoptosis, which impairs liver function. Inhibition of GCDC accumulation can be used as a marker in therapy. This study was aimed to quantify the serum level of GCDC in obstructive jaundice patients.Methodology.GCDC acid level in the serum was quantified using high performance liquid chromatography (HPLC) technique according to Muraca and Ghoos modified method. It was performed before and after decompression at day 7 and day 14. The sample was extracted with solid phase extraction (SPE) technique on SPE column. The results were analyzed using SPSS V 16.0 () and quantified with standard curve on GCDC acid.Result.There were 21 cases with range of GCDC acid serum level before decompression was 90.9 (SD 205.5)μmol/L and day 7 after decompression decreased to 4.0 (SD 46.4)μmol/L and then increased to 11.3 (SD 21.9)μmol/L (). This method could separate GCDC acid on serum with good resolution, high precision and accuracy, and linear calibration curve on measured level range.Conclusion. HPLC can quantify GCDC acid serum on obstructive jaundice patients and can be used to support its pharmacokinetic study.
Assessment of Malnutrition in Community Chinese Elderly: A Hidden Problem in a Developed Society
Authors: Chor Josette Sin-yee , Leung Jason , Griffiths Sian , Leung Ping-chung
Published: December 2012

Background. Malnutrition can lead to chronic disease especially in vulnerable population. This study is to explore the extent of the malnutrition problem in community Chinese elderly and its associating factors in Hong Kong. Method. This is a cross-sectional study using structured interview with 7-day food frequency questionnaires. 1960 men and 1954 women aged 65 or above were recruited from the community. Results. Less than half of the participants fulfilled the recommended intake level of the others. Less than 10% of participants met the daily requirement of fibre, Calcium, Vitamin D, Iodine, and Copper. 22.32% of male participants and 6.21% of female participants have cholesterol intake exceeding the recommended upper level. 41.19% men and 28.99% women exceeded the upper level of fat percentage of total energy. Educational level was demonstrated to have a consistent positive association with the adequate intake in most nutrients. Single or divorced marital status is a risk factor in over-intake of saturated fatty acid in men and under-intake in Zinc and meat in women. Conclusion. Our study has shown the serious malnutrition problem in a wide range of nutrients in community Chinese elderly in Hong Kong.
Synthesis, Structure, and Characterization of Keggin‐Type Germanate
Authors: Li Ya-feng , Qin Xiao-lin , Xu Yue , Gao Wen-yuan , Gao Yue
Published: December 2012

A novel Keggin‐type germanate, (NH4)9[Ge7O14F3]3·1.75H2O (I), is hydrothermally synthesized and structurally characterized by X‐ray single‐crystal diffraction, elemental analysis, XRD, and TG. (I) is tetragonal system with space group I4/mmm and unit cell: a = 28.280
(4) Å, c = 24.881(5) Å, V = 19899(6) Å3, Dc = 1.632 g/cm3, μ(Mo Kα) = 6.309 mm−1, Z = 2
, R1 = 0.1141 for 2576 reflections with Fo > 2(Fo). Ge7O14F3 entry is defined as the cluster including one octahedron, two edge‐sharing triganol bipyramids, and four tetrahedra. Every Ge7O14F3 entry links adjacent four Ge7O14F3 entries by four tetrahedra. Twelve Ge7O14F3 entries construct a cage with all octahedra of Ge7O14F3 pointing inside, which can be simplified into Keggin‐type cage through Ge7O14F3 as the node. The solvent experiment proves that (I) is stable in the water and sensitive to base and acid. The result of XRD shows that the structural water of (I) is easily lost to drop the crystalline. The thermal study indicates that the Keggin‐type cage of (I) begins to partly collapse at 200°C and finally changes into GeO2.
Synthesis and Characterization of Anatase Titanium Dioxide Nanoparticles Using Egg White Solution via Sol‐Gel Method
Authors: Bagheri Samira , Shameli Kamyar , Abd Hamid Sharifah Bee
Published: December 2012

Anatase titanium dioxide nanoparticles (TNPs) are synthesized by a simple and cost‐effective process with and without freshly water‐soluble egg white proteins (albumin) via sol‐gel method. The main advantage of using egg white proteins as a gelling agent is that it can provide long‐term stability for nanoparticles by preventing particles agglomeration. The X‐ray diffraction and FTIR results indicate that the synthesized nanoparticles have only the anatase structure without the presence of any other phase impurities. Additionally, the TNPs are characterized by a number of techniques such as thermogravimetric analysis (TGA), X‐ray diffraction analysis (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and ultraviolet visible spectra (UV‐vis). The sizes of titanium dioxide nanoparticles with and without using egg white solution are 12.55 ± 3.42 nm and 21.45 ± 4.21 nm, respectively. The results indicate that egg white solution is a reliable and cheap green gelling agent that can be used as a matrix in the sol‐gel method to synthesis tiny size TNPs.
Nitroreductase, a Near-Infrared Reporter Platform for In Vivo Time-Domain Optical Imaging of Metastatic Cancer
Authors: McCormack Emmet , Silden Elisabeth , West Richard M. , Pavlin Tina , Micklem David R. , Lorens James B. , Haug Bengt Erik , Cooper Michael E. , Gjertsen Bjørn Tore
Published: December 2012

The ability to visualize reporter gene expression in vivo has revolutionized all facets of biologic investigation and none more so than imaging applications in oncology. Near-infrared reporter gene imaging may facilitate more accurate evaluation of chemotherapeutic response in preclinical models of orthotopic and metastatic cancers. We report the development of a cell permeable, quenched squarine probe (CytoCy5S), which is reduced by Escherichia coli nitroreductase (NTR), resulting in a near-infrared fluorescent product. Time-domain molecular imaging of NTR/CytoCy5S reporter platform permitted noninvasive monitoring of disease progression in orthotopic xenografts of disseminated leukemia, lung, and metastatic breast cancer. This methodology facilitated therapeutic evaluation of NTR gene–directed enzymatic prodrug therapy with conventional metronidazole antibiotics. These studies show NTR/CytoCy5S as a near-infrared gene reporter system with broad preclinical and prospective clinical applications within imaging, and gene therapy, of cancer. Cancer Res; 73(4); 1276–86. ©2012 AACR.
Dysregulation of Cholesterol Homeostasis in Human Prostate Cancer through Loss of ABCA1
Authors: Lee Byron H. , Taylor Margaret G. , Robinet Peggy , Smith Jonathan D. , Schweitzer Jessica , Sehayek Ephraim , Falzarano Sara M. , Magi-Galluzzi Cristina , Klein Eric A. , Ting Angela H.
Published: December 2012

Recent epidemiologic data show that low serum cholesterol level as well as statin use is associated with a decreased risk of developing aggressive or advanced prostate cancer, suggesting a role for cholesterol in aggressive prostate cancer development. Intracellular cholesterol promotes prostate cancer progression as a substrate for de novo androgen synthesis and through regulation of AKT signaling. By conducting next-generation sequencing–based DNA methylome analysis, we have discovered marked hypermethylation at the promoter of the major cellular cholesterol efflux transporter, ABCA1, in LNCaP prostate cancer cells. ABCA1 promoter hypermethylation renders the promoter unresponsive to transactivation and leads to elevated cholesterol levels in LNCaP. ABCA1 promoter hypermethylation is enriched in intermediate- to high-grade prostate cancers and not detectable in benign prostate. Remarkably, ABCA1 downregulation is evident in all prostate cancers examined, and expression levels are inversely correlated with Gleason grade. Our results suggest that cancer-specific ABCA1 hypermethylation and loss of protein expression direct high intracellular cholesterol levels and hence contribute to an environment conducive to tumor progression. Cancer Res; 73(3); 1211–8. ©2012 AACR.
Bortezomib Sensitizes Human Acute Myeloid Leukemia Cells to All-Trans-Retinoic Acid–Induced Differentiation by Modifying the RARα/STAT1 Axis
Authors: Ying Meidan , Zhou Xinglu , Zhong Like , Lin Nengming , Jing Hui , Luo Peihua , Yang Xiaochun , Song Hua , Yang Bo , He Qiaojun
Published: December 2012

All-trans-retinoic acid (ATRA) has held great promise for differentiation-based therapy but reportedly downregulates retinoic acid receptor-α (RARα) in a proteasome-dependent manner, which leads to decreased acute myeloid leukemia (AML) cell differentiation efficiency. Therefore, research strategies that seek to further sensitize cells to retinoids and extend the range of retinoid-affected myeloid malignancies beyond acute promyelocytic leukemia (APL) are key investigative avenues. Here, we show that bortezomib, the first proteasome inhibitor approved for newly diagnosed and relapsed multiple myeloma, exhibited strong synergism with ATRA to promote HL60 and NB4 AML cell differentiation. We observed that bortezomib sensitized AML cells to ATRA-induced morphologic, biochemical, and functional changes, indicative of myeloid differentiation without cell death. In addition, treatment of human leukemia HL60 xenografts with bortezomib and ATRA together did not increase bortezomib-induced progressive weight loss but resulted in significant tumor growth inhibition in addition to increased differentiation (P < 0.05). These enhanced differentiation effects were accompanied by RARα stabilization and STAT1 activation. Taken together, our study was the first to evaluate bortezomib and ATRA synergy in AML cell differentiation and to assess new opportunities for bortezomib and ATRA combination as a promising approach for future differentiation therapy. Mol Cancer Ther; 12(2); 195–206. ©2012 AACR.
Allergen Sensitization Is Associated with Increased DNA Methylation in Older Men
Authors: Sordillo Joanne E. , Lange Nancy E. , Tarantini Letizia , Bollati Valentina , Zanobetti Antonella , Sparrow David , Vokonas Pantel , Schwartz Joel , Baccarelli Andrea , DeMeo Dawn , Litonjua Augusto A.
Published: December 2012

Background: Variation in epigenetic modifications, arising from either environmental exposures or internal physiological changes, can influence gene expression and may ultimately contribute to complex diseases such as asthma and allergies. We examined the association of asthma and allergic phenotypes with DNA methylation levels of retrotransposon-derived elements. Methods: We used data from 704 men (mean age 73 years) in the longitudinal Normative Aging Study to assess the relationship between asthma, allergic phenotypes and DNA methylation levels of the retrotransposon-derived elements Alu and long interspersed nuclear element (LINE)-1. Retrotransposons represent a large fraction of the genome (>30%) and are heavily methylated to prevent expression. Percent methylation of Alu and LINE-1 elements in peripheral white blood cells was quantified using PCR pyrosequencing. Data on sensitization to common allergens from skin prick testing, asthma and methacholine responsiveness were gathered approximately 8 years prior to DNA methylation analysis. Results: Prior allergen sensitization was associated with increased methylation of Alu (β = 0.32 for sensitized vs. nonsensitized patients; p = 0.003) in models adjusted for pack-years of smoking, body mass index, current smoking, air pollutants, percentage of eosinophils, white blood cell count and age. Of the men interviewed, 5% of subjects reported a diagnosis of asthma. Neither Alu nor LINE-1 methylation was associated with asthma. Conclusions: These data suggest that increased DNA methylation of repetitive elements may be associated with allergen sensitization but does not appear to be associated with asthma. Future work is needed to identify potential underlying mechanisms for these relationships.
Histopathological Diagnosis of Early HCC through Biopsy: Efficacy of Victoria Blue and Cytokeratin 7 Staining
Authors: Kobayashi Sawako , Kim Soo Ryang , Imoto Susumu , Ando Kenji , Hirakawa Makoto , Saito Jun , Fukuda Katsumi , Otono Yumi , Sakaki Madoka , Tsuchida Shinobu , Kim Soo Ki , Hayashi Yoshitake , Nakano Masayuki , Kudo Masatoshi
Published: December 2012

Objectives and Methods: Findings of histological analyses of 2 cases of liver biopsy revealing hypovascular nodules are described. Results: Ultrasound examination revealed hypovascular and hypoechoic nodules (8 mm in diameter) in segment 1 (case 1) and (8 mm) in segment 8 (case 2). The nodules were detected by only Gd-EOB-DTPA-enhanced MRI. Hematoxylin and eosin staining of ultrasound-guided biopsy of the nodules revealed slight hypercellularity without the features of early hepatocellular carcinoma (HCC) such as cell atypia, fatty change and pseudoglandular formation. Early HCC was suspected; however, Victoria blue staining disclosed terminal portal tract invasion, the most important finding of early HCC. Also, cytokeratin 7 staining revealed decreased ductular reaction compatible with early HCC. Taken together, these histological analyses confirmed the two nodules to be early HCC. Conclusion: Based on the criteria of the International Consensus Group, the two nodules were diagnosed as early HCC through biopsy.
Usefulness of the Multimodality Fusion Imaging for the Diagnosis and Treatment of Hepatocellular Carcinoma
Authors: Makino Yuki , Imai Yasuharu , Igura Takumi , Ohama Hideko , Kogita Sachiyo , Sawai Yoshiyuki , Fukuda Kazuto , Ohashi Hiroshi , Murakami Takamichi
Published: December 2012

A multimodality fusion imaging system has been introduced for the clinical practice of diagnosis and treatment of hepatocellular carcinoma (HCC), especially for loco-regional treatment. An ultrasonography (US) fusion imaging system can provide a side-by-side display of real-time US images and any cross-sectional images of multiplanar reconstruction of CT or MRI that synchronize real-time US. The US fusion imaging system enables us to perform radiofrequency ablation (RFA) for HCCs difficult to detect on conventional US safely. Besides, we can evaluate the treatment effects of RFA easily at the bedside by combining the contrast-enhanced US and the US fusion imaging system. Fusion images of pre- and post-RFA CT have been utilized for the assessment of the treatment effects of RFA. Although the treatment effects of RFA have been conventionally evaluated, comparing pre- and post-RFA CT side-by-side, the evaluation tends to be inaccurate. On CT fusion images, the tumor and the ablation zone are overlaid and we can grasp the positional relation easily, leading to quantitative and more accurate evaluation. The multimodality fusion imaging system has become quite an important tool for loco-regional treatment of HCC because of its usefulness for both the guidance during the RFA procedure and the evaluation of its treatment effects.
Effect of Nebulized Beclomethasone on Airway Inflammation and Clinical Status of Children with Allergic Asthma and Rhinitis: A Randomized, Double-Blind, Placebo-Controlled Study
Authors: Profita Mirella , Riccobono Loredana , Bonanno Anna , Chanez Pascal , Gagliardo Rosalia , Montalbano Angela Marina , Albano Giusy Daniela , Liotta Giuseppe , Gjomarkaj Mark , La Grutta Stefania
Published: December 2012

We aimed to evaluate the therapeutic effect of nebulized beclomethasone dipropionate (nBDP) on both allergic asthma and rhinitis. In a randomized, double-blind, placebo-controlled study, 40 children (mean age 10.7 ± 2.1 years) with allergic asthma and rhinitis received either nBDP (daily dose of 800 µg, administered twice daily) or placebo for 4 weeks (with a face mask), after a 2-week run-in period of clinical assessment. Nasal and oral fractional exhaled nitric oxide (FeNO) measurements together with pulmonary function tests, nasal and oral exhaled breath condensate (EBC) collection for pH and interleukin-5 (IL-5) measurements as well as nasal and bronchial symptom scores were obtained at baseline and after 4-week treatment. A significant improvement in oral FeNO, oral and nasal EBC IL-5 and nasal EBC pH was observed in the nBDP group when comparing the values with baseline, together with an improvement in symptom score of the visual analogue scale, nasal obstruction, sneezing, rhinorrhea, breathing difficulty, cough, wheezing and sleep disturbance (nBDP end treatment vs. baseline, Wilcoxon signed-rank test). nBDP was more effective than placebo (ANCOVA test) in improving [difference Δ = response after treatment at the last visit (active or placebo) – value at baseline] nasal pH, oral IL-5, oral FeNO, forced expiratory volume in 1 s, forced expiratory volume in 1 s/forced vital capacity, peek expiratory flow, visual analogue scale, breathing difficulty, cough, wheezing and sleep disturbance scores. No differences were observed between the nBDP and the placebo group for symptom score of rhinitis. nBDP is a useful treatment for airway inflammation and clinical status in children with concomitant allergic asthma and rhinitis.
Intraoperative Retinal Break Formation in 23-/25-Gauge Vitrectomy versus 20-Gauge Vitrectomy
Authors: Neuhann Irmingard M. , Hilgers Ralf-Dieter , Bartz-Schmidt Karl-Ulrich
Published: December 2012

Background: This study was undertaken to examine the possible effect of microcannula-guided entry sites on the rate of intraoperative retinal break formation. Methods: In this historical cohort study, all patients having undergone vitrectomy with epiretinal or internal limiting membrane peeling performed by one surgeon between January 2005 and March 2009 were included. All procedures with microcannula-guided entry sites (23- and 25-gauge vitrectomy) were compared to procedures without the use of microcannulas (20-gauge vitrectomy). Results: A total of 221 eyes with a follow-up of at least 30 days were analyzed. The total incidence of intraoperative retinal break formation was 25.2% (n = 28/111) for the 20-gauge group and 12.7% (n = 14/110) for the 23-/25-gauge group, resulting in an odds ratio of 2.313 (95% confidence interval 1.142–4.685) of an increased rate in the 20-gauge group. Conclusion: This study demonstrates that intraoperative retinal breaks during vitrectomy are reduced in the microcannula-guided techniques compared to 20-gauge vitrectomy. This effect may be attributed to the protection of the vitreous base during surgery. Further prospective studies are warranted.
An Intra- and Interobserver Reproducibility Analysis of the Ki-67 Proliferation Marker Assessment on Core Biopsies of Breast Cancer Patients and Its Potential Clinical Implications
Authors: Vörös András , Csörgő Erika , Nyári Tibor , Cserni Gábor
Published: December 2012

Objective: The Ki-67 proliferation index has received an important role in treatment tailoring and molecular classification of estrogen receptor-positive breast carcinomas. The aim was to analyze the reproducibility of assessing proliferation on the basis of Ki-67 immunohistochemistry. Methods: Thirty core biopsy samples of breast cancer patients were analyzed after immunostaining with B56, SP6 and MIB-1 monoclonal Ki-67 antibodies. All samples were evaluated twice and independently by 3 pathologists, with each observer performing his daily routine practice. The ratio of Ki-67-positive cells was estimated with 5% accuracy. Correlation was calculated for the results of each investigator for all pairs of antibodies and for the results of each antibody for all pairs of investigators. Ki-67 scores were divided into categories of either 4 quarters or into 3 groups reflecting the St. Gallen consensus recommendations with 15 and 30% as cutoff values. The reproducibility of classifying the tumors into these categories was assessed with ĸ statistics. Results: Altogether, 540 evaluations were made. Good to excellent correlation (Spearman’s and Pearson’s coefficient range 0.74–0.92 and 0.73–0.93, respectively) was noted for the pairwise comparison of antibodies by observer and of observers by antibody. The inter- and intraobserver reproducibility of the Ki-67 score classification into equal quarters (1–25, 26–50, 51–75 and 76–100%) or into 3 categories with cutoffs at 15 and 30% was fair to poor in the middle categories, but moderate to substantial in the low and high ranges. Interobserver differences in practice potentially impacted on less consistent classification. Conclusion: Our results indicate that the three different Ki-67 antibodies tested do not substantially influence the reproducibility of the estimated proliferation rates. Although reproducibility is better in the clinically more relevant distinction of high versus low proliferation, without standardization, the current practice of Ki-67 assessment in many laboratories does not allow proper and consistent therapeutic decision-making.
uPAR regulates pericellular proteolysis through a mechanism involving integrins and fMLF-receptors
Authors: Rinaldi Loredana , Rea Vincenza Elena Anna , Montuori Nunzia , Cosimato Vincenzo , Alfano Daniela , Ragno Pia
Published: December 2012

The expression of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR) can be regulated by several hormones, cytokines, and tumour promoters. uPAR is a glycosyl-phosphatidyl inositol (GPI)- linked cell-surface protein; however, it is capable to transduce signals inside the cell by interacting with other cell-surface proteins, such as integrins and G-protein coupled (GPC) receptors. We previously reported that uPAR cell-surface expression can be positively regulated by its ligand, uPA, independently of its proteolytic activity. We now demonstrate that uPAR overexpression induces or increases uPA secretion both in uPAR-negative and in uPAR-expressing cells. Accordingly, uPAR depletion impairs uPA expression in cells which constitutively express both uPA and its receptor. uPAR exerts its regulatory effect through the activation of the ERK mitogen-activated protein kinases (MAPKs), whereas the p-38 MAPK is not involved. Overexpression of truncated forms of uPAR, lacking the N-terminal domain (DI) and not able to interact with membrane co-receptors, failed to increase uPA expression. Inhibition of uPAR-integrin interaction by the specific P-25 peptide, as well as Gi-protein inhibition by cholera pertussin toxin or depletion of the GPC receptors for fMLF (fMLF-Rs) also impaired uPAR capability to regulate uPA expression. These findings demonstrate that uPAR, whose expression is regulated by uPA, can, in turn, regulate uPA expression through a mechanism involving its functional interaction with integrins and fMLF-Rs.
Platelet protein S directly inhibits procoagulant activity on platelets and microparticles
Authors: Stavenuiter Fabian , Davis Nicole , Duan Erning , Gale Andrew , Heeb Mary
Published: December 2012

Anticoagulant plasma protein S (PS) is essential for maintaining haemostatic balance. About 2.5% of PS is stored in platelets and released upon platelet stimulation. So far, little is known about the functionality and importance of platelet (plt)PS. A platelet-associated protease cleaves plasma-derived (pd)PS and pltPS in the “thrombin-sensitive region”, abolishing activated protein C (APC) cofactor activity. However, we showed that cleaved PS retains APC-independent anticoagulant activities (“PS-direct”). To investigate whether pltPS or pdPS exert PS-direct on platelets or platelet-shed microparticles, thrombin and factor (F)Xa generation on unstimulated or stimulated washed platelets and microparticles were measured. Western blotting revealed that pltPS and pdPS bound to washed, stimulated platelets and microparticles, and that pltPS had slower electrophoretic mobility than pdPS. Platelet stimulation in the presence of inhibitory anti-PS antibodies resulted in 2.6 ± 1.6-fold (p<0.0004, n=20) more thrombin generation upon addition of FXa and prothrombin. PltPS exerted PSdirect that was similar to or greater than that of Zn2+-containing pdPS and much greater than that of Zn2+-deficient pdPS. Findings were confirmed using purified pltPS. Platelet-bound pltPS and microparticlebound pltPS had similar PS-direct. Finally, platelet stimulation in the presence of inhibitory anti-PS antibodies resulted in 1.5 ± 0.2-fold (p<0.0001, n=11) more FXa generation upon addition of TF/FVIIa and FX. Thus, pltPS inhibits both prothrombinase and extrinsic FXase activities. Neutralising antibodies against APC and TFPI had no effect on the PS-direct of pltPS or pdPS on platelets. This study indicates that pltPS may be an essential pool of PS that counterbalances procoagulant activities on platelets.