bluuebunny/crossref_metadata_2025 huggingface dataset:
Agency Problems and Stock Repurchases: Evidence from Japan
Authors: Teng Min , Hachiya Toyohiko
Published: September 2013

This paper examines stock repurchases from an agency perspective by identifying agency costs across three dimensions — interest conflicts and information asymmetry, managerial discretion, and the use of alternative mechanisms to mitigate agency conflicts. We use ownership structure as a proxy for interest conflicts and information asymmetry, employ cash balance and free cash flow as two measures of managerial discretion, and consider cash dividends and interest-bearing liabilities as alternative vehicles for distributing cash. We find that a monitoring structure motivates managers to mitigate agency costs through stock repurchases. Particularly, monitored firms with higher levels of cash balance prefer cash dividends to stock repurchases, whereas monitored firms with more cash dividends repurchase more shares because of their stronger incentive to mitigate agency costs. However, when firms have a very high level of dividends, they substitute stock repurchases for dividends to avoid a dividend cut in the future.
Antidicer RNAse activity of monocyte chemotactic protein-induced protein-1 is critical for inducing angiogenesis
Authors: Roy Arpita , Zhang Miaojun , Saad Yasser , Kolattukudy Pappachan E.
Published: September 2013

Inflammatory angiogenesis involves the induction of a novel gene ZC3H12A encoding monocyte chemoattractant protein-1 (MCP-1)-induced protein-1 (MCPIP1) that has deubiquitinase and antidicer RNAse activities. If and how these enzymatic activities of MCPIP1 mediate the biological functions of MCPIP1 are unknown. Present studies with human umbilical vein endothelial cells suggest that MCPIP-induced angiogenesis is mediated via hypoxia-inducible factor (HIF-1α), vascular endothelial growth factor (VEGF), and silent information regulator (SIRT-1) induction that results in the inhibition of angiogenesis inhibitor thrombospondin-1. MCPIP1 expression inhibited the production of the antiangiogenic microRNA (miR)-20b and -34a that repress the translation of HIF-1α and SIRT-1, respectively. The RNase-dead MCPIP mutant D141N not only did not induce angiogenesis but also failed to inhibit the production of miR-20b and -34a suggesting that the antidicer RNase activity of MCPIP1 is involved in MCPIP-mediated angiogenesis. Mimetics of miR-20b and -34a inhibited MCPIP1-induced angiogenesis confirming that MCPIP1 suppresses the biogenesis of miR-20b and -34a. Furthermore, our results indicate that MCPIP expression induces nuclear translocation of HIF-1α. We show that under hypoxia angiogenesis is mediated via induction of MCPIP1 and under normoxia, in vitro, MCPIP deubiquitinates ubiquitinated HIF-1α and the stabilized HIF-1α enters the nucleus to promote the transcription of its target genes, cyclooxygenase-2 and VEGF, suggesting that the deubiquitinase activity of MCPIP may also promote angiogenesis. The present results show for the first time that the antidicer RNase activity of MCPIP1 is critical in mediating a biological function of MCPIP, namely angiogenesis.
Exercise alters the regulation of myocardial Na+/H+ exchanger-1 activity
Authors: Feger Bryan J. , Starnes Joseph W.
Published: September 2013

The myocardial Na+/H+ exchanger-1 (NHE1) plays a major role in regulation of intracellular pH, and its upregulation has been implicated in increased ischemia-reperfusion injury and other pathologies. Hydrogen peroxide (H2O2) increases NHE1 activity acutely via ERK1/2 signaling. Chronic strenuous exercise upregulates NHE1 in skeletal muscle, but we hypothesize this will not occur in the heart, because exercise creates a cardioprotective phenotype. NHE1 activity and its regulation by H2O2 were examined at physiological pH using isolated cardiomyocytes from female Sprague-Dawley rats exercised on a treadmill for 5 wk (E; n = 11). Compared with sedentary (S; n = 15), E displayed increases ( P < 0.05) in heart-to-body weight ratio (6.8%) and plantaris mitochondria content (89%). NHE1 activity (acid efflux rate following an acid load) was 209% greater in E (0.65 ± 0.12 vs. 2.01 ± 0.29 fmol/min). The difference was attributed primarily to greater cell volume (22.2 ± 0.6 vs. 34.3 ± 1.1 pl) and intracellular pH-buffering capacity (33.94 ± 1.59 vs. 65.82 ± 5.20 mM/pH unit) of E myocytes. H2O2 stimulation (100 μM) raised NHE1 activity significantly less in E (45%) than S (167%); however, activity remained 185% greater in E. ERK1/2 inhibition abrogated the increases. H2O2-stimulated ERK1/2 phosphorylation levels normalized to total ERK1/2 were similar between groups. Content of NHE1 and activities of H2O2 scavengers were also similar. We observed that intracellular pH-buffering capacity differences between groups became progressively less with declining pH, which may be an exercise-induced cardioprotective adaptation to lower NHE1 activity during certain pathological situations. We conclude that strenuous endurance exercise increases myocardial NHE1 activity at physiological pH, which would likely enhance cardiac performance under physiological conditions.
Increased tubulointerstitial recruitment of human CD141hiCLEC9A+and CD1c+myeloid dendritic cell subsets in renal fibrosis and chronic kidney disease
Authors: Kassianos Andrew J. , Wang Xiangju , Sampangi Sandeep , Muczynski Kimberly , Healy Helen , Wilkinson Ray
Published: September 2013

Dendritic cells (DCs) play critical roles in immune-mediated kidney diseases. Little is known, however, about DC subsets in human chronic kidney disease, with previous studies restricted to a limited set of pathologies and to using immunohistochemical methods. In this study, we developed novel protocols for extracting renal DC subsets from diseased human kidneys and identified, enumerated, and phenotyped them by multicolor flow cytometry. We detected significantly greater numbers of total DCs as well as CD141hiand CD1c+myeloid DC (mDCs) subsets in diseased biopsies with interstitial fibrosis than diseased biopsies without fibrosis or healthy kidney tissue. In contrast, plasmacytoid DC numbers were significantly higher in the fibrotic group compared with healthy tissue only. Numbers of all DC subsets correlated with loss of kidney function, recorded as estimated glomerular filtration rate. CD141hiDCs expressed C-type lectin domain family 9 member A (CLEC9A), whereas the majority of CD1c+DCs lacked the expression of CD1a and DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), suggesting these mDC subsets may be circulating CD141hiand CD1c+blood DCs infiltrating kidney tissue. Our analysis revealed CLEC9A+and CD1c+cells were restricted to the tubulointerstitium. Notably, DC expression of the costimulatory and maturation molecule CD86 was significantly increased in both diseased cohorts compared with healthy tissue. Transforming growth factor-β levels in dissociated tissue supernatants were significantly elevated in diseased biopsies with fibrosis compared with nonfibrotic biopsies, with mDCs identified as a major source of this profibrotic cytokine. Collectively, our data indicate that activated mDC subsets, likely recruited into the tubulointerstitium, are positioned to play a role in the development of fibrosis and, thus, progression to chronic kidney disease.
Fluid reabsorption in proximal convoluted tubules of mice with gene deletions of claudin-2 and/or aquaporin1
Authors: Schnermann Jurgen , Huang Yuning , Mizel Diane
Published: September 2013

Deletions of claudin-2 (Cldn2) and aquaporin1 (AQP1) reduce proximal fluid reabsorption (PFR) by about 30% and 50%, respectively. Experiments were done to replicate these observations and to determine in AQP1/claudin-2 double knockout mice (DKO) if the effects of deletions of these established water pores are additive. PFR was determined in inactin/ketamine-anesthetized mice by free-flow micropuncture using single-nephron I125-iothalamate (io) clearance. Animal means of PFR [% of glomerular filtration rate (GFR)] derived from TF/Piothalamateratios in 12 mice in each of four groups [wild type (WT), Cldn2−/−, AQP1−/−, and DKO) were 45.8 ± 0.85 (51 tubules), 35.4 ± 1 (54 tubules; P < 0.01 vs. WT), 36.8 ± 1 (63 tubules; P < 0.05 vs. WT), and 33.9 ± 1.4 (69 tubules; P < 0.01 vs. WT). Kidney and single-nephron GFRs (SNGFR) were significantly reduced in all mutant strains. The direct relationship between PFR and SNGFR was maintained in mutant mice, but the slope of this relationship was reduced in the absence of Cldn2 and/or AQP1. Transtubular osmotic pressure differences were not different between WT and Cldn2−/−mice, but markedly increased in DKO. In conclusion, the deletion of Cldn2, AQP1, or of both Cldn2 and AQP1 reduces PFR by 22.7%, 19.6%, and 26%, respectively. Our data are consistent with an up to 25% paracellular contribution to PFR. The reduced osmotic water permeability caused by absence of AQP1 augments luminal hypotonicity. Aided by a fall in filtered load, the capacity of non-AQP1-dependent transcellular reabsorption is sufficient to maintain PFR without AQP1 and claudin-2 at 75% of control.
A novel analysis of excitatory currents during an action potential from suprachiasmatic nucleus neurons
Authors: Clay John R.
Published: September 2013

A new application of the action potential (AP) voltage-clamp technique is described based on computational analysis. An experimentally recorded AP is digitized. The resulting V i vs. t i data set is applied to mathematical models of the ionic conductances underlying excitability for the cell from which the AP was recorded to test model validity. The method is illustrated for APs from suprachiasmatic nucleus (SCN) neurons and the underlying tetrodotoxin-sensitive Na+ current, INa, and the Ca2+ current, ICa. Voltage-step recordings have been made for both components from SCN neurons ( Jackson et al. 2004 ). The combination of voltage-step and AP clamp results provides richer constraints for mathematical models of voltage-gated ionic conductances than either set of results alone, in particular the voltage-step results. For SCN neurons the long-term goal of this work is a realistic mathematical model of the SCN AP in which the equations for INa and ICa obtained from this analysis will be a part. Moreover, the method described in this report is general. It can be applied to any excitable cell.
Age-related neuromuscular function and dynamic balance control during slow and fast balance perturbations
Authors: Piirainen Jarmo M. , Linnamo Vesa , Cronin Neil J. , Avela Janne
Published: September 2013

This study investigated age-related differences in dynamic balance control and its connection to reflexes and explosive isometric plantar flexor torque in 19 males (9 Young aged 20–33 yr, 10 Elderly aged 61–72 yr). Dynamic balance was measured during Slow (15 cm/s) and Fast (25 cm/s) anterior and posterior perturbations. H/M-ratio was measured at 20% of maximal M-wave (H/M20%) 10, 30, and 90 ms after perturbations. Stretch reflexes were measured from tibialis anterior and soleus during anterior and posterior perturbations, respectively. In Slow, Elderly exhibited larger peak center-of-pressure (COP) displacement (15%; P < 0.05) during anterior perturbations. In Fast, Young showed a trend for faster recovery (37%; P = 0.086) after anterior perturbations. M-wave latency was similar between groups (6.2 ± 0.7 vs. 6.9 ± 1.2 ms), whereas Elderly showed a longer H-reflex latency (33.7 ± 2.3 vs. 36.4 ± 1.7 ms; P < 0.01). H/M20% was higher in Young 30 ms after Fast anterior (50%; P < 0.05) and posterior (51%; P < 0.05) perturbations. Plantar flexor rapid torque was also higher in Young (26%; P < 0.05). After combining both groups' data, H/M20% correlated negatively with Slow peak COP displacement ( r = −0.510, P < 0.05) and positively with Fast recovery time ( r = 0.580, P < 0.05) for anterior perturbations. Age-related differences in balance control seem to be more evident in anterior than posterior perturbations, and rapid sensory feedback is generally important for balance perturbation recovery.
Dendritic SK channels convert NMDA-R-dependent LTD to burst timing-dependent plasticity
Authors: Harvey-Girard Erik , Maler Leonard
Published: September 2013

Feedback and descending projections from higher to lower brain centers play a prominent role in all vertebrate sensory systems. Feedback might be optimized for the specific sensory processing tasks in their target brain centers, but it has been difficult to connect the properties of feedback synapses to sensory tasks. Here, we use the electrosensory system of a gymnotiform fish ( Apteronotus leptorhynchus) to address this problem. Cerebellar feedback to pyramidal cells in the first central electrosensory processing region, the electrosensory lateral line lobe (ELL), is critical for canceling spatially and temporally redundant electrosensory input. The ELL contains four electrosensory maps, and we have previously analyzed the synaptic and network bases of the redundancy reduction mechanism in a map (centrolateral segment; CLS) believed to guide electrolocation behavior. In the CLS, only long-term depression was induced by pairing feedback presynaptic and pyramidal cell postsynaptic bursts. In this paper, we turn to an ELL map (lateral segment; LS) known to encode electrocommunication signals. We find remarkable differences in synaptic plasticity of the morphologically identical cerebellar feedback input to the LS. In the LS, pyramidal cell SK channels permit long-term potentiation (LTP) of feedback synapses when pre- and postsynaptic bursts occur at the same time. We hypothesize that LTP in this map is required for enhancing the encoding of weak electrocommunication signals. We conclude that feedback inputs that appear morphologically identical in sensory maps dedicated to different tasks, nevertheless display different synaptic plasticity rules contributing to differential sensory processing in these maps.
Comparison of Characteristics of Connective Tissue Disease-Associated Interstitial Lung Diseases, Undifferentiated Connective Tissue Disease-Associated Interstitial Lung Diseases, and Idiopathic Pulmonary Fibrosis in Chinese Han Population: A Retrospective Study
Authors: Pan Lin , Liu Yuan , Sun Rongfei , Fan Mingyu , Shi Guixiu
Published: September 2013

Our study compared the prevalence and characteristics of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD), undifferentiated connective tissue disease-associated interstitial lung disease (UCTD-ILD), or idiopathic pulmonary fibrosis (IPF) between January 2009 and December 2012 in West China Hospital, western China. Patients who met the criteria for ILD were included and were assigned to CTD-ILD, UCTD-ILD, or IPF group when they met the criteria for CTD, UCTD, or IPF, respectively. Clinical characteristics, laboratory tests, and high-resolution CT images were analyzed and compared among three groups. 203 patients were included, and all were Han nationality. CTD-ILD was identified in 31%, UCTD-ILD in 32%, and IPF in 37%. Gender and age differed among groups. Pulmonary symptoms were more common in IPF, while extrapulmonary symptoms were more common in CTD-ILD and UCTD-ILD group. Patients with CTD-ILD had more abnormal antibody tests than those of UCTD-ILD and IPF. Little significance was seen in HRCT images among three groups. A systematic evaluation of symptoms and serologic tests in patients with ILD can identify CTD-ILD, UCTD-ILD, and IPF.
Participation ofGABAAChloride Channels in the Anxiolytic-Like Effects of a Fatty Acid Mixture
Authors: Rodríguez-Landa Juan Francisco , García-Ríos Rosa Isela , Cueto-Escobedo Jonathan , Bernal-Morales Blandina , Contreras Carlos M.
Published: September 2013

Human amniotic fluid and a mixture of eight fatty acids (FAT-M) identified in this maternal fluid (C12:0, lauric acid, 0.9 μg%; C14:0, myristic acid, 6.9 μg%; C16:0, palmitic acid, 35.3 μg%; C16:1, palmitoleic acid, 16.4 μg%; C18:0, stearic acid, 8.5 μg%; C18:1cis, oleic acid, 18.4 μg%; C18:1trans, elaidic acid, 3.5 μg%; C18:2, linoleic acid, 10.1 μg%) produce anxiolytic-like effects that are comparable to diazepam in Wistar rats, suggesting the involvement ofγ-aminobutyric acid-A (GABAA) receptors, a possibility not yet explored. Wistar rats were subjected to the defensive burying test, elevated plus maze, and open field test. In different groups, threeGABAAreceptor antagonists were administered 30 min before FAT-M administration, including the competitive GABA binding antagonist bicuculline (1 mg/kg),GABAAbenzodiazepine antagonist flumazenil (5 mg/kg), and noncompetitiveGABAAchloride channel antagonist picrotoxin (1 mg/kg). The FAT-M exerted anxiolytic-like effects in the defensive burying test and elevated plus maze, without affecting locomotor activity in the open field test. TheGABAAantagonists alone did not produce significant changes in the behavioral tests. Picrotoxin but not bicuculline or flumazenil blocked the anxiolytic-like effect of the FAT-M. Based on the specific blocking action of picrotoxin on the effects of the FAT-M, we conclude that the FAT-M exerted its anxiolytic-like effects throughGABAAreceptor chloride channels.
Study of the Boson Peak and Fragility of Bioprotectant Glass-Forming Mixtures by Neutron Scattering
Authors: Migliardo F. , Magazù S. , Gonzalez M. A. , Mondelli C.
Published: September 2013

The biological relevance of trehalose, glycerol, and their mixtures in several anhydrobiotic and cryobiotic organisms has recently promoted both experimental and simulation studies. In addition, these systems are employed in different industrial fields, such as pharmaceutical and cosmetic industries, as additives in mixtures for cryopreservation and in several formulations. This review article shows an overview of Inelastic Neutron Scattering (INS) data, collected at different temperature values by the OSIRIS time-of-flight spectrometer at the ISIS Facility (Rutherford Appleton Laboratory, Oxford, UK) and by the IN4 and IN6 spectrometers at the Institut Laue Langevin (ILL, Grenoble, France), on trehalose/glycerol mixtures as a function of the glycerol content. The data analysis allows determining the Boson peak behavior and discussing the findings in terms of fragility in relation to the bioprotective action of trehalose and glycerol.
Observer-Based Robust Tracking Control for a Class of Switched Nonlinear Cascade Systems
Authors: Niu Ben , Zhao Deqing , Zhao Xudong , Li Hongyi , Chen Xiangyong , Dong Xiaoxiao
Published: September 2013

This paper is devoted to robust output feedback tracking control design for a class of switched nonlinear cascade systems. The main goal is to ensure the global input-to-state stable (ISS) property of the tracking error nonlinear dynamics with respect to the unknown structural system uncertainties and external disturbances. First, a nonlinear observer is constructed through state transformation to reconstruct the unavailable states, where only one parameter should be determined. Then, by virtue of the nonlinear sliding mode control (SMC), a discontinuous nonlinear output feedback controller is designed using a backstepping like design procedure to ensure the ISS property. Finally, an example is provided to show the effectiveness of the proposed approach.
Pre- and Postsynaptic Dopamine SPECT in Idiopathic Parkinsonian Diseases: A Follow-Up Study
Authors: Jakobson Mo Susanna , Linder Jan , Forsgren Lars , Holmberg Henrik , Larsson Anne , Riklund Katrine
Published: September 2013

We prospectively evaluated the diagnostic contribution of123I-FP-Cit (DAT) and123I-IBZM (IBZM) SPECT in 29 patients with Parkinson's disease (PD) (74.4±4.2years) and 28 patients with atypical parkinsonian diseases (APD) (74.3±9.2years). Twelve had multiple system atrophy (MSA) and 16 progressive supranuclear palsy (PSP). Sixteen age-matched healthy controls (HC) were included. DAT and IBZM SPECTs were made at baseline and after 1 year in all PD patients and in 20 (DAT) and 18 (IBZM) of the APD patients, and after 3 years in 22 (DAT) and 17 (IBZM) of the PD patients and in 10 (DAT) and 10 (IBZM) of the APD patients. The relative DAT uptake decrease was faster in PD and PSP than in HC and MSA. In PSP the DAT uptake was lower than in MSA after 1 year but not after 3 years. Baseline IBZM uptake was not significantly different between patients and HC or between PD and APD. One year after initiated dopaminergic treatment the mean IBZM uptake in the MSA patients remained high compared to PSP and after 3 years compared to PD, PSP, and HC. Thus, the pattern of uptake of these ligands over time may be of value in discriminating between these diagnoses.
Clinical and Imaging Findings of True Hemifacial Hyperplasia
Authors: Bhuta Bansari A. , Yadav Archana , Desai Rajiv S. , Bansal Shivani P. , Chemburkar Vipul V. , Dev Prashant V.
Published: September 2013

Congenital hemifacial hyperplasia is a rare developmental disorder of unknown etiology, characterized by a marked unilateral facial asymmetry. It involves the hard (bones and teeth) and soft tissues of the face. We report an interesting case of true hemifacial hyperplasia in a 25-year-old male highlighting the clinical and computed tomography imaging findings.
Ethical Issues in mHealth Research Involving Persons Living with HIV/AIDS and Substance Abuse
Authors: Labrique Alain B. , Kirk Gregory D. , Westergaard Ryan P. , Merritt Maria W.
Published: September 2013

We aim to raise awareness and stimulate dialogue among investigators and research ethics committees regarding ethical issues that arise specifically in the design and conduct of mHealth research involving persons living with HIV/AIDS and substance abuse. Following a brief background discussion of mHealth research in general, we offer a case example to illustrate the characteristics of mHealth research involving people living with HIV/AIDS and substance abuse. With reference to a well-established systematic general ethical framework for biomedical research with human participants, we identify a range of ethical issues that have particular salience for the protection of participants in mHealth research on HIV/AIDS and substance abuse.
Age-Related Changes in Trabecular Meshwork Imaging
Authors: Gold Mark E. , Kansara Seema , Nagi Kundandeep S. , Bell Nicholas P. , Blieden Lauren S. , Chuang Alice Z. , Baker Laura A. , Mankiewicz Kimberly A. , Feldman Robert M.
Published: September 2013

Purpose. To evaluate the normal aging effects on trabecular meshwork (TM) parameters using Fourier domain anterior segment optical coherence tomography (ASOCT) images.Patients and Methods. One eye from 45 participants with open angles was imaged. Two independent readers measured TM area, TM length, and area and length of the TM interface shadow from 3 age groups (18–40, 41–60, and 61–80). Measurements were compared using stepwise regression analysis.Results. The average TM parameters were 0.0487 (±0.0092) mm2for TM area, 0.5502 (±0.1033) mm for TM length, 0.1623 (±0.341) mm2for TM interface shadow area, and 0.7755 (±0.1574) mm for TM interface shadow length. Interobserver reproducibility coefficients ranged from 0.45 (TM length) to 0.82 (TM area). TM area and length were not correlated with age. While the TM interface shadow length did not correlate with age, the TM interface shadow area increased with age. Race, sex, intraocular pressure, and gonioscopy score were not correlated with any TM parameters.Conclusion. Although the TM measurements were not correlated with age, the TM interface shadow area increased with age. Further study is required to determine whether there is any relationship between the age-related ASOCT findings of the TM interface shadow area and physiologic function.
Grape Seed Procyanidins in Pre- and Mild Hypertension: A Registry Study
Authors: Belcaro Gianni , Ledda Andrea , Hu Shu , Cesarone Maria Rosa , Feragalli Beatrice , Dugall Mark
Published: September 2013

The efficacy of a standardized grape seed procyanidins extract (GSPE, Enovita) to decrease blood pressure when associated with nondrug intervention (diet and lifestyle modifications) was investigated in a controlled registry study involving 119 healthy, pre- and mildly hypertensive subjects. Two dosages of Enovita were evaluated (150 and 300 mg/die), using blood pressure and heart rate as the primary endpoints and complementing these observations with a laser Doppler flowmetry (LDF) investigation of the microcirculation state and an evaluation of the plasma oxidative status. After four months of treatment, a statistically significant higher, and dose-dependent, improvement in all endpoints was observed in the treatment groups compared to that of the control, with blood pressure normalizing in 93% of the higher dosage (300 mg) treatment group. Taken together, these observations suggest that GSPEs have beneficial cardiovascular effects that complement current intervention strategies in the hypertension area. The effect on blood pressure adds to the beneficial effects of GSPEs on the cardiovascular disease (CVD) phenotype associated with the oxidation of membrane lipids (endothelial dysfunction, formation of oxidized LDL, and activation of phagocytic cells).
Pricing Models of e-Books When Competing with p-Books
Authors: Li Yan , Liu Nan
Published: September 2013

With the rise in popularity of e-books, there is a growing need to reexamine the pricing strategy in the e-book supply chain. In this paper, we study two forms of pricing models widely used in the book industry: wholesale and agency pricing models. We first assume a stylized deterministic demand model in which the demand depends on the price, the degree of substitution, and the overall market potential. Subsequently, we employ the game theory to determine the price equilibriums and profit distribution under different pricing models. Finally, we explore the behavior of the publisher and the retailer under different preferences and degrees of substitution through a computational study. Our findings indicate that the e-book price will be lower under the agency pricing model than under the wholesale pricing model, which is counterintuitive. The publishers have higher incentives to adopt the agency pricing model than the wholesale pricing model. The agency pricing model benefits the whole system and can provide readers with books at lower prices. The degree of substitution between the two forms of books and the readers’ preference toward e-book will affect the books’ price and the profit distribution between the publisher and the retailers.
Spatial Competition with Entry Deterrence considering Horizontal Product Differentiations
Authors: Zhou Ai-nong
Published: September 2013

Spatial competition plays important roles in economics, which attracts extensive research. This paper addresses spatial competitions along with horizontal product differentiations and entry deterrence. By the dynamic game theory model about one firm and a potential entrant with different cost in a linear city, this paper finds that both the higher fixed setup cost and the higher transportation cost deter entrants. To efficiently deter the entrants, the establisher is inclined to locating at the middle point of the linear city.
Cardiac Diastolic Evaluation in Pregnant Women with Abnormal Glucose Tolerance: An Opportunity to Detect the Early and Subclinical Alterations and Prevent Cardiovascular Diseases
Authors: Pintaudi B. , Di Vieste G. , Corrado F. , Creazzo M. F. , Fazio A. , Valenti A. , D’Anna R. , Di Benedetto A.
Published: September 2013

Objectives of this study were to assess diastolic function in pregnant women with abnormal glucose tolerance (AGT), compared with normal glucose tolerance (NGT) women, and to evaluate the insulin resistance status and its association with Doppler-echocardiographic indexes. Echocardiograms of 108 consecutive Caucasian women with singleton pregnancies were performed. Insulin resistance status was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). All the studied women showed normal diastolic patterns. Patients with AGT (50.9%), as compared with NGT women, had higher HOMA-IR (1.70±1.30versus1.01±0.81,P=0.003), lower QUICKI (0.36±0.005versus0.40±0.06,P=0.004), higher lateral mitral annulus late diastolic velocity (13.6±4.9versus11.9±4.9,P=0.03), and higher A-wave velocity, the wave responsible for the active atrial contraction component (75.2±14.2versus67.7±16.2,P=0.01). At multivariate regression analysis HOMA-IR was the only parameter associated with A-wave velocity. In conclusion, women with AGT had an increased subclinical diastolic active participation, which is associated with higher levels of insulin resistance. For the increased risk of deterioration of cardiac diastolic function, earlier and more seriously than normal pregnancy, AGT women may have a careful followup to detect the early signs of cardiac alteration and to prevent cardiovascular diseases.
A General Self-Adaptive Relaxed-PPA Method for Convex Programming with Linear Constraints
Authors: Fu Xiaoling
Published: September 2013

We present an efficient method for solving linearly constrained convex programming. Our algorithmic framework employs an implementable proximal step by a slight relaxation to the subproblem of proximal point algorithm (PPA). In particular, the stepsize choice condition of our algorithm is weaker than some elegant PPA-type methods. This condition is flexible and effective. Self-adaptive strategies are proposed to improve the convergence in practice. We theoretically show under mild conditions that our method converges in a global sense. Finally, we discuss applications and perform numerical experiments which confirm the efficiency of the proposed method. Comparisons of our method with some state-of-the-art algorithms are also provided.
Simple, Inexpensive Technique for High-Quality Smartphone Fundus Photography in Human and Animal Eyes
Authors: Haddock Luis J. , Kim David Y. , Mukai Shizuo
Published: September 2013

Purpose. We describe in detail a relatively simple technique of fundus photography in human and rabbit eyes using a smartphone, an inexpensive app for the smartphone, and instruments that are readily available in an ophthalmic practice.Methods. Fundus images were captured with a smartphone and a 20D lens with or without a Koeppe lens. By using the coaxial light source of the phone, this system works as an indirect ophthalmoscope that creates a digital image of the fundus. The application whose software allows for independent control of focus, exposure, and light intensity during video filming was used. With this app, we recorded high-definition videos of the fundus and subsequently extracted high-quality, still images from the video clip.Results. The described technique of smartphone fundus photography was able to capture excellent high-quality fundus images in both children under anesthesia and in awake adults. Excellent images were acquired with the 20D lens alone in the clinic, and the addition of the Koeppe lens in the operating room resulted in the best quality images. Successful photodocumentation of rabbit fundus was achieved in control and experimental eyes.Conclusion. The currently described system was able to take consistently high-quality fundus photographs in patients and in animals using readily available instruments that are portable with simple power sources. It is relatively simple to master, is relatively inexpensive, and can take advantage of the expanding mobile-telephone networks for telemedicine.
The Usefulness of 3-Dimensional Virtual Simulation Using Haptics in Training Orotracheal Intubation
Authors: Lee Dong Hoon , Kim Jae Gyu , Kim Chan Woong , Lee Chang Ha , Lim Jae Hee
Published: September 2013

Objectives. Airway control is the most critical treatment. The most common and basic method of endotracheal intubation is orotracheal intubation. To perform accurate and rapid tracheal intubation, appropriate education and training are required. We developed the virtual simulation program utilizing the 3-dimensional display and haptic device to exercise orotracheal intubation, and the educational effect of this program was compared with that of the mannequin method.Method. The control group used airway mannequin and virtual intubation group was trained with new program. We videotaped both groups during objective structured clinical examination (OSCE) with airway mannequin. The video was reviewed and scored, and the rate of success and time were calculated.Result. The success rate was 78.6% in virtual intubation group and 93.3% in control group (P=0.273). There was no difference in overall score of OSCE (21.14 ± 4.28 in virtual intubation group and 23.33 ± 4.45 in control group,P=0.188), the time spent in successful intubation (P=0.432), and the number of trials (P>0.101).Conclusion. The virtual simulation with haptics had a similar effect compared with mannequin, but it could be more cost effective and convenient than mannequin training in time and space.
Investigation of In Vitro Drug Release from Porous Hollow Silica Nanospheres Prepared of ZnS@SiO2Core-Shell
Authors: Vafayi Leila , Gharibe Soodabe
Published: September 2013

In this contribution, porous hollow silica nanoparticles using inorganic nanosized ZnS as a template were prepared. The hydrothermal method was used to synthesize pure ZnS nanospheres material. The ZnS@SiO2core-shell nanocomposites were prepared using a simple sol-gel method successfully. The hollow silica nanostructures were achieved by selective removal of the ZnS core. The morphology, structure, and composition of the product were determined using powder X-ray diffraction (XRD), emission scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FT-IR). The results demonstrated clearly that the pure ZnS nanoparticles are in a spherical form with the average size of 40 nm and correspond with zinc blend structure. The porous hollow silica nanoparticles obtained were exploited as drug carriers to investigate in vitro release behavior of amoxicillin in simulated body fluid (SBF). UV-visible spectrometry was carried out to determine the amount of amoxicillin entrapped in the carrier. Amoxicillin release profile from porous hollow silica nanoparticles followed a three-stage pattern and indicated a delayed release effect.
A Partial Volume Effect Correction Tailored for18F-FDG-PET Oncological Studies
Authors: Gallivanone F. , Canevari C. , Gianolli L. , Salvatore C. , Della Rosa P. A. , Gilardi M. C. , Castiglioni I.
Published: September 2013

We have developed, optimized, and validated a method for partial volume effect (PVE) correction of oncological lesions in positron emission tomography (PET) clinical studies, based on recovery coefficients (RC) and on PET measurements of lesion-to-background ratio (L/Bm) and of lesion metabolic volume. An operator-independent technique, based on an optimised threshold of the maximum lesion uptake, allows to define an isocontour around the lesion on PET images in order to measure both lesion radioactivity uptake and lesion metabolic volume. RC are experimentally derived from PET measurements of hot spheres in hot background, miming oncological lesions. RC were obtained as a function of PET measured sphere-to-background ratio and PET measured sphere metabolic volume, both resulting from the threshold-isocontour technique. PVE correction of lesions of a diameter ranging from 10 mm to 40 mm and for measuredL/Bmfrom 2 to 30 was performed using measured RC curves tailored at answering the need to quantify a large variety of real oncological lesions by means of PET. Validation of the PVE correction method resulted to be accurate (>89%) in clinical realistic conditions for lesion diameter > 1 cm, recovering >76% of radioactivity for lesion diameter < 1 cm. Results from patient studies showed that the proposed PVE correction method is suitable and feasible and has an impact on a clinical environment.
HPLC Quantitative Analysis of Rhein and Antidermatophytic Activity ofCassia fistulaPod Pulp Extracts of Various Storage Conditions
Authors: Chewchinda Savita , Wuthi-udomlert Mansuang , Gritsanapan Wandee
Published: September 2013

Cassia fistulais well known for its laxative and antifungal properties due to anthraquinone compounds in the pods. This study quantitatively analyzed rhein in theC. fistulapod pulp decoction extracts kept under various storage conditions using HPLC. The antifungal activity of the extracts and their hydrolyzed mixture was also evaluated against dermatophytes. The contents of rhein in all stored decoction extracts remained more than 95% (95.69–100.66%) of the initial amount (0.0823±0.001% w/w). There was no significant change of the extracts kept in glass vials and in aluminum foil bags. The decoction extract ofC. fistulapod pulp and its hydrolyzed mixture containing anthraquinone aglycones were tested against clinical strains of dermatophytes by broth microdilution technique. The results revealed good chemical and antifungal stabilities against dermatophytes ofC. fistulapod pulp decoction extracts stored under various accelerated and real time storage conditions.
The Average Covering Number of a Graph
Authors: Dogan Derya , Dundar Pinar
Published: September 2013

There are occasions when an average value of a graph parameter gives more useful information than the basic global value. In this paper, we introduce the concept of the average covering number of a graph (the covering number of a graph is the minimum number of vertices in a set with the property that every edge has a vertex in the set). We establish relationships between the average covering number and some other graph parameters, find the extreme values of the average covering number among all graphs of a given order, and find the average covering number for some families of graphs.
3D DC Resistivity Inversion with Topography Based on Regularized Conjugate Gradient Method
Authors: Qiang Jian-ke , Han Xue , Dai Shi-kun
Published: September 2013

During the past decades, we observed a strong interest in 3D DC resistivity inversion and imaging with complex topography. In this paper, we implemented 3D DC resistivity inversion based on regularized conjugate gradient method with FEM. The Fréchet derivative is assembled with the electric potential in order to speed up the inversion process based on the reciprocity theorem. In this study, we also analyzed the sensitivity of the electric potential on the earth’s surface to the conductivity in each cell underground and introduced an optimized weighting function to produce new sensitivity matrix. The synthetic model study shows that this optimized weighting function is helpful to improve the resolution of deep anomaly. By incorporating topography into inversion, the artificial anomaly which is actually caused by topography can be eliminated. As a result, this algorithm potentially can be applied to process the DC resistivity data collected in mountain area. Our synthetic model study also shows that the convergence and computation speed are very stable and fast.
Combination Therapy with a Second-Generation Androgen Receptor Antagonist and a Metastasis Vaccine Improves Survival in a Spontaneous Prostate Cancer Model
Authors: Ardiani Andressa , Farsaci Benedetto , Rogers Connie J. , Protter Andy , Guo Zhimin , King Thomas H. , Apelian David , Hodge James W.
Published: September 2013

Purpose: Enzalutamide, a second-generation androgen antagonist, was approved by the U.S. Food and Drug Administration (FDA) for castration-resistant prostate cancer (CRPC) treatment. Immunotherapy has been shown to be a promising strategy for prostate cancer. This study was performed to provide data to support the combination of enzalutamide and immunotherapy for CRPC treatment.

Experimental Design: Male C57BL/6 or TRAMP (transgenic adenocarcinoma of the mouse prostate) prostate cancer model mice were exposed to enzalutamide and/or a therapeutic vaccine targeting Twist, an antigen involved in epithelial-to-mesenchymal transition and metastasis. The physiologic and immunologic effects of enzalutamide were characterized. The generation of Twist-specific immunity by Twist-vaccine was assessed. Finally, the combination of enzalutamide and Twist-vaccine to improve TRAMP mice overall survival was evaluated.

Results: Enzalutamide mediated immunogenic modulation in TRAMP-C2 cells. In vivo, enzalutamide mediated reduced genitourinary tissue weight, enlargement of the thymus, and increased levels of T-cell excision circles. Because no changes were seen in T-cell function, as determined by CD4+ T-cell proliferation and regulatory T cell (Treg) functional assays, enzalutamide was determined to be immune inert. Enzalutamide did not diminish the ability of Twist-vaccine to generate Twist-specific immunity. Twist was confirmed as a valid tumor antigen in TRAMP mice by immunohistochemistry. The combination of enzalutamide and Twist-vaccine resulted in significantly increased overall survival of TRAMP mice compared with other treatment groups (27.5 vs. 10.3 weeks). Notably, the effectiveness of the combination therapy increased with disease stage, i.e., the greatest survival benefit was seen in mice with advanced-stage prostate tumors.

Conclusions: These data support the combination of enzalutamide and immunotherapy as a promising treatment strategy for CRPC. Clin Cancer Res; 19(22); 6205–18. ©2013 AACR.
EGFR Inhibition Induces Proinflammatory Cytokines via NOX4 in HNSCC
Authors: Fletcher Elise V.M. , Love-Homan Laurie , Sobhakumari Arya , Feddersen Charlotte R. , Koch Adam T. , Goel Apollina , Simons Andrean L.
Published: September 2013

Chronic inflammation plays a fundamental role in tumor promotion, migration, and invasion. With the use of microarray profiling, a profound increase was observed for those transcripts involved in proinflammatory signaling in epidermal growth factor receptor (EGFR) inhibitor–treated head and neck squamous cell carcinoma (HNSCC) cells as compared with their respective controls. As such, it was hypothesized that EGFR inhibitor efficacy is offset by the proinflammatory response that these therapeutics conjure in HNSCC. Systematic evaluation of the clinical EGFR inhibitors—erlotinib, cetuximab, lapatinib, and panitumumab—revealed increased secretion of proinflammatory cytokines such as interleukins (IL-2, IL-4, IL-6, IL-8), granulocyte-macrophage colony-stimulating factor, TNF-α, and IFN-γ. Mechanistic focus on IL-6 revealed that erlotinib induced a time-dependent increase in IL-6 mRNA and protein expression. Importantly, exogenous IL-6 protected HNSCC cells from erlotinib-induced cytotoxicity, whereas tocilizumab, an IL-6 receptor antagonist, sensitized cells to erlotinib in vitro and in vivo. Inhibitors of NF-κB, p38, and JNK suppressed erlotinib-induced IL-6 expression, suggesting critical roles for NF-κB and MAPK in IL-6 regulation. Furthermore, knockdown of NADPH oxidase 4 (NOX4) suppressed erlotinib-induced proinflammatory cytokine expression. Taken together, these results demonstrate that clinical EGFR inhibitors induce the expression of proinflammatory cytokines via NOX4.

Implications: The antitumor activity of EGFR inhibitors is reduced by activation of NOX4-mediated proinflammatory pathways in HNSCC. Mol Cancer Res; 11(12); 1574–84. ©2013 AACR.
Vesical Paragonimiasis Diagnosed by Histopathology: A Case Report
Authors: Yue Xuan , Wei Xin , Zhu Yuchun , Han Ping , Li Xiang , Wei Qiang , Liu Liangren
Published: September 2013

Vesical paragonimiasis is an extremely rare form of ectopic infestation caused by Paragonimus spp. We reported a case of vesical paragonimiasis associated with urinary symptoms but without history of respiratory symptoms or cercarial dermatitis. The diagnosis was made by histopathological examination of the surgical specimens of the vesical masses. Identification of the species by morphometric analysis of the fluke body sections indicated that the vesical lesion was caused by Paragonimus. Postsurgical medication with the antiparasitic drug praziquantel was applied regularly, and the patient experienced a stable recovery.
Use of Healthy-Donor Granulocyte Transfusions to Treat Infections in Neutropenic Patients with Myeloid or Lymphoid Neoplasms: Experience in 74 Patients Treated with 373 Granulocyte Transfusions
Authors: Safdar Amar , Rodriguez Gilhen , Zuniga Jorge , Al Akhrass Fadi , Pande Anupam
Published: September 2013

Background/Aims: Despite limited evidence for efficacy, granulocyte transfusions (GTX) are used to prevent and treat opportunistic infections in patients with neutropenia. Methods: Three hundred and seventy-three GTX given to 74 patients were assessed retrospectively. Results: GTX were discontinued because of clinical improvement more often in patients with severe infections than in patients without severe infections (27 vs. 12%; p ≤ 0.002), whereas deaths resulted in discontinuation of GTX therapy less often in patients with severe infections than without (8 vs. 39%; p ≤ 0.002). Patients who died by 12 weeks after GTX initiation were more likely to have leukemia (p = 0.03), not to have recovery of neutrophil counts (p < 0.0001), and to have started GTX during a critical care unit stay (p < 0.001). Uses of granulocyte colony-stimulating factor (p ≤ 0.02) and interferon-γ (p ≤ 0.04) were more common in patients who survived. In patients with comorbidities (31%; odds ratio, OR, 12.6; 95% confidence interval, CI, 2.4-65.7; p ≤ 0.003), GTX was started in the critical care unit (OR 8.8; 95% CI 2.5-30.9; p < 0.001), and a high total bilirubin level at the end of GTX (OR 2.1; 95% CI 1.1-4.2; p = 0.03) had a higher probability of death 12 weeks after GTX therapy commenced. Conclusions: The possibility that a niche population may benefit from GTX requires further assessment.
Primary Synovial Sarcoma of the Kidney
Authors: Ozkanli Sidika Seyma , Yildirim Asif , Zemheri Ebru , Gucer Firdevs İkbal , Aydin Abdullah , Caskurlu Turhan
Published: September 2013

Synovial Sarcoma (SS) is a soft tissue neoplasm that occurs generally in the proximity of large joints. Here, we report a case of a 45-year-old man who was diagnosed with Primary SS of the kidney which is an extremely rare tumor that accounts for less than 2% of malignant renal tumors. We also review the literature on primary synovial sarcomas of the kidney and focus especially on the renal tumors' differential diagnosis.
Radical Cystectomy in the Elderly: National Trends and Disparities in Perioperative Outcomes and Quality of Care
Authors: Roghmann Florian , Sukumar Shyam , Ravi Praful , Trinh Vincent Q. , Meskawi Malek , Ghani Khurshid R. , Sammon Jesse D. , Friedman Ariella A. , Peabody James O. , Menon Mani , Noldus Joachim , Karakiewicz Pierre I. , Sun Maxine , Trinh Quoc-Dien
Published: September 2013

Introduction: To examine national trends of radical cystectomy (RC) for urothelial carcinoma of urinary bladder in octogenarian patients and to assess the rates of adverse outcomes. Materials and Methods: Within the Nationwide Inpatient Sample (NIS), we focused on RCs performed between 1998 and 2007. Age was stratified as <80 versus ≥80 years. Propensity-based matched analyses were used to account for treatment selection biases. Generalized linear regression analyses were fitted to predict adverse perioperative events according to age. Results: Of 12,274 RC patients, 1,605 were ≥80 years (13.1%). The RC rates in octogenarians increased significantly from 9.9% in 1998 to 13.7% in 2007. Most elderly patients were treated at low-/intermediate-volume hospitals (81.7%) and nonacademic centers (60.6%). After propensity score matching, the inpatient mortality rate was higher in octogenarians (4.6 vs. 2.6%, p < 0.001). In multivariable analyses, octogenarians were at increased risk of blood transfusions (OR: 1.30) and postoperative complications (OR: 1.22). Conclusions: Most octogenarians undergoing RC are treated at low-/intermediate-volume hospitals and at nonacademic centers. The inpatient hospital mortality is about twice as high in these patients, and adverse perioperative outcomes are more frequent. Such patients may benefit from RC at high-volume and/or academic centers to maximally reduce adverse perioperative outcomes.