bluuebunny/crossref_metadata_2025 huggingface dataset:
Tribological Performance Optimization of Al-7.5% SiCp Composites Using the Taguchi Method and Grey Relational Analysis
Authors: Ghosh Shouvik , Sahoo Prasanta , Sutradhar Goutam
Published: September 2013

The present study considers an experimental study of tribological performance of Al-7.5% SiCp metal matrix composite and optimization of tribological testing parameters based on the Taguchi method coupled with grey relational analysis. A grey relational grade obtained from grey relational analysis is used as a performance index to study the behaviour of Al-7.5% SiCp MMC with respect to friction and wear characteristics. The tribological experiments are carried out by utilizing the combinations of tribological test parameters based on the L27 Taguchi orthogonal design with three test parameters, namely, load, speed, and time. The material Al-7.5% SiCp metal matrix composite is developed by reinforcing LM6 aluminium alloy with 7.5% (by weight) SiC particle of 400 mesh size (~37 μm) in an electric melting furnace. It is observed that sliding time has a significant contribution in controlling the friction and wear behaviour of Al-7.5% SiCp MMC. Furthermore, all the interactions between the parameters have significant influence on tribological performance. A confirmation test is also carried out to verify the accuracy of the results obtained through the optimization problem. In addition, a scanning electron microscopy (SEM) test is performed on the wear tracks to study the wear mechanism.
Fluid Structural Analysis of Human Cerebral Aneurysm Using Their Own Wall Mechanical Properties
Authors: Valencia Alvaro , Burdiles Patricio , Ignat Miguel , Mura Jorge , Bravo Eduardo , Rivera Rodrigo , Sordo Juan
Published: September 2013

Computational Structural Dynamics (CSD) simulations, Computational Fluid Dynamics (CFD) simulation, and Fluid Structure Interaction (FSI) simulations were carried out in an anatomically realistic model of a saccular cerebral aneurysm with the objective of quantifying the effects of type of simulation on principal fluid and solid mechanics results. Eight CSD simulations, one CFD simulation, and four FSI simulations were made. The results allowed the study of the influence of the type of material elements in the solid, the aneurism’s wall thickness, and the type of simulation on the modeling of a human cerebral aneurysm. The simulations use their own wall mechanical properties of the aneurysm. The more complex simulation was the FSI simulation completely coupled with hyperelastic Mooney-Rivlin material, normal internal pressure, and normal variable thickness. The FSI simulation coupled in one direction using hyperelastic Mooney-Rivlin material, normal internal pressure, and normal variable thickness is the one that presents the most similar results with respect to the more complex FSI simulation, requiring one-fourth of the calculation time.
Trypanosoma evansiand Surra: A Review and Perspectives on Transmission, Epidemiology and Control, Impact, and Zoonotic Aspects
Authors: Desquesnes Marc , Dargantes Alan , Lai De-Hua , Lun Zhao-Rong , Holzmuller Philippe , Jittapalapong Sathaporn
Published: September 2013

This paper reviews the transmission modes ofTrypanosoma evansi. Its worldwide distribution is attributed to mechanical transmission. While the role of tabanids is clear, we raise questions on the relative role ofHaematobiasp. and the possible role ofStomoxyssp. in delayed transmission. A review of the available trypanocidal drugs and their efficacy in various host species is useful for understanding how they interact in disease epidemiology, which is complex. Although there are similarities with other mechanically transmitted trypanosomes,T. evansihas a more complex epidemiology due to the diversity of its hosts and vectors. The impact of clinical and subclinical disease is difficult to establish. A model was developed for buffaloes in the Philippines, which could be transferred to other places and livestock systems. SinceTrypanosoma evansiwas reported in humans, further research is required to investigate its zoonotic potential. Surra remains a potentially emerging disease that is a threat to Australia, Spain, and France. A number of questions about the disease have yet to be resolved. This brief review of the basic knowledge ofT. evansisuggests that there is renewed interest in the parasite, which is spreading and has a major economic impact.
Congenital Lumbar Hernia with Lumbocostovertebral Syndrome: A Case Report and Review of the Literature
Authors: Vagholkar Ketan , Dastoor Khojasteh
Published: September 2013

Introduction. Congenital lumbar hernia is one of the rare types of hernias. Anomalies of the ribs, spine, and muscles which constitute the lumbocostovertebral syndrome in association with congenital lumbar hernia make it the rarest of entities. In addition, a multitude of other organ systems may be involved.Case Report. A case of congenital lumbar hernia associated with lumbocostovertebral syndrome is presented in view of its rarity and diagnostic and therapeutic challenges.Discussion. Anatomical background of congenital lumbar hernia associated with various other anomalies especially of the musculoskeletal structures is discussed. All cases of congenital lumbar hernia should be investigated for other congenital anomalies. Both open and laparoscopic approaches have been described for surgical treatment.Conclusion. Open surgical intervention is the mainstay of treatment taking into consideration the technical challenges posed by distorted anatomy due to the associated congenital anomalies.
Angiotensin‐I‐Converting Enzyme Inhibitory and Antioxidant Activities of Protein Hydrolysate from Muscle of Barbel (Barbus callensis)
Authors: Sila Assaad , Haddar Anissa , Martinez-Alvarez Oscar , Bougatef Ali
Published: September 2013

The present study investigated angiotensin‐I‐converting enzyme (ACE) inhibitory and antioxidant activities of barbel muscle protein hydrolysate prepared with Alcalase. The barbel muscle protein hydrolysate displayed a high ACE inhibitory activity (CI50 = 0.92 mg/mL). The antioxidant activities of protein hydrolysate at different concentrations were evaluated using various in vitro antioxidant assays, including 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical method and reducing power assay. The barbel muscle protein hydrolysate exhibited an important radical scavenging effect and reducing power. These results obtained by in vitro systems obviously established the antioxidant potency of barbel hydrolysate to donate electron or hydrogen atom to reduce the free radical. Furthermore, these bioactive substances can be exploited into functional foods or used as source of nutraceuticals.
Neuroprotective Role of a Novel Copper Chelator againstAβ42Induced Neurotoxicity
Authors: Singh Sandeep Kumar , Sinha Priti , Mishra L. , Srikrishna S.
Published: September 2013

Alzheimer's disease (AD) is a progressive neurodegenerative disease and associated with the extracellular deposits of amyloid-βpeptide in hippocampus region. Metal ions like Cu, Fe and Zn are known to associate with the amyloid beta (Aβ) at high concentration and interaction of these ions with soluble and aggregated forms of Aβpeptide help in development of AD. Here we showed Cu mediated neurotoxicity in the eye tissues of transgenicDrosophilaexpressing human amyloidβand its rescue through a novel Cu chelator. In this context, we have synthesised and characterized the compound L 2,6-Pyridinedicarboxylic acid, 2,6-bis[2-[(4-carboxyphenyl) methylene] hydrazide] by Mass spectra (MS) and Elemental analysis (EA). The Cu chelation potential of the compound L is testedin vivoinDrosophila. Oral administration of Copper to the transgenic larvae resulted in severe degeneration in eye tissues, which was rescued by the supplementation of compound L. The levels of anti-oxidant markers like SOD and MDA were measured in compound L treated flies and found a significant rescue (P<0.001). Further rescue of the eye degeneration phenotypes as revealed by SEM affirm the role of copper in Aβtoxicity. Hence, use of compound L, an amidoamine derivative, could be a possible therapeutic measure for Aβinduced neurotoxicity.
Design Method for Channel Diffusers of Centrifugal Compressors
Authors: Kalinkevych Mykola , Skoryk Andriy
Published: September 2013

The design method for channel diffusers of centrifugal compressors, which is based on the solving of the inverse problem of gas dynamics, is presented in the paper. The concept of the design is to provide high pressure recovery of the diffuser by assuming the preseparation condition of the boundary layer along one of the channel surfaces. The channel diffuser was designed with the use of developed method to replace the vaned diffuser of the centrifugal compressor model stage. The numerical simulation of the diffusers was implemented by means of CFD software. Obtained gas dynamic characteristics of the designed diffuser were compared to the base vaned diffuser of the compressor stage.
Coupled Hydromechanical Model of Two-Phase Fluid Flow in Deformable Porous Media
Authors: Kim You-Seong , Kim Jaehong
Published: September 2013

A model of solid-water-air coupling in triphasic mixtures is compared with solid-water coupling in biphasic mixtures with an application to partially saturated porous media. Based on thermodynamics, the mathematical framework governing the behavior of a partially saturated soil is derived using balance equations, and the numerical implementation and drainage tests of a soil column are carried out to validate the obtained formulations. The role of the air phase in the hydro-mechanical behavior of triphasic mixtures can be analyzed from the interactions among multiple phases for the constitutive behavior of a solid skeleton, and the triphasic mixture model can be applied in geotechnical engineering problems, such asCO2sequestration and air storage in aquifers.
Dental Treatments under the General Anesthesia in a Child with Keratitis, Ichthyosis, and Deafness Syndrome
Authors: Derelioglu Sera Sımsek , Yılmaz Yücel , Keles Sultan
Published: September 2013

KID syndrome is a rare genodermatosis characterized by keratitis, ichthyosis, and sensorineural deafness. Although the dermatological, ophthalmologic, and sensorineural defects are emphasized in the literature, oral and dental evaluations are so superficial. In this case report, dental and oral symptoms of a three year and five months old boy with KID syndrome, suffering severe Early Childhood Caries (s-ECC) and dental treatments done under General Anesthesia (GA) were reported.
Anomalous Threshold Voltage Variability of Nitride Based Charge Storage Nonvolatile Memory Devices
Authors: Lee Meng Chuan , Wong Hin Yong
Published: September 2013

Conventional technology scaling is implemented to meet the insatiable demand of high memory density and low cost per bit of charge storage nonvolatile memory (NVM) devices. In this study, effect of technology scaling to anomalous threshold voltage (Vt) variability is investigated thoroughly on postcycled and baked nitride based charge storage NVM devices. After long annealing bake of high temperature, cell’s Vt variability of each subsequent bake increases within stable Vt distribution and found exacerbate by technology scaling. Apparent activation energy of this anomalous Vt variability was derived through Arrhenius plots. Apparent activation energy (Eaa) of this anomalous Vt variability is 0.67 eV at sub‐40 nm devices which is a reduction of approximately 2 times from 110 nm devices. Technology scaling clearly aggravates this anomalous Vt variability, and this poses reliability challenges to applications that demand strict Vt control, for example, reference cells that govern fundamental program, erase, and verify operations of NVM devices. Based on critical evidence, this anomalous Vt variability is attributed to lateral displacement of trapped charges in nitride storage layer. Reliability implications of this study are elucidated. Moreover, potential mitigation methods are proposed to complement technology scaling to prolong the front‐runner role of nitride based charge storage NVM in semiconductor flash memory market.
Radioactive Iodine and Krypton Control for Nuclear Fuel Reprocessing Facilities
Authors: Soelberg Nick R. , Garn Troy G. , Greenhalgh Mitchell R. , Law Jack D. , Jubin Robert , Strachan Denis M. , Thallapally Praveen K.
Published: September 2013

The removal of volatile radionuclides generated during used nuclear fuel reprocessing in the US is almost certain to be necessary for the licensing of a reprocessing facility in the US. Various control technologies have been developed, tested, or used over the past 50 years for control of volatile radionuclide emissions from used fuel reprocessing plants. The US DOE has sponsored, since 2009, an Off-gas Sigma Team to perform research and development focused on the most pressing volatile radionuclide control and immobilization problems. In this paper, we focus on the control requirements and methodologies for85Kr and129I. Numerous candidate technologies have been studied and developed at laboratory and pilot-plant scales in an effort to meet the need for high iodine control efficiency and to advance alternatives to cryogenic separations for krypton control. Several of these show promising results. Iodine decontamination factors as high as 105, iodine loading capacities, and other adsorption parameters including adsorption rates have been demonstrated under some conditions for both silver zeolite (AgZ) and Ag-functionalized aerogel. Sorbents, including an engineered form of AgZ and selected metal organic framework materials (MOFs), have been successfully demonstrated to capture Kr and Xe without the need for separations at cryogenic temperatures.
Breath Tests in Respiratory and Critical Care Medicine: From Research to Practice in Current Perspectives
Authors: Cheepsattayakorn Attapon , Cheepsattayakorn Ruangrong
Published: September 2013

Today, exhaled nitric oxide has been studied the most, and most researches have now focusd on asthma. More than a thousand different volatile organic compounds have been observed in low concentrations in normal human breath. Alkanes and methylalkanes, the majority of breath volatile organic compounds, have been increasingly used by physicians as a novel method to diagnose many diseases without discomforts of invasive procedures. None of the individual exhaled volatile organic compound alone is specific for disease. Exhaled breath analysis techniques may be available to diagnose and monitor the diseases in home setting when their sensitivity and specificity are improved in the future.
Midwives' Experiences in Providing Care and Counselling to Women with Female Genital Mutilation (FGM) Related Problems
Authors: Isman Elisabeth , Mahmoud Warsame Amina , Johansson Annika , Fried Sarah , Berggren Vanja
Published: September 2013

Aim. The aim of this study was to elucidate midwives experiences in providing care and counselling to women with FGM related problems.Setting. The study was conducted at a maternity clinic in Hargeisa, Somaliland.Method. A qualitative, inductive study were performed with eight midwives living in Somaliland. The interviews had semi-structured questions. Content analysis was used for the analysis.Findings. The main findings of the present study were how midwives are challenged by culture and religion when providing FGM counselling. The most prominent challenge is the perception that FGM is an important part of the culture and from this point of view the midwives work is apprehended as interfering and subverting the Somali culture. Having personal experience of FGM emerged as a benefit when counselling women.Conclusion. There is a contradiction between the professional actions of performing FGM despite a personal belief against FGM. Midwives as a professional group could be important agents of change and further research is needed about the midwives role in this process.
Sampled-Data Control of Spacecraft Rendezvous with Discontinuous Lyapunov Approach
Authors: Li Zhuoshi , Liu Ming , Karimi Hamid Reza , Cao Xibin
Published: September 2013

This paper investigates the sampled-data stabilization problem of spacecraft relative positional holding with improved Lyapunov function approach. The classical Clohessy-Wiltshire equation is adopted to describe the relative dynamic model. The relative position holding problem is converted into an output tracking control problem using sampling signals. A time-dependent discontinuous Lyapunov functionals approach is developed, which will lead to essentially less conservative results for the stability analysis and controller design of the corresponding closed-loop system. Sufficient conditions for the exponential stability analysis and the existence of the proposed controller are provided, respectively. Finally, a simulation result is established to illustrate the effectiveness of the proposed control scheme.
Skin Inqjuries Reduce Survival and Modulate Corticosterone, C-Reactive Protein, Complement Component 3, IgM, and Prostaglandin E2after Whole-Body Reactor-Produced Mixed Field (n +γ-Photons) Irradiation
Authors: Kiang Juliann G. , Ledney G. David
Published: September 2013

Skin injuries such as wounds or burns following whole-bodyγ-irradiation (radiation combined injury (RCI)) increase mortality more than whole-bodyγ-irradiation alone. Wound-induced decreases in survival after irradiation are triggered by sustained activation of inducible nitric oxide synthase pathways, persistent alteration of cytokine homeostasis, and increased susceptibility to systemic bacterial infection. Among these factors, radiation-induced increases in interleukin-6 (IL-6) concentrations in serum were amplified by skin wound trauma. Herein, the IL-6-induced stress proteins including C-reactive protein (CRP), complement 3 (C3), immunoglobulin M (IgM), and prostaglandin E2(PGE2) were evaluated after skin injuries given following a mixed radiation environment that might be found after a nuclear incident. In this report, mice received 3 Gy of reactor-produced mixed field (n+γ-photons) radiations at 0.38 Gy/min followed by nonlethal skin wounding or burning. Both wounds and burns reduced survival and increased CRP, C3, and PGE2in serum after radiation. Decreased IgM production along with an early rise in corticosterone followed by a subsequent decrease was noted for each RCI situation. These results suggest that RCI-induced alterations of corticosterone, CRP, C3, IgM, and PGE2cause homeostatic imbalance and may contribute to reduced survival. Agents inhibiting these responses may prove to be therapeutic for RCI and improve related survival.
A Generalization of Prešić Type Mappings in 0-Complete Ordered Partial Metric Spaces
Authors: Shukla Satish , Radenović Stojan
Published: September 2013

The purpose of this paper is to prove some coincidence and common fixed point results for mappings satisfying Prešić type contraction condition in 0-complete ordered partial metric spaces. The results proved in this paper generalize and extend the results of Prešić and Matthews in 0-complete ordered partial metric spaces. Some examples are included which show that the generalization is proper.
Effect of Gold/Fe3O4 Nanoparticles on Biocompatibility and Neural Differentiation of Rat Olfactory Bulb Neural Stem Cells
Authors: Wang Menghang , Li Zhou , Qiao Huiting , Chen Luoping , Fan Yubo
Published: September 2013

Transplantation of stem cells is a potential clinical therapy for repair of central nervous system injury. However, transplanted cells are especially difficult to arrive at the targeted site because of poor survival rate and low efficiency. Recently, gold nanoparticles (NPs) and Iron oxide NPs, as novel nanoparticles, have been used as auxiliary strategy to investigate the nervous system diseases. The present study demonstrates the effect of Gold/Fe3O4 NPs on biocompatibility and differentiated properties of rat olfactory bulb stem cells. Cell viability was assumed by MTT test and cytotoxicity was assessed by Hoechst 33342‐PI stain. Cells were cultured at Gold/Fe3O4 NPs concentration range of 40 to 200 μg/104 cells for 24 h. Differentiation was assessed by NSE (a neuronal marker) stain. Results showed that Gold/Fe3O4 NPs at the concentrations of 40 μg/104 cells enhanced cell viability and decreased the cell death rate. Furthermore, the differentiation properties were detected by NSE marker. These findings suggest that Gold/Fe3O4 NPs may thus be used as new nanotechnologies in stem‐cell‐based transplantation therapies for diagnosis and treatment of central nervous system diseases.
Serum Anti-CCNY Autoantibody Is an Independent Prognosis Indicator for Postoperative Patients with Early-Stage Nonsmall-Cell Lung Carcinoma
Authors: Ma Li , Yue Wentao , Teng Yu , Zhang Lina , Gu Meng , Wang Yue
Published: September 2013

Cyclin Y (CCNY) is a novel cyclin and almost nothing is known about its role in human cancers. To investigate the clinical significance of serum anti-CCNY autoantibodies in nonsmall-cell lung carcinoma (NSCLC), the serum levels of CCNY protein in 264 patients with NSCLC, 103 patients with tuberculosis, and 89 healthy controls were analyzed by immunohistochemistry. The result shows that, compared with normal lung tissues, the NSCLC tissues contained higher levels of CCNY protein. The levels of anti-CCNY autoantibodies were higher in the sera of the patients with NSCLC than in the sera of the healthy controls (P<0.001) or the patients with tuberculosis (P=0.027). Moreover, in a Cox regression analysis, anti-CCNY autoantibody was an independent factor that predicted poor prognosis for postoperative patients with early-stage NSCLC (P=0.026) as well as for those with distant metastasis (P=0.012). Our data indicated that Anti-CCNY autoantibody may be useful as a latent tumor marker to facilitate diagnosis and may represent a novel prognostic indicator for patients with early stage NSCLC.
Symbolic Implementation of Preliminary Group Classiffication for Ordinary Differential Equations
Authors: Govinder K. S.
Published: September 2013

We apply the method of preliminary group classification to ordinary differential equations of the formy(n)=E(x,y,y',…,y(n-1),fi(x)),  i=0,…,m.We show how this method can be implemented via the popular symmetry analysis packagePROGRAM LIEprovided that the package is supplemented with a small file. We then apply this method to an extension of the generalised Emden-Fowler equation given byy′′=∑i=25fixyi.
Skin Parameter Map Retrieval from a Dedicated Multispectral Imaging System Applied to Dermatology/Cosmetology
Authors: Jolivot Romuald , Benezeth Yannick , Marzani Franck
Published: September 2013

In vivo quantitative assessment of skin lesions is an important step in the evaluation of skin condition. An objective measurement device can help as a valuable tool for skin analysis. We propose an explorative new multispectral camera specifically developed for dermatology/cosmetology applications. The multispectral imaging system provides images of skin reflectance at different wavebands covering visible and near-infrared domain. It is coupled with a neural network-based algorithm for the reconstruction of reflectance cube of cutaneous data. This cube contains only skin optical reflectance spectrum in each pixel of the bidimensional spatial information. The reflectance cube is analyzed by an algorithm based on a Kubelka-Munk model combined with evolutionary algorithm. The technique allows quantitative measure of cutaneous tissue and retrieves five skin parameter maps: melanin concentration, epidermis/dermis thickness, haemoglobin concentration, and the oxygenated hemoglobin. The results retrieved on healthy participants by the algorithm are in good accordance with the data from the literature. The usefulness of the developed technique was proved during two experiments: a clinical study based on vitiligo and melasma skin lesions and a skin oxygenation experiment (induced ischemia) with healthy participant where normal tissues are recorded at normal state and when temporary ischemia is induced.
A Frequency Compensation Algorithm of Four-Wheel Coherence Random Road
Authors: Feng Jun , Zhang Xinjie , Guo Konghui , Ma Fangwu , Karimi Hamid Reza
Published: September 2013

The road surface roughness is the main source of kinematic excitation of a moving vehicle, which has an important influence on vehicle performance. In recent decades, random road models have been widely studied, and a four-wheel random road time domain model is usually generated based on the correlation of the four-wheel input, in which a coherence function is used to describe the coherence of the road input between the left and right wheels usually. However, during our research, there are some conditions that show that the road PSD (power spectral density) of one wheel is smaller than the other one on the same axle. Actually, it is caused by the uncorrelation between the left- and right-wheel road surface roughness. Hence, a frequency compensation algorithm is proposed to correct the deviation of the PSD of the road input between two wheels on the same axle, and it is installed in a 7-DOF vehicle dynamic study. The simulation result demonstrates the applicability of the proposed algorithm such that two-wheel road input deviation compensation has an important influence on vehicle performances, and it can be used for a control system installed in the vehicle to compensate road roughness for damper tuning in the future.
Molecular Imaging of Death Receptor 5 Occupancy and Saturation Kinetics In Vivo by Humanized Monoclonal Antibody CS-1008
Authors: Burvenich Ingrid J.G. , Lee Fook T. , Cartwright Glenn A. , O'Keefe Graeme J. , Makris Dahna , Cao Diana , Gong Sylvia , Chueh Anderly C. , Mariadason John M. , Brechbiel Martin W. , Beckman Robert A. , Fujiwara Kosaku , von Roemeling Reinhard , Scott Andrew M.
Published: September 2013

Purpose: CS-1008 (tigatuzumab; phase I/II), an antihuman death receptor 5 (DR5) agonist, induces apoptosis and has cytotoxic activity against human cancer cell lines. This study reports on the preclinical validation of 111In-labeled anti-DR5 humanized antibody CS-1008 as a diagnostic tool to study the DR5 occupancy in patients with cancer and establish dose ranges for receptor saturation kinetics in vivo.

Experimental Design: CS-1008 was radiolabeled and characterized for DR5 binding and labeling efficiency on TRAIL-sensitive DR5–positive colorectal cancer cells (COLO 205 and WiDr). Pharmacokinetic and biodistribution studies were conducted in BALB/c nu/nu mice bearing COLO 205, WiDr, or DR5-negative CT26 colon tumors. Planar gamma camera imaging and computerized tomography (CT) images were obtained to study receptor occupancy in vivo.

Results: Scatchard analysis showed high and specific binding affinity (Kd, 1.05 ± 0.12 nmol/L) of 111In-labeled CS-1008. 111In-labeled CS-1008 was specifically taken up in mice bearing COLO 205 and WiDr tumors with prolonged tumor retention (26.25 ± 2.85%ID/g vs. 12.20 ± 2.24 at 168 hours post injection; n = 5, SD), and uptake correlated both with DR5 expression on tumor cells and antitumor activity. DR5 saturation was shown in vivo via both biodistribution studies and planar gamma camera imaging/CT imaging of 111In-labeled CS-1008. Saturation of DR5 corresponded to maximal in vivo antitumor efficacy.

Conclusions: Imaging of DR5 receptor occupancy in vivo correlates with tumor concentration and in vivo efficacy, and is a novel molecular imaging technique that can be used to determine receptor occupancy and effective dose levels of DR5 agonist antibodies in the clinic. Clin Cancer Res; 19(21); 5984–93. ©2013 AACR.
A Phase I Study of the HSP90 Inhibitor Retaspimycin Hydrochloride (IPI-504) in Patients with Gastrointestinal Stromal Tumors or Soft-Tissue Sarcomas
Authors: Wagner Andrew J. , Chugh Rashmi , Rosen Lee S. , Morgan Jeffrey A. , George Suzanne , Gordon Michael , Dunbar Joi , Normant Emmanuel , Grayzel David , Demetri George D.
Published: September 2013

Purpose: Heat shock protein 90 (HSP90) is required for the proper folding, function, and stability of various client proteins, two of which (KIT and PDGFRα) are critical in the pathogenesis and progression of gastrointestinal stromal tumors (GIST). This phase I study investigated the safety and maximum tolerated dose (MTD) of retaspimycin hydrochloride (IPI-504), a novel potent and selective HSP90 inhibitor, in patients with metastatic and/or unresectable GIST or other soft-tissue sarcomas (STS).

Experimental Design: IPI-504 was administered intravenously at doses ranging from 90 to 500 mg/m2 twice weekly for 2 weeks on/1 week off. Safety, pharmacokinetic, and pharmacodynamic profiles were determined. Response was assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.0 and optionally via 18-fluorodeoxyglucose positron emission tomography (18-FDG-PET) imaging.

Results: Fifty-four patients received IPI-504; 37 with GIST and 17 with other STS. The MTD was 400 mg/m2 twice weekly for 2 weeks on/1 week off. Common related adverse events were fatigue (59%), headache (44%), and nausea (43%). Exposure to IPI-504, 17-AAG, and 17-AG increased with IPI-504 dose. Stable disease (SD) was observed in 70% (26 of 37) of patients with GIST and 59% (10 of 17) of patients with STS. There was one confirmed partial response (PR) in a patient with GIST and one PR in a patient with liposarcoma. Metabolic partial responses occurred in 11 of 29 (38%) patients with GIST.

Conclusions: In this study of advanced GIST or other STS, IPI-504 was generally well-tolerated with some evidence of antitumor activity, serving as a clinical proof-of-concept that HSP90 inhibition remains a promising strategy. Clin Cancer Res; 19(21); 6020–9. ©2013 AACR.
Harsh Voice Quality and Its Association with Blackness in Popular American Media
Authors: Moisik Scott Reid
Published: September 2013

Performers use various laryngeal settings to create voices for characters and personas they portray. Although some research demonstrates the sociophonetic associations of laryngeal voice quality, few studies have documented or examined the role of harsh voice quality, particularly with vibration of the epilaryngeal structures (growling). This article qualitatively examines phonetic properties of vocal performances in a corpus of popular American media and evaluates the association of voice qualities in these performances with representations of social identity and stereotype. In several cases, contrasting laryngeal states create sociophonetic contrast, and harsh voice quality is paired with the portrayal of racial stereotypes of black people. These cases indicate exaggerated emotional states and are associated with yelling/shouting modes of expression. Overall, however, the functioning of harsh voice quality as it occurs in the data is broader and may involve aggressive posturing, comedic inversion of aggressiveness, vocal pathology, and vocal homage.
Decreased Circulating Endothelial Progenitor Cell Levels in Patients with Heart Failure with Preserved Ejection Fraction
Authors: Chiang Chia-Hung , Huang Po-Hsun , Leu Hsin-Bang , Hsu Chien-Yi , Wang Ko-Fan , Chen Jaw-Wen , Lin Shing-Jong
Published: September 2013

Objectives: The purpose of this study was to explore the relationship between endothelial progenitor cell (EPC) levels, heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Methods: A total of 44 HFpEF patients, 40 HFrEF patients and 69 age-, gender- and comorbidity-matched controls were enrolled after evaluating their clinical manifestations and echocardiography findings. Flow cytometry with quantification of three EPC markers in peripheral blood samples was used to assess the number of circulating EPCs. Results: HFpEF and HFrEF patients had significantly decreased circulating EPC levels compared to controls. Among heart failure patients, patients with New York Heart Association functional class (FC) IV had fewer circulating EPCs compared to those with FC II and FC III (p = 0.053). A simple linear regression analysis of data showed that high sensitivity C-reactive protein, left ventricular ejection fraction, left atrium diameter and the ratio of medial early filling to early diastolic mitral annular velocity all correlated with the EPC count. In multivariate Cox regression analyses, both HFpEF and HFrEF were found to be independent predictors of a decreased EPC number. Conclusions: HFpEF and HFrEF patients have decreased circulating EPC numbers, which is an indication of impaired endothelial turnover.
Effects of Tadalafil on Hemorrhagic Cystitis and Testicular Dysfunction Induced by Cyclophosphamide in Rats
Authors: Yigitaslan Semra , Ozatik Orhan , Ozatik Fikriye Yasemin , Erol Kevser , Sirmagul Basar , Baseskioglu Ali Barbaros
Published: September 2013

Introduction: The protective and/or therapeutic potential of tadalafil (TDL) on cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) and testicular dysfunction in rats was evaluated. Materials and Methods: The animals except from the control group were divided into four groups and treated with saline, or 1, 5 or 10 mg/kg TDL orally (CP, TDL1, TDL5 and TDL10 groups, respectively) before and after CP injection. Body and organ weights, sperm count, cGMP, nitric oxide (NO), IL-6 and IL-10 levels in serum and bladder tissue, and serum testosterone (T), LH and FSH levels were determined. The histological analysis of bladder and testis was performed and the number of apoptotic cells was determined. Results and Conclusion: The CP group had decreased cGMP and NO levels in the bladder, serum T level (p < 0.05) and sperm count (p < 0.001) and higher IL-6 levels in serum and bladder (p < 0.01). Treatment with TDL resulted in increased cGMP (p < 0.001), NO (p < 0.05) and serum T (p < 0.05) levels. Histological analysis of the CP group showed severe HC in bladder and testicular damage. TDL-treated animals showed a dose-dependent improvement in all of these histological impairments. In conclusion, a selective inhibitor of phosphodiesterase-5 enzyme, TDL, showed a protective and/or therapeutic effect on CP-induced HC and testicular dysfunction in rats.
On How Accent Distribution Can Signal Speaker Adaptation
Authors: Kaland Constantijn , Krahmer Emiel , Swerts Marc
Published: September 2013

Some dialogues are perceived as running more smoothly than others. To some extent that impression could be related to how well speakers adapt their prosody to each other. Adaptation in prosody can be signaled by the use of pitch accents that indicate how utterances are structurally related to those of the interlocutor (prosodic function) or by copying the interlocutor's prosodic features (prosodic form). The same acoustic features, such as pitch, are involved in both ways of adaptation. Further, function and form may require a different prosody for successful adaptation in certain discourse contexts. In this study we investigate to what extent interlocutors are perceived as good adapters, depending on whether the prosody of both speakers is functionally coherent or similar in form. This is done in two perception tests using prosodically manipulated dialogues. Results show that coherent functional prosody can be a cue for speaker adaptation and that this cue is more powerful than similarity in prosodic form.
Short Stature before Puberty: Which Children Should Be Screened for SHOX Deficiency?
Authors: Wolters Barbara , Lass Nina , Wunsch Rainer , Böckmann Beatrix , Austrup Frank , Reinehr Thomas
Published: September 2013

Objective: We studied the prevalence of deficiency in the short stature homeobox containing gene (SHOX) in prepubertal short-statured children and analyzed the clinical and radiological signs. Methods: Screening for SHOX deficiency was performed in 449 prepubertal short-statured children (54% females, aged 4-10 years) by direct sequencing and multiplex ligation probe-dependent amplification. Children with SHOX deficiency were compared to 1:2 age- and gender-matched prepubertal children without SHOX deficiency with respect to left-hand radiographs and anthropometrics including different ratios to height and proposed scores. Results: We identified 22 (4.9%) patients with SHOX deficiency (64% point mutations). Children with SHOX deficiency demonstrated a mesomelic shortening of extremities. Lower leg lengths but not forearm length was reduced in children <8 years with SHOX deficiency. 36% of all children and none of the children <8 years with SHOX deficiency demonstrated any typical radiologic sign. Increased sitting height-to-height ratio and decreased extremities-to-trunk ratio demonstrated the best positive and negative predictive values to identify SHOX deficiency. Conclusions: Screening for SHOX deficiency seems rational, especially in children with increased sitting height-to-height ratio or decreased extremities-to-trunk ratio. These criteria were also valid in young children.
Pygopus Maintains Heart Function in Aging
Drosophila
Independently of Canonical Wnt Signaling
Authors: Tang Min , Yuan Wuzhou , Fan Xiongwei , Liu Ming , Bodmer Rolf , Ocorr Karen , Wu Xiushan
Published: September 2013

Background—

Heart function declines with age, but the genetic factors underlying such deterioration are largely unknown. Wnt signaling is known to play a role in heart development, but it has not been shown to be important in adult heart function. We have investigated the nuclear adapter protein encoded by
pygopus
(
pygo
), which mediates canonical Wnt signaling, for roles in aging-related cardiac dysfunction.

Methods and Results—

Using the
Drosophila
heart model, we show that cardiac-specific
pygo
knockdown in adult flies causes a significant (4- to 5-fold) increase in cardiac arrhythmias (
P
<0.001) that worsened with age and caused a significant decrease in contractility (−54%;
P
<0.001) with systolic dysfunction. Immunohistochemistry revealed structural abnormalities that worsened with age, and both functional and morphological alterations were ameliorated by
pygo
overexpression. Unexpectedly, knockdown of 2 other Wnt signaling components,
β-cat/armadillo
or
TCF/pangolin
, had relatively milder effects on cardiac function. Double-heterozygous combinations of mutants for
pygo
and canonical Wnt signaling components had no additional effect on heart function over
pygo
heterozygotes alone. However, double knockdown of pygo and Ca
2+
/calmodulin-dependent protein kinase II caused additional arrhythmia compared with pygo knockdown alone, suggesting that some of the effects of pygo are mediated by Ca
2+
signaling. In the isoproterenol-induced hypertrophic mouse model, we show that Pygo1 protein levels are increased.

Conclusions—

Our data indicate that Pygo plays a critical role in adult heart function that is Wnt signaling independent and is likely conserved in mammals.
Rejuvenation of Human Cardiac Progenitor Cells With Pim-1 Kinase
Authors: Mohsin Sadia , Khan Mohsin , Nguyen Jonathan , Alkatib Monique , Siddiqi Sailay , Hariharan Nirmala , Wallach Kathleen , Monsanto Megan , Gude Natalie , Dembitsky Walter , Sussman Mark A.
Published: September 2013

Rationale
:

Myocardial function is enhanced by adoptive transfer of human cardiac progenitor cells (hCPCs) into a pathologically challenged heart. However, advanced age, comorbidities, and myocardial injury in patients with heart failure constrain the proliferation, survival, and regenerative capacity of hCPCs. Rejuvenation of senescent hCPCs will improve the outcome of regenerative therapy for a substantial patient population possessing functionally impaired stem cells.

Objective
:

Reverse phenotypic and functional senescence of hCPCs by ex vivo modification with Pim-1.

Methods and Results
:

C-kit–positive hCPCs were isolated from heart biopsy samples of patients undergoing left ventricular assist device implantation. Growth kinetics, telomere lengths, and expression of cell cycle regulators showed significant variation between hCPC isolated from multiple patients. Telomere length was significantly decreased in hCPC with slow-growth kinetics concomitant with decreased proliferation and upregulation of senescent markers compared with hCPC with fast-growth kinetics. Desirable youthful characteristics were conferred on hCPCs by genetic modification using Pim-1 kinase, including increases in proliferation, telomere length, survival, and decreased expression of senescence markers.

Conclusions
:

Senescence characteristics of hCPCs are ameliorated by Pim-1 kinase resulting in rejuvenation of phenotypic and functional properties. hCPCs show improved cellular properties resulting from Pim-1 modification, but benefits were more pronounced in hCPC with slow-growth kinetics relative to hCPC with fast-growth kinetics. With the majority of patients with heart failure presenting advanced age, infirmity, and impaired regenerative capacity, the use of Pim-1 modification should be incorporated into cell-based therapeutic approaches to broaden inclusion criteria and address limitations associated with the senescent phenotype of aged hCPC.
Alloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-κB Signaling in Endothelial Cells
Authors: Jane-wit Dan , Manes Thomas D. , Yi Tai , Qin Lingfeng , Clark Pamela , Kirkiles-Smith Nancy C. , Abrahimi Parwiz , Devalliere Julie , Moeckel Gilbert , Kulkarni Sanjay , Tellides George , Pober Jordan S.
Published: September 2013

Background—

Cardiac allograft vasculopathy is the major cause of late allograft loss after heart transplantation. Cardiac allograft vasculopathy lesions contain alloreactive T cells that secrete interferon-γ, a vasculopathic cytokine, and occur more frequently in patients with donor-specific antibody. Pathological interactions between these immune effectors, representing cellular and humoral immunity, respectively, remain largely unexplored.

Methods and Results—

We used human panel reactive antibody to form membrane attack complexes on allogeneic endothelial cells in vitro and in vivo. Rather than inducing cytolysis, membrane attack complexes upregulated inflammatory genes, enhancing the capacity of endothelial cells to recruit and activate allogeneic interferon-γ––producing CD4
+
T cells in a manner dependent on the activation of noncanonical nuclear factor-κB signaling. Noncanonical nuclear factor-κB signaling was detected in situ within endothelial cells both in renal biopsies from transplantation patients with chronic antibody-mediated rejection and in panel-reactive antibody––treated human coronary artery xenografts in immunodeficient mice. On retransplantation into immunodeficient hosts engrafted with human T cells, panel-reactive antibody––treated grafts recruited more interferon-γ––producing T cells and enhanced cardiac allograft vasculopathy lesion formation.

Conclusions—

Alloantibody and complement deposition on graft endothelial cells activates noncanonical nuclear factor-κB signaling, initiating a proinflammatory gene program that enhances alloreactive T cell activation and development of cardiac allograft vasculopathy. Noncanonical nuclear factor-κB signaling in endothelial cells, observed in human allograft specimens and implicated in lesion pathogenesis, may represent a target for new pharmacotherapies to halt the progression of cardiac allograft vasculopathy.
Veto and Vacillation: A Neural Precursor of the Decision to Withhold Action
Authors: Misirlisoy Erman , Haggard Patrick
Published: September 2013

The capacity to inhibit a planned action gives human behavior its characteristic flexibility. How this mechanism operates and what factors influence a decision to act or not act remain relatively unexplored. We used EEG readiness potentials (RPs) to examine preparatory activity before each action of an ongoing sequence, in which one action was occasionally omitted. We compared RPs between sequences in which omissions were instructed by a rule (e.g., “omit every fourth action”) and sequences in which the participant themselves freely decided which action to omit. RP amplitude was reduced for actions that immediately preceded a voluntary omission but not a rule-based omission. We also used the regular temporal pattern of the action sequences to explore brain processes linked to omitting an action by time-locking EEG averages to the inferred time when an action would have occurred had it not been omitted. When omissions were instructed by a rule, there was a negative-going trend in the EEG, recalling the rising ramp of an RP. No such component was found for voluntary omissions. The results are consistent with a model in which spontaneously fluctuating activity in motor areas of the brain could bias “free” decisions to act or not.
The Impact of Early Amygdala Damage on Juvenile Rhesus Macaque Social Behavior
Authors: Bliss-Moreau Eliza , Moadab Gilda , Bauman Melissa D. , Amaral David G.
Published: September 2013

The present experiments continue a longitudinal study of rhesus macaque social behavior following bilateral neonatal ibotenic acid lesions of the amygdala or hippocampus, or sham operations. Juvenile animals (approximately 1.5–2.5 years) were tested in four different social contexts—alone, while interacting with one familiar peer, while interacting with one unfamiliar peer, and in their permanent social groups. During infancy, the amygdala-lesioned animals displayed more interest in conspecifics (indexed by increased affiliative signaling) and paradoxically demonstrated more submission or fear (Bauman, Lavenex, Mason, Capitanio, & Amaral, 2004a, this journal). When these animals were assessed as juveniles, differences were less striking. Amygdala-lesioned animals generated fewer aggressive and affiliative signals (e.g., vocalizations, facial displays) and spent less time in social interactions with familiar peers. When animals were observed alone or with an unfamiliar peer, amygdala-lesioned animals, compared with other subjects, spent more time being inactive and physically explored the environment less. Despite the subtle, lesion-based differences in the frequency and duration of specific social behaviors, there were lesion-based differences in the organization of behavior such that lesion groups could be identified based on the patterning of social behaviors in a discriminant function analysis. The findings indicate that, although overall frequencies of many of the observed behaviors do not differ between groups, the general patterning of social behavior may distinguish the amygdala-lesioned animals.
Extensive Left Temporal Pole Damage Does Not Impact on Theory of Mind Abilities
Authors: Michel Caroline , Dricot Laurence , Lhommel Renaud , Grandin Cécile , Ivanoiu Adrian , Pillon Agnesa , Samson Dana
Published: September 2013

The temporal poles (TPs) are among the brain regions that are often considered as the brain network sustaining our ability to understand other people's mental states or “Theory of Mind” (ToM). However, so far the functional role of the left and right TPs in ToM is still debated, and it is even not clear yet whether these regions are necessary for ToM. In this study, we tested whether the left TP is necessary for ToM by assessing the mentalizing abilities of a patient (C.M.) diagnosed with semantic dementia. Converging evidence from detailed MRI and 18F-fluoro-2-deoxy-d-glucose PET examinations showed a massive atrophy of the left TP with the right TP being relatively unaffected. Furthermore, C.M.'s atrophy encompassed most regions of the left TP usually activated in neuroimaging studies investigating ToM. Given C.M.'s language impairments, we used a battery of entirely nonverbal ToM tasks. Across five tasks encompassing 100 trials, which probed the patient's ability to attribute various mental states (intentions, knowledge, and beliefs), C.M. showed a totally spared performance. This finding suggests that, despite its consistently observed activation in neuroimaging studies involving ToM tasks, the left TP is not necessary for ToM reasoning, at least in nonverbal conditions and as long as its right counterpart is preserved. Implications for understanding the social abilities of patients with semantic dementia are discussed.