bluuebunny/crossref_metadata_2025 huggingface dataset:
On High-Temperature Materials: A Case on Creep and Oxidation of a Fully Austenitic Heat-Resistant Superalloy Stainless Steel Sheet
Authors: Kanni Raj A.
Published: February 2013

The creep behavior of AISI 310S stainless steel taken from SAIL’s Salem stainless steel plant has been investigated by constant load tensile creep test at the temperatures of 973, 1023, and 1073 K and loads of 66.6, 74.8, 86.6, and 94.8 MPa. It exhibits steady-state creep behavior in most test conditions. The double logarithm plot of rupture life and applied stress yielded straight lines at all the three test temperatures indicating that power-law creep due to dislocation climb is the operating mechanism of creep deformation. Linear relationship was obtained for plots of logarithm of rupture life against inverse temperature obeying Arrhenius type of temperature dependence with activation energy of 340 kJ/mol. The stress-rupture data yielded a master curve of Larson-Miller parameter. The plot of Monkman-Grant relationship is typical indicating that rupture is controlled by growth of grain boundary cavities. The metallographic examination of crept samples revealed formation of grain boundary voids and cracks leading to intergranular creep fracture. Deformation twins and carbide precipitates were also observed. Oxidation tests were also carried out isothermally at 973 K, 1023 K, and 1073 K in dry air. The plots of mass gain versus square root time were linear at all the three test temperatures obeying parabolic kinetics of oxidation. It was found that scales are well adherent to the substrate. The plot of parabolic rate constant and inverse temperature was linear giving an activation energy value of 210 kJ/mol. The metallographic examination of an oxidized sample reveals duplex types of scales. Finally, rupture properties are compared with that of AISI 600 iron-based superalloy and oxidation weight gain analysis with surface nanocrystalline AISI 310S stainless steel to analyze quantitatively its behavior.
Microbial Diversity and Biochemical Potential Encoded by Thermal Spring Metagenomes Derived from the Kamchatka Peninsula
Authors: Wemheuer Bernd , Taube Robert , Akyol Pinar , Wemheuer Franziska , Daniel Rolf
Published: February 2013

Volcanic regions contain a variety of environments suitable for extremophiles. This study was focused on assessing and exploiting the prokaryotic diversity of two microbial communities derived from different Kamchatkian thermal springs by metagenomic approaches. Samples were taken from a thermoacidophilic spring near the Mutnovsky Volcano and from a thermophilic spring in the Uzon Caldera. Environmental DNA for metagenomic analysis was isolated from collected sediment samples by direct cell lysis. The prokaryotic community composition was examined by analysis of archaeal and bacterial 16S rRNA genes. A total number of 1235 16S rRNA gene sequences were obtained and used for taxonomic classification. Most abundant in the samples were members ofThaumarchaeota,Thermotogae, andProteobacteria. The Mutnovsky hot spring was dominated by the Terrestrial Hot Spring Group,Kosmotoga, andAcidithiobacillus. The Uzon Caldera was dominated by uncultured members of the Miscellaneous Crenarchaeotic Group andEnterobacteriaceae. The remaining 16S rRNA gene sequences belonged to theAquificae,Dictyoglomi,Euryarchaeota,Korarchaeota,Thermodesulfobacteria,Firmicutes, and some potential new phyla. In addition, the recovered DNA was used for generation of metagenomic libraries, which were subsequently mined for genes encoding lipolytic and proteolytic enzymes. Three novel genes conferring lipolytic and one gene conferring proteolytic activity were identified.
Anti-Inflammatory Effects of Ellagic Acid on Acute Lung Injury Induced by Acid in Mice
Authors: Cornélio Favarin Daniely , Martins Teixeira Maxelle , Lemos de Andrade Ednéia , de Freitas Alves Claudiney , Lazo Chica Javier Emilio , Artério Sorgi Carlos , Faccioli Lúcia Helena , Paula Rogerio Alexandre
Published: February 2013

Acute lung injury (ALI) is characterized by alveolar edema and uncontrolled neutrophil migration to the lung, and no specific therapy is still available. Ellagic acid, a compound present in several fruits and medicinal plants, has shown anti-inflammatory activity in several experimental disease models. We used the nonlethal acid aspiration model of ALI in mice to determine whether preventive or therapeutic administration of ellagic acid (10 mg/kg; oral route) could interfere with the development or establishment of ALI inflammation. Dexamethasone (1 mg/kg; subcutaneous route) was used as a positive control. In both preventive and therapeutic treatments, ellagic acid reduced the vascular permeability changes and neutrophil recruitment to the bronchoalveolar lavage fluid (BALF) and to lung compared to the vehicle. In addition, the ellagic acid accelerated the resolution for lung neutrophilia. Moreover, ellagic acid reduced the COX-2-induced exacerbation of inflammation. These results were similar to the dexamethasone. However, while the anti-inflammatory effects of dexamethasone treatment were due to the reduced activation of NF-κB and AP-1, the ellagic acid treatment led to reduced BALF levels of IL-6 and increased levels of IL-10. In addition, dexamethasone treatment reduced IL-1β. Together, these findings identify ellagic acid as a potential therapeutic agent for ALI-associated inflammation.
Quantification of Scenario Distance within Generic WINNER Channel Model
Authors: Narandžić Milan , Schneider Christian , Kotterman Wim , Thomä Reiner S.
Published: February 2013

Starting from the premise that stochastic properties of a radio environment can be abstracted by defining scenarios, a generic MIMO channel model is built by the WINNER project. The parameter space of the WINNER model is, among others, described by normal probability distributions and correlation coefficients that provide a suitable space for scenario comparison. The possibility to quantify the distance between reference scenarios and measurements enables objective comparison and classification of measurements into scenario classes. In this paper we approximate the WINNER scenarios with multivariate normal distributions and then use the mean Kullback-Leibler divergence to quantify their divergence. The results show that the WINNER scenario groups (A, B, C, and D) or propagation classes (LoS, OLoS, and NLoS) do not necessarily ensure minimum separation within the groups/classes. Instead, the following grouping minimizes intragroup distances: (i) indoor-to-outdoor and outdoor-to-indoor scenarios (A2, B4, and C4), (ii) macrocell configurations for suburban, urban, and rural scenarios (C1, C2, and D1), and (iii) indoor/hotspot/microcellular scenarios (A1, B3, and B1). The computation of the divergence between Ilmenau and Dresden measurements and WINNER scenarios confirms that the parameters of the C2 scenario are a proper reference for a large variety of urban macrocell environments.
Infection and Coinfection of Human Rhinovirus C in Stem Cell Transplant Recipients
Authors: Canducci Filippo , Debiaggi Maurizia , Ceresola Elisa Rita , Sampaolo Michela , Alessandrino Emilio Paolo , Brerra Roberto , Piazza Aurora , Clementi Massimo
Published: February 2013

In 54 adult stem cell transplant recipients, the presence and persistence of human rhinoviruses (including the novel lineage C) were evaluated by molecular detection and phylogenetic analysis, independently from respiratory symptoms. In the same group of patients, the presence of other coinfecting respiratory pathogens, including the novel enterovirus 109, was also evaluated.
A Large Span Crossbeam Vibration Frequencies Analysis Based on an Analogous Beam Method
Authors: Liu Zhifeng , Luo Bing , Zhao Yongsheng , Yang Wentong , Cai Ligang
Published: February 2013

The novel method of an analogous beam is studied, which the flexural rigidity and mass per unit length correspond was described as the reciprocal of the mass per unit and the reciprocal of the flexural rigidity of the beam. It is shown that both beams possess the same natural frequencies of flexural vibration. In order to approximate calculation of these frequencies, the continuously distributed mass of the original beam is substituted for a number of concentrated masses. The analogous beam then becomes a chain of rigid links connected by pins and equipped with springs restraining the relative rotation of adjacent links. The equations of motion for the analogous beam can be solved by a procedure which consists of assuming a value for the natural frequency and calculating the deflections successively from one end of the beam to the other. Under normal circumstances, there will be a certain error, and one boundary condition will not be satisfied. The procedure is repeated with different values of the frequency until the error is removed. The method is illustrated by an example of a Crossbeam for which the fundamental frequency is found.
Quercetin Preservesβ-Cell Mass and Function in Fructose-Induced Hyperinsulinemia through Modulating Pancreatic Akt/FoxO1 Activation
Authors: Li Jian-Mei , Wang Wei , Fan Chen-Yu , Wang Ming-Xing , Zhang Xian , Hu Qing-Hua , Kong Ling-Dong
Published: February 2013

Fructose-induced hyperinsulinemia is associated with insulin compensative secretion and predicts the onset of type 2 diabetes. In this study, we investigated the preservation of dietary flavonoid quercetin on pancreaticβ-cell mass and function in fructose-treated rats and INS-1β-cells. Quercetin was confirmed to reduce serum insulin and leptin levels and blockade islet hyperplasia in fructose-fed rats. It also prevented fructose-inducedβ-cell proliferation and insulin hypersecretion in INS-1β-cells. High fructose increased forkhead box protein O1 (FoxO1) expressionsin vivoandin vitro, which were reversed by quercetin. Quercetin downregulated Akt and FoxO1 phosphorylation in fructose-fed rat islets and increased the nuclear FoxO1 levels in fructose-treated INS-1β-cells. The elevated Akt phosphorylation in fructose-treated INS-1β-cells was also restored by quercetin. Additionally, quercetin suppressed the expression of pancreatic and duodenal homeobox 1 (Pdx1) and insulin gene (Ins1 and Ins2)in vivoandin vitro. In fructose-treated INS-1β-cells, quercetin elevated the reduced janus kinase 2/signal transducers and activators of transcription 3 (Jak2/Stat3) phosphorylation and suppressed the increased suppressor of cytokine signaling 3 (Socs3) expression. These results demonstrate that quercetin protectsβ-cell mass and function under high-fructose induction through improving leptin signaling and preserving pancreatic Akt/FoxO1 activation.
Appendiceal Endometriosis and Carcinoid Presented as Acute Appendicitis in Pregnancy: A Rare Case Report and Review of the Literature
Authors: Dimitriadis Panagiotis A. , Makar Ragai R. , Kingston Gearoid , Farouk Ridzuan
Published: February 2013

A 22-year-old pregnant woman presented at the twenty-seventh week of gestation in the Emergency Department with acute abdominal pain and right iliac fossa tenderness. Urgent MRI was done and was suggestive of acute appendicitis. A laparoscopy was performed that confirmed an inflamed and purulent appendix that was removed. The technique used is described in detail. The histopathologic findings were those of acute appendicitis, carcinoid, and endometriosis of the appendix. We report the first case of this extremely rare triad presented in pregnancy.
Sweet Chestnut (Castanea sativaMill.) Bark Extract: Cardiovascular Activity and Myocyte Protection against Oxidative Damage
Authors: Chiarini Alberto , Micucci Matteo , Malaguti Marco , Budriesi Roberta , Ioan Pierfranco , Lenzi Monia , Fimognari Carmela , Gallina Toschi Tullia , Comandini Patrizia , Hrelia Silvana
Published: February 2013

This work was aimed at evaluating the cardioprotective effects ofCastanea sativaMill. (CSM) bark extract characterized in its phenolic composition by HPLC-DAD-MS analysis. The study was performed using primary cultures of neonatal rat cardiomyocytes to investigate the antioxidant and cytoprotective effects of CSM bark extract and isolated guinea pig left and right atria, left papillary muscle, and aorta to evaluate its direct effect on cholinergic and adrenergic response. In cultured cardiomyocytes the CSM bark extract reduced intracellular reactive oxygen species formation and improved cell viability following oxidative stress in dose-dependent manner. Moreover, the extract decreased the contraction induced by noradrenaline (1 μM) in guinea pig aortic strips and induced transient negative chronotropic and positive inotropic effects without involvement of cholinergic or adrenergic receptors in the guinea pig atria. Our results indicate that CSM bark extract exhibits antioxidant activity and might induce cardioprotective effect.
Chronobiological Analysis of Blood Pressure in a Patient with Atrial Fibrillation at the Development of Heart Failure and Its Therapeutic and Surgical Treatment
Authors: Chibisov Sergey , Katinas George , Brodskaya Inna , Ertman Aleksandr , Gromyko Grigory , Konradi Aleksandra , Mamontov Oleg , Merkuryeva Anna , Polunicheva Ekaterina , Shlyakhto Evgeny , Soboleva Anna , Yashin Sergey , Bhavdip Bharadva
Published: February 2013

Dynamics of blood pressure (BP) and heart rate (HR) was traced by automatic monitoring every 30 min uninterruptedly along several months in a patient suffering from combined atrial fibrillation and heart failure during the development of disease and its therapeutic and surgical treatment (pacemaker implanting and atrioventricular ablation). Analyses of spectral components as well as signal’s shape revealed instabilities in circadian and semicircadian parameters. A new approach for signal’s form description without using cosine approximation is suggested. The meaning that referring a patient as dipper, night peaker, or nondipper might be useful at choosing tactics of his treatment is impugned, because all these “types” can transform themselves in the same person in few days. Optimization timing of treatment provides better results if not the “types” of daily profile would be taken to account but the real form of the BP-signal and timing its first and second derivatives.
Complex Structure of the Four-Dimensional Kerr Geometry: Stringy System, Kerr Theorem, and Calabi-Yau Twofold
Authors: Burinskii Alexander
Published: February 2013

The 4D Kerr geometry displays many wonderful relations with quantum world and, in particular, with superstring theory. The lightlike structure of fields near the Kerr singular ring is similar to the structure of Sen solution for a closed heterotic string. Another string, open and complex, appears in the complex representation of the Kerr geometry initiated by Newman. Combination of these strings forms a membrane source of the Kerr geometry which is parallel to the structure of M-theory. In this paper we give one more evidence of this relationship, emergence of the Calabi-Yau twofold (K3 surface) in twistorial structure of the Kerr geometry as a consequence of the Kerr theorem. Finally, we indicate that the Kerr stringy system may correspond to a complex embedding of the criticalN=2superstring.
The Role of Laparoscopic Nephrectomy in Pediatric Xanthogranulomatous Pyelonephritis: A Case Report
Authors: F. Brown James , Chamberlain Jennifer C. , Roth Christopher C.
Published: February 2013

Xanthogranulomatous pyelonephritis (XGP) is a rare chronic renal infection characterized by the destruction of renal parenchyma. Traditional treatment involves open radical nephrectomy, which is challenging due to the inflammatory process associated with XGP. More recently, laparoscopic nephrectomy has been employed successfully in adult XGP. We present a case of a six-year-old female child with XGP who was successfully treated by laparoscopic nephrectomy with minor complications. Our case demonstrates the safety and feasibility of laparoscopic nephrectomy for childhood XGP, indicating that it should be considered a management option in such cases.
Identification of Robust Pathway Markers for Cancer through Rank-Based Pathway Activity Inference
Authors: Khunlertgit Navadon , Yoon Byung-Jun
Published: February 2013

One important problem in translational genomics is the identification of reliable and reproducible markers that can be used to discriminate between different classes of a complex disease, such as cancer. The typical small sample setting makes the prediction of such markers very challenging, and various approaches have been proposed to address this problem. For example, it has been shown that pathway markers, which aggregate the gene activities in the same pathway, tend to be more robust than gene markers. Furthermore, the use of gene expression ranking has been demonstrated to be robust to batch effects and that it can lead to more interpretable results. In this paper, we propose an enhanced pathway activity inference method that uses gene ranking to predict the pathway activity in a probabilistic manner. The main focus of this work is on identifying robust pathway markers that can ultimately lead to robust classifiers with reproducible performance across datasets. Simulation results based on multiple breast cancer datasets show that the proposed inference method identifies better pathway markers that can predict breast cancer metastasis with higher accuracy. Moreover, the identified pathway markers can lead to better classifiers with more consistent classification performance across independent datasets.
Decreasing Frequency of Osteonecrosis of the Jaw in Cancer and Myeloma Patients Treated with Bisphosphonates: The Experience of the Oncology Network of Piedmont and Aosta Valley (North-Western Italy)
Authors: Fusco Vittorio , Galassi Claudia , Berruti Alfredo , Ortega Cinzia , Ciuffreda Libero , Scoletta Matteo , Goia Franco , Migliario Mario , Baraldi Anna , Boccadoro Mario , Loidoris Anastasios , Bertetto Oscar
Published: February 2013

Background. Data concerning frequency of Osteonecrosis of Jaws (ONJ) are mostly based on single center experiences.
Patients and Methods. Since 2005 a multidisciplinary study group collected data of cases of ONJ in patients treated with Bisphosphonates (BP) and observed in oncology and hematology centers of a regional network. Results. By December 2008, 221 cases were registered. We report details of 200 cases, identified after cross-checking reports from centres of medical oncology, haematology, and oral care. Primary neoplasm was breast cancer (39%), myeloma (32%), prostate cancer (16%), and other types of cancer (8%). In about 50% of the cases a history of dental extraction was present. Zoledronic acid was administered (alone or with other BP) to 178 patients (89%). Median time from first infusion to ONJ diagnosis was 21.0 (zoledronic acid only) and 39.0 months (pamidronate only). The number of ONJ cases per year was 3 in 2003, 21 in 2004, 58 in 2005, 60 in 2006, 37 in 2007, and 21 in 2008. Conclusion. The number of new ONJ cases in cancer and myeloma patients increased until 2006 and then reduced. The possible reasons of this trend (introduction of zoledronic acid; increase of ONJ awareness; diffusion of preventive dental measures; late modifications of BP prescription) are herein discussed.
Anemia among Pediatric Critical Care Survivors: Prevalence and Resolution
Authors: Ngo Quang N. , Matsui Doreen M. , Singh Ram N. , Zelcer Shayna , Kornecki Alik
Published: February 2013

To determine the incidence of anemia among pediatric critical care survivors and to determine whether it resolves within 6 months of discharge.Design. A prospective observational study. Patients with anemia upon discharge from the pediatric critical care unit (PCCU) underwent in hospital and post hospital discharge followup (4–6 months) for hemoglobin (Hb) levels.Setting. A medical-surgical PCCU in a tertiary care center.Patients. Patients aged 28 days to 18 years who were treated in the PCCU for over 24 hours.Measurements and Main Results. 94 (24%) out of 392 eligible patients were anemic at time of discharge. Patients with anemia were older, median 8.0 yrs [(IQR 1.0–14.4) versus 3.2 yrs (IQR 0.65–9.9) (P<0.001)], and had higher PeLOD [median 11 (IQR 10–12) versus 1.5 (1–4) (P<0.001)], and PRISM [median 5 (IQR 2–11) versus 3 (IQR 0–6) (P<0.001)] scores. The Hb level normalized in 32% of patients before discharge from hospital. Of the 28 patients who completed followup, all had normalization of their Hb in the absence of medical intervention.Conclusions. Anemia is not common among patients discharged from the PCCU and recovers spontaneously within 4–6 months.
Communication Partners’ Journey through Their Partner’s Hearing Impairment
Authors: Manchaiah Vinaya K. C. , Stephens Dafydd , Lunner Thomas
Published: February 2013

The objective of this study was to further develop the Ida Institute model on communication partners’ (CPs) journey through experiences of person with hearing impairment (PHI), based on the perspectives of CPs. Nine CPs of hearing aid users participated in this study, recruited through the Swansea hearing impaired support group. Semi-structured interviews were conducted, the data were analysed using qualitative thematic analysis and presented with the use of process mapping approach. Seven main phases were identified in the CP journey which includes: (1) contemplation, (2) awareness, (3) persuasion, (4) validation, (5) rehabilitation, (6) adaptation, and (7) resolution. The Ida Institute model (based on professionals’ perspective) was compared with the new template developed (based on CPs’ perspectives). The results suggest some commonalities and differences between the views of professionals and CPs. A new phase, adaptation, was identified from CPs reported experiences, which was not identified by professionals in the Ida Institute model. The CP’s journey model could be a useful tool during audiological enablement/rehabilitation sessions to promote discussion between the PHI and the CP. In addition, it can be used in the training of hearing healthcare professionals.
Self-Inflicted Male Bladder Foreign Body: Its Endoscopic Removal Using a Rigid Cystoscope and a Suprapubic Forceps
Authors: Moslemi Mohammad Kazem , Sorani Mohamad
Published: February 2013

Introduction. Herein we present an interesting technique for the removal of bladder foreign body (BFB) in which a combination of endoscopic and suprapubic cystostomy was used.Case Presentation. The patient was a case of illicit drug abuser who self-introduced an electrical wire into his bladder. After its failed cystoscopic removal, the foreign body was removed suprapubically without open bladder surgery.Discussions. Bladder foreign bodies are not uncommon. Based on the literature review, mainly open surgeries were used for their treatment. Using of our less invasive technique is a good way for escaping from open cystostomy.Conclusion. Endoscopic removal of the bladder foreign bodies is possible without any need for open bladder surgery.
An Unusual Left Upper Quadrant Mass: A Bronchopulmonary Foregut Malformation
Authors: McDermott R. L. , Kavanagh D. O. , Bartosik W. , Quinn C. , O'Connell P. R.
Published: February 2013

We report a case of a lady who presented with epigastric discomfort. Physical examination revealed a large left upper quadrant mass filling the left upper quadrant. Following extensive preoperative evaluation, she underwent resection of this centimeter mass withen blocexcision of a portion of the left hemidiaphragm. She made an uneventful postoperative recovery. Histopathology revealed a bronchopulmonary foregut malformation with pulmonary sequestration. This developmental anomaly of the foregut typically occurs in the thoracic cavity; however, it can occur below the diaphragm. Herein we report a case and a detailed review of the embryology, clinical features, and management of these extremely rare clinical entities.
INS Assisted Fuzzy Tracking Loop for GPS-Guided Missiles and Vehicular Applications
Authors: Kamel Ahmed M. , Renaudin Valerie , Nielsen John , Lachapelle Gérard
Published: February 2013

Autonomous Navigation Systems used in missiles and other high dynamic platforms are mostly dependent on the Global Positioning System (GPS). GPS users face limitations in terms of missile high dynamics and signal interference. Receiver’s tracking loops bandwidth requirements to avoid these problems are conflicting. The paper presents a novel signal frequency and phase tracking algorithm for very high dynamic conditions, which mitigates the conflicting choice of bandwidths and reduces tracking loop measurement noise. It exploits the flexibility of fuzzy control systems for directly generating the required Numerically Controlled Oscillator (NCO) tuning frequency using phase and frequency discriminators information and is labeled Fuzzy Frequency Phase Lock Loop (FFPLL). Because Fuzzy Systems can be computationally demanding and an Inertial Navigation System (INS) is often onboard the vehicle, an assisted INS Doppler version has been designed and is also proposed. Assessment of the new GPS tracking method is performed with both simulated and experimental data under jamming conditions. The main enhancements of the proposed system consist in reduced processing time, improved tracking continuity and faster reacquisition time.
Metabolic Syndrome and Inflammation: A Critical Review ofIn Vitroand Clinical Approaches for Benefit Assessment of Plant Food Supplements
Authors: Di Lorenzo Chiara , Dell'Agli Mario , Colombo Elisa , Sangiovanni Enrico , Restani Patrizia
Published: February 2013

Metabolic syndrome is defined as the clustering in an individual of several metabolic abnormalities associated with insulin resistance, type 2 diabetes, and obesity, in which low-grade chronic inflammatory activity is commonly observed. Part of the European Project PlantLIBRA is concerned with methods to assess the benefits of plant food supplements (PFSs) in countering inflammatory activity and metabolic syndrome. This paper summarizes the current methods used for benefit assessment of PFS, taking into consideration onlyin vitro, in silico, and clinical methodologies used to investigate the anti-inflammatory properties of plants. No in silico studies (using computer simulation) related to metabolic syndrome were found; these methods appear to be used exclusively for identifying or testing potentially effective compounds in drug development. Mostin vitromethods for the assessment of beneficial effects of botanicals or plant food supplements in diabetes were based on a quantitative polymerase chain reaction (PCR), whereas the preferred kind of clinical study was the double-blind randomized controlled clinical trial. Only two parameters were observed to change after treatment with botanicals in bothin vitroandin vivostudies: interleukin-6 and tumour necrosis factor-α, and these biomarkers should be carefully considered in future studies for PFS benefit assessment.
Symmetry Reduced and New Exact Nontraveling Wave Solutions of (2+1)-Dimensional Potential Boiti-Leon-Manna-Pempinelli Equation
Authors: Han-Lin Chen , Da-Quan Xian
Published: February 2013

With the aid of Maple symbolic computation and Lie group method, (2+1)-dimensional PBLMP equation is reduced to some (1+1)-dimensional PDE with constant coefficients. Using the homoclinic test technique and auxiliary equation methods, we obtain new exact nontraveling solution with arbitrary functions for the PBLMP equation.
Adult Medication-Free Schizophrenic Patients Exhibit Long-Chain Omega-3 Fatty Acid Deficiency: Implications for Cardiovascular Disease Risk
Authors: McNamara Robert K. , Jandacek Ronald , Rider Therese , Tso Patrick , Dwivedi Yogesh , Pandey Ghanshyam N.
Published: February 2013

Deficiency in long-chain omega-3 (LCn− 3) fatty acids, eicosapentaenoic acid (EPA, 20:5n− 3) and docosahexaenoic acid (DHA, 22:6n− 3), has been implicated in the pathoetiology of cardiovascular disease, a primary cause of excess premature mortality in patients with schizophrenia (SZ). In the present study, we determined erythrocyte EPA + DHA levels in adult medication-free patients SZ (n=20) and age-matched healthy controls (n=24). Erythrocyte EPA + DHA composition exhibited by SZ patients (3.5%) was significantly lower than healthy controls (4.5%, −22%,P=0.007). The majority of SZ patients (72%) exhibited EPA+DHA levels ≤4.0% compared with 37% of controls (Chi-square,P=0.001). In contrast, the omega-6 fatty acid arachidonic acid (AA, 20:4n−6) (+9%,P=0.02) and the AA:EPA + DHA ratio (+28%,P=0.0004) were significantly greater in SZ patients. Linoleic acid (18:2n−6) was significantly lower (−12%,P=0.009) and the erythrocyte 20:3/18:2 ratio (an index of delta6-desaturase activity) was significantly elevated in SZ patients. Compared with same-gender controls, EPA + DHA composition was significantly lower in male (−19%,P=0.04) but not female (−13%,P=0.33) SZ patients, whereas the 20:3/18:2 ratio was significantly elevated in both male (+22%,P=0.008) and female (+22%,P=0.04) SZ patients. These results suggest that the majority of SZ patients exhibit low LCn− 3 fatty acid levels which may place them at increased risk for cardiovascular morbidity and mortality.
Simulation-Based Genetic Algorithm towards an Energy-Efficient Railway Traffic Control
Authors: Tuyttens Daniel , Fei Hongying , Mezmaz Mohand , Jalwan Jad
Published: February 2013

The real-time traffic control has an important impact on the efficiency of the energy utilization in the modern railway network. This study is aimed to develop an energy-efficient railway traffic control solution for any specified railway. In other words, it is expected to define suitable driving profiles for all the trains running within a specified period through the targeted network with an objective to minimize their total energy consumption. How to optimize the train synchronization so as to benefit from the energy regenerated by electronic braking is also considered in this study. A method based on genetic algorithm and empirical single train driving strategies is developed for this objective. Six monomode strategies and one multimode strategy are tested and compared with the four scenarios extracted from the Belgian railway system. The results obtained by simulation show that the multi-mode control strategy overcomes the mono-mode control strategies with regard to global energy consumption, while there is no firm relation between the utilization rate of energy regenerated by dynamic braking operations and the reduction of total energy consumption.
The Role of Para-Aortic Lymphadenectomy in the Surgical Staging of Women with Intermediate and High-Risk Endometrial Adenocarcinomas
Authors: May Taymaa , Shoni Melina , Vitonis Allison F. , Quick Charles M. , Growdon Whitfield B. , Muto Michael G.
Published: February 2013

Objectives. To characterize clinical outcomes in patients with intermediate or high-risk endometrial carcinoma who underwent surgical staging with or without para-aortic lymphadenectomy.Methods. This is a retrospective cohort study of patients with intermediate or high-risk endometrial adenocarcinoma who underwent surgical staging with (PPALN group) or without (PLN) para-aortic lymphadenectomy. Data were collected, Kaplan-Meier curves were generated, and univariate and multivariate analyses performed to compare differences in adjuvant therapy, disease recurrence, disease-free survival (DFS), and overall survival (OS).Results.118 patients were included in the PPALN group and 139 in the PLN group. Patients in the PPALN group were more likely to receive adjuvant vaginal brachytherapy (25.4% versus 11.5%,OR=2.5,P=0.03) and less likely to receive adjuvant multimodal combination therapy (17.81% versus 28.8%,OR=0.28,P=0.002). DFS was improved in the PLN group as compared to PPALN (80% versus 62%,P=0.02). OS was equivalent (P=0.93). Patients in the PPALN group who had less than 10 para-aortic nodes removed were twice as likely to recur than patients who had 10 or more para-aortic nodes or patients in the PLN group (HR 2.08, CI 1.20–3.60,P=0.009).Conclusions. Patients in the PLN group were more likely to receive multimodal adjuvant therapy and had better DFS than the PPALN group. Pelvic lymphadenectomy followed by adjuvant radiation and chemotherapy may represent an effective treatment option for patients with intermediate or high-risk disease. If systematic para-aortic lymphadenectomy is performed and less than 10 para-aortic lymph nodes are obtained, multimodality adjuvant therapy should be considered to improve DFS.
Optimization and Immobilization of Purified Labeo rohita Visceral Protease by Entrapment Method
Authors: Geethanjali S. , Subash Anitha
Published: February 2013

The purified fish visceral protease enzyme was immobilized by using various concentrations of sodium alginate and calcium chloride to optimize the best concentration for the formation of the beads. Then it was characterized by assaying the optimal pH, temperature, storage stability and reusability. The results on immobilization with sodium alginate and calcium chloride showed that a combination of 2% sodium alginate and 0.3 M calcium chloride weas found to be the optimum concentration for the formation of spherical and stable beads, this gave a maximal entrapped activity of 48.31%, and there was no change in the optimum pH 8.0 and temperature 40°C of protease before and after entrapment. The results on stability and reusability indicated that it was stable at 4°C retaining 100% residual activity after 5 days of storage and 67% loss of activity after ten days of storage and it retained 100% residual activity on the first reuse, 75% residual activity on the second reuse, 25% residual activity on the third use and complete loss in the activity on the fourth reuse.
A Rare Cause of Dyspnea: Sudden Rupture of Aortic Valsalva Sinus Aneurysm
Authors: Arıkan Erdinç , Karagöz Arif , Bayata Serdar , Yilik Levent , Ünlüer Erden Erol
Published: February 2013

Aneurysm of the sinus of Valsalva is an uncommon cardiac abnormality; however, the most common complication is rupture into the right heart chambers or rarely towards the left chambers. A ruptured aneurysm typically leads to an aortocardiac shunt and progressively worsening heart failure. We report a case of a 21-year-old male who suffered an aneurysm of the sinus of Valsalva rupture into the right atrium who underwent successful surgical repair.
Stability Switches in a First-Order Complex Neutral Delay Equation
Authors: Roales M. , Rodríguez F.
Published: February 2013

Stability of the first-order neutral delay equationx′(t)+ax′(t−τ)=bx(t)+cx(t−τ)with complex coefficients is studied, by analyzing the existence of stability switches.
A Mathematical Characterization for Patterns of a Keller-Segel Model with a Cubic Source Term
Authors: Fu Shengmao , Liu Ji
Published: February 2013

This paper deals with a Neumann boundary value problem for a Keller-Segel model with a cubic source term in ad-dimensional box(d=1,2,3), which describes the movement of cells in response to the presence of a chemical signal substance. It is proved that, given any general perturbation of magnitudeδ, its nonlinear evolution is dominated by the corresponding linear dynamics along a finite number of fixed fastest growing modes, over a time period of the order ln(1/δ). Each initial perturbation certainly can behave drastically differently from another, which gives rise to the richness of patterns. Our results provide a mathematical description for early pattern formation in the model.
Predicting Delirium Duration in Elderly Hip-Surgery Patients: Does Early Symptom Profile Matter?
Authors: Slor Chantal J. , Witlox Joost , Adamis Dimitrios , Meagher David J. , Ploeg Tjeerd van der , Jansen Rene W. M. M. , van Stijn Mireille F. M. , Houdijk Alexander P. J. , van Gool Willem A. , Eikelenboom Piet , de Jonghe Jos F. M.
Published: February 2013

Background. Features that may allow early identification of patients at risk of prolonged delirium, and therefore of poorer outcomes, are not well understood. The aim of this study was to determine if preoperative delirium risk factors and delirium symptoms (at onset and clinical symptomatology during the course of delirium) are associated with delirium duration.Methods. This study was conducted in prospectively identified cases of incident delirium. We compared patients experiencing delirium of short duration (1 or 2 days) with patients who had more prolonged delirium (≥3 days) with regard to DRS-R-98 (Delirium Rating Scale Revised-98) symptoms on the first delirious day. Delirium symptom profile was evaluated daily during the delirium course.Results. In a homogenous population of 51 elderly hip-surgery patients, we found that the severity of individual delirium symptoms on the first day of delirium was not associated with duration of delirium. Preexisting cognitive decline was associated with prolonged delirium. Longitudinal analysis using the generalised estimating equations method (GEE) identified that more severe impairment of long-term memory across the whole delirium episode was associated with longer duration of delirium.Conclusion. Preexisting cognitive decline rather than severity of individual delirium symptoms at onset is strongly associated with delirium duration.
Methylation of the hTERT Promoter: A Novel Cancer Biomarker for Leptomeningeal Metastasis Detection in Cerebrospinal Fluids
Authors: Bougel Stéphanie , Lhermitte Benoit , Gallagher Gabrielle , de Flaugergues Jeanne-Chantal , Janzer Robert C. , Benhattar Jean
Published: February 2013

Purpose: The diagnosis of leptomeningeal metastases is usually confirmed by the finding of malignant cells by cytologic examination in the cerebrospinal fluid (CSF). More sensitive and specific cancer biomarkers may improve the detection of tumor cells in the CSF. Promoter methylation of the human telomerase reverse transcriptase (hTERT) gene characterizes most cancer cells. The aim of this study was to develop a sensitive method to detect hTERT methylation and to explore its use as a cancer biomarker in CSF.

Experimental Design: In 77 CSF specimens from 67 patients, hTERT promoter methylation was evaluated using real-time methylation-sensitive high-resolution melting (MS-HRM) and real-time TaqMan PCR and MS-HRM in a single-tube assay.

Results: Real-time MS-HRM assay was able to detect down to 1% hTERT-methylated DNA in a background of unmethylated DNA. PCR products were obtained from 90% (69/77) of CSF samples. No false positive hTERT was detected in the 21 non-neoplastic control cases, given to the method a specificity of 100%. The sensitivity of the real-time MS-HRM compared with the cytologic gold standard analysis was of 92% (11/12). Twenty-six CSFs from 22 patients with an hTERT-methylated primary tumor showed cytologic results suspicious for malignancy; in 17 (65%) of them, a diagnosis of leptomeningeal metastases could be confirmed by the hTERT methylation test.

Conclusion: The hTERT real-time MS-HRM approach is fast, specific, sensitive, and could therefore become a valuable tool for diagnosis of leptomeningeal metastases as an adjunct to the traditional examination of CSF. Clin Cancer Res; 19(8); 2216–23. ©2013 AACR.
Cetuximab-Activated Natural Killer and Dendritic Cells Collaborate to Trigger Tumor Antigen–Specific T-cell Immunity in Head and Neck Cancer Patients
Authors: Srivastava Raghvendra M. , Lee Steve C. , Andrade Filho Pedro A. , Lord Christopher A. , Jie Hyun-Bae , Davidson H. Carter , López-Albaitero Andrés , Gibson Sandra P. , Gooding William E. , Ferrone Soldano , Ferris Robert L.
Published: February 2013

Purpose: Tumor antigen–specific monoclonal antibodies (mAb) block oncogenic signaling and induce Fcγ receptor (FcγR)–mediated cytotoxicity. However, the role of CD8+ CTL and FcγR in initiating innate and adaptive immune responses in mAb-treated human patients with cancer is still emerging.

Experimental Design: FcγRIIIa codon 158 polymorphism was correlated with survival in 107 cetuximab-treated patients with head and neck cancer (HNC). Flow cytometry was carried out to quantify EGF receptor (EGFR)–specific T cells in cetuximab-treated patients with HNC. The effect of cetuximab on natural killer (NK) cell, dendritic cell (DC), and T-cell activation was measured using IFN-γ release assays and flow cytometry.

Results: FcγRIIIa polymorphism did not predict clinical outcome in cetuximab-treated patients with HNC; however, elevated circulating EGFR853–861–specific CD8+ T cells were found in cetuximab-treated patients with HNC (P < 0.005). Cetuximab promoted EGFR-specific cellular immunity through the interaction of EGFR+ tumor cells and FcγRIIIa on NK cells but not on the polymorphism per se. Cetuximab-activated NK cells induced IFN-γ–dependent expression of DC maturation markers, antigen processing machinery components such as TAP-1/2 and T-helper cell (TH1) chemokines through NKG2D/MICA binding. Cetuximab initiated adaptive immune responses via NK cell–induced DC maturation, which enhanced cross-presentation to CTL specific for EGFR as well as another tumor antigen, MAGE-3.

Conclusion: Cetuximab-activated NK cells promote DC maturation and CD8+ T-cell priming, leading to tumor antigen spreading and TH1 cytokine release through “NK–DC cross-talk.” FcγRIIIa polymorphism did not predict clinical response to cetuximab but was necessary for NK–DC interaction and mAb-induced cross-presentation. EGFR-specific T cells in cetuximab-treated patients with HNC may contribute to clinical response. Clin Cancer Res; 19(7); 1858–72. ©2013 AACR.
Targeting the NF-κB and mTOR Pathways with a Quinoxaline Urea Analog That Inhibits IKKβ for Pancreas Cancer Therapy
Authors: Radhakrishnan Prakash , Bryant Vashti C. , Blowers Elizabeth C. , Rajule Rajkumar N. , Gautam Nagsen , Anwar Muhammad M. , Mohr Ashley M. , Grandgenett Paul M. , Bunt Stephanie K. , Arnst Jamie L. , Lele Subodh M. , Alnouti Yazen , Hollingsworth Michael A. , Natarajan Amarnath
Published: February 2013

Purpose: The presence of TNF-α in approximately 50% of surgically resected tumors suggests that the canonical NF-κB and the mTOR pathways are activated. Inhibitor of IκB kinase β (IKKβ) acts as the signaling node that regulates transcription via the p-IκBα/NF-κB axis and regulates translation via the mTOR/p-S6K/p-eIF4EBP axis. A kinome screen identified a quinoxaline urea analog 13-197 as an IKKβ inhibitor. We hypothesized that targeting the NF-κB and mTOR pathways with 13-197 will be effective in malignancies driven by these pathways.

Experimental Design: Retrospective clinical and preclinical studies in pancreas cancers have implicated NF-κB. We examined the effects of 13-197 on the downstream targets of the NF-κB and mTOR pathways in pancreatic cancer cells, pharmacokinetics, toxicity and tumor growth, and metastases in vivo.

Results: 13-197 inhibited the kinase activity of IKKβ in vitro and TNF-α–mediated NF-κB transcription in cells with low-μmol/L potency. 13-197 inhibited the phosphorylation of IκBα, S6K, and eIF4EBP, induced G1 arrest, and downregulated the expression of antiapoptotic proteins in pancreatic cancer cells. Prolonged administration of 13-197 did not induce granulocytosis and protected mice from lipopolysaccharide (LPS)-induced death. Results also show that 13-197 is orally available with extensive distribution to peripheral tissues and inhibited tumor growth and metastasis in an orthotopic pancreatic cancer model without any detectable toxicity.

Conclusion: These results suggest that 13-197 targets IKKβ and thereby inhibits mTOR and NF-κB pathways. Oral availability along with in vivo efficacy without obvious toxicities makes this quinoxaline urea chemotype a viable cancer therapeutic. Clin Cancer Res; 19(8); 2025–35. ©2013 AACR.
Clinical Correlates of Promoter Hypermethylation of Four Target Genes in Head and Neck Cancer: A Cooperative Group Correlative Study
Authors: Roh Jong-Lyel , Wang Xin Victoria , Manola Judith , Sidransky David , Forastiere Arlene A. , Koch Wayne M.
Published: February 2013

Purpose: Promoter hypermethylation is a well-documented mechanism for tumor-specific alteration of suppressor gene activity in human malignancy including head and neck cancer (HNC). The abrogation of specific suppressor gene activity may influence tumor behavior and clinical outcome. In this study we examined methylation of DCC, KIF1A, EDNRB, and p16INK4a in a large cohort of HNC patients from Eastern Cooperative Group (ECOG) 4393/Radiation Therapy Oncology Group (RTOG) 9614 to identify clinical correlates of methylation of these genes.

Experimental Design: Methylation was assessed by quantitative methylation-specific PCR in DNA from tumor specimens and was considered as a continuous and a binary variable. Clinical data including demographics, stage, risk factor exposure, treatment, and outcome were collected by ECOG and RTOG. Methylation status was also correlated with mutation of TP53 (previously reported) and human papilloma virus status.

Results: Methylation results were available for 368 cases, 353 of which also have p53 mutation status. At least one methylation event was present in all tumors. In multivariate analysis of the entire cohort, methylation of p16 was associated with decreased survival (HR = 1.008; P = 0.045). However, in tumors with disruptive TP53 mutation (poor prognostic group), the additional presence of methylation of p16 was protective (P = 0.019 considering p16 methylation as a continuous variable).

Conclusion: Methylation of tumor-related genes contributes to the biological behavior of HNC and influences overall survival in conjunction with other known prognostic molecular events. Clin Cancer Res; 19(9); 2528–40. ©2013 AACR.
CD44 and OTP Are Strong Prognostic Markers for Pulmonary Carcinoids
Authors: Swarts Dorian R.A. , Henfling Mieke E.R. , Van Neste Leander , van Suylen Robert-Jan , Dingemans Anne-Marie C. , Dinjens Winand N.M. , Haesevoets Annick , Rudelius Martina , Thunnissen Erik , Volante Marco , Van Criekinge Wim , van Engeland Manon , Ramaekers Frans C.S. , Speel Ernst-Jan M.
Published: February 2013

Purpose: Pulmonary carcinoids are well-differentiated neuroendocrine tumors showing usually a favorable prognosis. However, there is a risk for late recurrence and/or distant metastasis. Because histologic classification in typical and atypical carcinoids is difficult and its reliability to predict disease outcome varies, we evaluated three genes as potential prognostic markers, that is, orthopedia homeobox (OTP), CD44, and rearranged during transfection (RET).

Experimental Design: These genes were analyzed in 56 frozen carcinoids by quantitative real-time PCR (qRT-PCR). RET was further studied by methylation and mutation analysis. Immunohistochemistry for CD44 and OTP protein expression was conducted on 292 carcinoids.

Results: Low mRNA expression levels of CD44 (P = 1.8e−5) and OTP (P = 0.00054), and high levels of RET (P = 0.025), were strongly associated with a low 20-year survival of carcinoid patients. High RET expression was not related to promoter hypomethylation or gene mutations. A direct link between gene expression and protein levels was confirmed for CD44 and OTP but not for RET. Within all carcinoids as well as atypical carcinoids, absence of CD44 protein was significantly associated with low 20-year survival (P = 0.00014 and 0.00013, respectively). The absence of nuclear OTP followed by complete loss of expression was also significantly associated with unfavorable disease outcome in all carcinoids (P = 5.2−6). Multivariate analyses revealed that age at diagnosis, histopathology, stage, and cytoplasmic OTP immunoreactivity were independent predictors of prognosis.

Conclusions: Our study indicates that CD44 and OTP are strong indicators of poor outcome. We therefore argue for implementation of these markers in routine diagnostics in addition to histopathology to improve subclassification of pulmonary carcinoids into prognostically relevant categories. Clin Cancer Res; 19(8); 2197–207. ©2013 AACR.