bluuebunny/crossref_metadata_2025 huggingface dataset:
Symbiogenesis: Mechanisms, Evolutionary Consequences, and Systematic Implications
Authors: Cavalier-Smith Thomas
Published: August 2013

Symbiogenesis is the extremely rare, but permanent merger of two organisms from phylogenetically distant lineages into one radically more complex organism. Three examples are exceptionally important: intracellular enslavement by an early eukaryote of an α-proteobacterium by host protein insertion to make mitochondria; later conversion of a cyanobacterium into the first chloroplast, thereby forming kingdom Plantae; and secondary enslavement of a red alga to yield more complex membrane topology in the phagophototrophic kingdom Chromista. Two other cases involved independent acquisition of green-algal chloroplasts by ancestrally phagotrophic lineages, yielding chlorarachnean algae (phylum Cercozoa, within the chromist infrakingdom Rhizaria) and euglenophyte algae (phylum Euglenozoa, within the protozoan subkingdom Eozoa). Less radically, chloroplast replacement occurred within dinoflagellate Chromista by two symbiogeneses: Green-algal or haptophyte chloroplasts replaced ancestral peridinin-containing chloroplasts. These seven lineage mergers were all mediated by the evolution of novel modes of transmembrane protein import into the enslaved cell, allowing massive gene transfer from symbionts to host genomes.
The insulin receptor plays an important role in secretory differentiation in the mammary gland
Authors: Neville Margaret C. , Webb Patricia , Ramanathan Palaniappan , Mannino Meridee P. , Pecorini Chiara , Monks Jenifer , Anderson Steven M. , MacLean Paul
Published: August 2013

Insulin is known to be an important regulator of milk secretion in the lactating mammary gland. Here we examine the role of insulin signaling in mammary development in pregnancy using a mouse with a floxed insulin receptor (IR) crossed with a mouse expressing Cre specifically in the mammary gland. In the mammary glands of these IRfl/flCre+mice, expression of IR is significantly diminished throughout development. Glands from these mice had 50% fewer alveoli at midpregnancy; casein and lipid droplets were diminished by 60 and 75%, respectively, indicating a role for IR both in alveolar development and differentiation. In an acinar preparation from mammary epithelial cells (MEC) isolated from pregnant mice, insulin stimulated lumen formation, mammary cell size, acinar size, acinar casein content, and the formation of lipid droplets with a Kmof ∼1.7 nM. IGF-I and IGF-II had no effect at concentrations below 50 nM, and a function blocking antibody to the IGF type 1 receptor did not alter the response to insulin. We conclude that insulin interacting with IR is essential for mammary differentiation during murine pregnancy. Using array analysis, we then examined the expression of genes up- or downregulated >1.5-fold in the IRfl/flCre+MECs, finding significant downregulation of differentiation specific genes and upregulation of cell cycle and extracellular matrix genes. We conclude that insulin fosters differentiation and may inhibit cell proliferation in the mammary gland of the midpregnant mouse.
Identifying Core Herbal Treatments for Children with Asthma: Implication from a Chinese Herbal Medicine Database in Taiwan
Authors: Chen Hsing-Yu , Lin Yi-Hsuan , Thien Peck-Foong , Chang Shih-Chieh , Chen Yu-Chun , Lo Su-Shun , Yang Sien-Hung , Chen Jiun-Liang
Published: August 2013

Asthma is one of the most common allergic respiratory diseases around the world and places great burden on medical payment. Chinese herbal medicine (CHM) is commonly used for Taiwanese children to control diseases. The aim of this study is to analyze the CHM prescriptions for asthmatic children by using a nationwide clinical database. The National Health Insurance Research Database (NHIRD) was used to perform this study. Medical records from 1997 to 2009 with diagnosis with asthma made for children aged 6 to 18 were included into the analysis. Association rule mining and social network analysis were used to analyze the prevalence of single CHM and its combinations. Ma-Xing-Gan-Shi-Tang (MXGST) was the most commonly used herbal formula (HF) (20.2% of all prescriptions), followed by Xiao-Qing-Long-Tang (13.1%) and Xing-Su-San (12.8%). Zhe Bei Mu is the most frequently used single herb (SH) (14.6%), followed by Xing Ren (10.7%). MXGST was commonly used with Zhe Bei Mu (3.5%) and other single herbs capable of dispelling phlegm. Besides, MXGST was the core formula to relieve asthma. Further studies about efficacy and drug safety are needed for the CHM commonly used for asthma based on the result of this study.
Preoperative Screening and Case Cancellation in Cocaine-Abusing Veterans Scheduled for Elective Surgery
Authors: Elkassabany Nabil , Speck Rebecca M. , Oslin David , Hawn Mary , Chaichana Khan , Sum-Ping John , Sepulveda Jorge , Whitley Mary , Sakawi Yasser
Published: August 2013

Background. Perioperative management of cocaine-abusing patients scheduled for elective surgery varies widely based on individual anecdotes and personal experience.Methods. Chiefs of the anesthesia departments in the Veterans Affairs (VA) health system were surveyed to estimate how often they encounter surgical patients with cocaine use. Respondents were asked about their screening criteria, timing of screening, action resulting from positive screening, and if they have a formal policy for management of these patients. Interest in the development of VA guidelines for the perioperative management of patients with a history of cocaine use was also queried.Results. 172 VA anesthesia departments’ chiefs were surveyed. Response rate was 62%. Over half of the facilities see cocaine-abusing patients at least once a week (52%). Two thirds of respondents canceled or delayed patients with a positive screen regardless of clinical symptoms. Only eleven facilities (10.6%) have a formal policy. The majority of facilities (80%) thought that having formal guidelines for perioperative management of cocaine-abusing patients would be helpful to some extent. Results. 172 VA anesthesia departments’ chiefs were surveyed. Response rate was 62%. Over half of the facilities see cocaine-abusing patients at least once a week (52%). Two thirds of respondents canceled or delayed patients with a positive screen regardless of clinical symptoms. Only eleven facilities (10.6%) have a formal policy. The majority of facilities (80%) thought that having formal guidelines for perioperative management of cocaine-abusing patients would be helpful to some extent.Conclusions. There is a general consensus that formal guidelines would be helpful. Further studies are needed to help formulate evidence-based guidelines for managing patients screening positive for cocaine prior to elective surgery.
Utility of the Mini-Cog for Detection of Cognitive Impairment in Primary Care: Data from Two Spanish Studies
Authors: Carnero-Pardo Cristóbal , Cruz-Orduña Isabel , Espejo-Martínez Beatriz , Martos-Aparicio Carolina , López-Alcalde Samuel , Olazarán Javier
Published: August 2013

Objectives. To study the utility of the Mini-Cog test for detection of patients with cognitive impairment (CI) in primary care (PC).Methods. We pooled data from two phase III studies conducted in Spain. Patients with complaints or suspicion of CI were consecutively recruited by PC physicians. The cognitive diagnosis was performed by an expert neurologist, after formal neuropsychological evaluation. The Mini-Cog score was calculatedpost hoc, and its diagnostic utility was evaluated and compared with the utility of the Mini-Mental State (MMS), the Clock Drawing Test (CDT), and the sum of the MMS and the CDT (MMS+CDT) using the area under the receiver operating characteristic curve (AUC). The best cut points were obtained on the basis of diagnostic accuracy (DA) and kappa index.Results. A total sample of 307 subjects (176 CI) was analyzed. The Mini-Cog displayed an AUC (±SE) of0.78±0.02, which was significantly inferior to the AUC of the CDT (0.84±0.02), the MMS (0.84±0.02), and theMMS+CDT(0.86±0.02). The best cut point of the Mini-Cog was 1/2 (sensitivity 0.60, specificity 0.90, DA 0.73, and kappa index0.48±0.05).Conclusions. The utility of the Mini-Cog for detection of CI in PC was very modest, clearly inferior to the MMS or the CDT. These results do not permit recommendation of the Mini-Cog in PC.
Evaluation ofIn VitroCytoxicity and Genotoxicity of Size-Fractionated Air Particles Sampled during Road Tunnel Construction
Authors: Dominici Luca , Guerrera Elena , Villarini Milena , Fatigoni Cristina , Moretti Massimo , Blasi Paolo , Monarca Silvano
Published: August 2013

In tunnel construction, workers exposed to dust from blasting, gases, diesel exhausts, and oil mist have shown higher risk for pulmonary diseases. A clear mechanism to explain how these pollutants determine diseases is lacking, and alveolar epithelium’s capacity to ingest inhaled fine particles is not well characterized. The objective of this study was to assess the genotoxic effect exerted by fine particles collected in seven tunnels using the cytokinesis-block micronuclei test in anin vitromodel on type II lung epithelium A549 cells. For each tunnel, five fractions with different aerodynamic diameters of particulate matter were collected with a multistage cascade sampler. The human epithelial cell line A549 was exposed to 0.2 m3/mL equivalent of particulate for 24 h before testing. The cytotoxic effects of particulate matter on A549 cells were also evaluated in two different viability tests. In order to evaluate the cells’ ability to take up fine particles, imaging with transmission electron microscopy of cells after exposure to particulate matter was performed. Particle endocytosis after 24 h exposure was observed as intracellular aggregates of membrane-bound particles. This morphologic evidence did not correspond to an increase in genotoxicity detected by the micronucleus test.
Convergence Analysis of Particle Swarm Optimizer and Its Improved Algorithm Based on Velocity Differential Evolution
Authors: Ye Hongtao , Luo Wenguang , Li Zhenqiang
Published: August 2013

This paper presents an analysis of the relationship of particle velocity and convergence of the particle swarm optimization. Its premature convergence is due to the decrease of particle velocity in search space that leads to a total implosion and ultimately fitness stagnation of the swarm. An improved algorithm which introduces a velocity differential evolution (DE) strategy for the hierarchical particle swarm optimization (H-PSO) is proposed to improve its performance. The DE is employed to regulate the particle velocity rather than the traditional particle position in case that the optimal result has not improved after several iterations. The benchmark functions will be illustrated to demonstrate the effectiveness of the proposed method.
A Type of Localization Method Using Mobile Beacons Based on Spiral-Like Moving Path for Wireless Sensor Networks
Authors: Sha Chao , Wang Ru-chuan
Published: August 2013

A type of energy optimization localization method with mobile beacon is proposed in this paper. Traverse point of the mobile beacon is marked with the help of the optimum deployment model and the clockwise spiral-like moving path with fixed step size is also established. According to the moving path and the localization time, energy consumption of the network could be estimated and we could also give the sleep scheduling strategy for the node to be localized. Simulation results show that this method could not only promote the accuracy and success rate of localization, but also reduce the energy consumption.
Malignant Peripheral Nerve Sheath Tumor of the Small Bowel: An Unusual Presentation with Fatal Outcome
Authors: Mohtaram Amina , Mesmoudi Siham , M’rabti Hind , Rami Amal , Latib Rachida , Bernoussi Zakia , Aaribi Imane , Ben Ameur El Youbi Meryam , Errihani Hassan
Published: August 2013

Malignant peripheral nerve sheath tumor of the small bowel is an extremely rare disease. Histologic distinction from other types of soft tissue sarcoma especially fibrosarcoma and leiomyosarcoma requires electron microscopy. Complete surgery remains the only curative treatment. However, late diagnosis makes curative surgery more difficult. The contribution of chemotherapy to incomplete surgery has been proved without controlled studies. We report a case of this type of lesion discovered following a small bowel perforation.
Performance of a Novel Decentralised Sewage Treatment Reactor
Authors: Shen Dong Sheng , Huang Bao Cheng , Feng Hua Jun , Zhao Bo , Zhao Jiang Ming , Zhang Hai Yang , Liu Pei-Qing
Published: August 2013

A novel decentralised sewage treatment reactor (DSTR) for treating domestic sewage in rural areas was designed and investigated. The reactor was started aerobically after inoculation with biomass; the amount of initial mixed liquid suspended solids was 1.5 g/L. Oxygen was supplied to the reactor and the dissolved oxygen concentration was maintained at 1.3 ± 0.2 mg/L. The pollutant removal performance was investigated, and the average removal efficiencies of total chemical oxygen demand (TCOD), , suspended solids, and turbidity were 76%, 77.15%, 84.17%, and 83.93%, respectively. The DSTR exhibited good performance compared with the traditional activated sludge (AS) reactor. The resistance to impact load of the DSTR was superior to that of the AS reactor during surface load experiments. During the 120 days of operation, no sludge bulking was observed. The DSTR effluent and TCOD levels were a little higher than those for the AS reactor, but the disparity was not major.
Synchronizability of Small-World Networks Generated from a Two-Dimensional Kleinberg Model
Authors: Zhao Yi , Feng Jianwen , Wang Jingyi
Published: August 2013

This paper investigates the synchronizability of small-world networks generated from a two-dimensional Kleinberg model, which is more general than NW small-world network. The three parameters of the Kleinberg model, namely, the distance of neighbors, the number of edge-adding, and the edge-adding probability, are analyzed for their impacts on its synchronizability and average path length. It can be deduced that the synchronizability becomes stronger as the edge-adding probability increases, and the increasing edge-adding probability could make the average path length of the Kleinberg small-world network go smaller. Moreover, larger distance among neighbors and more edges to be added could play positive roles in enhancing the synchronizability of the Kleinberg model. The lorentz oscillators are employed to verify the conclusions numerically.
An Efficient Clustering Protocol for Wireless Sensor Networks Based on Localized Game Theoretical Approach
Authors: Xie Dongfeng , Sun Qi , Zhou Qianwei , Qiu Yunzhou , Yuan Xiaobing
Published: August 2013

Game theory has emerged as a brand new approach to model and analyse several problems of wireless sensor networks, such as routing, data collection, and topology control. Recently, a novel clustering mechanism called clustered routing for selfish sensors (CROSS) has been proposed based on game theory. The sensor nodes, which are modelled as players, join in a clustering game to campaign for cluster heads with an equilibrium probability. However, the CROSS algorithm needs the global information of how many nodes participate in the game at every round. Considering that this global way introduces much more packets exchange and energy consumption, we present a Localized game theoretical clustering algorithm (LGCA). In our protocol, each node selfishly plays a localized clustering game only with its neighbours within a communication radius [Formula: see text]. Moreover, exactly one node can successfully bid for a position of the cluster head in one district, thus achieving an optimal payoff. Simulation results show that our method achieves a better result compared with CROSS and LEACH in terms of network lifetime.
Relationship between Birth Weight and Metabolic Status in Obese Adolescents
Authors: Hill David J. , Prapavessis Harry , Shoemaker J. Kevin , Jackman Michelle , Mahmud Farid H. , Clarson Cheril
Published: August 2013

Objective. To examine the relationships between birth weight and body mass index, percent body fat, blood lipids, glycemia, insulin resistance, adipokines, blood pressure, and endothelial function in a cohort of obese adolescents. Design and Methods. Ninety-five subjects aged 10–16 years (mean age 13.5 years) with a body mass index >95th centile (mean [±SEM] 33.0 ± 0.6) were utilized from two prospective studies for obesity prevention prior to any interventions. The mean term birth weight was 3527 ± 64 g (range 1899–4990 g;). Results. Body mass index z-score correlated positively with birth weight (r2=0.05, P=0.03), but not percent body fat. Insulin resistance negatively correlated with birth weight (r2=0.05, P<0.001), as did fasting plasma insulin (r2=0.05, P<0.001); both being significantly greater for subjects of small versus large birth weight (Δ Homeostasis Model Assessment = 2.5 and Δ insulin = 10 pmol/L for birth weight <2.5 kg versus >4.5 kg). Adiponectin, but not leptin, blood pressure z-scores or peripheral arterial tomography values positively correlated with birth weight (r2=0.07, P=0.008). Conclusions. Excess body mass index in obese adolescents was positively related to birth weight. Birth weight was not associated with cardiovascular risk factors but represented a significant determinant of insulin resistance.
Inferring Phylogenetic Networks from Gene Order Data
Authors: Morozov Alexey Anatolievich , Galachyants Yuri Pavlovich , Likhoshway Yelena Valentinovna
Published: August 2013

Existing algorithms allow us to infer phylogenetic networks from sequences (DNA, protein or binary), sets of trees, and distance matrices, but there are no methods to build them using the gene order data as an input. Here we describe several methods to build split networks from the gene order data, perform simulation studies, and use our methods for analyzing and interpreting different real gene order datasets. All proposed methods are based on intermediate data, which can be generated from genome structures under study and used as an input for network construction algorithms. Three intermediates are used: set of jackknife trees, distance matrix, and binary encoding. According to simulations and case studies, the best intermediates are jackknife trees and distance matrix (when used with Neighbor-Net algorithm). Binary encoding can also be useful, but only when the methods mentioned above cannot be used.
Grape-Derived Polyphenols Prevent Doxorubicin-Induced Blunted EDH-Mediated Relaxations in the Rat Mesenteric Artery: Role of ROS and Angiotensin II
Authors: Idris-Khodja Noureddine , Di Marco Paola , Farhat Mona , Geny Bernard , Schini-Kerth Valérie B.
Published: August 2013

This study determined whether doxorubicin, an anticancer agent, impairs endothelium-dependent relaxations mediated by nitric oxide (NO) and endothelium-derived hyperpolarization (EDH) in the mesenteric artery and, if so, the mechanism underlying the protective effect of red wine polyphenols (RWPs), a rich natural source of antioxidants. Male Wistar rats were assigned into 4 groups: control, RWPs, doxorubicin, and doxorubicin + RWPs. Vascular reactivity was assessed in organ chambers; the vascular formation of reactive oxygen species (ROS) using dihydroethidine and the expression levels of small and intermediate conductance calcium-activated potassium channels (SKCa,IKCa) and connexin 40 (Cx40), which are involved in EDH-type relaxations, endothelial NO synthase (eNOS), angiotensin II, and AT1 receptors by immunofluorescence. The doxorubicin treatment impaired EDH-mediated relaxations, whereas those mediated by NO were minimally affected. This effect was associated with reduced expression levels ofSKCa,IKCa, and Cx40, increased expression levels of eNOS, angiotensin II, and AT1 receptors, and formation of ROS in mesenteric arteries. RWPs prevented both the doxorubicin-induced blunted EDH-type relaxations and the increased vascular oxidative stress, and they improved the expression levels of target proteins. These findings suggest that polyphenol-rich natural products might be of interest in the management of doxorubicin-induced vascular injury possibly by improving the vascular angiotensin system.
Sympathetic Innervation Induced in Engrafted Engineered Cardiomyocyte Sheets by Glial Cell Line Derived Neurotrophic FactorIn Vivo
Authors: Fu Xian-ming , Lee Jong-Kook , Miwa Keiko , Shimizu Tatsuya , Takagishi Yoshiko , Hirabayashi Masumi , Watabe Kazuhiko , Usui Akihiko , Kodama Itsuo , Ueda Yuichi
Published: August 2013

The aim of myocardial tissue engineering is to repair or regenerate damaged myocardium with engineered cardiac tissue. However, this strategy has been hampered by lack of functional integration of grafts with native myocardium. Autonomic innervation may be crucial for grafts to function properly with host myocardium. In this study, we explored the feasibility ofin vivoinduction of autonomic innervation to engineered myocardial tissue using genetic modulation by adenovirus encoding glial cell line derived neurotrophic factor (GDNF). GFP-transgene (control group) or GDNF overexpressing (GDNF group) engineered cardiomyocyte sheets were transplanted on cryoinjured hearts in rats. Nerve fibers in the grafts were examined by immunohistochemistry at 1, 2, and 4 weeks postoperatively. Growth associated protein-43 positive growing nerves and tyrosine hydroxylase positive sympathetic nerves were first detected in the grafts at 2 weeks postoperatively in control group and 1 week in GDNF group. The densities of growing nerve and sympathetic nerve in grafts were significantly increased in GDNF group. No choline acetyltransferase immunopositive parasympathetic nerves were observed in grafts. In conclusion, sympathetic innervation could be effectively induced into engrafted engineered cardiomyocyte sheets using GDNF.
Analytical Solutions for the Mathematical Model Describing the Formation of Liver Zones via Adomian’s Method
Authors: Ebaid Abdelhalim
Published: August 2013

The formation of liver zones is modeled by a system of two integropartial differential equations. In this research, we introduce the mathematical formulation of these integro-partial differential equations obtained by Bass et al. in 1987. For better understanding of this mathematical formulation, we present a medical introduction for the liver in order to make the formulation as clear as possible. In applied mathematics, the Adomian decomposition method is an effective procedure to obtain analytic and approximate solutions for different types of operator equations. This Adomian decomposition method is used in this work to solve the proposed model analytically. The stationary solutions (as time tends to infinity) are also obtained through it, which are in full agreement with those obtained by Bass et al. in 1987.
Energy Tree Dynamics of Smart Grid Based on Industrial Internet of Things
Authors: Wang Yang , Zeng Peng , Yu Haibin , Zhang Yanyu , Wang Xu
Published: August 2013

Service-oriented architectures make establishing comprehensive profiles of smart factories feasible. In this paper, an energy tree model is used to describe a profile that shapes energy system dynamics. The energy tree shows an overall and detailed profile that combines information communication technologies and ontology knowledge bases. A 7-level network protocol defines sustainable communication services for accumulating local information to maintain the global energy tree in real time. The communication protocol manages everchanging temporal and spatial misalignments by aligning groups of energy resources that are temporally or spatially related. Meanwhile, correlated domain information regarding industrial processes is formulized into ontology models. Ontology-based semantic contexts allocate knowledge-supported attributes to energy resources, including systems, resources, and users. The key objective of context awareness is to align attributes and to intensify couplings between different energy resources by decomposing and aggregating internal ontology models. Intertemporal and interspatial correlations of energy resources are made available by the cooperative transmission of ontology-based semantic contexts in the protocol framework. An informational architecture based on the conceptual energy tree finally can be established using incomplete measurement data and reasoning for large-scale industrial networks. A Smart Grid application instance is given to demonstrate the functionalities of energy tree dynamics.
A Tent Map BasedA/DConversion Circuit for Robot Tactile Sensor
Authors: Liu Jianxin , Zhang Xuan , Li Zhiming , Li Xuling
Published: August 2013

Force and tactile sensors are basic elements for robot perception and control, which call for large range and high-accuracy amplifier. In this paper, a novelA/Dconversion circuit for array tactile sensor is proposed by using nonlinear tent map phenomenon, which is characterized by sensitivity to small signal and nonlinear amplifying function. The tent map basedA/Dconversion circuits can simultaneously realize amplifying andA/Dconverting functions. The proposed circuit is not only simple but also easy to integrate and produce. It is very suited for multipath signal parallel sampling andA/Dconverting of large array tactile sensor.
Response of Rice Nitrogen Physiology to High Nighttime Temperature during Vegetative Stage
Authors: Chen Song , Zhang Xiaoguo , Zhao Xia , Wang Danying , Xu Chunmei , Ji Chenglin , Zhang Xiufu
Published: August 2013

The effects of night temperature on plant morphology and nitrogen accumulation were examined in rice (Oryza sativa L.) during vegetative growth. The results showed that the shoot biomass of the plants was greater at 27°C (high nighttime temperature, HNT) than at 22°C (CK). However, the increase in both shoot and root biomasses was not significant under 10 mg N/L. The shoot nitrogen concentrations were 16.1% and 16.7% higher in HNT than in CK under 160 and 40 mg N/L. These results suggest that plant N uptake was enhanced under HNT; however, the positive effect might be limited by the N status of the plants. In addition, leaf area, plant height, root maximum length, root and shoot nitrogen concentrations, soluble leaf protein content, and soluble leaf carbohydrate content were greater in HNT than in CK under 40 and 160 mg N/L, while fresh root volume, root number, and the content of free amino acid in leaf were not significantly different between HNT and CK regardless of nitrogen levels. Moreover, leaf GS activity under HNT was increased at 160 mg N/L compared with that under CK, which might partly explain the positive effect of HNT on soluble protein and carbohydrate content.
Design Feed Forward Neural Network to Solve Singular Boundary Value Problems
Authors: Tawfiq Luma N. M. , Hussein Ashraf A. T.
Published: August 2013

The aim of this paper is to design feed forward neural network for solving second-order singular boundary value problems in ordinary differential equations. The neural networks use the principle of back propagation with different training algorithms such as quasi-Newton, Levenberg-Marquardt, and Bayesian Regulation. Two examples are considered to show that effectiveness of using the network techniques for solving this type of equations. The convergence properties of the technique and accuracy of the interpolation technique are considered.
Mixed Convection Flow Adjacent to a Stretching Vertical Sheet in a Nanofluid
Authors: Yacob Nor Azizah , Ishak Anuar , Nazar Roslinda , Pop Ioan
Published: August 2013

The characteristics of fluid flow and heat transfer over a stretching vertical sheet immersed in a nanofluid are investigated numerically in this paper. Three different types of nanoparticles, namely, copper Cu, alumina Al2O3, and titania TiO2, are considered, using water as the base fluid. It is found that nanofluid with titania nanoparticles has better enhancement on the heat transfer rate compared to copper and alumina nanoparticles. For a particular nanoparticle, increasing the nanoparticle fraction is to reduce the skin friction coefficient and the heat transfer rate at the surface.
Etiology and Outcome of Patients with HIV Infection and Respiratory Failure Admitted to the Intensive Care Unit
Authors: Orsini Jose , Ahmad Noeen , Butala Ashvin , Flores Rosemarie , Tran Truc , Llosa Alfonso , Fishkin Edward
Published: August 2013

Background. Although access to HAART has prolonged survival and improved quality of life, HIV-infected patients with severe immunosuppression or comorbidities may develop complications that require critical care support. Our objective is to evaluate the etiology of respiratory failure in patients with HIV infection admitted to the ICU, its relationship with the T-lymphocytes cell count as well as the use of HAART, and its impact on outcome.Methods. A single-center, prospective, and observational study among all patients with HIV-infection and respiratory failure admitted to the ICU from December 1, 2011, to February 28, 2013, was conducted.Results. A total of 42 patients were admitted during the study period. Their median CD4cell count was 123 cells/μL (mean 205.7, range 2.0–694.0), with a median HIV viral load of 203.5 copies/mL (mean 58,676, range <20–367,649). At the time of admission, 23 patients (54.8%) were receiving HAART. Use of antiretroviral therapy at ICU admission was not associated with survival, but it was associated with higher CD4cell counts and lower HIV viral loads. Twenty-five patients (59.5%) had respiratory failure secondary to non-HIV-related diseases. Mechanical ventilation was required in 36 patients (85.1%). Thirteen patients (31.0%) died.Conclusions. Noninfectious etiologies of respiratory failure account for majority of HIV-infected patients admitted to ICU. Increased mortality was observed among patients with sepsis as etiology of respiratory failure (HIV related and non-AIDS related), in those receiving mechanical ventilation, and in patients with decreased CD4cell count. Survival was not associated with the use of HAART. Complementary studies are warranted to address the impact of HAART on outcomes of HIV-infected patients with respiratory failure admitted to ICU.
Class A -Lactamases as Versatile Scaffolds to Create Hybrid Enzymes: Applications from Basic Research to Medicine
Authors: Huynen Céline , Filée Patrice , Matagne André , Galleni Moreno , Dumoulin Mireille
Published: August 2013

Designing hybrid proteins is a major aspect of protein engineering and covers a very wide range of applications from basic research to medical applications. This review focuses on the use of class Aβ-lactamases as versatile scaffolds to design hybrid enzymes (referred to asβ-lactamase hybrid proteins, BHPs) in which an exogenous peptide, protein or fragment thereof is inserted at various permissive positions. We discuss how BHPs can be specifically designed to create bifunctional proteins, to produce and to characterize proteins that are otherwise difficult to express, to determine the epitope of specific antibodies, to generate antibodies against nonimmunogenic epitopes, and to better understand the structure/function relationship of proteins.
Longwall Mining Stability in Take-Off Phase
Authors: Prendes-Gero María-Belén , Alcalde-Gonzalo José , Ramírez-Oyanguren Pedro , Suárez-Domínguez Francisco-José , Álvarez-Fernández Martina-Inmaculada
Published: August 2013

Mechanised longwall mining is one of the more commonly employed exploitation methods in underground mines in the north of Spain as well as in the rest of the world. It is continuously changing and evolving, with new techniques, technology, equipment, and face management practices and systems appearing for the purposes of improving aspects such as operational and financial performances and, above all, the safety of the miners. Despite its importance, there are no regulations for the mining of longwall coal seams. This work aims to contribute to an advance in the design and optimisation of the roof support in longwall mining, analysing the stability of the roof using a method based on the resistance of materials, which considers the characteristics of the properties of the roof materials. The influence of not only the individual elements of support but also the coalface, which is considered one more supporting element, is investigated. The longitudinal and transverse spacings of the support and the number of walkways constituting the exploitation panel are analysed. The proposed formulation is validated by information gathered in a mine located in the region of Castilla-Leon.
A Rough Penalty Genetic Algorithm for Multicast Routing in Mobile Ad Hoc Networks
Authors: Lin Chih-Hao , Chuang Chia-Chun
Published: August 2013

Multicast routing is an effective way to transmit messages to multiple hosts in a network. However, it is vulnerable to intermittent connectivity property in mobile ad hoc network (MANET) especially for multimedia applications, which have some quality of service (QoS) requirements. The goal of QoS provisioning is to well organize network resources to satisfy the QoS requirement and achieve good network delivery services. However, there remains a challenge to provide QoS solutions and maintain end-to-end QoS with user mobility. In this paper, a novel penalty adjustment method based on the rough set theory is proposed to deal with path-delay constraints for multicast routing problems in MANETs. We formulate the problem as a constrained optimization problem, where the objective function is to minimize the total cost of the multicast tree subject to QoS constraints. The RPGA is evaluated on three multicast scenarios and compared with two state-of-the-art methods in terms of cost, success rate, and time complexity. The performance analyses show that this approach is a self-adaptive method for penalty adjustment. Remarkably, the method can address a variety of constrained multicast routing problems even though the initial routes do not satisfy all QoS requirements.
Viral Hepatitis Markers in Liver Tissue in Relation to Serostatus in Hepatocellular Carcinoma
Authors: Hernandez Brenda Y. , Zhu Xuemei , Kwee Sandi , Chan Owen T.M. , Tsai Naoky , Okimoto Gordon , Horio David , McGlynn Katherine A. , Altekruse Sean , Wong Linda L.
Published: August 2013

Background: Hepatocellular carcinoma (HCC) incidence is increasing in the United States. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of HCC. Hepatitis infection in patients with HCC is generally diagnosed by serology, which is not always consistent with the presence of HBV and HCV in the liver. The relationship of liver viral status to serostatus in hepatocarcinogenesis is not fully understood.

Methods: HBV and HCV were evaluated in formalin-fixed, paraffin-embedded liver tissue specimens in a retrospective study of 61 U.S. HCC cases of known serologic status. HBV DNA and HCV RNA were detected by PCR, reverse transcription PCR (RT-PCR), and pyrosequencing, and HBsAg and HBcAg were evaluated by immunohistochemistry.

Results: Viral markers were detected in the liver tissue of 25 of 61 (41%) HCC cases. Tissue viral and serologic status were discordant in 27 (44%) cases, including those with apparent “occult” infection. Specifically, HBV DNA was detected in tissue of 4 of 39 (10%) serum HBsAg (−) cases, including 1 anti-HCV(+) case; and HCV RNA was detected in tissue of 3 of 42 (7%) anti-HCV seronegative cases, including two with serologic evidence of HBV.

Conclusions: Viral hepatitis, including HBV-HCV coinfection, may be unrecognized in up to 17% of patients with HCC when based on serology alone. Further research is needed to understand the clinical significance of viral makers in liver tissue of patients with HCC in the absence of serologic indices.

Impact: The contribution of HBV and HCV to the increasing incidence of HCC in the United States may be underestimated. Cancer Epidemiol Biomarkers Prev; 22(11); 2016–23. ©2013 AACR.
Phase I Pharmacokinetic and Pharmacodynamic Study of the First-in-Class Spliceosome Inhibitor E7107 in Patients with Advanced Solid Tumors
Authors: Eskens Ferry A.L.M. , Ramos Francisco J. , Burger Herman , O'Brien James P. , Piera Adelaida , de Jonge Maja J.A. , Mizui Yoshiharu , Wiemer Erik A.C. , Carreras Maria Josepa , Baselga José , Tabernero Josep
Published: August 2013

Purpose: To assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of E7107 administered as 5-minute bolus infusions on days 1, 8, and 15 in a 28-day schedule.

Experimental Design: Patients with solid tumors refractory to standard therapies or with no standard treatment available were enrolled. Dose levels of 0.6 to 4.5 mg/m2 were explored.

Results: Forty patients [24M/16F, median age 61 years (45–79)] were enrolled. At 4.5 mg/m2, dose-limiting toxicity (DLT) consisted of grade 3 diarrhea, nausea, and vomiting and grade 4 diarrhea, respectively, in two patients. At 4.0 mg/m2, DLT (grade 3 nausea, vomiting, and abdominal cramps) was observed in one patient. Frequently occurring side effects were mainly gastrointestinal. After drug discontinuation at 4.0 mg/m2, one patient experienced reversible grade 4 blurred vision. The maximum tolerated dose (MTD) is 4.0 mg/m2. No complete or partial responses during treatment were observed; one patient at 4.0 mg/m2 had a confirmed partial response after drug discontinuation. Pharmacokinetic analysis revealed a large volume of distribution, high systemic clearance, and a plasma elimination half-life of 5.3 to 15.1 hours. Overall drug exposure increased in a dose-dependent manner. At the MTD, mRNA levels of selected target genes monitored in peripheral blood mononuclear cells showed a reversible 15- to 25-fold decrease, whereas unspliced pre-mRNA levels of DNAJB1 and EIF4A1 showed a reversible 10- to 25-fold increase.

Conclusion: The MTD for E7107 using this schedule is 4.0 mg/m2. Pharmacokinetics is dose-dependent and reproducible within patients. Pharmacodynamic analysis revealed dose-dependent reversible inhibition of pre-mRNA processing of target genes, confirming proof-of-principle activity of E7107. Clin Cancer Res; 19(22); 6296–304. ©2013 AACR.
Targeting CD73 Enhances the Antitumor Activity of Anti-PD-1 and Anti-CTLA-4 mAbs
Authors: Allard Bertrand , Pommey Sandra , Smyth Mark J. , Stagg John
Published: August 2013

Purpose: Monoclonal antibodies (mAb) that block programmed death (PD)-1 or cytotoxic T lymphocyte antigen (CTLA-4) receptors have been associated with durable clinical responses against a variety of cancer types and hold great potential as novel cancer therapeutics. Recent evidence suggest that targeted blockade of multiple immunosuppressive pathways can induce synergistic antitumor responses.

Experimental Design: In this study, we investigated whether targeted blockade of CD73, an ectonucleotidase that catabolizes the hydrolysis of extracellular adenosine monophosphate (AMP) to adenosine, can enhance the antitumor activity of anti-CTLA-4 and anti-PD-1 mAbs against transplanted and chemically induced mouse tumors.

Results: Anti-CD73 mAb significantly enhanced the activity of both anti-CTLA-4 and anti-PD-1 mAbs against MC38-OVA (colon) and RM-1 (prostate) subcutaneous tumors, and established metastatic 4T1.2 breast cancer. Anti-CD73 mAb also significantly enhanced the activity of anti-PD-1 mAb against 3-methylcholanthrene (MCA)-induced fibrosarcomas. Gene-targeted mice revealed that single-agent therapies and combinatorial treatments were dependent on host IFN-γ and CD8+ T cells, but independent of perforin. Interestingly, anti-CD73 mAb preferentially synergized with anti-PD-1 mAb. We investigated the effect of extracellular adenosine on tumor-infiltrating T cells and showed that activation of A2A adenosine receptor enhances PD-1 expression, but not CTLA-4 expression, on tumor-specific CD8+ T cells and CD4+ Foxp3+ T regulatory cells.

Conclusions: Taken together, our study revealed that targeted blockade of CD73 can enhance the therapeutic activity of anti-PD-1 and anti-CTLA-4 mAbs and may thus potentiate therapeutic strategies targeting immune checkpoint inhibitors in general. Clin Cancer Res; 19(20); 5626–35. ©2013 AACR.
A Phase I Study of an Agonist CD40 Monoclonal Antibody (CP-870,893) in Combination with Gemcitabine in Patients with Advanced Pancreatic Ductal Adenocarcinoma
Authors: Beatty Gregory L. , Torigian Drew A. , Chiorean E. Gabriela , Saboury Babak , Brothers Alex , Alavi Abass , Troxel Andrea B. , Sun Weijing , Teitelbaum Ursina R. , Vonderheide Robert H. , O'Dwyer Peter J.
Published: August 2013

Purpose: This phase I study investigated the maximum-tolerated dose (MTD), safety, pharmacodynamics, immunologic correlatives, and antitumor activity of CP-870,893, an agonist CD40 antibody, when administered in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDA).

Experimental Design: Twenty-two patients with chemotherapy-naïve advanced PDA were treated with 1,000 mg/m2 gemcitabine once weekly for three weeks with infusion of CP-870,893 at 0.1 or 0.2 mg/kg on day three of each 28-day cycle.

Results: CP-870,893 was well-tolerated; one dose-limiting toxicity (grade 4, cerebrovascular accident) occurred at the 0.2 mg/kg dose level, which was estimated as the MTD. The most common adverse event was cytokine release syndrome (grade 1 to 2). CP-870,893 infusion triggered immune activation marked by an increase in inflammatory cytokines, an increase in B-cell expression of costimulatory molecules, and a transient depletion of B cells. Four patients achieved a partial response (PR). 2-[18F]fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) showed more than 25% decrease in FDG uptake within primary pancreatic lesions in six of eight patients; however, responses observed in metastatic lesions were heterogeneous, with some lesions responding with complete loss of FDG uptake, whereas other lesions in the same patient failed to respond. Improved overall survival correlated with a decrease in FDG uptake in hepatic lesions (R = −0.929; P = 0.007).

Conclusions: CP-870,893 in combination with gemcitabine was well-tolerated and associated with antitumor activity in patients with PDA. Changes in FDG uptake detected on PET/CT imaging provide insight into therapeutic benefit. Phase II studies are warranted. Clin Cancer Res; 19(22); 6286–95. ©2013 AACR.
REM (Risk of Endometrial Malignancy): A Proposal for a New Scoring System to Evaluate Risk of Endometrial Malignancy
Authors: Angioli Roberto , Capriglione Stella , Aloisi Alessia , Luvero Daniela , Cafà Ester Valentina , Dugo Nella , Montera Roberto , De Cicco Nardone Carlo , Terranova Corrado , Plotti Francesco
Published: August 2013

Purpose: It is often difficult to distinguish a benign endometrial disease from a malignancy and tools to help the physician are needed to triage patients into high and low risk of endometrial cancer. The purpose of this study was to obtain a predictive model to assess the risk of endometrial malignancy (REM) in women with ultrasound endometrial abnormalities.

Experimental Design: Women, between ages 45 to 80 years, diagnosed through ultrasound with endometrial abnormalities and scheduled to have surgery were enrolled on a prospective study at the Department of Gynaecologic Oncology of Campus Bio-Medico, University of Rome. Preoperative clinical, ultrasound and laboratory characteristics were taken into account. Logistic regression algorithm was used to categorize patients into low- and high-risk groups for endometrial cancer.

Results: A total of 675 patients were considered for the analysis: 88 with endometrial cancer and 587 with benign endometrial disease. We divided the patients into two groups: training set (TS) and verification set (VS). Preoperative age, symptom, HE4 levels, and ultrasound endometrial thickness were found statistically significant, and were included into a multivariate logistic regression model to determine the probability to have endometrial cancer. In the TS, REM reported 93.3% sensitivity and 97.1% specificity [positive predictive value (PPV), 0.83; negative predictive value (NPV), 0.98; AUC, 0.957; 95% confidence interval (CI), 0.908–0.984]. In the VS, REM reported 89.3% sensitivity and 95.4% specificity (PPV, 0.73; NPV, 0.98; AUC, 0.919; 95% CI, 0.829–0.970).

Conclusions: Our data support the use of REM to triage patients into low- and high-risk groups for endometrial cancer, even if an external validation of the model is needed. Clin Cancer Res; 19(20); 5733–9. ©2013 AACR.
Anti-Genotoxic Potential of Bilirubin In Vivo: Damage to DNA in Hyperbilirubinemic Human and Animal Models
Authors: Wallner Marlies , Antl Nadja , Rittmannsberger Barbara , Schreidl Stephanie , Najafi Khatereh , Müllner Elisabeth , Mölzer Christine , Ferk Franziska , Knasmüller Siegfried , Marculescu Rodrig , Doberer Daniel , Poulsen Henrik E. , Vitek Libor , Bulmer Andrew C. , Wagner Karl-Heinz
Published: August 2013

The bile pigment bilirubin is a known antioxidant and is associated with protection from cancer and cardiovascular disease (CVD) when present in too strong concentrations. Unconjugated bilirubin (UCB) might also possess anti-genotoxic potential by preventing oxidative damage to DNA. Moderately elevated bilirubin levels are found in individuals with Gilbert syndrome and more severe in the hyperbilirubinemic Gunn rat model. This study was therefore aimed to assess the levels of oxidative damage to DNA in Gilbert syndrome subjects and Gunn rats compared to matched controls. Seventy-six individuals (age- and sex-matched) were allocated into Gilbert syndrome (UCB ≥17.1 μmol/L; n = 38) or control groups (UCB < 17.1 μmol/L; n = 38). In addition, 40 Gunn rats were used to support the results of the human trial. Single-cell gel electrophoresis (SCGE) assay measuring standard conditions (strand breaks, apurinic/apyrimidinic sites) and formamidopyrimidine glycosylase (FPG)-sensitive sites was conducted in human peripheral blood mononuclear cells (PBMC) and rat PBMCs, colon, and hepatocytes. Furthermore, urinary 8-oxo-2′-deoxyguanosine (8oxodGuo, DNA oxidation) and 8-oxo-guanosine (8oxoGuo, RNA oxidation) were measured in humans. The Gilbert syndrome and Gunn rat groups had significantly higher UCB levels (P < 0.001) than the corresponding controls. No further differences in damage to DNA or RNA were detected between the two groups, except higher strand breaks (PBMCs) in Gunn rats when compared with controls. However, when demographic effects were analyzed, lower 8oxodGuo concentrations were detected in the human group with a BMI ≥25 kg/m2 (1.70 ± 0.67 vs. 1.38 ± 0.43 nmol/mmol creatinine, P < 0.05), although this group showed lower UCB levels than normal weight subjects. This study suggests that the disease preventative effect of UCB is unrelated to DNA oxidation/strand breaks in human and animal models of hyperbilirubinaemia. Cancer Prev Res; 6(10); 1056–63. ©2013 AACR.