bluuebunny/crossref_metadata_2025 huggingface dataset:
Epithelial Sodium Channel/Degenerin Family of Ion Channels: A Variety of Functions for a Shared Structure
Authors: Kellenberger Stephan , Schild Laurent
Published: July 2015

The recently discovered epithelial sodium channel (ENaC)/degenerin (DEG) gene family encodes sodium channels involved in various cell functions in metazoans. Subfamilies found in invertebrates or mammals are functionally distinct. The degenerins in Caenorhabditis elegansparticipate in mechanotransduction in neuronal cells, FaNaC in snails is a ligand-gated channel activated by neuropeptides, and the Drosophila subfamily is expressed in gonads and neurons. In mammals, ENaC mediates Na+transport in epithelia and is essential for sodium homeostasis. The ASIC genes encode proton-gated cation channels in both the central and peripheral nervous system that could be involved in pain transduction. This review summarizes the physiological roles of the different channels belonging to this family, their biophysical and pharmacological characteristics, and the emerging knowledge of their molecular structure. Although functionally different, the ENaC/DEG family members share functional domains that are involved in the control of channel activity and in the formation of the pore. The functional heterogeneity among the members of the ENaC/DEG channel family provides a unique opportunity to address the molecular basis of basic channel functions such as activation by ligands, mechanotransduction, ionic selectivity, or block by pharmacological ligands.
Free Radicals in the Physiological Control of Cell Function
Authors: Dröge Wulf
Published: July 2015

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, however, nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS) play an important role as regulatory mediators in signaling processes. Many of the ROS-mediated responses actually protect the cells against oxidative stress and reestablish “redox homeostasis.” Higher organisms, however, have evolved the use of NO and ROS also as signaling molecules for other physiological functions. These include regulation of vascular tone, monitoring of oxygen tension in the control of ventilation and erythropoietin production, and signal transduction from membrane receptors in various physiological processes. NO and ROS are typically generated in these cases by tightly regulated enzymes such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. In a given signaling protein, oxidative attack induces either a loss of function, a gain of function, or a switch to a different function. Excessive amounts of ROS may arise either from excessive stimulation of NAD(P)H oxidases or from less well-regulated sources such as the mitochondrial electron-transport chain. In mitochondria, ROS are generated as undesirable side products of the oxidative energy metabolism. An excessive and/or sustained increase in ROS production has been implicated in the pathogenesis of cancer, diabetes mellitus, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and other diseases. In addition, free radicals have been implicated in the mechanism of senescence. That the process of aging may result, at least in part, from radical-mediated oxidative damage was proposed more than 40 years ago by Harman ( J Gerontol 11: 298–300, 1956). There is growing evidence that aging involves, in addition, progressive changes in free radical-mediated regulatory processes that result in altered gene expression.
Aquaporins in the Kidney: From Molecules to Medicine
Authors: Nielsen Søren , Frøkiær Jørgen , Marples David , Kwon Tae-Hwan , Agre Peter , Knepper Mark A.
Published: July 2015

The discovery of aquaporin-1 (AQP1) answered the long-standing biophysical question of how water specifically crosses biological membranes. In the kidney, at least seven aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have demonstrated that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells, and AQP8 is present intracellularly at low abundance in proximal tubules and collecting duct principal cells, but the physiological function of these two channels remains undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. Body water balance is tightly regulated by vasopressin, and multiple studies now have underscored the essential roles of AQP2 in this. Vasopressin regulates acutely the water permeability of the kidney collecting duct by trafficking of AQP2 from intracellular vesicles to the apical plasma membrane. The long-term adaptational changes in body water balance are controlled in part by regulated changes in AQP2 and AQP3 expression levels. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting are seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy, and syndrome of inappropriate antidiuretic hormone secretion, both AQP2 expression levels and apical plasma membrane targetting are increased, suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.
The Transporter Associated With Antigen Processing: Function and Implications in Human Diseases
Authors: Lankat-Buttgereit Brigitte , Tampé Robert
Published: July 2015

The adaptive immune systems have evolved to protect the organism against pathogens encountering the host. Extracellular occurring viruses or bacteria are mainly bound by antibodies from the humoral branch of the immune response, whereas infected or malignant cells are identified and eliminated by the cellular immune system. To enable the recognition, proteins are cleaved into peptides in the cytosol and are presented on the cell surface by class I molecules of the major histocompatibility complex (MHC). The transport of the antigenic peptides into the lumen of the endoplasmic reticulum (ER) and loading onto the MHC class I molecules is an essential process for the presentation to cytotoxic T lymphocytes. The delivery of these peptides is performed by the transporter associated with antigen processing (TAP). TAP is a heterodimer of TAP1 and TAP2, each subunit containing transmembrane domains and an ATP-binding motif. Sequence homology analysis revealed that TAP belongs to the superfamily of ATP-binding cassette transporters. Loss of TAP function leads to a loss of cell surface expression of MHC class I molecules. This may be a strategy for tumors and virus-infected cells to escape immune surveillance. Structure and function of the TAP complex as well as the implications of loss or downregulation of TAP is the topic of this review.
Function and Genetics of Dystrophin and Dystrophin-Related Proteins in Muscle
Authors: Blake Derek J. , Weir Andrew , Newey Sarah E. , Davies Kay E.
Published: July 2015

The X-linked muscle-wasting disease Duchenne muscular dystrophy is caused by mutations in the gene encoding dystrophin. There is currently no effective treatment for the disease; however, the complex molecular pathology of this disorder is now being unravelled. Dystrophin is located at the muscle sarcolemma in a membrane-spanning protein complex that connects the cytoskeleton to the basal lamina. Mutations in many components of the dystrophin protein complex cause other forms of autosomally inherited muscular dystrophy, indicating the importance of this complex in normal muscle function. Although the precise function of dystrophin is unknown, the lack of protein causes membrane destabilization and the activation of multiple pathophysiological processes, many of which converge on alterations in intracellular calcium handling. Dystrophin is also the prototype of a family of dystrophin-related proteins, many of which are found in muscle. This family includes utrophin and α-dystrobrevin, which are involved in the maintenance of the neuromuscular junction architecture and in muscle homeostasis. New insights into the pathophysiology of dystrophic muscle, the identification of compensating proteins, and the discovery of new binding partners are paving the way for novel therapeutic strategies to treat this fatal muscle disease. This review discusses the role of the dystrophin complex and protein family in muscle and describes the physiological processes that are affected in Duchenne muscular dystrophy.
Annexins: From Structure to Function
Authors: Gerke Volker , Moss Stephen E.
Published: July 2015

Annexins are Ca2+and phospholipid binding proteins forming an evolutionary conserved multigene family with members of the family being expressed throughout animal and plant kingdoms. Structurally, annexins are characterized by a highly α-helical and tightly packed protein core domain considered to represent a Ca2+-regulated membrane binding module. Many of the annexin cores have been crystallized, and their molecular structures reveal interesting features that include the architecture of the annexin-type Ca2+binding sites and a central hydrophilic pore proposed to function as a Ca2+channel. In addition to the conserved core, all annexins contain a second principal domain. This domain, which NH2-terminally precedes the core, is unique for a given member of the family and most likely specifies individual annexin properties in vivo. Cellular and animal knock-out models as well as dominant-negative mutants have recently been established for a number of annexins, and the effects of such manipulations are strikingly different for different members of the family. At least for some annexins, it appears that they participate in the regulation of membrane organization and membrane traffic and the regulation of ion (Ca2+) currents across membranes or Ca2+concentrations within cells. Although annexins lack signal sequences for secretion, some members of the family have also been identified extracellularly where they can act as receptors for serum proteases on the endothelium as well as inhibitors of neutrophil migration and blood coagulation. Finally, deregulations in annexin expression and activity have been correlated with human diseases, e.g., in acute promyelocytic leukemia and the antiphospholipid antibody syndrome, and the term annexinopathies has been coined.
Linear Matrix Inequality Based Fuzzy Synchronization for Fractional Order Chaos
Authors: Wang Bin , Cao Hongbo , Wang Yuzhu , Zhu Delan
Published: July 2015

This paper investigates fuzzy synchronization for fractional order chaos via linear matrix inequality. Based on generalized Takagi-Sugeno fuzzy model, one efficient stability condition for fractional order chaos synchronization or antisynchronization is given. The fractional order stability condition is transformed into a set of linear matrix inequalities and the rigorous proof details are presented. Furthermore, through fractional order linear time-invariant (LTI) interval theory, the approach is developed for fractional order chaos synchronization regardless of the system with uncertain parameters. Three typical examples, including synchronization between an integer order three-dimensional (3D) chaos and a fractional order 3D chaos, anti-synchronization of two fractional order hyperchaos, and the synchronization between an integer order 3D chaos and a fractional order 4D chaos, are employed to verify the theoretical results.
Study on Load Characteristics of Underwater Explosion Using RKDG-LS-DGF and BEM
Authors: Wang Longkan , Chen Hailong , Ye Xi , Yao Xiongliang
Published: July 2015

This study numerically investigates the underwater explosion bubble dynamics during the process from detonation to bubble jet with a hybrid algorithm based on Runge Kutta Discontinuous Galerkin-Level Set-Direct Ghost Fluid method (RKDG-LS-DGF) and boundary element method (BEM). RKDG-LS-DGF method is used to simulate the physical process from the detonation of a column charge at one end to the formation of a nonspherical initial bubble and the process of bubble jet. And BEM is adopted to simulate bubble pulsing characteristics. In addition, the numerical results are compared with the experimental results to verify the feasibility of the numerical method. It is found that, during the detonation process of a column charge, the detonation product experiences a shape change from an initial ellipsoid into a sphere during expansion. After the detonation, the bubble experiences expansion and contraction and develops a jet. The jet threads through the bubble in the opposite direction to gravity and induces a high-pressure region. Subsequently, the pressure of this region decreases when the bubble reexpands after being penetrated by the jet. The numerical results agree well with the experimental data, which proves that axisymmetric RKDG-LS-DGF method and BEM are successfully combined to simulate the whole process of underwater explosion.
Effects of Surface Inclination on the Vertical Loading Rates and Landing Pattern during the First Attempt of Barefoot Running in Habitual Shod Runners
Authors: An W. , Rainbow M. J. , Cheung R. T. H.
Published: July 2015

Barefoot running has been proposed to reduce vertical loading rates, which is a risk factor of running injuries. Most of the previous studies evaluated runners on level surfaces. This study examined the effect of surface inclination on vertical loading rates and landing pattern during the first attempt of barefoot running among habitual shod runners. Twenty habitual shod runners were asked to run on treadmill at 8.0 km/h at three inclination angles (0°; +10°; −10°) with and without their usual running shoes. Vertical average rate (VALR) and instantaneous loading rate (VILR) were obtained by established methods. Landing pattern was decided using high-speed camera. VALR and VILR in shod condition were significantly higher (p<0.001) in declined than in level or inclined treadmill running, but not in barefoot condition (p>0.382). There was no difference (p>0.413) in the landing pattern among all surface inclinations. Only one runner demonstrated complete transition to non-heel strike landing in all slope conditions. Reducing heel strike ratio in barefoot running did not ensure a decrease in loading rates (p>0.15). Conversely, non-heel strike landing, regardless of footwear condition, would result in a softer landing (p<0.011).
Improvement of Analytical Methods for the Determination of Polyphenolic Bioactive Compounds in Berry Fruits
Authors: Caruso Marisa Carmela , Galgano Fernanda , Pecora Maria , Tolve Roberta , Verrastro Maria , Favati Fabio
Published: July 2015

Berry fruits contain high levels of different phytochemicals, most of which are phenolic molecules. Fruits of the same cultivar from different locations and different harvest years have different chemical compositions, particularly related to polyphenols. The difference may be due to specific climatic conditions, the type of soil in which the plants grow, and the stresses to which the plants were subjected because these phytochemicals are produced as a defense mechanism through a secondary metabolic process. For this reason, it is important to establish simple and reliable procedure to determine polyphenolic compounds in berry fruits considering the increasing attention on these compounds for different potential uses. In order to choose and to improve the most adequate analytical procedure for the determination of the polyphenolic substances in berry fruits, different methods were applied and compared on samples of elderberry and blackberry.
The Energy Conservation in Our Universe and the Pressureless Dark Energy
Authors: Chan Man Ho
Published: July 2015

Recent observations confirm that a certain amount of unknown dark energy exists in our universe so that the current expansion of our universe is accelerating. It is commonly believed that the pressure of the dark energy is negative and the
density of the dark energy is almost a constant throughout the universe expansion. In this paper, we show that the law of energy
conservation in our universe has to be modified because more vacuum energy is gained due to the universe expansion. As a result, the pressure of dark energy would be zero if the total energy of our universe is increasing. This pressureless dark energy model basically agrees with the current observational results.
An Exact Analytical Solution to Exponentially Tapered Piezoelectric Energy Harvester
Authors: Salmani H. , Rahimi G. H. , Hosseini Kordkheili S. A.
Published: July 2015

It has been proven that tapering the piezoelectric beam through its length optimizes the power extracted from vibration based energy harvesting. This phenomenon has been investigated by some researchers using semianalytical, finite element and experimental methods. In this paper, an exact analytical solution is presented to calculate the power generated from vibration of exponentially tapered unimorph and bimorph with series and parallel connections. The mass normalized mode shapes of the exponentially tapered piezoelectric beam with tip mass are implemented to transfer the proposed electromechanical coupled equations into modal coordinates. The steady states harmonic solution results are verified both numerically and experimentally. Results show that there exist values for tapering parameter and electric resistance in a way that the output power per mass of the energy harvester will be maximized. Moreover it is concluded that the electric resistance must be higher than a specified value for gaining more power by tapering the beam.
Effects of Oxygen Element and Oxygen-Containing Functional Groups on Surface Wettability of Coal Dust with Various Metamorphic Degrees Based on XPS Experiment
Authors: Zhou Gang , Xu Cuicui , Cheng Weimin , Zhang Qi , Nie Wen
Published: July 2015

To investigate the difference of surface oxygen element and oxygen-containing functional groups among coal dusts with different metamorphic degrees and their influence on surface wettability, a series of X-ray photoelectron spectroscopy experiments on 6 coal samples are carried out. The result demonstrates that the O/C ratio of coal surface shows an overall increasing trend compared with the result of its elements analysis. As the metamorphic degree increases, the O/C ratio on the surface gradually declines and the hydrophilic groups tend to fall off from coal surface. It could be found that different coals show different surface distributions of carboxyl and hydroxyl which are considered as the greatest promoter to the wettability of coal surface. With the change of metamorphic degree, the distribution of ether group is irregular while the carbonyl distribution keeps stable. In general, as the metamorphic degree goes higher, the content of oxygen-containing polar group tends to reduce. According to the measurement results, the contact angle is negatively related to the content of oxygen element, surface oxygen, and polar groups. In addition, compared with surface oxygen content, the content of oxygen-containing polar group serves as a more reasonable indicator of coal dust wettability.
Adaptive Sensing with Reliable Guarantee under White Gaussian Noise Channels of Sensor Networks
Authors: Long Jun , He An , Liu Anfeng , Chen Xue
Published: July 2015

Quality of sensing is a fundamental research topic in sensor networks. In this paper, we propose an adaptive sensing technique to guarantee the end-to-end reliability while maximizing the lifetime of sensor networks under additive white Gaussian noise channels. First, we conduct theoretical analysis to obtain optimal node numberN∗, node placementd∗, and node transmission structureP∗under minimum total energy consumption and minimum unit data transmission energy consumption. Then, because sensor nodes closer to the sink consume more energy, nodes far from the sink have more residual energy. Based on this observation, we propose an adaptive sensing technique to achieve balanced network energy consumption. It adopts lower reliability requirement and shorter transmission distance for nodes near the sink and adopts higher reliability requirement and farther transmission distance for nodes far from the sink. Theoretical analysis and experimental results show that our design can improve the network lifetime by several times (1–5 times) and network utility by 20% and the desired reliability level is also guaranteed.
Choledochal Cyst in Adults: Etiopathogenesis, Presentation, Management, and Outcome—Case Series and Review
Authors: Machado Norman Oneil , Chopra Pradeep J. , Al-Zadjali Adil , Younas Shahzad
Published: July 2015

Background. Choledochal cyst, a rare congenital cystic dilatation of biliary tree, is uncommon in adults. Their presentations differ from children and surgical management has evolved.Methods. A retrospective review of the records of all the patients above 15 years, who underwent therapeutic intervention in our hospital, was carried out.Results. Ten cases of choledochal cyst were found; 8 female, with mean age 31 years. These included 8 cases of Todani type I and one case each of type II and type III. The predominant symptoms were abdominal pain and jaundice. Abdominal mass and past history of cholangitis and pancreatitis were seen in 2 patients. Investigations included ultrasound in 8 patients, CT in 7, ERCP in 3, and MRCP in 5. Surgical intervention included complete excision of the cyst with hepaticojejunostomy and cholecystectomy (type I), excision of the diverticulum (type II), and ERCP sphincterotomy (type III). Malignancy was not seen in any patients. The long-term postoperative complications included cholangitis in two patients.Conclusion. Choledochal cyst is rare in adults. The typical triad of abdominal pain, jaundice, and mass is uncommon in adults. The surgical strategy aims for single stage complete excision of the cyst with hepaticojejunostomy.
Mesenchymal Stromal Cell Therapy in Ischemia/Reperfusion Injury
Authors: Rowart Pascal , Erpicum Pauline , Detry Olivier , Weekers Laurent , Grégoire Céline , Lechanteur Chantal , Briquet Alexandra , Beguin Yves , Krzesinski Jean-Marie , Jouret François
Published: July 2015

Ischemia/reperfusion injury (IRI) represents a worldwide public health issue of increasing incidence. IRI may virtually affect all organs and tissues and is associated with significant morbidity and mortality. Particularly, the duration of blood supply deprivation has been recognized as a critical factor in stroke, hemorrhagic shock, or myocardial infarction, as well as in solid organ transplantation (SOT). Pathophysiologically, IRI causes multiple cellular and tissular metabolic and architectural changes. Furthermore, the reperfusion of ischemic tissues induces both local and systemic inflammation. In the particular field of SOT, IRI is an unavoidable event, which conditions both short- and long-term outcomes of graft function and survival. Clinically, the treatment of patients with IRI mostly relies on supportive maneuvers since no specific target-oriented therapy has been validated thus far. In the present review, we summarize the current literature on mesenchymal stromal cells (MSC) and their potential use as cell therapy in IRI. MSC have demonstrated immunomodulatory, anti-inflammatory, and tissue repair properties in rodent studies and in preliminary clinical trials, which may open novel avenues in the management of IRI and SOT.
Short-Term Wind Speed Forecasting Study and Its Application Using a Hybrid Model Optimized by Cuckoo Search
Authors: Chen Xuejun , Jin Shiqiang , Qin Shanshan , Li Laping
Published: July 2015

The support vector regression (SVR) and neural network (NN) are both new tools from the artificial intelligence field, which have been successfully exploited to solve various problems especially for time series forecasting. However, traditional SVR and NN cannot accurately describe intricate time series with the characteristics of high volatility, nonstationarity, and nonlinearity, such as wind speed and electricity price time series. This study proposes an ensemble approach on the basis of 5-3 Hanning filter (5-3H) and wavelet denoising (WD) techniques, in conjunction with artificial intelligence optimization based SVR and NN model. So as to confirm the validity of the proposed model, two applicative case studies are conducted in terms of wind speed series from Gansu Province in China and electricity price from New South Wales in Australia. The computational results reveal that cuckoo search (CS) outperforms both PSO and GA with respect to convergence and global searching capacity, and the proposed CS-based hybrid model is effective and feasible in generating more reliable and skillful forecasts.
Cross-Platform Android/iOS-Based Smart Switch Control Middleware in a Digital Home
Authors: Jie Guo , Bo Cheng , Shuai Zhao , Junliang Chen
Published: July 2015

With technological and economic development, people’s lives have been improved substantially, especially their home environments. One of the key aspects of these improvements is home intellectualization, whose core is the smart home control system. Furthermore, as smart phones have become increasingly popular, we can use them to control the home system through Wi-Fi, Bluetooth, and GSM. This means that control with phones is more convenient and fast and now becomes the primary terminal controller in the smart home. In this paper, we propose middleware for developing a cross-platform Android/iOS-based solution for smart switch control software, focus on the Wi-Fi based communication protocols between the cellphone and the smart switch, achieved a plugin-based smart switch function, defined and implemented the JavaScript interface, and then implemented the cross-platform Android/iOS-based smart switch control software; also the scenarios are illustrated. Finally, tests were performed after the completed realization of the smart switch control system.
Endoscopic Management of Foreign Bodies in the Upper Gastrointestinal Tract of Adults
Authors: Yao Chih-Chien , Wu I-Ting , Lu Lung-Sheng , Lin Sheng-Chieh , Liang Chih-Ming , Kuo Yuan-Hung , Yang Shih-Cheng , Wu Cheng-Kun , Wang Hsing-Ming , Kuo Chung-Huang , Chiou Shue-Shian , Wu Keng-Liang , Chiu Yi-Chun , Chuah Seng-Kee , Tai Wei-Chen
Published: July 2015

Background. Foreign object ingestion and food bolus impaction are a common clinical problem. We report our clinical experiences in endoscopic management for adults, foreign body ingestion, and food bolus impaction.Method. A retrospective chart review study was conducted on adult patients with foreign body ingestion and food bolus impaction between January 2011 and November 2014. Patients with incomplete medical records were excluded.Results. A total of 198 patients (226 incidents) were included in the study (male/female: 1.54/1; age 57 ± 16 years). Among them, 168 foreign bodies were found successfully (74.3%). 75.6% of the foreign bodies were located in the esophagus. Food bolus impaction was most common (41.6%). 93.5% of foreign bodies in current study cohort were successfully extracted and 5 patients required surgical interventions. Comparisons between symptomatic and asymptomatic patients revealed that locations of foreign bodies in the pharynx and esophagus were the significant relevant factors (P<0.001). Shorter time taken to initiate endoscopic interventions increased detection rate (289.75 ± 465.94 versus 471.06 ± 659.93 minutes,P=0.028).Conclusion. Endoscopic management is a safe and highly effective procedure in extracting foreign body ingestion and food bolus impaction. Prompt endoscopic interventions can increase the chance of successful foreign bodies’ detection.
Strong Manual Acupuncture Manipulation Could Better Inhibit Spike Frequency of the Dorsal Horn Neurons in Rats with Acute Visceral Nociception
Authors: Hong Shouhai , Ding Shasha , Wu Fei , Xi Qiang , Li Qiang , Liu Yangyang , Zhou Tao , Qing Cai , Guo Yongming , Guo Yi
Published: July 2015

Afferent impulses from visceral nociception can be regulated by acupuncture at spinal cord level; however, the effects of different manual acupuncture (MA) manipulations on the afferent impulses are still unknown. Here, we analyzed the spike frequency of excitatory gastric-related wide dynamic range (WDR) neurons in spinal dorsal horn (SDH) following acute gastric distension (GD) in rats and compared their responses to MA manipulations with four different frequencies (0.5, 1, 2, and 3 Hz) at Zusanli (ST36). Results indicated that the spike frequency was increased by acute GD stimulation. Under acute GD circumstances, the spike frequency was further activated by weak MA stimulation (0.5 and 1 Hz), while being significantly inhibited by strong MA stimulation (2 and 3 Hz). After 10 minutes of the strong MA stimulation, same intensity of acute GD caused less spike frequency. Our previous researches had demonstrated that different MA manipulations could increase spike frequency in an intensity-dependent manner in normal rats; these findings suggest that acupuncture may have different modulatory effects depending on the state of the stomach. Since neuronal spike frequency was related to the level of nociception, the results suggest that strong MA manipulation may have better effect on acute visceral nociception.
Evaluating Adult’s Competency: Application of the Competency Assessment Process
Authors: Giroux Dominique , Tétreault Sylvie , Landry Marie-Pier
Published: July 2015

Competency assessment of adults with cognitive impairment or mental illness is a complex process that can have significant consequences for their rights. Some models put forth in the scientific literature have been proposed to guide health and social service professionals with this assessment process, but none of these appear to be complete. A new model, the Competency Assessment Process (CAP), was presented and validated in other studies. This paper adds to this corpus by presenting both the CAP model and the results of a survey given to health and social service professionals on its practical application in their clinical practice. The survey was administered to 35 participants trained in assessing competency following the CAP model. The results show that 40% of participants use the CAP to guide their assessment and the majority of those who do not yet use it plan to do so in the future. A large majority of participants consider this to be a relevant model and believe that all interdisciplinary teams should use it. These results support the relevance of the CAP model. Further research is planned to continue the study of the application of CAP in healthcare facilities.
Multiperiod Coordination Models of Coal-Electricity Supply Chain with Double Price Regulations
Authors: Peng Hongjun , Zhou Meihua , Wang Fudong
Published: July 2015

Using game models, we study multiperiod coordination contract and model of coal-electricity supply chain under the condition of double price regulations to alleviate the price conflicts of coal and electricity enterprises. The study reveals that, in boom seasons of coal demand, the multiperiod coordination mechanism may not only reduce the price of thermal coal but also increase the fulfillment rate of thermal coal. Meanwhile, the ordering quantity of thermal coal is increased and the shortage probability of electricity supply is decreased. Thereby, the conflicts between coal and electricity are also alleviated effectively.
Prediction of Pressing Quality for Press-Fit Assembly Based on Press-Fit Curve and Maximum Press-Mounting Force
Authors: You Bo , Lou Zhifeng , Luo Yi , Xu Yang , Wang Xiaodong
Published: July 2015

In order to predict pressing quality of precision press-fit assembly, press-fit curves and maximum press-mounting force of press-fit assemblies were investigated by finite element analysis (FEA). The analysis was based on a 3D Solidworks model using the real dimensions of the microparts and the subsequent FEA model that was built using ANSYS Workbench. The press-fit process could thus be simulated on the basis of static structure analysis. To verify the FEA results, experiments were carried out using a press-mounting apparatus. The results show that the press-fit curves obtained by FEA agree closely with the curves obtained using the experimental method. In addition, the maximum press-mounting force calculated by FEA agrees with that obtained by the experimental method, with the maximum deviation being 4.6%, a value that can be tolerated. The comparison shows that the press-fit curve and max press-mounting force calculated by FEA can be used for predicting the pressing quality during precision press-fit assembly.
Laryngeal Neuroendocrine Carcinomas: A Retrospective Study of 14 Cases
Authors: Zhu Yingying , Gao Liming , Meng Yunxiao , Diao Wenwen , Zhu Xiaoli , Li Guojun , Gao Zhiqiang , Chen Xingming
Published: July 2015

Laryngeal neuroendocrine carcinomas (LNECs) are rare and highly heterogeneous which present a wide spectrum of pathological and clinical manifestations. Fourteen patients with histologically demonstrated LNEC were collected and analyzed retrospectively. The 14 cases were classified into 3 subtypes: typical carcinoid in 2, atypical carcinoid in 5, and small cell neuroendocrine carcinoma in 7. The mean survival time of the 14 patients in this study was 112.5 months (95% CI, 81.5–143.6). Surgeries were performed for 2 patients of typical carcinoid, and they were alive with no evidence of recurrence after 24 and 47 months of follow-ups. Patients in the atypical carcinoid group were treated with surgeries and postoperative radiotherapy. After 58.4 months of follow-ups (range: 9–144), 2 patients showed no evidence of disease and 1 was lost to follow-up after 72 months. The other 2 patients died of other unrelated diseases. In the small cell neuroendocrine carcinoma group, a combination of chemotherapy and radiotherapy was applied. The mean survival time was 79.7 months (95% CI, 37.9–121.4), and the 5-year survival rate was 53.6%. In conclusion, the clinical behaviors, treatment protocols, and prognosis are different for each subtype of LNECs.
Expression of Prostacyclin‐Synthase in Human Breast Cancer: Negative Prognostic Factor and Protection against Cell Death In Vitro
Authors: Klein Thomas , Benders Jens , Roth Friederike , Baudler Monika , Siegle Isabel , Kömhoff Martin
Published: July 2015

Endogenously formed prostacyclin (PGI2) and synthetic PGI2 analogues have recently been shown to regulate cell survival in various cell lines. To elucidate the significance of PGI2 in human breast cancer, we performed immunohistochemistry to analyze expression of prostacyclin‐synthase (PGIS) in 248 human breast cancer specimens obtained from surgical pathology files. We examined patients’ 10‐year survival retrospectively by sending a questionnaire to their general practitioners and performed univariate analysis to determine whether PGIS expression correlated with patient survival. Lastly, the effects of PGI2 and its analogues on cell death were examined in a human breast cancer cell line (MCF‐7) and a human T‐cell leukemia cell line (CCRF‐CEM). PGIS expression was observed in tumor cells in 48.7% of samples and was associated with a statistically significant reduction in 10‐year survival (P = 0.038; n = 193). Transient transfection of PGIS into MCF‐7 cells exposed to sulindac increased cell viability by 50% and exposure to carbaprostacyclin protected against sulindac sulfone induced apoptosis in CCRF‐CEM cells.
Expression of PGIS is correlated with a reduced patient survival and protects against cell death in vitro, suggesting that PGIS is a potential therapeutic target in breast cancer.
Toll-Like Receptor 9 Inactivation Alleviated Atherosclerotic Progression and Inhibited Macrophage Polarized to M1 Phenotype in ApoE−/−Mice
Authors: Ma Chunmei , Ouyang Qiufang , Huang Ziyang , Chen Xiaoqing , Lin Ye , Hu Weiping , Lin Ling
Published: July 2015

Objective. Toll-like receptor 9 (TLR9) is involved in many inflammatory diseases, but its role in atherosclerosis remains controversial. This study aimed to investigate the role of TLR9 in atherosclerosis development and macrophage polarization.Methods. ApoE−/−mice were treated with vehicle or IRS869 for 12 weeks. Plaque vulnerability was assessed with immunohistochemical analysis, picro-sirius red, and oil red O staining. The expressions of M1- and M2-associated markers in plaques were detected by RT-PCR and immunofluorescence. The aorta TLR9 and its downstream molecules including myeloid differentiation protein 88 (MyD88), phosphorylated nuclear factor-kappa B (p-NF-κB), and interferon regulatory factor 7 (IRF7) were determined by western blot analysis. The frequency of M1 and M2 subtype in RAW264.7 cells treated with IRS869 and/or ODN1826 was evaluated with flow cytometry.Results. In ApoE−/−mice, functional inactivation of TLR9 pathway resulted in attenuated atherosclerosis development, as manifested by reduced plaque burden and by decreased plaque vulnerability. Mechanistically, TLR9 inhibition prevented the activation of MyD88/NF-κB pathway and shifted the balance of M1/M2 toward M2 macrophages that were involved.Conclusions. Our data indicated that TLR9 inactivation ameliorated atherosclerosis via skewing macrophage plasticity to M2 phenotype in ApoE-deficient mice. These findings may provide a promising therapeutic strategy for atherosclerosis.
MMP-2 and MMP-9 Activities and TIMP-1 and TIMP-2 Expression in the Prostatic Tissue of Two Ethanol-Preferring Rat Models
Authors: Fioruci-Fontanelli Beatriz Aparecida , Chuffa Luiz Gustavo A. , Mendes Leonardo O. , Pinheiro Patricia Fernanda F. , Delella Flávia Karina , Kurokawa Cilmery S. , Felisbino Sérgio Luis , Martinez Francisco Eduardo
Published: July 2015

We investigated whether chronic ethanol intake is capable of altering the MMP-2 and MMP-9 activities and TIMP-2 and TIMP-1 expression in the dorsal and lateral prostatic lobes of low (UChA) and high (UChB) ethanol-preferring rats. MMP-2 and MMP-9 activities and TIMP-1 and TIMP-2 expression were significantly reduced in the lateral prostatic lobe of the ethanol drinking animals. Dorsal prostatic lobe was less affected showing no significant alterations in these proteins, except for a reduction in the TIMP-1 expression in UChA rats. These important findings demonstrate that chronic ethanol intake impairs the physiological balance of the prostate extracellular matrix turnover, through downregulation of MMPs, which may contribute to the development of prostatic diseases. Furthermore, since these proteins are also components of prostate secretion, the negative impact of chronic ethanol intake on fertility may also involve reduction of MMPs and TIMPs in the seminal fluid.
Mesenchymal Stromal Cells Affect Disease Outcomes via Macrophage Polarization
Authors: Zheng Guoping , Ge Menghua , Qiu Guanguan , Shu Qiang , Xu Jianguo
Published: July 2015

Mesenchymal stromal cells (MSCs) are multipotent and self-renewable cells that reside in almost all postnatal tissues. In recent years, many studies have reported the effect of MSCs on the innate and adaptive immune systems. MSCs regulate the proliferation, activation, and effector function of T lymphocytes, professional antigen presenting cells (dendritic cells, macrophages, and B lymphocytes), and NK cells via direct cell-to-cell contact or production of soluble factors including indoleamine 2,3-dioxygenase, prostaglandin E2, tumor necrosis factor-αstimulated gene/protein 6, nitric oxide, and IL-10. MSCs are also able to reprogram macrophages from a proinflammatory M1 phenotype toward an anti-inflammatory M2 phenotype capable of regulating immune response. Because of their capacity for differentiation and immunomodulation, MSCs have been used in many preclinical and clinical studies as possible new therapeutic agents for the treatment of autoimmune, degenerative, and inflammatory diseases. In this review, we discuss the central role of MSCs in macrophage polarization and outcomes of diseases such as wound healing, brain/spinal cord injuries, and diseases of heart, lung, and kidney in animal models.
The Association between Leisure Time Physical Activity and Pancreatic Cancer Risk in Adults: A Systematic Review and Meta-analysis
Authors: Farris Megan S. , Mosli Mohammed H. , McFadden Alison A. , Friedenreich Christine M. , Brenner Darren R.
Published: July 2015

We conducted a meta-analysis of the association between leisure time physical activity (LTPA) and risk of pancreatic cancer to update previous analyses in light of newly published studies, to examine subgroups of interest and potential sources of heterogeneity. We searched the PubMed and MEDLINE databases for studies until February 2015. Study information was collected using a standardized form to abstract relevant data on study design, number of cases, participant and study characteristics, assessment of LTPA, risk estimates, and adjustments for confounding by two independent abstractors. We used random-effects models to pool estimates from included studies of lowest versus highest comparison of LTPA. The search identified 26 studies eligible for inclusion into the meta-analysis. The combined summary risk estimate was [relative risk (RR), 0.89; 95% confidence interval (CI), 0.82–0.96]. There was evidence of heterogeneity across studies (I2 = 22.1%, Pheterogeneity = 0.130). Some of the heterogeneity could be explained by study design, with stronger protective effects observed among case–control studies (RR, 0.69; 95% CI, 0.59–0.81) compared with cohort studies (RR, 0.96; 95% CI, 0.91–1.02). Across study designs, age of population was a source of heterogeneity, with stronger effects observed among younger (<50 years) populations. The present meta-analysis supports a protective association between LTPA and pancreatic cancer with an 11% risk reduction observed. LTPA appears to have the strongest effect among young populations. Additional investigations are needed to provide insights regarding the impact of LTPA in healthy adult populations, to reduce the risk of pancreatic cancer and encourage increases in LTPA. Cancer Epidemiol Biomarkers Prev; 24(10); 1462–73. ©2015 AACR.
Nanotechnology: Future of Oncotherapy
Authors: Gharpure Kshipra M. , Wu Sherry Y. , Li Chun , Lopez-Berestein Gabriel , Sood Anil K.
Published: July 2015

Recent advances in nanotechnology have established its importance in several areas including medicine. The myriad of applications in oncology range from detection and diagnosis to drug delivery and treatment. Although nanotechnology has attracted a lot of attention, the practical application of nanotechnology to clinical cancer care is still in its infancy. This review summarizes the role that nanotechnology has played in improving cancer therapy, its potential for affecting all aspects of cancer care, and the challenges that must be overcome to realize its full promise. Clin Cancer Res; 21(14); 3121–30. ©2015 AACR.
A Phase I/II Study for Analytic Validation of 89Zr-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer
Authors: Pandit-Taskar Neeta , O'Donoghue Joseph A. , Durack Jeremy C. , Lyashchenko Serge K. , Cheal Sarah M. , Beylergil Volkan , Lefkowitz Robert A. , Carrasquillo Jorge A. , Martinez Danny F. , Fung Alex Mak , Solomon Stephen B. , Gönen Mithat , Heller Glenn , Loda Massimo , Nanus David M. , Tagawa Scott T. , Feldman Jarett L. , Osborne Joseph R. , Lewis Jason S. , Reuter Victor E. , Weber Wolfgang A. , Bander Neil H. , Scher Howard I. , Larson Steven M. , Morris Michael J.
Published: July 2015

Purpose: Standard imaging for assessing osseous metastases in advanced prostate cancer remains focused on altered bone metabolism and is inadequate for diagnostic, prognostic, or predictive purposes. We performed a first-in-human phase I/II study of 89Zr-DFO-huJ591 (89Zr-J591) PET/CT immunoscintigraphy to assess performance characteristics for detecting metastases compared with conventional imaging modalities (CIM) and pathology.

Experimental Design: Fifty patients with progressive metastatic castration-resistant prostate cancers were injected with 5 mCi of 89Zr-J591. Whole-body PET/CT scans were obtained, and images were analyzed for tumor visualization. Comparison was made to contemporaneously obtained bone scintigraphy and cross-sectional imaging on a lesion-by-lesion basis and with biopsies of metastatic sites.

Results: Median standardized uptake value for 89Zr-J591–positive bone lesions (n = 491) was 8.9 and for soft-tissue lesions (n = 90), it was 4.8 (P < 0.00003). 89Zr-J591 detected 491 osseous sites compared with 339 by MDP and 90 soft-tissue lesions compared with 124 by computed tomography (CT). Compared with all CIMs combined, 89Zr-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone and 25 soft tissue) were biopsied in 34 patients; 18 of 19 89Zr-J591–positive osseous sites and 14 of 16 89Zr-J591–positive soft tissue sites were positive for prostate cancer. The overall accuracy of 89Zr-J591 was 95.2% (20 of 21) for osseous lesions and 60% (15 of 25) for soft-tissue lesions.

Conclusions: 89Zr-J591 imaging demonstrated superior targeting of bone lesions relative to CIMs. Targeting soft-tissue lesions was less optimal, although 89Zr-J591 had similar accuracy as individual CIMs. This study will provide benchmark data for comparing performance of proposed prostate-specific membrane antigen (PSMA) targeting agents for prostate cancer. Clin Cancer Res; 21(23); 5277–85. ©2015 AACR.
Lipopolysaccharide-Induced Preconditioning Attenuates Apoptosis and Differentially Regulates TLR4 and TLR7 Gene Expression after Ischemia in the Preterm Ovine Fetal Brain
Authors: Dhillon Simerdeep K. , Gunn Alistair J. , Jung Yewon , Mathai Sam , Bennet Laura , Fraser Mhoyra
Published: July 2015

Acute exposure to subclinical infection modulates subsequent hypoxia-ischemia (HI) injury in a time-dependent manner, likely by cross-talk through Toll-like receptors (TLRs), but the specific pathways are unclear in the preterm-equivalent brain. In the present study, we tested the hypothesis that repeated low-dose exposure to lipopolysaccharide (LPS) before acute ischemia would be associated with induction of specific TLRs that are potentially neuroprotective. Fetal sheep at 0.65 gestation (term is ∼145 days) received intravenous boluses of low-dose LPS for 5 days (day 1, 50 ng/kg; days 2-5, 100 ng/kg) or the same volume of saline. Either 4 or 24 h after the last bolus of LPS, complete carotid occlusion was induced for 22 min. Five days after LPS, brains were collected. Pretreatment with LPS for 5 days decreased cellular apoptosis, microglial activation and reactive astrogliosis in response to HI injury induced 24 but not 4 h after the last dose of LPS. This was associated with upregulation of TLR4, TLR7 and IFN-β mRNA, and increased fetal plasma IFN-β concentrations. The association of reduced white matter apoptosis and astrogliosis after repeated low-dose LPS finishing 24 h but not 4 h before cerebral ischemia, with central and peripheral induction of IFN-β, suggests the possibility that IFN-β may be an important mediator of endogenous neuroprotection in the developing brain.