bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Factor VIII as a Risk Factor in Indian Patients with DVT
Authors: Hazra Darpanarayan , Sen Indrani , Stephen Edwin , Agarwal Sunil , Nair Sukesh Chandran , Mammen Joy
Published: September 2015

Introduction. Elevated factor VIII population in the Indian population has not been studied as a possible risk factor for deep vein thrombosis (DVT). High factor VIII level is considered a predisposing factor for DVT and its recurrence. However it is known to vary between populations and its exact role in the etiopathogenesis of thrombophilia remains unknown.Material and Methods. Factor VIII levels of patients with DVT who had undergone a prothrombotic workup as a part of their workup was compared to normal age matched controls in a 1 : 3 ratio.Results. There were 75 patients with DVT who had undergone a prothrombotic workup in the course of their treatment for lower limb DVT. In these, 64% had levels of factor VIII more than 150 as compared to 63% of normal controls (p>0.05, not significant).Conclusion. Elevated factor VIII in the Indians may not be associated with the same thrombotic risk as seen in the West. We find a variation in the levels of factor VIII with a different “normal” than what is reported in other populations. This needs further study to elucidate the role of factor VIII in the evaluation and treatment of thrombophilia.
An Approach for Prediction of Acute Hypotensive Episodes via the Hilbert-Huang Transform and Multiple Genetic Programming Classifier
Authors: Jiang Dazhi , Li Liyu , Hu Bo , Fan Zhun
Published: August 2015

Acute hypotensive episodes (AHEs) are one of the hemodynamic instabilities with high mortality rate that is frequent among many groups of patients. This study presents a methodology to predict AHE for ICU patients based on big data time series. The experimental data we used is mean arterial pressure (MAP), which is transformed from arterial blood pressure (ABP) data. Then, the Hilbert-Huang transform method was used to calculate patient's MAP time series and some features, which are the bandwidth of the amplitude modulation, the frequency modulation, and the power of intrinsic mode function (IMF), were extracted. Finally, the multiple genetic programming (Multi-GP) is used to build the classification models for detection of AHE. The methodology is applied in the datasets of the 10th PhysioNet and Computers Cardiology Challenge in 2009 and Multiparameter Intelligent Monitoring for Intensive Care (MIMIC-II). We achieve the accuracy of 83.33% in the training set and 91.89% in the testing set of the 2009 challenge's dataset and the 84.13% in the training set and 82.41% in the testing set of the MIMIC-II dataset.
Bilateral Coats’ Disease Combined with Retinopathy of Prematurity
Authors: Gursoy Huseyin , Erol Nazmiye , Bilgec Mustafa Deger , Basmak Hikmet , Kutlay Ozden , Aslan Huseyin
Published: August 2015

Purpose. To report a case of bilateral Coats’ disease combined with retinopathy of prematurity (ROP).Case. Retinal vascularization was complete in the right eye, whereas zone III, stage 3 ROP and preplus disease were observed in the left eye at 43 weeks of postmenstrual age (PMA) in a 31-week premature, 1200-g neonate. Intraretinal exudates developed and retinal hemorrhages increased in the left eye at 51 weeks of PMA. Diode laser photocoagulation (LP) was applied to the left eye. Exudates involved the macula, and telangiectatic changes developed one month following LP. Additional LP was applied to the left eye combined with intravitreal bevacizumab (IVB) injection at 55 weeks of PMA. Disease regressed one month after the additional therapy. At the 14-month examination of the baby, telangiectatic changes and intraretinal exudates were observed in the right eye. Diode LP was applied to the right eye combined with IVB injection. Exudates did not resolve completely, and cryotherapy was applied one month following LP. Retinal findings regressed three months following the cryotherapy.Conclusion. This is the first report of presumed bilateral Coats’ disease combined with ROP. If Coats’ disease could be diagnosed at early stages, it would be a disease associated with better prognosis.
IDUC: An Improved Distributed Unequal Clustering Protocol for Wireless Sensor Networks
Authors: Chen Chuanqing , Feng Li , Gu Xin , Yu Jiguo , Yu Dongxiao , Huang Baogui
Published: August 2015

Due to the imbalanced energy consumption among nodes in wireless sensor networks, some nodes die prematurely, which decreases the network lifetime. To solve this problem, existing clustering protocols usually construct unequal clusters by exploiting uneven competition radius. Taking their imperfection on designing the uneven competition radius and intercluster communication into consideration, this paper proposes an improved distributed unequal clustering protocol (IDUC) for wireless sensor networks, where nodes are energy heterogeneous and scattered unevenly. The cores of IDUC are the formation of unequal cluster topology and the construction of intercluster communication routing tree. Compared with previous protocols, IDUC is suitable for various network scenarios, and it can balance the energy consumption more efficiently and extend the lifetime of networks significantly.
Solitary Peripheral Osteoma of the Angle of the Mandible
Authors: Kshirsagar Kapil , Bhate Kalyani , Pawar Vivek , SanthoshKumar S. N. , Kheur Supriya , Dusane Shrikant
Published: September 2015

Solitary peripheral osteoma is a benign, slow-growing osteogenic tumor arising from craniofacial bones such as the sinus, temporal, or jaw bones but rarely originating from the mandible. Osteoma consists of compact or cancellous bone that may be of peripheral, central, or extraskeletal type. Peripheral osteoma arises from the periosteum and is commonly a unilateral, pedunculated mushroom-like mass. Solitary peripheral osteomas are characterized by well-defined, rounded, or oval radiopaque mass in the computed tomography. Although multiple osteomas of the jaws are a hallmark of Gardner’s syndrome (familial adenomatous polyposis), nonsyndromic cases are typically solitary. Herein, we report a rare case of solitary peripheral osteoma of the angle of the mandible in a 27-year-old female with clinical, radiologic, and histopathologic findings.
A Novel Pharmacological Method to Study the Chinese Medicinal Formula Hua-Zheng-Hui-Sheng-Dan
Authors: Cao Rui , Zhang Hong , Guo Jie , Liu Xiao-hui , Liu Chang , Zhu Cui-hong , Wu Xiong-zhi
Published: September 2015

Objectives. Hua-Zheng-Hui-Sheng-Dan (HZHSD) was used as an experimental model to explore research methods of large formulae in traditional Chinese medicine (TCM) using current molecular biology approaches.Materials and Methods. The trypan blue exclusion assay was used to determine cell viability and cell numbers. Flow cytometry was used to assess cell cycle distribution and apoptosis. The concentration of cyclin D1 was analyzed by enzyme-linked immunosorbent assay. The median effect principle was used in drug combination studies. An orthogonal experimental design was used to estimate the effects of each herb at different concentrations. The HeLa xenograft mouse model was used to compare the antitumor activity of drugs in vivo.Results. Among the 35 herbs that comprise HZHSD, Radix Rehmanniae Preparata (RRP),Caesalpinia sappan(CS),Evodia rutaecarpa(ER), Folium Artemisiae Argyi (FAA),Leonurus japonicusHoutt (LJH), Tumeric (Tu), Radix Paeoniae Alba (RPA), and Trogopterus Dung (TD) effectively inhibited the proliferation of HeLa and SKOV3 cells. Only RRR had an effect on HeLa and SKOV3 cell viability. According to the median effect principle,Angelica sinensis(Oliv.) (AS),Tabanus(Ta), and Pollen Typhae (PT), which were proven to have a significant synergistic inhibitory effect on the proliferation of HeLa cells, were added to the original eight positive herbs. The combination of RPA and AS had a synergistic effect on inducing cell cycle S phase arrest and decreasing intracellular cyclin D1 in HeLa cells. By orthogonal experimental design, LJH and Tu were considered unnecessary herbs. The small formula (SHZHSD) consisted of RPA, AS, RRR, Ta., TD, PT, ER, CS, and FAA and was able to inhibit cell proliferation and induce cell apoptosis. The antitumor effects of HZHSD and SHZHSD were also compared in vivo.Conclusions. Through molecular biology approaches both in vitro and in vivo, research into single drugs, and analysis using the median effect principle and orthogonal experimental design, the small formula (SHZHSD) was determined from the original formula (HZHSD). SHZHSD exhibited superior antitumor activity compared with the original formula both in vitro and in vivo.
A Genetic-Algorithm-Based Approach for Task Migration in Pervasive Clouds
Authors: Zhang Weishan , Tan Shouchao , Lu Qinghua , Liu Xin , Gong Wenjuan
Published: August 2015

Pervasive computing is converging with cloud computing which becomes pervasive cloud computing as an emerging computing paradigm. Users can run their applications or tasks in pervasive cloud environment in order to gain better execution efficiency and performance leveraging powerful computing and storage capacities of pervasive clouds through task migration. During task migration, there are possibly a number of conflicting objectives to be considered when making migration decisions, such as less energy consumption and quick response, in order to find an optimal migration path. In this paper, we propose a genetic algorithms- (GAs-) based approach which is effective in addressing multiobjective optimization problems. We have performed some preliminary evaluations of the proposed approach which shows quite promising results, using one of the classical genetic algorithms. The conclusion is that GAs can be used for decision making in task migrations in pervasive clouds.
Focused Ion Beam Assisted Interface Detection for Fabricating Functional Plasmonic Nanostructures
Authors: Wang Houxiao , Zhou Wei , Li Er Ping
Published: September 2015

Plasmonic nanoscale devices/structures have gained more attention from researchers due to their promising functions and/or applications. One important technical focus on this rapidly growing optical device technology is how to precisely control and fabricate nanostructures for different functions or applications (i.e., patterning end points should locate at/near the interface while fabricating these plasmonic nanostructures), which needs a systematic methodology for nanoscale machining, patterning, and fabrication when using the versatile nanoprecision tool focused ion beam (FIB), that is, the FIB‐assisted interface detection for fabricating functional plasmonic nanostructures. Accordingly, in this work, the FIB‐assisted interface detection was proposed and then successfully carried out using the sample‐absorbed current as the detection signal, and the real‐time patterning depth control for plasmonic structure fabrication was achieved via controlling machining time. Besides, quantitative models for the sample‐absorbed currents and the ion beam current were also established. In addition, some nanostructures for localized surface plasmon resonance biosensing applications were developed based on the proposed interface detection methodology for FIB nanofabrication of functional plasmonic nanostructures. It was shown that the achieved methodology can be conveniently used for real‐time control and precise fabrication of different functional plasmonic nanostructures with different geometries and dimensions.
Radiological Imaging for Assessing the Respectability of Hilar Cholangiocarcinoma: A Systematic Review and Meta-Analysis
Authors: Zhang Hongchen , Zhu Jian , Ke Fayong , Weng Mingzhe , Wu Xiangsong , Li Maolan , Quan Zhiwei , Liu Yingbin , Zhang Yong , Gong Wei
Published: September 2015

Hilar cholangiocarcinoma (HCC) remains one of the most difficult tumors to stage and treat. The aim of the study was to assess the diagnostic efficiency of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computer tomography (PET/CT) in evaluating the resectability of HCC. A systematic search was performed of the PubMed, EMBASE, and Cochrane databases. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated for individual studies and pooled data as well as test for heterogeneity and public bias. Our data showed that CT had the highest pooled sensitivity at 95% (95% CI: 91–97), whereas PET/CT had the highest pooled specificity at 81% (95% CI: 69–90). The area under the curve (AUC) of CT, MRI, and PET/CT was 0.9269, 0.9194, and 0.9218, respectively. In conclusion, CT is the most frequently used imaging modality to assess HCC resectability with a good sensitivity and specificity. MRI was generally comparable with that of CT and can be used as an alternative imaging technique. PET/CT appears to be the best technique in detecting lymph node and distant metastasis in HCC but has no clear role in helping to evaluate issues of local resectability.
Dynamic Euler-Bernoulli Beam Equation: Classification and Reductions
Authors: Naz R. , Mahomed F. M.
Published: August 2015

We study a dynamic fourth-order Euler-Bernoulli partial differential equation having a constant elastic modulus and area moment of inertia, a variable lineal mass densityg(x), and the applied load denoted byf(u), a function of transverse displacementu(t,x). The complete Lie group classification is obtained for different forms of the variable lineal mass densityg(x)and applied loadf(u). The equivalence transformations are constructed to simplify the determining equations for the symmetries. The principal algebra is one-dimensional and it extends to two- and three-dimensional algebras for an arbitrary applied load, general power-law, exponential, and log type of applied loads for different forms ofg(x). For the linear applied load case, we obtain an infinite-dimensional Lie algebra. We recover the Lie symmetry classification results discussed in the literature wheng(x)is constant with variable applied loadf(u). For the general power-law and exponential case the group invariant solutions are derived. The similarity transformations reduce the fourth-order partial differential equation to a fourth-order ordinary differential equation. For the power-law applied load case a compatible initial-boundary value problem for the clamped and free end beam cases is formulated. We deduce the fourth-order ordinary differential equation with appropriate initial and boundary conditions.
Toxic Markers of Matrine Determined Using1H-NMR-Based Metabolomics in Cultured CellsIn Vitroand RatsIn Vivo
Authors: Li Zhonghuang , Zheng Liang , Shi Jian , Zhang Guiyu , Lu Linlin , Zhu Lijun , Zhang Jiajie , Liu Zhongqiu
Published: August 2015

Matrine is one of the main bioactive alkaloids ofSophora flavescensAiton, which has been widely used to treat various diseases in China. These diseases include viral hepatitis, liver fibrosis, cardiac arrhythmia, skin diseases, and tumors. However, matrine is also the main toxic compound of this herb, and the available biomarkers are not reliable in detecting or quantifying matrine risk. Metabolomics is a powerful tool used to identify early toxicity biomarkers that are specific indicators of damage to biosystems. This study aimed to find the potential biomarkers of the matrine-induced toxic effects in rats and HepG2 cells. The toxicological effects of rats induced by matrine could be derived from the elevated taurine and trimethylamine N-oxide levels and the depletion in hippurate and tricarboxylic acid cycle intermediates, such as 2-oxoglutarate, citrate, and succinate in the urine. Cell metabolomics revealed that the levels of alanine, choline, glutathione, lactate, phosphocholine, and cholesterol showed dose-dependent decreases, whereas the levels of taurine, fatty acid, and unsaturated fatty acid showed dose-dependent increases. Overall, a significant perturbation of metabolites in response to high dose of matrine was observed bothin vivoandin vitro, and the selected metabolites particularly represent an attractive marker for matrine-induced toxicity.
Fuzzy Inference System Approach for Locating Series, Shunt, and Simultaneous Series-Shunt Faults in Double Circuit Transmission Lines
Authors: Swetapadma Aleena , Yadav Anamika
Published: August 2015

Many schemes are reported for shunt fault location estimation, but fault location estimation of series or open conductor faults has not been dealt with so far. The existing numerical relays only detect the open conductor (series) fault and give the indication of the faulty phase(s), but they are unable to locate the series fault. The repair crew needs to patrol the complete line to find the location of series fault. In this paper fuzzy based fault detection/classification and location schemes in time domain are proposed for both series faults, shunt faults, and simultaneous series and shunt faults. The fault simulation studies and fault location algorithm have been developed using Matlab/Simulink. Synchronized phasors of voltage and current signals of both the ends of the line have been used as input to the proposed fuzzy based fault location scheme. Percentage of error in location of series fault is within 1% and shunt fault is 5% for all the tested fault cases. Validation of percentage of error in location estimation is done using Chi square test with both 1% and 5% level of significance.
Investigations into Recycling Zinc from Used Metal Oxide Varistors via pH Selective Leaching: Characterization, Leaching, and Residue Analysis
Authors: Gutknecht Toni , Gustafsson Anna , Forsgren Christer , Ekberg Christian , Steenari Britt-Marie
Published: September 2015

Metal oxide varistors (MOVs) are a type of resistor with significantly nonlinear current‐voltage characteristics commonly used in power lines to protect against overvoltages. If a proper recycling plan is developed MOVs can be an excellent source of secondary zinc because they contain over 90 weight percent zinc oxide. The oxides of antimony, bismuth, and to a lesser degree cobalt, manganese, and nickel are also present in varistors. Characterization of the MOV showed that cobalt, nickel, and manganese were not present in the varistor material at concentrations greater than one weight percent. This investigation determined whether a pH selective dissolution (leaching) process can be utilized as a starting point for hydrometallurgical recycling of the zinc in MOVs. This investigation showed it was possible to selectively leach zinc from the MOV without coleaching of bismuth and antimony by selecting a suitable pH, mainly higher than 3 for acids investigated. It was not possible to leach zinc without coleaching of manganese, cobalt, and nickel. It can be concluded from results obtained with the acids used, acetic, hydrochloric, nitric, and sulfuric, that sulfate leaching produced the most desirable results with respect to zinc leaching and it is also used extensively in industrial zinc production.
A Case of Giant Cowper’s Gland Syringocele in an Adult Male Patient
Authors: Surana Santosh , Elshazly Mohamed , Allam Adel , Jayappa Sateesh , AlRefai Deena
Published: August 2015

Cowper’s gland syringocele is an uncommon, underdiagnosed cystic dilatation of Cowper’s gland ducts showing various radiological patterns. Herein we report a rare case of giant Cowper’s gland syringocele in an adult male patient, with description of MRI findings and management outcome.
Economic Analysis of Lagrangian and Genetic Algorithm for the Optimal Capacity Planning of Photovoltaic Generation
Authors: Ling Jeeng-Min , Liu Ping-Hsun
Published: September 2015

The optimal allocation problem for a stand-alone photovoltaic (SPV) generation can be achieved by good compromise between system objective and constraint requirements. The Lagrange technique (LGT) is a traditional method to solve such constrained optimization problem. To consider the nonlinear features of reliability constraints evolving from the consideration of different scenarios, including variations of component cost, load profile and installation location, the implementation of SPV generation planning is time-consuming and conventionally implemented by a probability method. Genetic Algorithm (GA) has been successfully applied to many optimization problems. For the optimal allocation of photovoltaic and battery devices, the cost function minimization is implemented by GA to attain global optimum with relative computation simplicity. Analytical comparisons between the results from LGT and GA were investigated and the performance of simulation was discussed. Different planning scenarios show that GA performs better than the Lagrange optimization technique.
A Dynamic Processing System for Sensor Data in IoT
Authors: Li Minbo , Liu Yanling , Cai Yuanfeng
Published: August 2015

With the development of the Internet of Things (IoT for short), innumerable Wireless Sensor Networks (WSNs) are deployed to capture the information of environmental status in the surrounding physical environment. The data from WSNs, called sensor data, are generated in high frequency. Similar to data of other open-loop applications, for example, network monitoring data, sensor data are heterogeneous, redundant, real-time, massive, and streaming. Hence, sensor data cannot be treated as the IoT business data, which brings complexity and difficulty to information sharing in the open-loop environment. This paper proposes a dynamic sensor data processing (SDP) system to capture and process sensor data continuously on the basis of data streaming technology. Particle Swarm Optimization (PSO) algorithm is employed to train threshold dynamically for data compression avoiding redundancy. With the help of rules setting, the proposed SDP is able to detect exception situations. Meanwhile, the storage models in SQL and NOSQL databases are analyzed and compared trying to seek an appropriate type of database for sensor data storage. The experimental results show that our SDP can compress sensor data through dynamically balancing the accuracy and compression rate and the model on NOSQL database has better performance than the model on SQL database.
Sex Differences in Immunology: More Severe Development of Experimental Pulmonary Hypertension in Male Rats Exposed to Vascular Endothelial Growth Factor Receptor Blockade
Authors: Guihaire Julien , Deuse Tobias , Wang Dong , Fadel Elie , Reichenspurner Hermann , Schrepfer Sonja
Published: September 2015

Background.The epidemiology of pulmonary hypertension (PH) is characterized by a female preponderance, whereas males share higher severity of the disease.Objective.To compare the severity of experimental PH between male and female athymic rats.Methods.PH was induced in 11 male and 11 female athymic rats (resp., SU_M and SU_F groups) using an inhibitor of VEGF-receptors I and II, semaxanib (40 mg/kg). After 28 days, right ventricular (RV) remodeling, systolic function, and hemodynamics were measured using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV myocardium were performed.Results.Four weeks after semaxanib injection, RV end-systolic pressure was higher in SU_M than in SU_F. Males developed marked RV enlargement and systolic dysfunction compared to females. Impairment of RV-PA coupling efficiency was observed only in SU_M. The smooth muscle cells of the pulmonary arteries switched from a contractile state to a dedifferentiated state only in males.Conclusions.Female athymic rats were protected against the development of severe PH. RV-PA coupling was preserved in females through limitation of pulmonary artery muscularization. Control of smooth muscle cells plasticity may be a promising therapeutic approach to reverse established vascular remodeling in PH patients.
Solving the Problem of Multiple-Criteria Building Design Decisions with respect to the Fire Safety of Occupants: An Approach Based on Probabilistic Modelling
Authors: Vaidogas Egidijus Rytas , Šakėnaitė Jurgita
Published: August 2015

The design of buildings may include a comparison of alternative architectural and structural solutions. They can be developed at different levels of design process. The alternative design solutions are compared and ranked by applying methods of multiple-criteria decision-making (MCDM). Each design is characterised by a number of criteria used in a MCDM problem. The paper discusses how to choose MCDM criteria expressing fire safety related to alternative designs. Probability of a successful evacuation of occupants from a building fire and difference between evacuation time and time to untenable conditions are suggested as the most important criteria related to fire safety. These two criteria are treated as uncertain quantities expressed by probability distributions. Monte Carlo simulation of fire and evacuation processes is natural means for an estimation of these distributions. The presence of uncertain criteria requires applying stochastic MCDM methods for ranking alternative designs. An application of the safety-related criteria is illustrated by an example which analyses three alternative architectural floor plans prepared for a reconstruction of a medical building. A MCDM method based on stochastic simulation is used to solve the example problem.
A Case of Delayed Interval Delivery with a Successful Hospital Move
Authors: Yodoshi Toshifumi , Tipton Elizabeth , Rouse Christopher A.
Published: August 2015

This report is the first case of delayed interval twin delivery in which the first infant and mother survived without major morbidity following transport to another facility. In addition, this case is only the second report of asynchronous delivery in which both twins survived and neither suffered any major morbidity. A 30-year-old G5P1031African American female with a diamniotic/dichorionic twin pregnancy presented to U.S. Naval Hospital Okinawa, Japan, at 22 + 5 weeks due to vaginal bleeding. At 23 + 2 weeks, Twin A was born secondary to advanced cervical dilation. Twin A’s birth weight was 650 g with APGAR scores of 6 (1 min) and 7 (5 min). Following delivery of Twin A, Placenta A was left in utero with high ligation of the umbilical cord. Due to a scheduled hospital move, the mother and Twin A were transported to the new facility at Camp Foster. Three weeks later, Twin B was delivered at 26 + 4 weeks. Twin B’s birth weight was 930 g with APGAR scores of 3 (1 min) and 7 (5 min). Both twins were discharged without IVH, PVL, ROP, or CLD. This case demonstrates the possibility of transporting both the mother and surviving infant A to a higher level of care prior to delivery of subsequent fetuses.
The Strategic Role of Nonbinding Communication
Authors: Palacio Luis A. , Cortés-Aguilar Alexandra , Muñoz-Herrera Manuel
Published: September 2015

This paper studies the conditions that improve bargaining power using threats and promises. We develop a model of strategic communication, based on theconflict game with perfect information, in which a noisycommitment messageis sent by a better-informed sender to a receiver who takes an action that determines the welfare of both. Our model captures different levels of aligned-preferences, for which classical games such asstag hunt,hawk-dove, andprisoner’s dilemmaare particular cases. We characterise the Bayesian perfect equilibrium with nonbinding messages undertruth-telling beliefsandsender’s bargaining powerassumptions. Through our equilibrium selection we show that the less conflict the game has, the more informative the equilibrium signal is and less credibility is necessary to implement it.
Clinical Epidemiology of Low-Grade and Dedifferentiated Osteosarcoma in Norway during 1975 and 2009
Authors: Berner Kjetil , Johannesen Tom Børge , Bruland Øyvind S.
Published: August 2015

Purpose. To describe epidemiological, clinical characteristics and treatment outcomes of low-grade osteosarcoma (LGOS), including dedifferentiated osteosarcoma (DLGOS).Method. We analysed a nationwide cohort comprised of patients with histologically verified LGOS and DLGOS between 1975 and 2009, based on registry sources supplemented with clinical records from hospitals involved in sarcoma management.Results. Fifty-four patients were identified, 12 of whom had DLGOS. The annual incidence for all patients was 0.3 per million, with the peak incidence in the third decade of the life. Fifteen patients experienced local relapses during follow-up and ten developed metastatic diseases, including three at primary diagnosis. Patients with DLGOS dominated the metastatic relapse group. The five-year sarcoma-specific survival rate was 91%, with no documented improvement over time. Free margin following surgical resection of the primary tumour had a positive impact on survival. As expected, both local relapse and metastasis during follow-up were associated with an unfavourable outcome. Radiotherapy predicted poor survival due to the selection of high-risk patients in need of such treatment. Neither higher age nor axial tumour localisation was adverse prognostic factors.Conclusion. LGOS has an excellent prognosis when surgically resected with a free margin; however, LGOS has the potential to dedifferentiate and metastasize with a poor outcome.
Laminar Wall Jet Flow and Heat Transfer over a Shallow Cavity
Authors: Maheandera Prabu P. , Padmanaban K. P.
Published: August 2015

This paper presents the detailed simulation of two‐dimensional incompressible laminar wall jet flow over a shallow cavity. The flow characteristics of wall jet with respect to aspect ratio (AR), step length (Xu), and Reynolds number (Re) of the shallow cavity are expressed. For higher accuracy, third‐order discretization is applied for momentum equation which is solved using QUICK scheme with SIMPLE algorithm for pressure‐velocity coupling. Low Reynolds numbers 25, 50, 100, 200, 400, and 600 are assigned for simulation. Results are presented for streamline contour, velocity contour, and vorticity formation at wall and also velocity profiles are reported. The detailed study of vortex formation on shallow cavity region is presented for various AR, Xu, and Re conditions which led to key findings as Re increases and vortex formation moves from leading edge to trailing edge of the wall. Distance between vortices increases when the step length (Xu) increases. When Re increases, the maximum temperature contour distributions take place in shallow cavity region and highest convection heat transfer is obtained in heated walls. The finite volume code (FLUENT) is used for solving Navier‐Stokes equations and GAMBIT for modeling and meshing.
Distributed Robust Attitude Tracking of Multiple Spacecraft with Disturbances and Unmodelled Dynamics
Authors: Yang Dapeng , Liu Xiangdong
Published: September 2015

This paper considers the distributed robust attitude tracking problem of multiple spacecraft subject to disturbances and unmodelled dynamics. We designed a distributed robust attitude controller for each spacecraft using the relative attitudes and relative angular velocities of neighbors to ensure that the attitude tracking errors between the leader and the followers converge to zero under the condition that the communication graph among the followers is undirected and connected and at least one follower has the access to the leader. The control algorithm achieves robust attitude tracking under the existence of the disturbances and unmodelled dynamics by selecting the control gains according to the given condition.
Leishmaniasis Panamensis Masquerading as Myiasis and Sporotrichosis: A Clinical Pitfall
Authors: Pavlidakey Peter G. , Huynh Thy , McKay Kristopher Michael , Sami Naveed
Published: August 2015

We report a case of cutaneous leishmaniasis panamensis in nonendemic Costa Rica. A 19-year-old female presented with nonhealing, unilateral eruption of erythematous papules with superficial central ulceration in a sporotrichoid pattern on right upper arm and back. Given the clinical picture and geographic locale, the patient was initially diagnosed with myiasis or human botfly infestation; however, the sporotrichoid pattern of the bites is an unlikely finding in myiasis. Peripheral blood smear, Giemsa stain, and polymerase chain reaction (PCR) were consistent forLeishmaniaspp. Ulceration resolved with 20-day course of IV sodium stibogluconate.
Dyons, Superstrings, and Wormholes: Exact Solutions of the Non-Abelian Dirac-Born-Infeld Action
Authors: Olszewski Edward A.
Published: August 2015

We construct dyon solutions on coincidentD4-branes, obtained by applyingT-duality transformations to type ISO(32)superstring theory in 10 dimensions. These solutions, which are exact, are obtained from an action comprising the non-Abelian Dirac-Born-Infeld action and a Wess-Zumino-like action. When one spatial dimension of theD4-branes is taken to be vanishingly small, the dyons are analogous to the ’t Hooft/Polyakov monopole residing in a3+1-dimensional spacetime, where the component of the Yang-Mills potential transforming as a Lorentz scalar is reinterpreted as a Higgs boson transforming in the adjoint representation of the gauge group. Applying aT-duality transformation to the vanishingly small spatial dimension, we obtain a collection ofD3-branes, not all of which are coincident. Two of theD3-branes, distinct from the others, acquire intrinsic, finite curvature and are connected by a wormhole. The dyons possess electric and magnetic charges whose values on eachD3-brane are the negative of one another. The gravitational effects, which arise after theT-duality transformation, occur despite the fact that the action of the system does not explicitly include the gravitational interaction. These solutions provide a simple example of the subtle relationship between the Yang-Mills and gravitational interactions, that is, gauge/gravity duality.
Affinity-Tuned ErbB2 or EGFR Chimeric Antigen Receptor T Cells Exhibit an Increased Therapeutic Index against Tumors in Mice
Authors: Liu Xiaojun , Jiang Shuguang , Fang Chongyun , Yang Shiyu , Olalere Devvora , Pequignot Edward C. , Cogdill Alexandria P. , Li Na , Ramones Melissa , Granda Brian , Zhou Li , Loew Andreas , Young Regina M. , June Carl H. , Zhao Yangbing
Published: September 2015

Target-mediated toxicity is a major limitation in the development of chimeric antigen T-cell receptors (CAR) for adoptive cell therapy of solid tumors. In this study, we developed a strategy to adjust the affinities of the scFv component of CAR to discriminate tumors overexpressing the target from normal tissues that express it at physiologic levels. A CAR-expressing T-cell panel was generated with target antigen affinities varying over three orders of magnitude. High-affinity cells recognized target expressed at any level, including at levels in normal cells that were undetectable by flow cytometry. Affinity-tuned cells exhibited robust antitumor efficacy similar to high-affinity cells, but spared normal cells expressing physiologic target levels. The use of affinity-tuned scFvs offers a strategy to empower wider use of CAR T cells against validated targets widely overexpressed on solid tumors, including those considered undruggable by this approach. Cancer Res; 75(17); 3596–607. ©2015 AACR.
Toxicity Attribution in Phase I Trials: Evaluating the Effect of Dose on the Frequency of Related and Unrelated Toxicities
Authors: Eaton Anne , Iasonos Alexia , Gounder Mrinal M. , Pamer Erika G. , Drilon Alexander , Vulih Diana , Smith Gary L. , Ivy S. Percy , Spriggs David R. , Hyman David M.
Published: September 2015

Purpose: Phase I studies rely on investigators to accurately attribute adverse events as related or unrelated to study drug. This information is ultimately used to help establish a safe dose. Attribution in the phase I setting has not been widely studied and assessing the accuracy of attribution is complicated by the lack of a gold standard. We examined dose–toxicity relationships as a function of attribution and toxicity category to evaluate for evidence of toxicity misattribution.

Experimental Design: Individual patient records from 38 phase I studies activated between 2000 and 2010 were used. Dose was defined as a percentage of maximum dose administered on each study. Relationships between dose and patient-level toxicity were explored graphically and with logistic regression. All P values were two-sided.

Results: 11,909 toxicities from 1,156 patients were analyzed. Unrelated toxicity was not associated with dose (P = 0.0920 for grade ≥3, P = 0.4194 for grade ≥1), whereas related toxicity increased with dose (P < 0.0001, both grade ≥3 and ≥1). Similar results were observed across toxicity categories. In the five-tier system, toxicities attributed as “possibly,” “probably,” or “definitely” related were associated with dose (all P < 0.0001), whereas toxicities attributed as “unlikely” or “unrelated” were not (all P > 0.1).

Conclusions: Reassuringly, we did not observe an association between unrelated toxicity rate and dose, an association that could only have been explained by physician misattribution. Our findings also confirmed our expectation that related toxicity rate increases with dose. Our analysis supports simplifying attribution to a two-tier system by collapsing “possibly,” “probably,” and “definitely” related. Clin Cancer Res; 22(3); 553–9. ©2015 AACR.

See related commentary by Sharma and Ratain, p. 527
Molecular Pathways: Anticancer Activity by Inhibition of Nucleocytoplasmic Shuttling
Authors: Conforti Fabio , Wang Yisong , Rodriguez Jose A. , Alberobello Anna Teresa , Zhang Yu-Wen , Giaccone Giuseppe
Published: September 2015

A dynamic distribution between nucleus and cytoplasm (nucleocytoplasmic shuttling) is one of the control mechanisms adapted by normal cells to regulate the activity of a variety of molecules. Growing evidence suggests that dysregulation of the nucleocytoplasmic shuttling is involved in promoting abnormal cell survival, tumor progression, and drug resistance, and is associated with poor cancer prognosis. Aberrant nucleocytoplasmic shuttling in cancer cells may result from a hyperactive status of diverse signal-transduction pathways, such as the PI3K–AKT and MAPK pathways, or from alterations in the general nuclear import/export machinery. Among the large number of molecules involved in the shuttling process, exportin XPO1, also known as chromosome region maintenance 1, appears to play a particularly prominent role in pathogenesis of both hematological malignancies and solid tumors. Given the importance of nucleocytoplasmic shuttling in cancer pathogenesis and the rapidly expanding knowledge in this field, attempts have been made to develop compounds able to revert the aberrant nucleocytoplasmic shuttling. A promising new drug, KPT-330 (Selinexor), which belongs to the class of XPO1 inhibitors called selective inhibitors of nuclear export, is now being tested in phase I/II clinical trials. Clin Cancer Res; 21(20); 4508–13. ©2015 AACR.
Indole-3-Carbinol Synergizes with and Restores Fludarabine Sensitivity in Chronic Lymphocytic Leukemia Cells Irrespective of p53 Activity and Treatment Resistances
Authors: Perez-Chacon Gema , Martinez-Laperche Carolina , Rebolleda Nerea , Somovilla-Crespo Beatriz , Muñoz-Calleja Cecilia , Buño Ismael , Zapata Juan M.
Published: September 2015

Purpose: Chronic lymphocytic leukemia (CLL) still is lacking a cure. Relapse and development of refractoriness to current treatments are common. New therapies are needed to improve patient prognosis and survival.

Experimental design: Indole-3-carbinol (I3C) is a natural product with antitumor properties already clinically tested. The effect of I3C, F-ara-A, and combinations of both drugs on CLL cells from patients representing different Rai stages, IGHV mutation status, cytogenetic alterations, p53 functionality, and treatment resistances was tested, as well as the toxicity of these treatments in mice.

Results: I3C induces cytotoxicity in CLL cells but not in normal lymphocytes. I3C strongly synergized with F-ara-A in all CLL cells tested, including those with p53 deficiency and/or F-ara-A resistance. The mechanism of cell death involved p53-dependent and -independent apoptosis. The combination of I3C + F-ara-A was equally effective in CLL cells irrespective of IGHV mutation stage and patient refractoriness. Moreover, CLL survival and treatment resistance induced by co-culturing CLL cells on stroma cells were overcome by the combinatory I3C + F-ara-A treatment. No toxicity was associated with the combined I3C + fludarabine treatment in mice.

Conclusions: I3C in combination with F-ara-A is highly cytotoxic in CLL cells from refractory patients and those with p53 deficiency. The striking dose reduction index for F-ara-A in combination with I3C would reduce fludarabine toxicity while having a similar or better anti-CLL effectiveness. Moreover, the low toxicity of I3C, already clinically tested, supports its use as adjuvant and combinatory therapy in CLL, particularly for patients with relapsed or refractory disease. Clin Cancer Res; 22(1); 134–45. ©2015 AACR.
Puerarin Suppresses the Self-Renewal of Murine Embryonic Stem Cells by Inhibition of REST-MiR-21 Regulatory Pathway
Authors: Yin Mengmeng , Yuan Yin , Cui Yurong , Hong Xian , Luo Hongyan , Hu Xinwu , Tang Ming , Hescheler Jurgen , Xi Jiaoya
Published: September 2015

Background/Aims: Puerarin shows a wide range of biological activities, including affecting the cardiac differentiation from murine embryonic stem (mES) cells. However, little is known about its effect and mechanism of action on the self-renewal of mES cells. This study aimed to determine the effect of puerarin on the self-renewal and pluripotency of mES cells and its underlying mechanisms. Methods: RT-PCR and real-time PCR were used to detect the transcripts of core transcription factors, specific markers for multiple lineages, REST and microRNA-21 (miR-21). Colony-forming assay was performed to estimate the self-renewal capacity of mES cells. Western blotting and wortmannin were employed to explore the role of PI3K/Akt signaling pathway in the inhibitory action of puerarin on REST transcript. Transfected mES cells with antagomir21 were used to confirm the role of miR-21 in the action of puerarin on cell self-renewal. Results: Puerarin significantly decreased the percentage of the self-renewal colonies, and suppressed the transcripts of Oct4, Nanog, Sox2, c-Myc and REST. Besides, PECAM, NCAM and miR-21 were up-regulated both under the self-renewal conditions and at day 4 of differentiation. The PI3K inhibitor wortmannin successfully reversed the mRNA expression changes of REST, Nanog and Sox2. Transfection of antagomir21 efficiently reversed the effects of puerarin on mES cells self-renewal. Conclusion: Inhibition of REST-miR-21 regulatory pathway may be the key mechanism of puerarin-induced suppression of mES cells self-renewal.
Obesity Modifies the Effect of Fitness on Heart Rate Indices during Exercise Stress Testing in Asymptomatic Individuals
Authors: Aneni Ehimen C. , Oni Ebenezer T. , Osondu Chukwuemeka U. , Martin Seth S. , Blaha Michael J. , Veledar Emir , Agatston Arthur S. , Feldman Theodore , Carvalho Jose A.M. , Conceição Raquel D. , Santos Raul D. , Nasir Khurram
Published: September 2015

Objective: To assess the impact of aerobic fitness on exercise heart rate (HR) indices in an asymptomatic cohort across different body mass index (BMI) categories. Methods: We performed a cross-sectional analysis of 506 working-class Brazilian subjects, free of known clinical cardiovascular disease (e.g. ischemic heart disease and stroke) who underwent an exercise stress test. Results: There was a significant trend towards decreased HR at peak exercise, HR recovery and chronotropic index (CI) measures as BMI increased, but resting HR increased significantly across BMI categories. In multivariate analysis, the change in CI per unit change in metabolic equivalents of task was greater among the obese subjects than the normal-weight (2.7 vs. -0.07; p interaction = 0.029) and overweight (2.7 vs. 0.7; p interaction = 0.044) subjects. A similar pattern was seen with peak HR and HR recovery, although the formal tests of interaction did not achieve statistical significance. Conclusion: Our findings strongly suggest that fitness is associated with a favorable HR profile and is modified by BMI. Intervention programs should place emphasis on fitness and not only on weight loss.
Toxicity Associated with Capecitabine in Patients Suffering from Dihydropyrimidine Dehydrogenase Deficiency
Authors: Bermejo-Pérez Maria José , Galeote-Miguel Ana Maria , Rodelo-Haad Luis Enrique , Alés-Díaz Inmaculada , Durán-Ogalla Gema , Benavides-Orgaz Manuel
Published: September 2015

Dihydropyrimidine dehydrogenase (DPD) is a metabolic enzyme that is crucial in 5-fluorouracil (5-FU) degradation. A deficiency in it is associated with the occurrence of adverse events following fluoropyrimidine-based therapies. We describe a case of toxicity grade 5 after the administration of capecitabine and oxaliplatin in a patient with stage III colorectal cancer and DPD congenital deficiency, which was identified later. Several polymorphisms have been associated with the global toxicity of 5-FU; however, genetic tests are low in sensitivity and therefore they cannot as yet be used as prescreening techniques in clinical practice.
Microparticles from Patients with the Acute Coronary Syndrome Impair Vasodilatation by Inhibiting the Akt/eNOS-Hsp90 Signaling Pathway
Authors: Han Wen-Qi , Chang Feng-Jun , Wang Qun-Rang , Pan Jun-Qiang
Published: September 2015

Objectives: Endothelial dysfunction is involved in the development of the acute coronary syndrome (ACS). Plasma microparticles (MPs) from other diseases have been demonstrated to initiate coagulation and endothelial dysfunction. However, whether MPs from ACS patients impair vasodilatation and endothelial function remains unclear. Methods: Patients (n = 62) with ACS and healthy controls (n = 30) were recruited for MP isolation. Rat thoracic aortas were incubated with MPs from ACS patients or healthy controls to determine the effects of MPs on endothelial-dependent vasodilatation, the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), the interaction of eNOS with heat shock protein 90 (Hsp90), and nitric oxide (NO) and superoxide anion (O2-) production. The origin of MPs was assessed by flow cytometry. Results: MP concentrations were increased in patients with ACS compared with healthy controls. They were positively correlated with the degree of coronary artery stenosis. MPs from ACS patients impair endothelial-dependent vasodilatation, decrease both Akt and eNOS phosphorylation, decrease the interaction between eNOS and Hsp90, and decrease NO production but increase O2- generation in rat thoracic aortas. Endothelial-derived MPs and platelet-derived MPs made up nearly 75% of MPs. Conclusions: Our data indicate that MPs from ACS patients negatively affect endothelial-dependent vasodilatation via Akt/eNOS-Hsp90 pathways.