bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomics of elite sporting performance: what little we know and necessary advances
Authors: Pitsiladis Yannis , Wang Guan , Wolfarth Bernd , Scott Robert , Fuku Noriyuki , Mikami Eri , He Zihong , Fiuza-Luces Carmen , Eynon Nir , Lucia Alejandro
Published: May 2013

Numerous reports of genetic associations with performance-related phenotypes have been published over the past three decades but there has been limited progress in discovering and characterising the genetic contribution to elite/world-class performance, mainly owing to few coordinated research efforts involving major funding initiatives/consortia and the use primarily of the candidate gene analysis approach. It is timely that exercise genomics research has moved into a new era utilising well-phenotyped, large cohorts and genome-wide technologies—approaches that have begun to elucidate the genetic basis of other complex traits/diseases. This review summarises the most recent and significant findings from sports genetics and explores future trends and possibilities.
Effect of ambient temperature during acute aerobic exercise on short-term appetite, energy intake, and plasma acylated ghrelin in recreationally active males
Authors: Wasse Lucy K. , King James A. , Stensel David J. , Sunderland Caroline
Published: May 2013

Ambient temperature during exercise may affect energy intake regulation. Compared with a temperate (20 °C) environment, 1 h of running followed by 6 h of rest tended to decrease energy intake from 2 ad libitum meals in a hot (30 °C) environment but increase energy intake in a cool (10 °C) environment (p = 0.08). Core temperature changes did not appear to mediate this trend; whether acylated ghrelin is involved is unclear. Further research is warranted to clarify these findings.
A simple method for the detection of Leptolegnia chapmanii from infected Aedes aegypti larvae
Authors: Leles Renan N. , López Lastra Cláudia C. , García Juan J. , Fernandes Éverton K.K. , Luz Christian
Published: May 2013

Significant progress in developing Leptolegnia chapmanii as a biological control agent against mosquitoes will be accelerated by improved and simpler methods to detect and to isolate this virulent and rapidly lethal watermold from field-collected mosquito larvae. To date, however, this oomycete has remained understudied and little used. This study presents a simplified method to detect Leptolegnia in infected Aedes aegypti larvae. The development of L. chapmanii inside mosquitoes is easily monitored when pathogen-treated larvae are quasi-immobilized for an initial 48 h in the water film on plates of water agar amended with antibiotic (chloramphenicol, 0.5–1 g/L) and fungicide (thiabendazole, 4–8 g/L) and then transferred to a larger volume of water for an additional 48 h. Surprisingly, chloramphenicol stimulated oosporogenesis by L. chapmanii. The method permits processing of large numbers of A. aegypti and other culicid larvae and is useful for both obtaining new strains and also monitoring the efficacy of L. chapmanii during field tests.
Nonstandard fractional exponential Lagrangians, fractional geodesic equation, complex general relativity, and discrete gravity
Authors: El-Nabulsi R.A.
Published: May 2013

Nonstandard Lagrangians are generating functions of different equations of motion. They have gained increasing importance in many different fields. In fact, nonstandard Lagrangians date back to 1978, when Arnold entitled them “non-natural” in his classic book, Mathematical Methods of Classical Mechanics (Springer, New York. 1978). In applied mathematics, most dynamical equations can be obtained by using generating Lagrangian functions (e.g., power-law and exponential Lagrangians), which has been shown by mathematicians, who have also demonstrated that there is an infinite number of such functions. Besides this interesting field, the topic of fractional calculus of variations has gained growing importance because of its wide application in different fields of science. In this paper, we generalize the fractional actionlike variational approach for the case of a nonstandard exponential Lagrangian. To appreciate this new approach, we explore some of its main consequences in Einstein’s general relativity. Some results are revealed and discussed accordingly mainly the transition from general relativity to complex relativity and emergence of a discrete gravitational coupling constant.
Elevated dopamine D2 receptor in prefrontal cortex of CUMS rats is associated with downregulated cAMP-independent signaling pathway
Authors: Chen Cheng , Yang Jing-mo , Hu Ting-ting , Xu Ting-juan , Xu Wei-ping , Wei Wei
Published: May 2013

Because depression is associated with significant morbidity and functional disability, it is important to reveal the mechanism of action. A variety of studies have suggested the involvement of dopaminergic receptors in the pathophysiological mechanism of non-stress-associated depression-like behavior in rodents. Nevertheless, controversy exists about whether chronic stress acts on dopaminergic receptors in the prefrontal cortex. Thus, we investigated the level of dopamine D2 receptors (DRD2) and the possible mechanisms involved in a chronic unpredictable mild stress (CUMS) rat model of depression. The results showed CUMS-induced, depression-like symptoms in the rat, characterized by reduced sucrose consumption and body mass, and increased duration of immobility in a forced swimming test. Moreover, chronic stress upregulated the expression of DRD2 but downregulated protein kinase A (PKA), transcription factor cAMP response element binding protein (CREB), and phospho-CREB (p-CREB) in the prefrontal cortex, as demonstrated by Western blot. Notably, in the rat model of depression, decreased cyclic adenine monophosphate (cAMP) levels and PKA activity were present at the same time, which is consistent with clinical findings in depressed patients. Our findings suggested that dopaminergic system dysfunction could play a central role in stress-related disorders such as depression.
Asynchronous gossip
Authors: Georgiou Chryssis , Gilbert Seth , Guerraoui Rachid , Kowalski Dariusz R.
Published: May 2013

We study the complexity of
gossip
in an asynchronous, message-passing fault-prone distributed system. We show that an
adaptive
adversary can significantly hamper the spreading of a rumor, while an
oblivious
adversary cannot. The algorithmic techniques proposed in this article can be used for improving the message complexity of distributed algorithms that rely on an all-to-all message exchange paradigm and are designed for an asynchronous environment. As an example, we show how to improve the message complexity of asynchronous randomized consensus.
Efficient generalized Hessenberg form and applications
Authors: Bosner Nela , Bujanović Zvonimir , Drmač Zlatko
Published: May 2013

This article proposes an efficient algorithm for reducing matrices to generalized Hessenberg form by unitary similarity, and recommends using it as a preprocessor in a variety of applications. To illustrate its usefulness, two cases from control theory are analyzed in detail: a solution procedure for a sequence of shifted linear systems with multiple right hand sides (e.g. evaluating the transfer function of a MIMO LTI dynamical system at many points) and computation of the staircase form. The proposed algorithm for the generalized Hessenberg reduction uses two levels of aggregation of Householder reflectors, thus allowing efficient BLAS 3-based computation. Another level of aggregation is introduced when solving many shifted systems by processing the shifts in batches. Numerical experiments confirm that the proposed methods have superior efficiency.
Algorithm 928
Authors: Rios Joseph
Published: May 2013

Dantzig--Wolfe Decomposition is recognized as a powerful, algorithmic tool for solving linear programs of block-angular form. While use of the approach has been reported in a wide variety of domains, there has not been a general implementation of Dantzig--Wolfe decomposition available. This article describes an open-source implementation of the algorithm. It is general in the sense that any properly decomposed linear program can be provided to the software for solving. While the original description of the algorithm was motivated by its reduced memory usage, modern computers can also take advantage of the algorithm's inherent parallelism. This implementation is parallel and built upon the POSIX threads (pthreads) library. Some computational results are provided to motivate use of such parallel solvers, as this implementation outperforms state-of-the-art commercial solvers in terms of wall-clock runtime by an order of magnitude or more on several problem instances.
A throughput optimal algorithm for map task scheduling in mapreduce with data locality
Authors: Wang Weina , Zhu Kai , Ying Lei , Tan Jian , Zhang Li
Published: May 2013

MapReduce/Hadoop framework has been widely used to process large-scale datasets on computing clusters. Scheduling map tasks to improve data locality is crucial to the performance of MapReduce. Many works have been devoted to increasing data locality for better efficiency. However, to the best of our knowledge, fundamental limits of MapReduce computing clusters with data locality, including the capacity region and throughput optimal algorithms, have not been studied. In this paper, we address these problems from a stochastic network perspective. Our focus is to strike the right balance between data-locality and load-balancing to maximize throughput. We present a new queueing architecture and propose a map task scheduling algorithm constituted by the Join the Shortest Queue policy together with the MaxWeight policy. We identify an outer bound on the capacity region, and then prove that the proposed algorithm can stabilize any arrival rate vector strictly within this outer bound. It shows that the algorithm is throughput optimal and the outer bound coincides with the actual capacity region. The proofs in this paper deal with random processing time with different parameters and nonpreemptive tasks, which differentiate our work from many other works, so the proof technique itself is also a contribution of this paper.
Modelling exogenous variability in cloud deployments
Authors: Casale Giuliano , Tribastone Mirco
Published: May 2013

Describing exogenous variability in the resources used by a cloud application leads to stochastic performance models that are difficult to solve. In this paper, we describe the blending algorithm, a novel approximation for queueing network models immersed in a random environment. Random environments are Markov chain-based descriptions of timevarying operational conditions that evolve independently of the system state, therefore they are natural descriptors for exogenous variability in a cloud deployment. The algorithm adopts the principle of solving a separate transient-analysis subproblem for each state of the random environment. Each subproblem is then approximated by a system of ordinary differential equations formulated according to a fluid limit theorem, making the approach scalable and computationally inexpensive. A validation study on several hundred models shows that blending can save up to two orders of magnitude of computational time compared to simulation, enabling efficient exploration of a decision space, which is useful in particular at design-time.
An informal history of ACM SIGCOMM computer communication review 1970-2012
Authors: Partridge Craig
Published: May 2013

A brief history of the evolution of ACM SIGCOMM Computer Communication Review as a newsletter and journal is presented.
miR-222 contributes to sex-dimorphic cardiac eNOS expression via ets-1
Authors: Evangelista Alicia M. , Deschamps Anne M. , Liu Delong , Raghavachari Nalini , Murphy Elizabeth
Published: May 2013

It is well recognized that there is sex-dimorphic expression of mRNA and protein in the heart; however, the underlying mechanism is poorly understood. Endothelial nitric oxide synthase (eNOS) is an important regulator of cardiac function, and the expression levels of eNOS differ between male and female hearts. The aim of this study was to examine whether expression of specific microRNA (miRNA, miR) in males and females contributes to changes in the expression of eNOS. miRNA was extracted from the myocardium of male and female C57BL/6 mice and subjected to an Affymetrix miRNA array. Decreased expression of miR-222 was discovered in females and confirmed by qRT-PCR from whole heart or isolated cardiomyocytes. The transcription factor V-ets erythroblastosis virus E26 oncogene homolog-1 (ets-1) was identified as a potential target of miR-222 using TargetScan, and fivefold increased ets-1 protein expression in females was confirmed by Western blot. Targeting of ets-1 by miR-222 was determined in HEK293 cells overexpressing luciferase under regulation of either the ets-1 3′-UTR, a null 3′-UTR control, or a scrambled ets-1 3′-UTR and treated with a small molecule miR-222 mimic or inhibitor. Additionally qRT-PCR confirmed that mRNA levels of the ets-1 transcriptional target, eNOS, were 25% higher in females. Compared with untreated myocyte controls, 50% inhibition of eNOS expression was achieved by treatment with a miR-222 mimic, compared with a 25% increase due to miR-222 inhibitor. Our findings indicate that sex-dependent miR-222 regulation alters the expression of the cardiac regulatory protein eNOS.
Recycling of Badger/Fox Burrows in Late Pleistocene Loess by Hyenas at the Den Site Bad Wildungen-Biedensteg (NW, Germany): Woolly Rhinoceros Killers and Scavengers in a Mammoth Steppe Environment of Europe
Authors: Diedrich Cajus
Published: May 2013

The Late Pleistocene (MIS 5c-d) Ice Age spotted hyena open air den and bone accumulation site Bad Wildungen-Biedensteg (Hesse, NW, Germany) represents the first open air loess fox/badger den site in Europe, which must have been recycled by Crocuta crocuta spelaea (Goldfuss, 1823) as a birthing den. Badger and fox remains, plus remains of their prey (mainly hare), have been found within the loess. Hyena remains from that site include parts of cub skeletons which represent 10% of the megafauna bones. Also a commuting den area existed, which was well marked by hyena faecal pellets. Most of the hyena prey bones expose crack, bite, and nibbling marks, especially the most common bones, the woolly rhinoceros Coelodonta antiquitatis (NISP  =  32%). The large amount of woolly rhinoceros bones indicate hunting/scavenging specializing on this large prey by hyenas. Other important mammoth steppe hyena prey remains are from Mammuthus primigenius, Equus caballus przewalskii, Bison/Bos, Megaloceros giganteus, Cervus elaphus, and Rangifer tarandus. The few damaged bone remains of a scavenged cave bear Ursus spelaeus subsp. are unique for an open air situation. Abundant micromammal, frog, and some fish remains were concentrated in “pellets” that contain mainly mammoth steppe micromammals and also frog and fish remains that seem to originate from the nearby river/lake.
Mortality Predicted Accuracy for Hepatocellular Carcinoma Patients with Hepatic Resection Using Artificial Neural Network
Authors: Chiu Herng-Chia , Ho Te-Wei , Lee King-Teh , Chen Hong-Yaw , Ho Wen-Hsien
Published: May 2013

The aim of this present study is firstly to compare significant predictors of mortality for hepatocellular carcinoma (HCC) patients undergoing resection between artificial neural network (ANN) and logistic regression (LR) models and secondly to evaluate the predictive accuracy of ANN and LR in different survival year estimation models. We constructed a prognostic model for 434 patients with 21 potential input variables by Cox regression model. Model performance was measured by numbers of significant predictors and predictive accuracy. The results indicated that ANN had double to triple numbers of significant predictors at 1‐, 3‐, and 5‐year survival models as compared with LR models. Scores of accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) of 1‐, 3‐, and 5‐year survival estimation models using ANN were superior to those of LR in all the training sets and most of the validation sets. The study demonstrated that ANN not only had a great number of predictors of mortality variables but also provided accurate prediction, as compared with conventional methods. It is suggested that physicians consider using data mining methods as supplemental tools for clinical decision‐making and prognostic evaluation.
Histochemical and Immunohistochemical Study of Peripolar Cells in Sheep
Authors: Joana Passos , Justina Prada , Lígia Bento , Paula Rodrigues , Isabel Pires
Published: May 2013

Peripolar cells are granulated cells located in the vascular pole of the renal corpuscle. Even though these cells have already been described, there are still many unknown histological and physiological characteristics. We carried out histochemical and immunohistochemical analyses of peripolar cells in sheep and compared their number in both normal and injured kidneys, discriminating according to the age of the animal. We tested HE, Toluidine Blue, PAS, and Masson's Trichrome stains to select the best stain for identification and quantification. Masson Trichrome yielded the best results and was selected for this purpose. We identified the cells by the presence of cytoplasmatic granules and by their position in the vascular pole. We found no statistically significant association between the number of peripolar cells and the age of the animal or the occurrence of lesions. In the immunohistochemical analysis, we found that the cells were positive to α-smooth muscle actin and less consistently positive to NSE and S100 protein. Chromogranin A, cyclooxygenase-2, AE1/AE3, and Wide Spectrum Cytokeratin and desmin yielded negative results. We conclude that although there was evidence of a contractile function, there was no evidence to support that peripolar cells have either a neuroendocrine or an epithelial nature.
Determination of Free Fatty Acid by FT-NIR Spectroscopy in Esterification Reaction for Biodiesel Production
Authors: Raspe Djéssica Tatiana , da Silva Camila
Published: May 2013

This work reports the use of FT-NIR spectroscopy coupled with multivariate calibration to determine the percentage of free fatty acids (FFA) in samples obtained by the esterification of FFA in vegetable oils. The analytical method used as calibration matrix samples of the reaction medium of esterification of oleic acid in soybean oil in proportions of 0.3 to 40 wt% (by weight) of oleic acid obtained under different experimental conditions and utilized the partial least squares (PLS) regression. The efficiency of the method was tested to predict the content of FFA in reactions of esterification of oleic acid in soybean oil catalysed by KSF clay and Amberlyst 15 commercial resin, both in a batch mode. Good Correlations were observed between the FT-NIR/PLS method and the reference method (AOCS). The results confirm that FT-NIR spectroscopy, in combination with multivariate calibration, is a promising technique for monitoring esterification reaction for biodiesel production.
QSAR Investigation on Quinolizidinyl Derivatives in Alzheimer’s Disease
Authors: Ghasemi Ghasem , Arshadi Sattar , Rashtehroodi Alireza Nemati , Nirouei Mahyar , Shariati Shahab , Rastgoo Zinab
Published: May 2013

Sets of quinolizidinyl derivatives of bi- and tri-cyclic (hetero) aromatic systems were studied as selective inhibitors. On the pattern, quantitative structure-activity relationship (QSAR) study has been done on quinolizidinyl derivatives as potent inhibitors of acetylcholinesterase in alzheimer’s disease (AD). Multiple linear regression (MLR), partial least squares (PLSs), principal component regression (PCR), and least absolute shrinkage and selection operator (LASSO) were used to create QSAR models. Geometry optimization of compounds was carried out by B3LYP method employing 6–31 G basis set. HyperChem, Gaussian 98 W, and Dragon software programs were used for geometry optimization of the molecules and calculation of the quantum chemical descriptors. Finally, Unscrambler program was used for the analysis of data. In the present study, the root mean square error of the calibration andR2using MLR method were obtained as 0.1434 and 0.95, respectively. Also, theRandR2values were obtained as 0.79, 0.62 from stepwise MLR model. TheR2and mean square values using LASSO method were obtained as 0.766 and 3.226, respectively. The root mean square error of the calibration andR2using PLS method were obtained as 0.3726 and 0.62, respectively. According to the obtained results, it was found that MLR model is the most favorable method in comparison with other statistical methods and is suitable for use in QSAR models.
Economic Impact of Harvesting Corn Stover under Time Constraint: The Case of North Dakota
Authors: Maung Thein A. , Gustafson Cole R.
Published: May 2013

This study examines the impact of stochastic harvest field time on profit maximizing potential of corn cob/stover collection in North Dakota. Three harvest options are analyzed using mathematical programming models. Our findings show that under the first corn grain only harvest option, farmers are able to complete harvesting corn grain and achieve maximum net income in a fairly short amount of time with existing combine technology. However, under the second simultaneous corn grain and cob (one-pass) harvest option, farmers generate lower net income compared to the net income of the first option. This is due to the slowdown in combine harvest capacity as a consequence of harvesting corn cobs. Under the third option of separate corn grain and stover (two-pass) harvest option, time allocation is the main challenge and our evidence shows that with limited harvest field time available, farmers find it optimal to allocate most of their time harvesting grain and then proceed to harvest and bale stover if time permits at the end of harvest season. The overall findings suggest is that it would be more economically efficient to allow a firm that is specialized in collecting biomass feedstock to participate in cob/stover harvest business.
Vision Target Tracker Based on Incremental Dictionary Learning and Global and Local Classification
Authors: Yang Yang , Li Ming , Nian Fuzhong , Zhao Huiya , He Yongfeng
Published: May 2013

Based on sparse representation, a robust global and local classification algorithm for visual target tracking in uncertain environment was proposed in this paper. The global region of target and the position of target would be found, respectively by the proposed algorithm. Besides, overcompleted dictionary was obtained and updated by biased discriminate analysis with the divergence of positive and negative samples at current frame. And this over-completed dictionary not only discriminates the positive samples accurately but also rejects the negative samples effectively. Experiments on challenging sequences with evaluation of the state-of-the-art methods show that the proposed algorithm has better robustness to illumination changes, perspective changes, and targets rotation itself.
CMOS Ultra-Wideband Low Noise Amplifier Design
Authors: Yousef K. , Jia H. , Pokharel R. , Allam A. , Ragab M. , Kanaya H. , Yoshida K.
Published: May 2013

This paper presents the design of ultra-wideband low noise amplifier (UWB LNA). The proposed UWB LNA whose bandwidth extends from 2.5 GHz to 16 GHz is designed using a symmetric 3D RF integrated inductor. This UWB LNA has a gain of 11 ± 1.0 dB and a NF less than 3.3 dB. Good input and output impedance matching and good isolation are achieved over the operating frequency band. The proposed UWB LNA is driven from a 1.8 V supply. The UWB LNA is designed and simulated in standard TSMC 0.18 µm CMOS technology process.
Quantification of Stretching in the Ventricular Wall and Corpus Callosum and Corticospinal Tracts in Hydrocephalus before and after Ventriculoperitoneal Shunt Operation
Authors: von Holst Hans , Li Xiaogai
Published: May 2013

In this study, we establish a quantitative model to define the stretching of brain tissue, especially in ventricular walls, corpus callosum (CC) and corticospinal (CS) fiber tracts, and to investigate the correlation between stretching and regional cerebral blood flow (rCBF) before and after ventriculoperitoneal shunt operations. A nonlinear image registration method was used to calculate the degree of displacement and stretching of axonal fiber tracts based on the medical images of six hydrocephalus patients. Also, the rCBF data from the literature was analyzed and correlated with the strain level quantified in the present study. The results showed substantial increased displacement and strain levels in the ventricular walls as well as in the CC and CS fiber tracts on admission. Following shunt operations the displacement as well as the strain levels reduced substantially. A linear correlation was found to exist between strain level and the rCBF. The reduction in postoperative strain levels correlated with the improvement of rCBF. All patients improved clinically except for one patient due to existing dementia. These new quantitative data provide us with new insight into the mechanical cascade of events due to tissue stretching, thereby provide us with more knowledge into understanding of the role of brain tissue and axonal stretching in some of the hydrocephalus clinical symptoms.
Advanced Prostate Cancer Presenting as Hemolytic Uremic Syndrome
Authors: Ramos R. , Lopes F. , Rodrigues T. , Rolim N. , Rodrigues I. , Monteiro H.
Published: May 2013

Introduction. Hemolytic uremic syndrome (HUS) is characterized by endothelial dysfunction, consumption thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. HUS generally has a dismal prognosis, except when associated with gastroenteritis caused by verotoxin-producing bacteria. Cancer associated HUS is uncommon, and there are only scarce reports on prostate cancer presenting with HUS.Case Presentation. A 72-year-old man presented to the emergency department with oliguria, hematuria, and hematemesis. Clinical evaluation revealed acute renal failure, hemolysis, normal blood-clotting studies, and prostate-specific antigen value of 1000 ng/mL. The patient was started on hemodialysis, ultrafiltration with plasma exchange, and androgen blockade with bicalutamide and completely recovered from HUS. The authors review the 14 published cases on this association.Conclusion. The association of HUS and prostate cancer occurs more frequently in patients with high-grade, clinically advanced prostate cancer. When readily recognized and appropriately treated, HUS does not seem to worsen prognosis in prostate cancer patients.
Development of Low-Fat Soft Dough Biscuits Using Carbohydrate-Based Fat Replacers
Authors: Chugh Bhawna , Singh Gurmukh , Kumbhar B. K.
Published: May 2013

Experiments were conducted to develop low-fat soft dough biscuits using carbohydrate-based fat replacers (maltodextrin and guar gum). A central composite rotatable design was used to optimise the level of sugar 24–36%, composite fat (fat 10.5–24.5%, maltodextrin 10.4–24%, and guar gum 0.1–0.5%), ammonium bicarbonate 0.5–2.5%, and water 20–24% for production of low-fat biscuits. Diameter and stress-strain ratio decreased significantly with increase in the amount of sugar. There was a significant decrease in spread ratio at high amount of water. Hardness was significantly affected by the interactions of ammonium bicarbonate with sugar and fat . The optimum level of ingredients obtained for low-fat biscuits was sugar 31.7 g, fat 13.55 g, maltodextrin 21.15 g, guar gum 0.3 g, ammonium bicarbonate 2.21 g, and water 21 mL based on 100 g flour. The fat level in the optimised low-fat biscuit formulation was found to be 8.48% as compared to 22.65% in control; therefore, the reduction in fat was 62.5%.
Impact of High Glucose and Proteasome Inhibitor MG132 on Histone H2A and H2B Ubiquitination in Rat Glomerular Mesangial Cells
Authors: Gao Chenlin , Chen Guo , Liu Li , Li Xia , He Jianhua , Jiang Lan , Zhu Jianhua , Xu Yong
Published: May 2013

Background. Hyperglycemia plays a pivotal role in the development of diabetic nephropathy (DN) and may be related to epigenetic metabolic memory. One of the most crucial epigenetic mechanisms is histone modification, which is associated with the expression of a fibrosis factor in vascular injury.Aim.In this study, we investigated the ubiquitination of histones H2A and H2B to explore the epigenetic mechanisms of DN.Materials and Methods. The GMCs were cultured as follows: normal group, high glucose group, mannitol group, and intervention group. After 12 hr, 24 hr, and 48 hr, histones ubiquitination, transforming growth factor-β(TGF-β), and fibronectin (FN) were measured using WB, RT-PCR, and IF.Result. High glucose can induce the upregulation of FN. H2A ubiquitination in GMCs increased in high glucose group(P<0.01), whereas it decreased significantly in intervention group(P<0.05). In contrast, H2B ubiquitination decreased with an increasing concentration of glucose, but it was recovered in the intervention group(P<0.05). Expression of TGF-βchanged in response to abnormal histone ubiquitination.Conclusions.The high glucose may induce H2A ubiquitination and reduce H2B ubiquitination in GMCs. The changes of histone ubiquitination may be due in part to DN by activating TGF-βsignaling pathway.
Effect of Growth Parameters and Annealing Atmosphere on the Properties of Cu2ZnSnS4Thin Films Deposited by Cosputtering
Authors: Khalkar Arun , Lim Kwang-Soo , Yu Seong-Man , Patole Shashikant P. , Yoo Ji-Beom
Published: May 2013

Cu2ZnSnS4(CZTS) thin films were deposited using the cosputtering technique. The growth parameters, such as working pressure, target powers, and postannealing atmosphere, were optimized for CZTS films deposition. A comparative study between post annealing using sulfur vapor in a quartz tube furnace and sulfurization chamber using H2S gas was carried out to optimize the kesterite Cu2ZnSnS4phase. 10 min annealing at 530°C in the furnace in sulfur vapor eliminated all the secondary phases and formed kesterite Cu2ZnSnS4. The diffusion of sulfur in the film during the annealing process enhanced the crystallinity of the film. The kesterite Cu2ZnSnS4phase was confirmed by X-ray diffraction, Raman scattering, and optical measurements. The film showed phonon peaks corresponding to the kesterite CZTS, high-absorption coefficient (1.1 × 105 cm−1), and desired optical direct band gap (1.5 eV).
Chromosome 22q11.2 Deletion Syndrome Presenting as Adult Onset Hypoparathyroidism: Clues to Diagnosis from Dysmorphic Facial Features
Authors: Korpaisarn Sira , Trachoo Objoon , Sriphrapradang Chutintorn
Published: May 2013

We report a 26-year-old Thai man who presented with hypoparathyroidism in adulthood. He had no history of cardiac disease and recurrent infection. His subtle dysmorphic facial features and mild intellectual impairment were suspected for chromosome 22q11.2 deletion syndrome. The diagnosis was confirmed by fluorescence in situ hybridization, which found microdeletion in 22q11.2 region. The characteristic facial appearance can lead to clinical suspicion of this syndrome. The case report emphasizes that this syndrome is not uncommon and presents as a remarkable variability in the severity and extent of expression. Accurate diagnosis is important for genetic counseling and long-term health supervision by multidisciplinary team.
Collision Resolution Schemes with Nonoverlapped Contention Slots for Heterogeneous and Homogeneous WLANs
Authors: Upadhyay Raksha , Vyavahare Prakash D. , Tokekar Sanjiv
Published: April 2013

CSMA/CA-based DCF of 802.11 MAC layer employs a best-effort delivery model, in which stations compete for channel access with the same priority. In a heterogeneous network, providing different priorities to different applications for required quality of service is a challenging task, since heterogeneous conditions result in unfairness among stations and degradation in the throughput. This paper proposes a class of collision resolution schemes for 802.11 having contention window control with nonoverlapped contention slots. In the first scheme, window ranges of two consecutive stages are nonoverlapped, and it is called nonoverlapped contention slots (NOCS) scheme. In the other scheme, termed as NOCS-offset, an offset is introduced between window ranges of two stages. Selection of a random value by a station for its contention with discontinuous distribution results in reduced probability of collision. Analytical and simulation results show that the proposed scheme exhibits higher throughput and fairness with reduced delay and collision probability in homogeneous and heterogeneous networks. Performance of the proposed scheme is evaluated for mix traffic and high data rate environment with advanced back-off management techniques to meet the requirements of the present applications.
Energy-Efficient Bridge Detection Algorithms for Wireless Sensor Networks
Authors: Dagdeviren Orhan , Akram Vahid Khalilpour
Published: May 2013

A bridge is a critical edge whose fault disables the data delivery of a WSN component. Because of this, it is important to detect bridges and take preventions before they are corrupted. Since WSNs are battery powered, protocols running on WSN should be energy efficient. In this paper, we propose two distributed energy-efficient bridge detection algorithms for WSNs. The first algorithm is the improved version of Pritchard's algorithm where two phases are merged into a single phase and radio broadcast communication is used instead of unicast in order to remove a downcast operation and remove extra message headers. The second algorithm runs proposed rules on 2-hop neighborhoods of each node and tries to detect all bridges in a breadth-first search (BFS) execution session using O( N) messages with O[Formula: see text] bits where N is the node count and [Formula: see text] is the maximum node degree. Since BFS is a natural routing algorithm for WSNs, the second algorithm achieves both routing and bridge detections. If the second proposed algorithm is not able to to classify all edges within the BFS phase, improved version of Turau's algorithm is executed as the second phase. We show the operation of the algorithms, analyze them, and provide extensive simulation results on TOSSIM environment. We compare our proposed algorithms with the other bridge detection algorithms and show that our proposed algorithms provide less resource consumption. The energy saving of our algorithms is up to 4.3 times, while it takes less time in most of the situations.
Simultaneous Targeting of Tumor Antigens and the Tumor Vasculature Using T Lymphocyte Transfer Synergize to Induce Regression of Established Tumors in Mice
Authors: Chinnasamy Dhanalakshmi , Tran Eric , Yu Zhiya , Morgan Richard A. , Restifo Nicholas P. , Rosenberg Steven A.
Published: May 2013

Most systemic cancer therapies target tumor cells directly, although there is increasing interest in targeting the tumor stroma that can comprise a substantial portion of the tumor mass. We report here a synergy between two T-cell therapies, one directed against the stromal tumor vasculature and the other directed against antigens expressed on the tumor cell. Simultaneous transfer of genetically engineered syngeneic T cells expressing a chimeric antigen receptor targeting the VEGF receptor-2 (VEGFR2; KDR) that is overexpressed on tumor vasculature and T-cells specific for the tumor antigens gp100 (PMEL), TRP-1 (TYRP1), or TRP-2 (DCT) synergistically eradicated established B16 melanoma tumors in mice and dramatically increased the tumor-free survival of mice compared with treatment with either cell type alone or T cells coexpressing these two targeting molecules. Host lymphodepletion before cell transfer was required to mediate the antitumor effect. The synergistic antitumor response was accompanied by a significant increase in the infiltration and expansion and/or persistence of the adoptively transferred tumor antigen–specific T cells in the tumor microenvironment and thus enhanced their antitumor potency. The data presented here emphasize the possible beneficial effects of combining antiangiogenic with tumor-specific immunotherapeutic approaches for the treatment of patients with cancer. Cancer Res; 73(11); 3371–80. ©2013 AACR.
Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors
Authors: Duraiswamy Jaikumar , Kaluza Karen M. , Freeman Gordon J. , Coukos George
Published: May 2013

Tumor progression is facilitated by regulatory T cells (Treg) and restricted by effector T cells. In this study, we document parallel regulation of CD8+ T cells and Foxp3+ Tregs by programmed death-1 (PD-1, PDCD1). In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8+ T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). Two thirds of CD8+ tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8+ TIL coexpressed PD-1 and CTLA-4. Double-positive (PD-1+CTLA-4+) CD8+ TIL had characteristics of more severe dysfunction than single-positive (PD-1+ or CTLA-4+) TIL, including an inability to proliferate and secrete effector cytokines. Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8+ TIL dysfunction and led to tumor rejection in two thirds of mice. Double blockade was associated with increased proliferation of antigen-specific effector CD8+ and CD4+ T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function. When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor–expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice. Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression. Cancer Res; 73(12); 3591–603. ©2013 AACR.
Regulation of FANCD2 by the mTOR Pathway Contributes to the Resistance of Cancer Cells to DNA Double-Strand Breaks
Authors: Shen Changxian , Oswald Duane , Phelps Doris , Cam Hakan , Pelloski Christopher E. , Pang Qishen , Houghton Peter J.
Published: May 2013

Deregulation of the mTOR pathway is closely associated with tumorigenesis. Accordingly, mTOR inhibitors such as rapamycin and mTOR-selective kinase inhibitors have been tested as cancer therapeutic agents. Inhibition of mTOR results in sensitization to DNA-damaging agents; however, the molecular mechanism is not well understood. We found that an mTOR-selective kinase inhibitor, AZD8055, significantly enhanced sensitivity of a pediatric rhabdomyosarcoma xenograft to radiotherapy and sensitized rhabdomyosarcoma cells to the DNA interstrand cross-linker (ICL) melphalan. Sensitization correlated with drug-induced downregulation of a key component of the Fanconi anemia pathway, FANCD2 through mTOR regulation of FANCD2 gene transcripts via mTORC1-S6K1. Importantly, we show that FANCD2 is required for the proper activation of ATM-Chk2 checkpoint in response to ICL and that mTOR signaling promotes ICL-induced ATM-Chk2 checkpoint activation by sustaining FANCD2. In FANCD2-deficient lymphoblasts, FANCD2 is essential to suppress endogenous and induced DNA damage, and FANCD2-deficient cells showed impaired ATM-Chk2 and ATR-Chk1 activation, which was rescued by reintroduction of wild-type FANCD2. Pharmacologic inhibition of PI3K–mTOR–AKT pathway in Rh30 rhabdomyosarcoma cells attenuated ICL-induced activation of ATM, accompanied with the decrease of FANCD2. These data suggest that the mTOR pathway may promote the repair of DNA double-strand breaks by sustaining FANCD2 and provide a novel mechanism of how the Fanconi anemia pathway modulates DNA damage response and repair. Cancer Res; 73(11); 3393–401. ©2013 AACR.
SENP1 deSUMOylates and Regulates Pin1 Protein Activity and Cellular Function
Authors: Chen Chun-Hau , Chang Che-Chang , Lee Tae Ho , Luo ManLi , Huang Pengyu , Liao Pei-Hsin , Wei Shuo , Li Fu-An , Chen Ruey-Hwa , Zhou Xiao Zhen , Shih Hsiu-Ming , Lu Kun Ping
Published: May 2013

The Pin1 prolyl isomerase regulates phosphorylation signaling by controlling protein conformation after phosphorylation, and its upregulation promotes oncogenesis via acting on numerous oncogenic molecules. SUMOylation and deSUMOylation are dynamic mechanisms regulating a spectrum of protein activities. The SUMO proteases (SENP) remove SUMO conjugate from proteins, and their expression is deregulated in cancers. However, nothing is known about the role of SUMOylation in regulating Pin1 function. Here, we show that Pin1 is SUMOylated on Lys6 in the WW domain and on Lys63 in the PPIase domain. Pin1 SUMOylation inhibits its protein activity and oncogenic function. We further identify that SENP1 binds to and deSUMOylates Pin1. Importantly, either overexpression of SENP1 or disruption of Pin1 SUMOylation promotes the ability of Pin1 to induce centrosome amplification and cell transformation. Moreover, SENP1 also increases Pin1 protein stability in cell cultures, and Pin1 levels are positively correlated with SENP1 levels in human breast cancer specimens. These results not only uncover Pin1 SUMOylation on Lys6/63 as a novel mechanism to inhibit its activity and function but also identify a critical role for SENP1-mediated deSUMOylation in promoting Pin1 function during tumorigenesis. Cancer Res; 73(13); 3951–62. ©2013 AACR.
Dynamic Mast Cell–Stromal Cell Interactions Promote Growth of Pancreatic Cancer
Authors: Ma Ying , Hwang Rosa F. , Logsdon Craig D. , Ullrich Stephen E.
Published: May 2013

Pancreatic ductal adenocarcinoma (PDAC) exists in a complex desmoplastic microenvironment, which includes cancer-associated fibroblasts [also known as pancreatic stellate cells (PSC)] and immune cells that provide a fibrotic niche that impedes successful cancer therapy. We have found that mast cells are essential for PDAC tumorigenesis. Whether mast cells contribute to the growth of PDAC and/or PSCs is unknown. Here, we tested the hypothesis that mast cells contribute to the growth of PSCs and tumor cells, thus contributing to PDAC development. Tumor cells promoted mast cell migration. Both tumor cells and PSCs stimulated mast cell activation. Conversely, mast cell–derived interleukin (IL)-13 and tryptase stimulated PSC proliferation. Treating tumor-bearing mice with agents that block mast cell migration and function depressed PDAC growth. Our findings suggest that mast cells exacerbate the cellular and extracellular dynamics of the tumor microenvironment found in PDAC. Therefore, targeting mast cells may inhibit stromal formation and improve therapy. Cancer Res; 73(13); 3927–37. ©2013 AACR.
Cap-Translation Inhibitor, 4EGI-1, Restores Sensitivity to ABT-737 Apoptosis through Cap-Dependent and -Independent Mechanisms in Chronic Lymphocytic Leukemia
Authors: Willimott Shaun , Beck Daniel , Ahearne Matthew J. , Adams Victoria C. , Wagner Simon D.
Published: May 2013

Purpose: The lymph node microenvironment promotes resistance to chemotherapy in chronic lymphocytic leukemia (CLL), partly through induction of BCL2 family prosurvival proteins. Currently available inhibitors do not target all BCL2 family prosurvival proteins and their effectiveness is also modified by proapoptotic BCL2 homology domain 3 (BH3) only protein expression. The goal of this study was to evaluate synergy between the eIF4E/eIF4G interaction inhibitor, 4EGI-1, and the BH3 mimetic, ABT-737.

Experimental Design: CLL cells were cultured in conditions to mimic the lymph node microenvironment. Protein synthesis and cap-complex formation were determined. Polysome association of mRNAs from BCL2 family survival genes was analyzed by translational profiling. The effects of 4EGI-1 and the BCL2/BCL2L1 antagonist, ABT-737, on CLL cell apoptosis were determined.

Results: Protein synthesis was increased approximately 6-fold by stromal cell/CD154 culture in a phosphoinositide 3-kinase α (PI3Kα)–specific manner and was reduced by 4EGI-1. PI3K inhibitors and 4EGI-1 also reduced cap-complex formation but only 4EGI-1 consistently reduced BCL2L1 and BCL2A1 protein levels. 4EGI-1, but not PI3K inhibitors or rapamycin, induced an endoplasmic reticulum stress response including proapoptotic NOXA and the translation inhibitor phosphorylated eIF2α. 4EGI-1 and ABT-737 synergized to cause apoptosis, independent of levels of prosurvival protein expression in individual patients.

Conclusions: Overall protein synthesis and cap-complex formation are induced by microenvironment stimuli in CLL. Inhibition of the cap-complex was not sufficient to repress BCL2 family prosurvival expression, but 4EGI-1 inhibited BCL2A1 and BCL2L1 while inducing NOXA through cap-dependent and -independent mechanisms. 4EGI-1 and ABT-737 synergized to produce apoptosis, and these agents may be the basis for a therapeutically useful combination. Clin Cancer Res; 19(12); 3212–23. ©2013 AACR.
PIK3CA and PTEN Gene and Exon Mutation-Specific Clinicopathologic and Molecular Associations in Colorectal Cancer
Authors: Day Fiona L. , Jorissen Robert N. , Lipton Lara , Mouradov Dmitri , Sakthianandeswaren Anuratha , Christie Michael , Li Shan , Tsui Cary , Tie Jeannie , Desai Jayesh , Xu Zheng-Zhou , Molloy Peter , Whitehall Vicki , Leggett Barbara A. , Jones Ian T. , McLaughlin Stephen , Ward Robyn L. , Hawkins Nicholas J. , Ruszkiewicz Andrew R. , Moore James , Busam Dana , Zhao Qi , Strausberg Robert L. , Gibbs Peter , Sieber Oliver M.
Published: May 2013

Purpose: PIK3CA and PTEN mutations are prevalent in colorectal cancer and potential markers of response to mitogen-activated protein/extracellular signal–regulated kinase inhibitors and anti-EGF receptor antibody therapy. Relationships between phosphoinositide 3-kinase (PI3K) pathway mutation, clinicopathologic characteristics, molecular features, and prognosis remain controversial.

Experimental Design: A total of 1,093 stage I–IV colorectal cancers were screened for PIK3CA (exons 9 and 20), KRAS (codons 12–13), BRAF (codon 600) mutations, and microsatellite instability (MSI). PTEN (exons 3–8) and CpG island methylator phenotype (CIMP) status were determined in 744 and 489 cases. PIK3CA data were integrated with 17 previous reports (n = 5,594).

Results: PIK3CA and PTEN mutations were identified in 11.9% and 5.8% of colorectal cancers. PTEN mutation was associated with proximal tumors, mucinous histology, MSI-high (MSI-H), CIMP-high (CIMP-H), and BRAF mutation (P < 0.02). PIK3CA mutation was related to older age, proximal tumors, mucinous histology, and KRAS mutation (P < 0.04). In integrated cohort analysis, PIK3CA exon 9 and 20 mutations were overrepresented in proximal, CIMP-low (CIMP-L), and KRAS-mutated cancers (P ≤ 0.011). Comparing PIK3CA exonic mutants, exon 20 mutation was associated with MSI-H, CIMP-H, and BRAF mutation, and exon 9 mutation was associated with KRAS mutation (P ≤ 0.027). Disease-free survival for stage II/III colorectal cancers did not differ by PI3K pathway status.

Conclusion: PI3K pathway mutation is prominent in proximal colon cancers, with PIK3CA exon 20 and PTEN mutations associated with features of the sessile-serrated pathway (MSI-H/CIMP-H/BRAFmut), and PIK3CA exon 9 (and to a lesser extent exon 20) mutation associated with features of the traditional serrated pathway (CIMP-L/KRASmut) of tumorigenesis. Our data highlight the PI3K pathway as a therapeutic target in distinct colorectal cancer subtypes. Clin Cancer Res; 19(12); 3285–96. ©2013 AACR.