bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrophysiological characterization and computational models of HVC neurons in the zebra finch
Authors: Daou Arij , Ross Matthew T. , Johnson Frank , Hyson Richard L. , Bertram Richard
Published: May 2013

The nucleus HVC (proper name) within the avian analog of mammal premotor cortex produces stereotyped instructions through the motor pathway leading to precise, learned vocalization by songbirds. Electrophysiological characterization of component HVC neurons is an important requirement in building a model to understand HVC function. The HVC contains three neural populations: neurons that project to the RA (robust nucleus of arcopallium), neurons that project to Area X (of the avian basal ganglia), and interneurons. These three populations are interconnected with specific patterns of excitatory and inhibitory connectivity, and they fire with characteristic patterns both in vivo and in vitro. We performed whole cell current-clamp recordings on HVC neurons within brain slices to examine their intrinsic firing properties and determine which ionic currents are responsible for their characteristic firing patterns. We also developed conductance-based models for the different neurons and calibrated the models using data from our brain slice work. These models were then used to generate predictions about the makeup of the ionic currents that are responsible for the different responses to stimuli. These predictions were then tested and verified in the slice using pharmacological manipulations. The model and the slice work highlight roles of a hyperpolarization-activated inward current ( Ih), a low-threshold T-type Ca2+ current ( ICa-T), an A-type K+ current ( IA), a Ca2+-activated K+ current ( ISK), and a Na+-dependent K+ current ( IKNa) in driving the characteristic neural patterns observed in the three HVC neuronal populations. The result is an improved characterization of the HVC neurons responsible for song production in the songbird.
The training schedule affects the stability, not the magnitude, of the interlimb transfer of learned dynamics
Authors: Joiner Wilsaan M. , Brayanov Jordan B. , Smith Maurice A.
Published: May 2013

The way that a motor adaptation is trained, for example, the manner in which it is introduced or the duration of the training period, can influence its internal representation. However, recent studies examining the gradual versus abrupt introduction of a novel environment have produced conflicting results. Here we examined how these effects determine the effector specificity of motor adaptation during visually guided reaching. After adaptation to velocity-dependent dynamics in the right arm, we estimated the amount of adaptation transferred to the left arm, using error-clamp measurement trials to directly measure changes in learned dynamics. We found that a small but significant amount of generalization to the untrained arm occurs under three different training schedules: a short-duration (15 trials) abrupt presentation, a long-duration (160 trials) abrupt presentation, and a long-duration gradual presentation of the novel dynamic environment. Remarkably, we found essentially no difference between the amount of interlimb generalization when comparing these schedules, with 9–12% transfer of the trained adaptation for all three. However, the duration of training had a pronounced effect on the stability of the interlimb transfer: The transfer elicited from short-duration training decayed rapidly, whereas the transfer from both long-duration training schedules was considerably more persistent (<50% vs. >90% retention over the first 20 trials). These results indicate that the amount of interlimb transfer is similar for gradual versus abrupt training and that interlimb transfer of learned dynamics can occur after even a brief training period but longer training is required for an enduring effect.
Important Developments in Romanian Propolis Research
Authors: Mărghitaş Liviu Al , Dezmirean Daniel S. , Bobiş Otilia
Published: May 2013

The most important developments in propolis analysis and pharmacological properties are discussed. In order to help in the Romanian propolis standardization, different methodologies for chemical composition analysis (UV-VIS, HP-TLC, and HPLC-DAD) are reviewed using new approaches and software (fuzzy divisive hierarchical clustering approach and ChromQuest software) and compared with international studies made until now in propolis research. Practical applications of Romanian propolis in medicinal therapy and cosmetics are reviewed, and quality criteria for further standardization are proposed.
The Performance of a New Hybrid PLL in an Interconnected Renewable Energy Systems under Fault Ride Through Operation
Authors: Hadjidemetriou Lenos , Kyriakides Elias
Published: May 2013

Modern renewable energy systems (RES) require fault ride through (FRT) operation in order to provide voltage and frequency support to the power grid when faults occur. The grid synchronization of a RES could be ensured by the appropriate operation of a phase-locked loop (PLL). A new hybrid PLL (dαβPLL) has recently been suggested by the authors and could operate accurately and faster than the other existing PLLs. The dαβPLL could be a very useful tool in the FRT operation of a RES, since the faster performance of the new PLL could boost the time performance of the FRT algorithm when a disturbance occurs. This paper investigates the performance of the flexible positive and negative sequence control (FPNSC) when the new dαβPLL is used. The paper also deals with the improvement on the FRT operation of the RES that could be obtained from the outstanding performance of the dαβPLL.
Darboux Transformation and Explicit Solutions for a Generalized Sawada-Kotera Equation
Authors: He Guo-Liang , Su Ting
Published: May 2013

A generalized Sawada-Kotera equation and its Lax pairs are proposed. With the help of the gauge transformation between spectral problems, a Darboux transformation for the generalized SK equation is constructed. As an application of the Darboux transformation, we give some explicit solutions of the generalized SK equation such as the rational solutions, soliton solutions, and periodic solutions.
Low-Grade Fibromyxoid Sarcoma: Incidence, Treatment Strategy of Metastases, and Clinical Significance of theFUSGene
Authors: Maretty-Nielsen Katja , Baerentzen Steen , Keller Johnny , Dyrop Heidi Buvarp , Safwat Akmal
Published: May 2013

Aim. The aim of this study was to assess the incidence of low-grade fibromyxoid sarcoma (LGFMS), present treatment results of metastatic LGFMS, and investigate the clinical significance of theFUSgene rearrangement.Methods. This study included 14 consecutive LGFMS patients treated at the Aarhus Sarcoma Centre in 1979–2010. Fluorescent in situ hybridization (FISH) analysis forFUSbreak-apart was performed for all patients.Results. The incidence of LGFMS was 0.18 per million, representing 0.6% of all soft tissue sarcomas. Four patients needed multiple biopsies/resections before the correct diagnosis was made. Four patients experienced local recurrence, and three patients developed metastases. The treatment of metastatic LGFMS varied from multiagent chemotherapy to repeated, selective surgery of operable metastases. The best response to chemotherapy was short-term stabilization of disease progression, seen with Trabectedin. The prevalence of theFUSbreak-apart was 21.4%. We found no significant difference in clinical characteristics and outcomes in correlation with theFUSbreak-apart.Conclusion. LGFMS is a rare disease with multiple challenges. TheFUSbreak-apart was not associated with local recurrence or metastases in our study. To date the only treatment resulting in disease-free periods is surgery; however further investigation into the management of metastatic LGFMS is necessary.
Obstructive Jaundice as an Initial Manifestation of Non-Hodgkin Lymphoma: Treatment Dilemma and High Mortality
Authors: Chaudhari Dhara , Khan Sarah , Saleem Atif , Taylor Tamarro , Reddy Chakradhar , Borthwick Thomas , Young Mark
Published: May 2013

Introduction. Non Hodgkin lymphoma (NHL) presenting with obstructive jaundice is a rare occurrence. Because of rarity of combination, it is seldom considered in differential diagnosis of patients presenting with obstructive jaundice. It is considered treatable due to the chemosensitive nature of the disease and the recent advances in chemotherapy.Case Series. We present a case series of 2 patients with NHL presenting with obstructive jaundice as an initial manifestation. Both patients presented with obstructive jaundice and were diagnosed by CT guided liver biopsy. One patient died of sepsis and multiorgan failure before initiating chemotherapy and the second patient did not choose to undergo chemotherapy.Conclusion. Biliary obstruction is a sign of poor prognosis. The diagnosis of NHL needs to be considered in patients presenting with biliary obstruction. It can be associated with high mortality and poses treatment dilemma.
A Comparative Analysis of Burned Area Datasets in Canadian Boreal Forest in 2000
Authors: Núñez-Casillas Laia , García Lázaro José Rafael , Moreno-Ruiz José Andrés , Arbelo Manuel
Published: May 2013

The turn of the new millennium was accompanied by a particularly diverse group of burned area datasets from different sensors in the Canadian boreal forests, brought together in a year of low global fire activity. This paper provides an assessment of spatial and temporal accuracy, by means of a fire‐by‐fire comparison of the following: two burned area datasets obtained from SPOT‐VEGETATION (VGT) imagery, a MODIS Collection 5 burned area dataset, and three different datasets obtained from NOAA‐AVHRR. Results showed that burned area data from MODIS provided accurate dates of burn but great omission error, partially caused by calibration problems. One of the VGT‐derived datasets (L3JRC) represented the largest number of fire sites in spite of its great overall underestimation, whereas the GBA2000 dataset achieved the best burned area quantification, both showing delayed and very variable fire timing. Spatial accuracy was comparable between the 5 km and the 1 km AVHRR‐derived datasets but was remarkably lower in the 8 km dataset leading, us to conclude that at higher spatial resolutions, temporal accuracy was lower. The probable methodological and contextual causes of these differences were analyzed in detail.
Measures of Cultural Competence in Nurses: An Integrative Review
Authors: Loftin Collette , Hartin Vicki , Branson Marietta , Reyes Helen
Published: May 2013

Background. There is limited literature available identifying and describing the instruments that measure cultural competence in nursing students and nursing professionals. Design. An integrative review was undertaken to identify the characteristics common to these instruments, examine their psychometric properties, and identify the concepts these instruments are designed to measure. Method. There were eleven instruments identified that measure cultural competence in nursing. Of these eleven instruments, four had been thoroughly tested in either initial development or in subsequent testing, with developers providing extensive details of the testing. Results. The current literature identifies that the instruments to assess cultural competence in nurses and nursing students are self‐administered and based on individuals′ perceptions. The instruments are commonly utilized to test the effectiveness of educational programs designed to increase cultural competence. Conclusions. The reviewed instruments measure nurses’ self‐perceptions or self‐reported level of cultural competence but offer no objective measure of culturally competent care from a patient’s perspective which can be problematic. Comparison of instruments reveals that they are based on a variety of conceptual frameworks and that multiple factors should be considered when deciding which instrument to use.
Factors Contributing toDe Qiin Acupuncture Randomized Clinical Trials
Authors: Yang Yi , Wang Lin-Peng , Zhang Lei , Wang Li-Chen , Wei Jia , Li Jia-Jian , Sun Yi-Le
Published: May 2013

De qiis a core concept of acupuncture and is necessary to produce therapeutic effect. In 2010,de qihas been received as a term in the official extension of the CONSORT Statement. However, there are few articles that discuss which factors have influences on obtainingde qiin clinical trials. This paper aims to explore these factors and give advice on trial design in order to optimizede qiin acupuncture RCTs.
A New Logistic Dynamic Particle Swarm Optimization Algorithm Based on Random Topology
Authors: Ni Qingjian , Deng Jianming
Published: May 2013

Population topology of particle swarm optimization (PSO) will directly affect the dissemination of optimal information during the evolutionary process and will have a significant impact on the performance of PSO. Classic static population topologies are usually used in PSO, such as fully connected topology, ring topology, star topology, and square topology. In this paper, the performance of PSO with the proposed random topologies is analyzed, and the relationship between population topology and the performance of PSO is also explored from the perspective of graph theory characteristics in population topologies. Further, in a relatively new PSO variant which named logistic dynamic particle optimization, an extensive simulation study is presented to discuss the effectiveness of the random topology and the design strategies of population topology. Finally, the experimental data are analyzed and discussed. And about the design and use of population topology on PSO, some useful conclusions are proposed which can provide a basis for further discussion and research.
Convergence Analysis of a Class of Computational Intelligence Approaches
Authors: Chen Junfeng , Ni Jianjun , Hua Mingang
Published: May 2013

Computational intelligence approaches is a relatively new interdisciplinary field of research with many promising application areas. Although the computational intelligence approaches have gained huge popularity, it is difficult to analyze the convergence. In this paper, a computational model is built up for a class of computational intelligence approaches represented by the canonical forms of generic algorithms, ant colony optimization, and particle swarm optimization in order to describe the common features of these algorithms. And then, two quantification indices, that is, the variation rate and the progress rate, are defined, respectively, to indicate the variety and the optimality of the solution sets generated in the search process of the model. Moreover, we give four types of probabilistic convergence for the solution set updating sequences, and their relations are discussed. Finally, the sufficient conditions are derived for the almost sure weak convergence and the almost sure strong convergence of the model by introducing the martingale theory into the Markov chain analysis.
Finite Element Analysis Design of a Split Rotor Bracket for a Bulb Turbine Generator
Authors: Luo Yongyao , Wang Zhengwei , Chen Liangnian , Wu Jinshui
Published: May 2013

The rotor bracket is a key component of the generator rotor with cracks in the rotor bracket leading to rubbing between the rotor and stator, which threatens safe operation of the unit. The rotor rim is so complicated that the equivalent radial stiffness of rim was determined by numerical simulation other than engineering experience. A comprehensive numerical method including finite element analyses and the contact method for multibody dynamics has been used to design the split rotor bracket. The com-putational results showed that cracks would occur in the initial design of the bracket when the turbine operated at the runaway speed, and the bracket design should be improved. The improved design of the bracket was strong enough to avoid cracks and rub between the rotor and stator. This design experience will help improve the design of split rotor brackets for bulb turbine generators.
A New Herbal Formula, KSG-002, Suppresses Breast Cancer Growth and Metastasis by Targeting NF-κB-Dependent TNFαProduction in Macrophages
Authors: Woo Sang-Mi , Choi Youn Kyung , Cho Sung-Gook , Park Sunju , Ko Seong-Gyu
Published: May 2013

Tumor-associated macrophages (TAMs) in tumor microenvironment regulate cancer progression and metastases. In breast cancer, macrophage infiltration is correlated with a poor prognosis. While metastatic breast cancer is poor prognostic with a severe mortality, therapeutic options are still limited. In this study, we demonstrate that KSG-002, a new herbal composition of radicesAstragalus membranaceusandAngelica gigas, suppresses breast cancer via inhibiting TAM recruitment. KSG-002, an extract of radicesAstragalus membranaceusandAngelica gigasat 3 : 1 ratio, respectively, inhibited MDA-MB-231 xenograft tumor growth and pulmonary metastasis in nude mice, while KSG-001, another composition (1 : 1 ratio,w/w), enhanced tumor growth, angiogenesis, and pulmonary metastasis,in vivo. KSG-002 further decreased the infiltrated macrophage numbers in xenograft tumor cohorts. In Raw264.7 cells, KSG-002 but not KSG-001 inhibited cell proliferation and migration and reduced TNF-alpha (TNFα) production by inhibiting NF-κB pathway. Furthermore, a combinatorial treatment of KSG-002 with TNFαinhibited a proliferation and migration of both MDA-MB-231 and Raw264.7 cells. Taken together, we conclude that KSG-002 suppresses breast cancer growth and metastasis through targeting NF-κB-mediated TNFαproduction in macrophages.
Synchronization of Switched Complex Bipartite Neural Networks with Infinite Distributed Delays and Derivative Coupling
Authors: Bian Qiuxiang , Cao Jinde , Wu Jie , Yao Hongxing , Zhang Tingfang , Ling Xiaoxu
Published: May 2013

A new model of switched complex bipartite neural network (SCBNN) with infinite distributed delays and derivative coupling is established. Using linear matrix inequality (LMI) approach, some synchronization criteria are proposed to ensure the synchronization between two SCBNNs by constructing effective controllers. Some numerical simulations are provided to illustrate the effectiveness of the theoretical results obtained in this paper.
Exponential Stability in Mean Square for Neutral Stochastic Partial Functional Differential Equations with Impulses
Authors: Ding Nan
Published: May 2013

We discuss the exponential stability in mean square of mild solution for neutral stochastic partial functional differential equations with impulses. By applying impulsive Gronwall-Bellman inequality, the stochastic analytic techniques, the fractional power of operator, and semigroup theory, we obtain some completely new sufficient conditions ensuring the exponential stability in mean square of mild solution for neutral stochastic partial functional differential equations with impulses. Finally, an example is provided to illustrate the obtained theory.
Extralaryngeal Terminal Division of the Inferior Laryngeal Nerve: Anatomical Classification by a Surgical Point of View
Authors: Gurleyik Emin
Published: May 2013

Background. Complete anatomic knowledge including all variations of the inferior laryngeal nerve (ILN) is mandatory for thyroid surgeon. Extralaryngeal terminal division (ETD) of the ILN has significant importance for the safety of thyroidectomy.Material and Methods. Surgical dissection of 200 ILNs was performed on 100 cases. The presence of ETD of the nerve was determined intraoperatively. We propose by a surgical point of view a regional (segmental) classification of ETD of the ILN along its cervical course.Results. ETD has been observed in 54/200 nerves (27%). Great majority are bifurcated nerves (trifurcation 2%). Four types of ETD are classified. In type 1 (arterial; 46.3%), ETD has occurred near inferior thyroid artery (ITA). In type 2 (postarterial; 31.5%), division has been found on postarterial segment. In type 3 (prelaryngeal; 11%), division has been located very close to laryngeal entry point. In type 4 (prearterial; 11%), ETD has occurred before the nerve crossing the ITA.Conclusions. ETD of the ILN is a common anatomical variation. The bifurcation occurs in the ILN at various distances from laryngeal entry point. The classification increasing surgeons’ awareness may help to simplify identification and exposure of terminal branches. Preservation of both extralaryngeal terminal branches of the ILN has paramount importance for the safety of thyroid operations.
Metabolic Syndrome in Iranian Youths: A Population-Based Study on Junior and High Schools Students in Rural and Urban Areas
Authors: Ahmadi Alireza , Gharipour Mojgan , Nouri Fatemeh , Sarrafzadegan Nizal
Published: May 2013

Aim. The present population-based study aimed to assess prevalence of metabolic syndrome and itsrelated components in Iranian youth in the different sex, age, and residential subgroups.Method. Overall, 1039 junior high school and 953 high school students were selected using multistage random sampling. Fasting blood sugar, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were determined. Trained individuals measured waist circumference and blood pressure. Subjects with MetS were selected according to two definitions provided by the IDF and de Ferranti.Results. Among girls in intervention area, hypertriglyceridemia was more prevalent in rural than in urban areas using IDF definition. Significant differences were observed between boys in rural and urban areas regarding some components of metabolic syndrome including hypertriglyceridemia and high waist circumference. Besides, boys who are residents in urban areas had higher blood pressure, as well as higher waist circumference, than boys in rural areas.Conclusion. Our youth population is at significant risk of developing metabolic syndrome, and the pattern of this phenomenon seems to be discrepant in boys as well as in rural and urban areas probably due to the different lifestyle aspects, genetic factors, and racial differences.
Research on the Behavior of the Steel Plated Shear Wall by Finite Element Method
Authors: Mortazavi S. M. R. , Ghassemieh M. , Ghobadi M. S.
Published: May 2013

From the early’ 70s till today, steel shear walls have been used as the primary lateral force resisting system in some of the significant buildings around the world. To assist understanding the behavior of this system, there have been research programs in USA, Canada, Japan, and UK. This research presents the dynamic and cyclic behavior of steel plated shear wall. In order to simulate the behavior of such a wall structure, finite element method of analysis is implemented. Several analytical models are implemented, in order to obtain the dynamic as well as cyclic behavior of such system. The material nonlinearity as well as geometrical nonlinearity along with the postbuckling behavior of steel plate subjected to cyclic loading has also been employed. The hysteresis diagrams of steel shear wall system in terms of storey shear drift are presented. The results obtained from the analyses are compared to some experimental results reported by other researchers previously. The nonlinear time history analysis of such system is carried out for different seismic response spectra. Finally, the significant factors and parameters of the steel plated shear wall which affect the overall behavior of such system are acknowledged and their effects were recognized.
Developing a New Two-Step Protocol to Generate Functional Hepatocytes from Wharton’s Jelly-Derived Mesenchymal Stem Cells under Hypoxic Condition
Authors: Prasajak Patcharee , Leeanansaksiri Wilairat
Published: May 2013

The shortage of donor livers and hepatocytes is a major limitation of liver transplantation. Thus, generation of hepatocyte-like cells may provide alternative choice for therapeutic applications. In this study, we developed a new method to establish hepatocytes from Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) cell lines named WJMSCs-SUT1 and WJMSCs-SUT2 under hypoxic condition. This new method could rapidly drive both WJ-MSCs cell lines into hepatic lineage within 18 days. The achievement of hepatogenic differentiation was confirmed by the characterization of both phenotypes and functions. More than 80% MSCs-derived hepatocyte-like cells (MSCDHCs) achieved functional hepatocytes including hepatic marker expressions both at gene and protein levels, glycogen storage, low-density lipoprotein uptake, urea production, and albumin secretion. This study highlights the establishment of new hepatogenic induction protocol under hypoxic condition in order to mimic hypoxic microenvironment in typical cell physiology. In conclusion, we present a simple, high-efficiency, and time saving protocol for the generation of functional hepatocyte-like cells from WJ-MSCs in hypoxic condition. The achievement of this method may overcome the limitation of donor hepatocytes and provides a new avenue for therapeutic value in cell-based therapy for life-threatening liver diseases, regenerative medicine, toxicity testing for pharmacological drug screening, and other medical related applications.
Posterior Lamellar Graft Preparation: A Prospective Review from an Eye Bank on Current and Future Aspects
Authors: Parekh Mohit , Salvalaio Gianni , Ruzza Alessandro , Camposampiero Davide , Griffoni Carlo , Zampini Alfonso , Ponzin Diego , Ferrari Stefano
Published: May 2013

Descemet membrane endothelial keratoplasty (DMEK) is a corneal surgical technique which selectively replaces the damaged posterior part of the cornea with a healthy donor graft retaining the rest of the tissue intact. There is a need to validate and standardize the donor tissue before grafting due to certain issues that can lead to consequences such as graft failure due to poor endothelial cell count, higher mortality, detachment of the graft, or increased surgical expenses, time, and effort. Thus, prospective potential surgeons and eye banks should now aim at developing new improved surgical techniques in order to prepare the best suited, validated, precut, preloaded, and easy to transplant tissue to reduce pre- and postsurgical complications. This could be achieved by defining parameters like graft thickness, accepted mortality threshold of the endothelial cells, and behavior of grafts during preservation and transportation along with using more sophisticated instruments like microkeratome and femtosecond lasers for graft preparation. Thus, a rapport between the eye banks and the surgeons along with the advanced instruments can overcome this challenge to find the best possible solution for endothelial keratoplasty (EK).
Experiments on the Porch Swing Bearing of Michelson Interferometer for Low Resolution FTIR
Authors: Välikylä Tuomas , Kauppinen Jyrki
Published: May 2013

Porch swing bearing for the linear motion of the mirror in Michelson interferometer for mid-infrared low resolution Fourier transform spectrometer was studied experimentally using the modulation depth of the collimated laser beam. The mirror tilting was measured to be lower than 5 μrad over 3 mm mirror travel using two different bearings assemblies. Additionally, the manufacturing tolerances of the bearing type were proved to be loose enough not to limit the interferometer application. These demonstrate that the porch swing without any adjustment mechanisms provides the sufficient motion linearity.
Chromatin Regulator PRC2 Is a Key Regulator of Epigenetic Plasticity in Glioblastoma
Authors: Natsume Atsushi , Ito Motokazu , Katsushima Keisuke , Ohka Fumiharu , Hatanaka Akira , Shinjo Keiko , Sato Shinya , Takahashi Satoru , Ishikawa Yuta , Takeuchi Ichiro , Shimogawa Hiroki , Uesugi Motonari , Okano Hideyuki , Kim Seung U. , Wakabayashi Toshihiko , Issa Jean-Pierre J. , Sekido Yoshitaka , Kondo Yutaka
Published: May 2013

Tumor cell plasticity contributes to functional and morphologic heterogeneity. To uncover the underlying mechanisms of this plasticity, we examined glioma stem-like cells (GSC) where we found that the biologic interconversion between GSCs and differentiated non-GSCs is functionally plastic and accompanied by gain or loss of polycomb repressive complex 2 (PRC2), a complex that modifies chromatin structure. PRC2 mediates lysine 27 trimethylation on histone H3 and in GSC it affected pluripotency or development-associated genes (e.g., Nanog, Wnt1, and BMP5) together with alterations in the subcellular localization of EZH2, a catalytic component of PRC2. Intriguingly, exogenous expression of EZH2-dNLS, which lacks nuclear localization sequence, impaired the repression of Nanog expression under differentiation conditions. RNA interference (RNAi)–mediated attenuation or pharmacologic inhibition of EZH2 had little to no effect on apoptosis or bromodeoxyuridine incorporation in GSCs, but it disrupted morphologic interconversion and impaired GSC integration into the brain tissue, thereby improving survival of GSC-bearing mice. Pathologic analysis of human glioma specimens revealed that the number of tumor cells with nuclear EZH2 is larger around tumor vessels and the invasive front, suggesting that nuclear EZH2 may help reprogram tumor cells in close proximity to this microenvironment. Our results indicate that epigenetic regulation by PRC2 is a key mediator of tumor cell plasticity, which is required for the adaptation of glioblastoma cells to their microenvironment. Thus, PRC2-targeted therapy may reduce tumor cell plasticity and tumor heterogeneity, offering a new paradigm for glioma treatment. Cancer Res; 73(14); 4559–70. ©2013 AACR.
Molecular Pathways: Reactive Oxygen Species Homeostasis in Cancer Cells and Implications for Cancer Therapy
Authors: Nogueira Veronique , Hay Nissim
Published: May 2013

Reactive oxygen species (ROS) are important in regulating normal cellular processes, but deregulated ROS contribute to the development of various human diseases, including cancers. Cancer cells have increased ROS levels compared with normal cells, because of their accelerated metabolism. The high ROS levels in cancer cells, which distinguish them from normal cells, could be protumorigenic, but are also their Achilles' heel. The high ROS content in cancer cells renders them more susceptible to oxidative stress–induced cell death, and can be exploited for selective cancer therapy. In this review, we describe several potential therapeutic strategies that take advantage of ROS imbalance in cancer cells by further increasing oxidative stress, either alone or in combination with drugs that modulate certain signaling pathways. Clin Cancer Res; 19(16); 4309–14. ©2013 AACR.
Strengthening Context-Dependent Anticancer Effects on Non–Small Cell Lung Carcinoma by Inhibition of Both MET and EGFR
Authors: Zhang Yu-Wen , Staal Ben , Essenburg Curt , Lewis Steven , Kaufman Dafna , Vande Woude George F.
Published: May 2013

The MET and EGFR receptor tyrosine kinases (RTK) are often coexpressed and may cross-talk in driving the development and progression of non–small cell lung carcinoma (NSCLC). In addition, MET amplification is an alternative resistance mechanism for escaping EGFR-targeted therapy. To assess the benefits of combined targeting of MET and EGFR for treating NSCLCs, we investigated the activities of these two RTK pathways in NSCLC cell lines and evaluated their responses to SGX523 and erlotinib, the small-molecule kinase inhibitors of MET and EGFR, respectively. We showed that MET interacts with and cross-activates EGFR in MET-amplified or -overexpressed cells. The inhibition of both MET and EGFR results in maximal suppression of downstream signaling and of cell proliferation when their ligands are present. Furthermore, we showed that SGX523 plus erlotinib strengthens anticancer activity in vivo in a cellular context–dependent manner. The combination led to the regression of H1993 tumors by enhancing the suppression of proliferation and inducing apoptosis, whereas H1373 tumor growth was significantly reduced by the combination via suppression of proliferation without inducing apoptosis. SGX523 alone was sufficient to achieve near-complete regression of EBC-1 tumors; its combination with erlotinib strongly inhibited the viability of a population of insensitive cells emerging from an SGX523-treated EBC-1 tumor recurrence. Our data suggest that inhibition of both MET and EGFR can enhance anticancer effects against NSCLCs in a context-dependent manner and thus provide a strong rationale for combining MET and EGFR inhibitors in treating NSCLCs. Mol Cancer Ther; 12(8); 1429–41. ©2013 AACR.
Pharmacologic Activation of PKM2 Slows Lung Tumor Xenograft Growth
Authors: Parnell K. Mark , Foulks Jason M. , Nix Rebecca N. , Clifford Adrianne , Bullough Jeremy , Luo Bai , Senina Anna , Vollmer David , Liu Jihua , McCarthy Virgil , Xu Yong , Saunders Michael , Liu Xiao-Hui , Pearce Scott , Wright Kevin , O'Reilly Marc , McCullar Michael V. , Ho Koc-Kan , Kanner Steven B.
Published: May 2013

Inactivation of the M2 form of pyruvate kinase (PKM2) in cancer cells is associated with increased tumorigenicity. To test the hypothesis that tumor growth may be inhibited through the PKM2 pathway, we generated a series of small-molecule PKM2 activators. The compounds exhibited low nanomolar activity in both biochemical and cell-based PKM2 activity assays. These compounds did not affect the growth of cancer cell lines under normal conditions in vitro, but strongly inhibited the proliferation of multiple lung cancer cell lines when serine was absent from the cell culture media. In addition, PKM2 activators inhibited the growth of an aggressive lung adenocarcinoma xenograft. These findings show that PKM2 activation by small molecules influences the growth of cancer cells in vitro and in vivo, and suggest that such compounds may augment cancer therapies. Mol Cancer Ther; 12(8); 1453–60. ©2013 AACR.
Preclinical Evaluation of Transcriptional Targeting Strategy for Human Hepatocellular Carcinoma in an Orthotopic Xenograft Mouse Model
Authors: Sia Kian Chuan , Huynh Hung , Chung Alexander Yaw Fui , Ooi London Lucien Peng Jin , Lim Kiat Hon , Hui Kam Man , Lam Paula Yeng Po
Published: May 2013

Gene regulation of many key cell-cycle players in S-, G2 phase, and mitosis results from transcriptional repression in their respective promoter regions during the G0 and G1 phases of cell cycle. Within these promoter regions are phylogenetically conserved sequences known as the cell-cycle–dependent element (CDE) and cell-cycle genes homology regions (CHR) sites. Thus, we hypothesize that transcriptional regulation of cell-cycle regulation via the CDE/CHR region together with liver-specific apolipoprotein E (apoE)-hAAT promoter could bring about a selective transgene expression in proliferating human hepatocellular carcinoma. We show that the newly generated vector AH-6CC-L2C could mediate hepatocyte-targeted luciferase gene expression in tumor cells and freshly isolated short-term hepatocellular carcinoma cultures from patient biopsy. In contrast, normal murine and human hepatocytes infected with AH-6CC-L2C expressed minimal or low luciferase activities. In the presence of prodrug 5-fluorocytosine (5-FC), AH-6CC-L2C effectively suppressed the growth of orthotopic hepatocellular carcinoma patient-derived xenograft mouse model via the expression of yeast cytosine deaminase (yCD) that converts 5-FC to anticancer metabolite 5-fluoruracil. More importantly, we show that combination treatment of AH-6CC-L2C with an EZH2 inhibitor, DZNep, that targets EpCAM-positive hepatocellular carcinoma, can bring about a greater therapeutic efficacy compared with a single treatment of virus or inhibitor. Our study showed that targeting proliferating human hepatocellular carcinoma cells through the transcriptional control of therapeutic gene could represent a feasible approach against hepatocellular carcinoma. Mol Cancer Ther; 12(8); 1651–64. ©2013 AACR.
An Unusual Location of Extraosseous Ewing's Sarcoma
Authors: Geens Lisanne , Van Robays Johan , Geert Verswijvel , Van der Speeten Kurt
Published: May 2013

Ewing's sarcoma (ES) is the second most common malignant bone tumor in children and young adults. ES also occurs as a primary soft tissue neoplasm without involvement of bone. We report the second case of extraosseous (EO) ES emerging from the omentum and a review of the relevant literature. EO ES should be included in the differential diagnosis of soft tissue neoplasms in the abdomen.
ATP-Binding Cassette B10 Regulates Early Steps of Heme Synthesis
Authors: Bayeva Marina , Khechaduri Arineh , Wu Rongxue , Burke Michael A. , Wasserstrom J. Andrew , Singh Neha , Liesa Marc , Shirihai Orian S. , Langer Nathaniel B. , Paw Barry H. , Ardehali Hossein
Published: May 2013

Rationale:

Heme plays a critical role in gas exchange, mitochondrial energy production, and antioxidant defense in cardiovascular system. The mitochondrial transporter ATP-binding cassette (ABC) B10 has been suggested to export heme out of the mitochondria and is required for normal hemoglobinization of erythropoietic cells and protection against ischemia–reperfusion injury in the heart; however, its primary function has not been established.

Objective:

The aim of this study was to identify the function of ABCB10 in heme synthesis in cardiac cells.

Methods and Results:

Knockdown of ABCB10 in cardiac myoblasts significantly reduced heme levels and the activities of heme-containing proteins, whereas supplementation with δ-aminolevulinic acid reversed these defects. Overexpression of mitochondrial δ-aminolevulinic acid synthase 2, the rate-limiting enzyme upstream of δ-aminolevulinic acid export, failed to restore heme levels in cells with ABCB10 downregulation. ABCB10 and heme levels were increased by hypoxia, and reversal of ABCB10 upregulation caused oxidative stress and cell death. Furthermore, ABCB10 knockdown in neonatal rat cardiomyocytes resulted in a significant delay of calcium removal from the cytoplasm, suggesting a relaxation defect. Finally, ABCB10 expression and heme levels were altered in failing human hearts and mice with ischemic cardiomyopathy.

Conclusions:

ABCB10 plays a critical role in heme synthesis pathway by facilitating δ-aminolevulinic acid production or export from the mitochondria. In contrast to previous reports, we show that ABCB10 is not a heme exporter and instead is required for the early mitochondrial steps of heme biosynthesis.
Book Reviews
Authors: Wils J. , Drabbe P. , Teeuw A. , Hooykaas C. , Teeuw A. , Hooykaas C. , Teeuw A. , Hooykaas C. , Gonda J. , Nobel Joh. , Hooykaas C.
Published: May 2013

- J. Wils, P. Drabbe, Spraakkunst van het Ekagi, Wisselmeren Ned. N. Guinea, XXI + 90 pag., ‘s-Gravenhage, M. Nijhoff 1952. - A. Teeuw, C. Hooykaas, Literatuur in Maleis en Indonesisch, J.B. Wolters, Groningen-Djakarta 1952, 406 ppg. - A. Teeuw, C. Hooykaas, Perintis sastera, terdjemahan Raihoel Amar gl. Datoek Besar; J.B. Wolters, Groningen-Djakarta 1951, 406 pgg. - A. Teeuw, C. Hooykaas, Penjedar sastera, terdjemahan Raihoel Amar gl. Datoek Besar; J.B. Wolters, Groningen-Djakarta 1952, 245 pgg. - C. Hooykaas, Sedjarah Melaju, menurut terbitan Abdullah (ibn Abdulkadir Munsji) diselenggarakan kembali dan diberi anotasi oleh T.D. Situmorang dan Prof. Dr A. Teeuw dengan bantuan Amal Hamzah. Penerbit Djambatan. Djakarta/Amsterdam 1952. - J. Gonda, Joh. Nobel, Central Asia: The connecting link between east and west, and other lectures delivered at The International Academy of Indian Culture, Nagpur 1952.
Mededelingen
Authors: KITLV Redactie
Published: May 2013

Gegevens betreffende het Lembaga Kebudajaan Indonesia (= Koninklijk Bataviaasch Genootschap)
The identity of Aster lushiensis (Asteraceae)
Authors: FU ZHIXI , ZHANG CAIFEI , GAO TIANGANG
Published: May 2013

Aster lushiensis (J.Q.Fu 1983: 110) Brouillet, Semple & Y.L.Chen (2011: 607) (Astereae, Asteraceae) was recently combined from the genus Gymnaster Kitamura (1937: 301) (=Miyamayomena Kitamura (1982: 409)) without a study of specimens. It is only known from the type specimens collected in Lushi County, Henan Province, China. Examination of morphological characters of types showed that it is conspecific with Chrysanthemum vestitum (Hemsley 1888: 438) Stapf (1933: t. 9330) (Anthemideae; Shih et al. 2011), and is here reduced to a synonym of the latter species.
The Ancient Blue Oak Woodlands of California: Longevity and Hydroclimatic History
Authors: Stahle D. W. , Griffin R. D. , Meko D. M. , Therrell M. D. , Edmondson J. R. , Cleaveland M. K. , Stahle L. N. , Burnette D. J. , Abatzoglou J. T. , Redmond K. T. , Dettinger M. D. , Cayan D. R.
Published: May 2013

Ancient blue oak trees are still widespread across the foothills of the Coast Ranges, Cascades, and Sierra Nevada in California. The most extensive tracts of intact old-growth blue oak woodland appear to survive on rugged and remote terrain in the southern Coast Ranges and on the foothills west and southwest of Mt. Lassen. In the authors' sampling of old-growth stands, most blue oak appear to have recruited to the canopy in the middle to late nineteenth century. The oldest living blue oak tree sampled was over 459 years old, and several dead blue oak logs had over 500 annual rings. Precipitation sensitive tree-ring chronologies up to 700 years long have been developed from old blue oak trees and logs. Annual ring-width chronologies of blue oak are strongly correlated with cool season precipitation totals, streamflow in the major rivers of California, and the estuarine water quality of San Francisco Bay. A new network of 36 blue oak chronologies records spatial anomalies in growth that arise from latitudinal changes in the mean storm track and location of landfalling atmospheric rivers. These long, climate-sensitive blue oak chronologies have been used to reconstruct hydroclimatic history in California and will help to better understand and manage water resources. The environmental history embedded in blue oak growth chronologies may help justify efforts to conserve these authentic old-growth native woodlands.
International Framework Agreements and the democratic deficit of global labour governance
Authors: Niforou Christina
Published: May 2013

Democratization beyond the nation-state level has been on the scholarly agenda of international political economists since the early 1990s. Academic debates have generated a mushrooming literature on the ‘democratic deficit’ of global governance. In the field of industrial relations, scholarly interest on the relevance of democracy has translated into a rich body of literature on workplace democracy. Yet, research has been concerned with the national and local levels largely neglecting the transnational dimension. This article discusses the potential of International Framework Agreements (IFAs) to address the democratic deficit of the global governance of labour. In doing so, it borrows notions largely established in the field of international political economy and applies them to an industrial relations problem (i.e. impact of IFAs on the ground) drawing on case-study evidence from three IFAs in the telecoms, energy and apparel sectors. The article examines what accounts for IFAs’ capacity for representation, legitimacy, accountability and transparency.
Insecure Status Relations Shape Preferences for the Content of Intergroup Contact
Authors: Saguy Tamar , Dovidio John F.
Published: May 2013

Recent work demonstrated that whereas high-status and low-status group members seek to address cross-group commonalities during intergroup contact, members of low-status groups show a greater desire to discuss status differences between the groups. Drawing on social identity theory, the current research investigated the combined influence of status legitimacy and status stability on these contact preferences. In Study 1, perceived stability and perceived legitimacy were measured among members of a high-status ethnic group in Israel. In Study 2, group status, status stability, and status legitimacy were experimentally manipulated in a U.S. sample. Although they generally preferred to discuss commonalities over status differences, across studies high-status group members’ willingness to discuss status differences increased when they perceived the hierarchy as illegitimate but stable. By contrast, low-status group members were particularly inclined to address status differences and least interested in discussing commonalties, when the hierarchy was illegitimate and unstable.
Facial Lesions Negatively Impact Affect Display
Authors: Godoy Andres , Ishii Masaru , Dey Jacob , Boahene Kofi D. O. , Byrne Patrick J. , Ishii Lisa E.
Published: May 2013

Objective

To evaluate the impact of facial lesions on affect display in patients as compared with individuals without lesions.

Study Design

Prospective randomized controlled experiment.

Setting

Academic tertiary referral center.

Subjects and Methods

Forty‐five normal observers viewed photographs of normal faces in repose and faces with lesions in repose. Observers classified the affect display of the patients and the normals using a survey containing choices of primary emotions and personal attributes. Latent class analysis was used to find the unmeasured or “latent” classes. Latent class regression was used to determine the impact of lesion size and location on class membership. Finally, lesion classes and normal classes were checked for differences.

Results

Latent class analysis identified 4 independent latent classes for faces with lesions. The normal data were best fit by 3 latent classes. As a group, faces with lesions were most likely to be classified as either negative‐sad or negative‐angry, accounting for a combined probability of 44%. This was in contrast to the normal group, where 62% were classified as positive and only 13.9% as negative. Size and location significantly affected negative class membership. There were significant differences in the lesion classes as compared with the normal classes.

Conclusion

Faces with lesions were reported to display different affect in repose than normal faces in repose. The classification of the lesion faces was dependent on lesion size and location. These findings provide the first objective evidence of the affect display penalty caused by facial lesions.
Traversing the Heavens: The State of Scholarship on 3 Baruch
Authors: Hilton Naomi Henare
Published: May 2013

It is often remarked that 3 Baruch has been largely overlooked by scholarship. This article explores how this situation has arisen and what the implications might be. By examining the history of scholarship on 3 Baruch, this article proposes that several factors have been at work. First, the challenging nature of the text itself: it is often confusing, it assumes significant prior knowledge in the audience, and it exists in Greek and Old Church Slavonic versions that vary in content. Second, and more significantly, the initial negative reception set a tone that influenced much subsequent scholarship. Third, the vagaries of academic interest have often consigned 3 Baruch to the sidelines. Instances where it has fit the trend have generally produced introductory material, but little exegesis. These factors have, until recently, led scholarship to overlook the exegetical value of the Slavonic tradition, and more broadly, to undervalue 3 Baruch as a source for the study of early Judaism and Christianity. This article encourages a more sympathetic attitude to 3 Baruch and a more critical approach to academic inquiry.
Was Daniel 7.13's ‘Son of Man’ Modeled after the ‘New Adam’ of the Animal Apocalypse (1 Enoch 90)? A Comparative Study
Authors: Joseph Simon J.
Published: May 2013

1 Enoch (1 En.) has become a major site of discussion in contemporary biblical scholarship. Its evident use by the Qumran community, citation in Jude, and canonical status in the Ethiopian Church all illustrate its significance in Second Temple Judaism despite its non-canonical status in rabbinical Judaism and orthodox Christianity. This article compares the ‘son of man’ figure from Daniel 7 and the eschatological ‘Adam’ or ‘white bull’ from the Animal Apocalypse ( 1 En. 90) in an attempt to determine whether direct literary dependence between these two contemporary texts can be posited in either direction.