bluuebunny/crossref_metadata_2025 huggingface dataset:
Velocity of Entrainments Formed by High Velocity Air Jet Flow in Stagnant Water
Authors: Akabane Masaaki , Koizumi Yasuo , Uchibori Akihiro , Kamide Hideki , Ohshima Hiroyuki
Published: November 2014

This study was intended to examine sodium entrainment behavior in the case that a hole was formed on a tube wall in the steam generator of a fast breeder reactor and high pressure and high temperature water jetted out into sodium. Flow visualization experiments of an air jet in liquid were performed. The test vessel was 270 mm wide, 5 mm depth and 300 mm high. The air jet was blown vertically upward into stagnant liquid in the test vessel from a rectangular cross-section nozzle of 1 mm wide, 5 mm depth and 20 mm long which was located at the bottom of the test vessel. A flow state of the jet in the liquid was recorded with a high speed video camera at the fastest 150,000 frame/s. The test liquid was water and kerosene. Filament-like ears and wisps pulled out from the wavy interface were noticed on the interface between liquid and the air jet. The ears and the wisps were broken off and entrained into the air jet. The droplets broke up to small entrainments. This process seemed quite similar to the entrainment process in the annular dispersed flow in a pipe. Entrainment was initiated at a little bit downstream from the nozzle outlet. The entrainment inception point moved downstream as the air jet velocity increased. Axial directional entrainment velocity increased as the air jet velocity increased and the entrainment proceeded downstream. Transversal directional entrainment velocity was much slower than the axial directional entrainment velocity. The variation of the entrainment velocity in the transversal direction was not so prominent. The entrainments produced at the interface of the air jet moved to gather at the center portion of the air jet as those were accelerated.
Nodalization of NEK in APROS and Steady State Simulation
Authors: Polach Tadeja , Debelak Klemen , Bašić Ivica , Štrubelj Luka
Published: November 2014

A model of the primary circuit and part of the secondary circuit of the Slovenian Krško NPP – NEK was built using APROS - Advanced PROcess Simulation environment. The data used to describe the properties of the system modelled in APROS, were the data describing Krško NPP and its operational properties after the uprating and the introduction of the 18-month cycle. Basis for data collections, nodalization, structure and simplifications was NEK RELAP5\MOD3.3 Engineering Handbook and the 23rd cycle.

In order to build a model describing all the important parameters, the available elements in APROS environment were used as building blocks for each system. The goal was to create a detailed model nodalization, which would give accurate results and would run on reasonable processing power. Each submodel was checked to verify that the partial results are within the allowable limits and that the description of the physical parameters is consistent with the real components. The model includes reactor pressure vessel, reactor coolant pumps and primary piping, steam generator, part of main steam, part of feedwater, pressurizer and reactor core kinetics. The regulation of pressurizer level and pressure, steam generator level and control rod is also modelled. The model consists of more than 400 thermal hydraulic volumes. The aim of building this model was a through thermal hydraulic analysis of the PWR systems present in the NPP Krško. Several simulations of the steady states at different power levels were performed. The resulting data describing the flow rates in steam generator feedwater, reactor pressure vessel, including bypass flows, heat transfer in reactor core and steam generator, thermal losses to containment, liquid level in pressurizer and steam generator, pressure drops in primary circuit and other parameters were then compared to the results of different types of calculation and to the testing data obtained from Krško NPP. The next step was to identify variations in results and determine whether they are consequence of wrong parameters, measurement deviation or numerical error. In that manner the model was verified and validated (in the sense of comparison with available system surveillance plant test results) to ensure the correct setup, initial and boundary conditions were applied in order to get reliable steady state results.
Sub-Channel Analysis of Pb-Bi-Cooled Reactor With Modified COBRA-EN
Authors: Tian Yonghong , Tian Wenxi , Meng Zhaoming , Wu Yingwei , Su Guanghui , Qiu Suizheng
Published: November 2014

Lead-bismuth eutectic (LBE) cooled fast reactor, one of the six types of reactors in Gen-IV, has very good inherent safety and significant advantages in reducing and burning nuclear wastes, enhancing economy. Also LBE cooled accelerator driven system (ADS) has been a very innovative and potential waste burner. COBRA-EN is a mature, stable and widely-used sub-channel analysis code for light water cooled reactor but it couldn’t be applied in Pb-Bi-cooled reactor directly. Some modifications were made for COBRA-EN in the present work, then the code was named COBRA-PB and was suitable for the sub-channel analysis of Pb-Bi-cooled reactor. The modified code was verified and validated with CFX and experimental results. There was a good agreement between the two results. Then sub-channel analysis of Pb-Bi-cooled reactor was done with the modified code.
Research on the Local Neutronics Thermal-Hydraulic Coupled Response of a PWR During Hypothetical Blockage Scenarios
Authors: Li Xiaorong , Peng Shinian
Published: November 2014

The phenomenon of the partial flow blockage of a fuel assembly in a reactor core is investigated with a coupled 3D neutronics/thermal-hydraulics code in order to account for the space reactivity feedback effect which is of great importance during hypothetical blockage scenarios. This paper identifies the neutronics thermal-hydraulics coupled response in the blocked assembly during the transient and analyzes the details of the phenomenon.
Development of a Quality Manual for Radioisotope Production Plants
Authors: Tawfik Yasser E.
Published: November 2014

The purpose of issuing a quality manual for the radioisotope production plants is to define and describe the quality system implemented by the plant. It provides general procedures for all activities comprising the quality system, defines the authorities and responsibilities of all personnel affected by the system and provides a way to inform our customers of the specific controls that are in place at radioisotope production plants to assure continued product quality. Such a quality manual is regularly updated to depict the quality management system implemented by radioisotope production plant as accurately as possible.

Example of this type of quality manual is developed for the radioisotope production facility (RPF) located in ETRR-2 Complex site – Egyptian Atomic Energy Authority – Inshas-EGYPT.
Kalman Filter Based Predictive Trip Detection for Nuclear Power Plant Safety Systems
Authors: Rankin Drew J. , Jiang Jin
Published: November 2014

The primary aim of this work is to utilize a Kalman filter (KF) to predict reaching the trip set-point for a trip parameter in a nuclear power plant (NPP). To address uncertainty in the predicted measurements, prediction bounds are calculated by propagating the state error covariance. These predicted bounds enable the calculation of levels of confidence in making trip decisions. Further, to address uncertainty in the estimation model, the observed prediction error is used to offset the predicted measurements.

The predictive trip detection routines are evaluated through simulations of a single NPP sub-system. More specifically, the water level parameter in a steam generator of a NPP is considered. The model of this sub-system is represented by the Irving linear parameter varying (LPV) model with inverse response characteristics. The simulations include a level low postulated initiating event (PIE) made to occur during two different common power transients for various estimation models. The results of this paper are a proof of concept for KF-based predictive trip detection which is demonstrated to achieve reduced time-to-trip when applied to a single sub-system.
Synthesis of Nanostructured Fuels: Mimicking the High Burn-Up Structure
Authors: Tyrpekl Vaclav , Jovani-Abril Raquel , Holzhäuser Michael
Published: November 2014

During its lifetime in the core of a nuclear reactor, the fuel undergoes significant changes in its physical, chemical and morphological characteristics. In outer regions of the fuel pellets the so called “high burn-up” or “rim” structure may form. In this region UO2 grains, with an original size of about 10 μm in fresh dense fuel, are reorganized into a porous structure with grain size 0.1–0.3 μm and porosity fraction up to 20 %. The mechanical, thermal and fission product retention properties of the high burn-up structure have encouraged further interest and attempts to mimic this morphology in fresh fuel. The JRC-ITU has studied various techniques for the synthesis of uranium and thorium dioxide in aqueous or nonaqueous media. Such nanoparticles can serve as starting material for production of material having similar characteristics as the high burn-up structure, as has been proved using Zr(Y)O2 nanoparticles. Recently, efforts have been focused on the compaction of the nanoparticle powders. A spark plasma sintering device (SPS, FCT Systeme GmbH) has been commissioned in the JRC-ITU and tested using various nonradioactive materials. The present study is oriented on pressing and sintering of Hf(Y)O2 and ZrO2 into nanostructured pellets. Final products have been characterized by optical and electron microscopy, X-ray powder diffraction and density measurements.
Exposure to Low Doses of Ionizing Radiation: Is the Linear No-Threshold Model Valid?
Authors: Giannoni Luca , Mazzini Marino
Published: November 2014

The risk assessment for population’s exposures to low doses and low dose-rates of ionizing radiation is still subject to clear uncertainties. The issue has outstanding societal importance in relation to radiologic occupational safety, medical applications of radiation, effects of the natural background radioactivity and the future of nuclear power, due to its particular influence on the public acceptance of this form of energy.

This review article analyzes, in a critical, historical and bibliographical manner, the worldwide accepted hypothesis of linearity without a threshold dose (LNT model). As well known, it rejects, from its first proposal in 1946 by American geneticist and Nobel laureate Hermann J. Muller, the concept of zero-risk for exposures to any dose level of ionizing radiation.

The starting point is the dose-effects relationship provided by this model and related risk’s excess graphic curve. The biological and physical motivations for the linearity assumption are argued and challenged by the explanation of human body’s natural defense mechanisms and its repair capacity of the radiation damage.

Furthermore, the historical and political truthfulness of the LNT model is also contested by the review of a recent investigation by Prof. Edward Calabrese, regarding the lack of scientific sources behind Muller’s Nobel Prize Lecture. Calabrese’s inquiry demonstrates that Muller, at the moment of his declaration on LNT model’s validity, had experimental proofs contradicting his conclusions about the unacceptability of a threshold dose. This finding is of historical importance since Muller’s Nobel Lecture is a turning point in the acceptance of the linearity model in risk assessment by the major regulatory agencies till today.

Finally, the results of many epidemiological and statistical studies are shown specifically. They give further evidences concerning the inapplicability of the LNT model and its overestimation of the risk for various cases of exposures to low doses of ionizing radiation in different fields. By that, hormesis model is also discussed, with its assumption of possible benefits for the organism following low dose exposures: a dose-response model characterized by low-dose stimulation and high-dose inhibition, which has been frequently observed in the aforementioned studies.

The argumentations and the experimental evidences provided here challenge the validity of the LNT model. We contest the fact that its establishment is principally based on a cautionary philosophy on nuclear public safety, rather than on actual scientific comprehension of the phenomenon. As such, it implies an exaggerated conception of the radiological hazard. In particular, this article calls attention to the need for a deeper understanding of the biological impact of low doses of ionizing radiation and the development of further specific and exhaustive researches.
Using the Reflectometric Technique for Monitoring the Boiling Flow Dynamics in a Once Through Steam Generator
Authors: Cordella Francesco , Cappelli Mauro , Sepielli Massimo
Published: November 2014

In control systems design for nuclear facilities, the correct choice for sensors, transducers and actuators is not an easy task when different options must be evaluated. In particular, for a Once Through Steam Generator (OTSG), the control of its boiling flow dynamics is usually performed with sensors that may be slow in response, must be placed all through the zone of interest (or need heavy mechanical modifications) and may not distinguish correctly when the liquid/steam interface is not so well defined at high temperatures and pressures. In this paper, a theoretical study about a reflectometric technique applied to an OTSG is proposed. This technique can be used also for the liquid/steam levels monitoring of the boiling flow. The overall behaviour of the variables of interest and the first theoretical results show the benefits of such an innovative approach.
Design of Control Systems for Nuclear Plant Processes: A Hardware-in-the-Loop Simulation Approach
Authors: Cappelli Mauro , Di Gennaro Stefano , Memmi Fabrizio
Published: November 2014

Nuclear domain can be considered as a challenging field of application for control systems and the related electronic technology. A prototypal version for controllers is often mandatory for a preventive test and performance evaluation. Control engineers often develop very accurate model of a specific process with very sophisticated control laws using a simulation environment. Even if simulations are fundamental for studying the process and selecting the best control technique, this theoretical effort can be a critical issue for the subsequent hardware implementation of the controller on real electronic devices, leading to a difficult conversion from software to hardware. In this context, the so called Hardware-In-the-Loop HIL simulations is a valid help, allowing a plant process to be simulated in a real time environment and the control unit to be realized on a real component and included in the whole simulation. In this work, HIL simulations are presented and compared to fully software simulations in case of the prototype realization of a pressure controller for a Pressurized Water Reactor PWR. Digital hardware technology is here introduced from the scratch into the project, and the physical implementation of the control unit is taken into account from the beginning, with a significant improvement of the accuracy of the controller in the real process. The control unit is based on a Field-Progammable-Gate-Array (FPGA), a widespread device for real-time control. FPGAs let designers to program a wide number of digital gates in their functionalities with a intrinsic determinism. In addition, processes can be managed in a real parallelism and without the resource sharing as in a CPU operating system. Results demonstrate the effectiveness of such an approach.
Experimental Study of Moderator Circulation in CANDU6 Calandria Tank
Authors: Kim Hyoung Tae , Seo Han , Im Sunghyuk , Rhee Bo Wook , Cha Jae Eun
Published: November 2014

As a CANDU6 reactor has a high pressure primary cooling system and an independently cooled moderator system, the moderator in the calandria would act as a supplementary heat sink during a loss of coolant accident (LOCA) if the primary cooling and emergency coolant injection systems fail to remove the decay heat from the fuel. For the safety concern it is required to predict the 3-dimensional velocity and temperature distribution of moderator fluid to confirm the effectiveness of moderator heat sink.

Korea Atomic Energy Research Institute (KAERI) is carrying out a scaled-down moderator test program to simulate the CANDU6 moderator circulation phenomena during steady state operation and accident conditions. This research program includes the construction of the Moderator Circulation Test (MCT) facility, production of the validation data for self-reliant CFD tools, and development of optical measurement system using the Particle Image Velocimetry (PIV). In the present work the PIV technique is used to measure the velocity distributions in the scaled moderator tank of MCT under iso-thermal test conditions. The preliminary PIV measurement data are obtained and compared with CFX code predictions.
Study of Refractory Material Installation in the Reactor Cavity
Authors: Moon Young Tae , Ryu In Chul , Zhou Quan , McMinn Paul , Paik Chan Y.
Published: November 2014

During a severe accident with a vessel failure, corium relocates from the vessel into the reactor cavity (PWR) or pedestal (BWR) and accumulates on top of the cavity floor to form a corium pool. This corium pool is hot enough to cause a Molten Corium-Concrete Interaction (MCCI) that can ablate the concrete structure even if water is present on top of the corium. MCCI will also produce steam and other gases that increase containment pressure as well as generate combustible gases (Hydrogen and Carbon Monoxide). Current MAAP5* calculations with conservative assumptions have shown that the ablation depth in a basemat constructed of siliceous concrete can be larger than the depth of liner, even if the reactor cavity is flooded by water. To retain the melt in the containment and to cool the corium pool before the erosion reaches the liner plate, several approaches are being considered. One of these approaches is the installation of a protective layer on top of the concrete floor to retard MCCI. The purpose of this paper is to study the performance of different protective materials under postulated severe accident conditions. The candidates for the protective materials are refractory materials and limestone/limestone-common-sand (LCS) concrete. The refractory material was chosen based on the thermal performance and dissolution rate of the refractory material calculated by analytical calculations and also by MAAP5. Adding the refractory protective material protects the underlying concrete basemat from melting temporarily, so that water ingression into the surface of the corium is not initially affected by addition of the concrete material.

*MAAP5 is an integrated severe accident code owned by the Electric Power Research Institute and developed by Fauske and Associates, LLC.
Genome Sequence of Tumebacillus flagellatus GST4, the First Genome Sequence of a Species in the Genus
Tumebacillus
Authors: Wang Qing-Yan , Xie Neng-Zhong , Huang Yan-Yan , Song Li-Fu , Du Qi-Shi , Yu Bo , Chen Dong , Huang Ri-Bo
Published: November 2014

We present here the first genome sequence of a species in the genus
Tumebacillus
. The draft genome sequence of
Tumebacillus flagellatus
GST4 provides a genetic basis for future studies addressing the origins, evolution, and ecological role of
Tumebacillus
organisms, as well as a source of acid-resistant amylase-encoding genes for further studies.
How to use: the direct antiglobulin test in newborns
Authors: Keir Amy , Agpalo Minda , Lieberman Lani , Callum Jeannie
Published: November 2014

The direct antiglobulin test (DAT) detects the presence of immunoglobulin, complement or both bound to the red blood cell membrane. The test, historically called the ‘Coombs test’, was first described in 1945 by Cambridge immunologist Robin Coombs. Suspected haemolytic disease of the newborn, due to either Rhesus disease or ABO incompatibility, is one of most common reasons for requesting a DAT in newborns. In this article, we discuss the physiological background and technological background of the DAT. We also provide a clinical framework for a rational approach to the use and interpretation of the DAT in newborns.
BALToma masquerading as pulmonary tuberculosis
Authors: Magazine Rahul , Shahul Hameed Aboobackar , Monappa Vidya , Chogtu Bharti
Published: November 2014

A 53-year-old man with a significant smoking history presented with chronic cough, exertional breathlessness, intermittent fever, weight loss and anorexia. A review of his past medical records revealed he was diagnosed to have sputum smear-positive pulmonary tuberculosis 5 years earlier, for which he had received multiple courses of incomplete antitubercular therapy. This time, though he was primarily suspected to have active pulmonary tuberculosis, lack of microbiological evidence and further investigations including histopathological evaluation of lung lesions confirmed a diagnosis of Marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALToma/BALToma). The patient was managed with radical radiation therapy to which he responded well.
The educational gradient in coronary heart disease: the association with cognition in a cohort of 57 279 male conscripts
Authors: Ariansen Inger , Mortensen Laust , Igland Jannicke , Tell Grethe S , Tambs Kristian , Graff-Iversen Sidsel , Strand Bjørn Heine , Næss Øyvind
Published: November 2014

Background

Independently of cardiovascular disease (CVD) risk factors, cognitive ability may account for some of the excess risk of coronary heart disease (CHD) associated with lower education. We aimed to assess how late adolescence cognitive ability and midlife CVD risk factors are associated with the educational gradient in CHD in Norway.

Methods

In a cohort of 57 279 men born during 1949–1959, health survey information was linked to military conscription records of cognitive ability, to national educational data, to hospitalisation records from the Cardiovascular Disease in Norway (CVDNOR) project and to the Norwegian Cause of Death Registry.

Results

Age and period adjusted HR for incident CHD events was 3.62 (95% CI 2.50 to 5.24) for basic relative to tertiary education, and was attenuated after adjustment; to 2.86 (1.87 to 4.38) for cognitive ability, to 1.90 (1.30 to 2.78) for CVD risk factors, and to 1.84 (1.20 to 2.83) when adjusting for both. Age and period adjusted absolute rate difference was 51 (33 to 70) incident CHD events per 100 000 person years between basic and tertiary educated, and was attenuated after adjustment; to 42 (22 to 61) for cognitive ability, to 25 (7 to 42) for CVD risk factors, and to 24 (5 to 43) when adjusting for both.

Conclusions

Late adolescence cognitive ability attenuated the educational gradient in incident CHD events. CVD risk factors further attenuated the gradient, and to the same extent regardless of whether cognitive ability was included or not. Cognitive ability might be linked to the educational gradient through CVD risk factors.
Conformational space analysis of neutral and protonated glycine using a genetic algorithm for multi-modal search
Authors: El Merbouh B. , Bourjila M. , Tijar R. , El Bouzaidi R. Drissi , El Gridani A. , El Mouhtadi M.
Published: November 2014

The genetic algorithm based on the Multi-Niche Crowding (MNC) method is used with the semi-empirical methods AM1 and PM3 in order to scan the potential energy surface (PES) of neutral and protonated glycine. The algorithm is implemented as a package of programs interfaced with MOPAC and piloted by scripts. Both methods AM1 and PM3 located six minima on the PES of neutral glycine and seven on the protonated glycine one, of which three are those of the N -protonated form and four of the O -protonated one.
Liquid crystalline properties of unsymmetrically substituted phthalocyanines: structural features leading to nematic mesophase materials
Authors: Garland Andrew D. , Bryant Geoffrey C. , Chambrier Isabelle , Cammidge Andrew N. , Cook Michael J.
Published: November 2014

A novel homologous series of four 1,4,8,11,15,18-hexakis(pentyl)-22-methyl-25-hydroxyalkylphthalocyanine derivatives with the hydroxyalkyl chain varying from hydroxynonyl through to hydroxydodecyl has been synthesized to investigate the role of the hydroxyalkyl chain in promoting thermotropic liquid crystalline behavior. Polarizing optical miscoscopy reveals that the compound with the shortest hydroxyalkyl chain (hydroxynonyl) exhibits a mesophase with a texture characteristic of a columnar mesophase, common among liquid crystalline phthalocyanine derivatives. However, as the chain is lengthened along the series, there appears a second type of mesophase that shows a schlieren texture. Such a texture is characteristic of a nematic phase and rare among liquid crystalline phthalocyanine derivatives. A fifth compound, the novel 1,4,8,11,15,18-hexakis(pentyl)-22-methyl-25-dodecylphthalocyanine, exhibits only columnar mesophase behavior suggesting that the hydroxyl group at the end of the longer chains of the former compounds is important in developing the nematic phase.
Neurally mediated propagating discrete clustered contractions superimposed on myogenic ripples in ex vivo segments of human ileum
Authors: Kuizenga Merel H. , Sia Tiong C. , Dodds Kelsi N. , Wiklendt Lukasz , Arkwright John W. , Thomas A. , Brookes Simon J. , Spencer Nick J. , Wattchow David A. , Dinning Phil G. , Costa Marcello
Published: November 2014

Narrow muscle strips have been extensively used to study intestinal contractility. Larger specimens from laboratory animals have provided detailed understanding of mechanisms that underlie patterned intestinal motility. Despite progress in animal tissue, investigations of motor patterns in large, intact specimens of human gut ex vivo have been sparse. In this study, we tested whether neurally dependent motor patterns could be detected in isolated specimens of intact human ileum. Specimens ( n = 14; 7–30 cm long) of terminal ileum were obtained with prior informed consent from patients undergoing colonic surgery for removal of carcinomas. Preparations were set up in an organ bath with an array of force transducers, a fiberoptic manometry catheter, and a video camera. Spontaneous and distension-evoked motor activity was recorded, and the effects of lidocaine, which inhibits neural activity, were studied. Myogenic contractions (ripples) occurred in all preparations (6.17 ± 0.36/min). They were of low amplitude and formed complex patterns by colliding and propagating in both directions along the specimen at anterograde velocities of 4.1 ± 0.3 mm/s and retrogradely at 4.9 ± 0.6 mm/s. In five specimens, larger amplitude clusters of contractions were seen (discrete clustered contractions), which propagated aborally at 1.05 ± 0.13 mm/s and orally at 1.07 ± 0.09 mm/s. These consisted of two to eight phasic contractions that aligned with ripples. These motor patterns were abolished by addition of lidocaine (0.3 mM). The ripples continued unchanged in the presence of this neural blocking agent. These results demonstrate that both myogenic and neurogenic motor patterns can be studied in isolated specimens of human small intestine.
Role of p38 MAPK pathway in 17β-estradiol-mediated attenuation of hemorrhagic shock-induced hepatic injury
Authors: Hsu Jun-Te , Chen Tsung-Hsing , Chiang Kun-Chun , Kuo Chia-Jung , Lin Chun-Jung , Yeh Ta-Sen
Published: November 2014

Although 17β-estradiol (E2) treatment following hemorrhagic shock or ischemic reperfusion prevents organs from dysfunction and injury, the precise mechanism remains unknown. We hypothesize that the E2-mediated attenuation of liver injury following hemorrhagic shock and fluid resuscitation occurs via the p38 mitogen-activated protein kinase (MAPK)-dependent heme oxygenase (HO)-1 pathway. After a 5-cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood pressure ∼40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, E2(1 mg/kg) alone, or E2plus p38 MAPK inhibitor SB-203580 (2 mg/kg), HO-1 inhibitor chromium mesoporphyrin-IX chloride (2.5 mg/kg) or estrogen receptor antagonist ICI 182,780 (3 mg/kg). At 2 h after hemorrhagic shock and fluid resuscitation, the liver injury markers were significantly increased compared with sham-operated control. Hemorrhagic shock resulted in a significant decrease in p38 MAPK phosphorylation compared with the shams. Administration of E2following hemorrhagic shock normalized liver p38 MAPK phosphorylation, further increased HO-1 expression, and reduced cleaved caspase-3 levels. Coadministration of SB-203580 abolished the E2-mediated attenuation of the shock-induced liver injury markers. In addition, administration of chromium mesoporphyrin-IX chloride or ICI 182,780 abolished E2-mediated increases in liver HO-1 expression or p38 MAPK activation following hemorrhagic shock. Our results collectively suggest that the salutary effects of E2on hepatic injury following hemorrhagic shock and resuscitation are in part mediated through an estrogen-receptor-related p38 MAPK-dependent HO-1 upregulation.
The Evolving Role of Molecular Markers in the Diagnosis and Management of Diffuse Glioma
Authors: Huse Jason T. , Aldape Kenneth D.
Published: November 2014

While the classification of diffuse gliomas has relied on the examination of morphologic features supplemented with techniques such as immunohistochemistry, there is an increasing recognition of substantial biologic diversity within morphologically defined entities. High-throughput technologies, in particular studies that integrate genome-wide data from diverse molecular platforms, increasingly identify the existence of robust and distinct glioma subtypes. While treatment advances and improvement of outcomes for patients with diffuse glioma have been modest, there may be benefit to integrate findings from biologic studies into clinical practice to enhance the precision of treatment for these diseases. Recent examples such as the identification of mutations in IDH1 and IDH2 as an early genetic event that is predominantly in lower-grade gliomas (grades 2 and 3) underscore the importance of molecular discovery leading to the ability to develop subclassifications with prognostic and potentially therapeutic implications. In contrast, glioblastoma (grade 4), the most common and aggressive glioma, typically arises without IDH mutation, supporting the need for different therapeutic approaches. Additional genomic and epigenomic signatures are generally nonoverlapping between IDH-mutant and IDH wild-type diffuse glioma, and despite comparable histopathology, IDH-mutant gliomas can be considered as biologically distinct from IDH wild-type gliomas. In this CCR Focus article, we highlight and summarize the current understanding of recent molecular findings and the relationships of these findings to clinical trials and clinical management.

See all articles in this CCR Focus section, “Discoveries, Challenges, and Progress in Primary Brain Tumors.”

Clin Cancer Res; 20(22); 5601–11. ©2014 AACR.
Universes Collide: Combining Immunotherapy with Targeted Therapy for Cancer
Authors: Wargo Jennifer A. , Cooper Zachary A. , Flaherty Keith T.
Published: November 2014

There have been significant advances in the past several years with regard to targeted therapy and immunotherapy for cancer. This is highlighted in melanoma, where treatment with targeted therapy (against the BRAF oncoprotein) results in responses in the majority of patients, although the duration of response is limited. In contrast, treatment with immunotherapy results in a lower response rate, but one that tends to be more durable. Insights about mechanisms of response and potential synergy between these treatment strategies for melanoma are a focus of this review, with opportunities to extend these insights to the treatment of other cancers.

Significance: Two major advances in melanoma have occurred concurrently and involve treatment with targeted therapy and immune checkpoint blockade. However, each of these approaches has limitations with regard to overall response rates or duration of response. To address this, investigators have proposed combining these strategies, and this concept is being tested empirically in clinical trials. There is a scientific rationale supporting the combination of targeted therapy and immunotherapy, and these concepts are discussed herein. Cancer Discov; 4(12); 1377–86. ©2014 AACR.
Probe-Based Confocal Laser Endomicroscopy Imaging of Endobronchial Hamartomas
Authors: Shafiek Hanaa , Gómez Cristina , Pierola Javier , Sauleda Jaume , Cosío Borja G.
Published: November 2014

Probe-based confocal laser endomicroscopy (pCLE) is a new technique that can microscopically image the airways in vivo during ordinary flexible bronchoscope procedures. pCLE can visualize the basement membrane of the bronchial epithelium, allowing the study of the different changes in benign or malignant/premalignant bronchial lesions. We present 2 cases of pathology-proven endobronchial hamartoma diagnosed by biopsy which show characteristic images under pCLE examination. The tumor was removed in both cases by rigid bronchoscopy using a diathermy loop and a cryoprobe.
Enhanced Nutrient Supply to Very Low Birth Weight Infants is Associated with Improved White Matter Maturation and Head Growth
Authors: Strømmen Kenneth , Blakstad Elin W. , Moltu Sissel J. , Almaas Astrid N. , Westerberg Ane C. , Amlien Inge K. , Rønnestad Arild E. , Nakstad Britt , Drevon Christian A. , Bjørnerud Atle , Courivaud Frederic , Hol Per K. , Veierød Marit B. , Fjell Anders M. , Walhovd Kristine B. , Iversen Per O.
Published: November 2014

Background: Extrauterine growth restriction is common among very low birth weight infants (VLBW, BW <1,500 g). Optimal postnatal nutrient supply is essential to limit growth restriction and ensure adequate growth and neurodevelopment. Objectives: We compared an enhanced postnatal nutrient supply to a standard supply and evaluated the effects on growth velocity, head circumference growth and cerebral maturation - the latter by magnetic resonance diffusion tensor imaging (DTI). We hypothesized increased growth velocity, head circumference growth and decreased mean diffusivity (MD) in cerebral white matter (WM) areas, suggesting improved cerebral maturation among infants on the enhanced nutrient supply. Methods: In this randomized controlled trial, infants on the enhanced nutrient supply received increased amounts of energy, protein, fat, essential fatty acids and vitamin A until discharge. DTI was performed close to term equivalent age. Outcomes were growth velocity, head circumference growth and WM mean diffusivity. Results: Among the 50 included infants, 14 in the intervention group and 11 controls underwent a successful DTI. Infants on the enhanced diet achieved improved growth velocity (16.5 vs. 13.8 g/kg/day, p = 0.01) and increased head circumference (Δz score: 0.24 vs. -0.12, p = 0.15). A significantly lower MD was seen in a large WM area such as the superior longitudinal fasciculi (1.19 × 10-3 vs. 1.24 × 10-3 mm2/s, p = 0.04, adjusted for age when scanned). Conclusions: Enhanced nutrient supply to VLBW infants is associated with improved growth velocity, increased head circumference growth and decreased regional WM mean diffusivity, suggesting improved maturation of cerebral connective tracts.
Resveratrol Treatment of Mice With Pressure-Overload–Induced Heart Failure Improves Diastolic Function and Cardiac Energy Metabolism
Authors: Sung Miranda M. , Das Subhash K. , Levasseur Jody , Byrne Nikole J. , Fung David , Kim Ty T. , Masson Grant , Boisvenue Jamie , Soltys Carrie-Lynn , Oudit Gavin Y. , Dyck Jason R.B.
Published: November 2014

Background—

Although resveratrol has multiple beneficial cardiovascular effects, whether resveratrol can be used for the treatment and management of heart failure (HF) remains unclear. In the current study, we determined whether resveratrol treatment of mice with established HF could lessen the detrimental phenotype associated with pressure-overload–induced HF and identified physiological and molecular mechanisms contributing to this.

Methods and Results—

C57Bl/6 mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Three weeks post surgery, a cohort of mice with established HF (% ejection fraction <45) was administered resveratrol (≈320 mg/kg per day). Despite a lack of improvement in ejection fraction, resveratrol treatment significantly increased median survival of mice with HF, lessened cardiac fibrosis, reduced gene expression of several disease markers for hypertrophy and extracellular matrix remodeling that were upregulated in HF, promoted beneficial remodeling, and improved diastolic function. Resveratrol treatment of mice with established HF also restored the levels of mitochondrial oxidative phosphorylation complexes, restored cardiac AMP-activated protein kinase activation, and improved myocardial insulin sensitivity to promote glucose metabolism and significantly improved myocardial energetic status. Finally, noncardiac symptoms of HF, such as peripheral insulin sensitivity, vascular function, and physical activity, were improved with resveratrol treatment.

Conclusions—

Resveratrol treatment of mice with established HF lessens the severity of the HF phenotype by lessening cardiac fibrosis, improving molecular and structural remodeling of the heart, and enhancing diastolic function, vascular function, and energy metabolism.
Brain-Derived Neurotrophic Factor Administration Mediated Oligodendrocyte Differentiation and Myelin Formation in Subcortical Ischemic Stroke
Authors: Ramos-Cejudo Jaime , Gutiérrez-Fernández María , Otero-Ortega Laura , Rodríguez-Frutos Berta , Fuentes Blanca , Vallejo-Cremades Maria Teresa , Hernanz Teresa Navarro , Cerdán Sebastián , Díez-Tejedor Exuperio
Published: November 2014

Background and Purpose—

Translational research is beginning to reveal the importance of trophic factors as a therapy for cellular brain repair. The purpose of this study was to analyze whether brain-derived neurotrophic factor (BDNF) administration could mediate oligodendrogenesis and remyelination after white matter injury in subcortical stroke.

Methods—

Ischemia was induced in rats by injection of endothelin-1. At 24 hours, 0.4 μg/kg of BDNF or saline was intravenously administered to the treatment and control groups, respectively. Functional evaluation, MRI, and fiber tract integrity on tractography images were analyzed. Proliferation (KI-67) and white matter repair markers (A2B5, 2',3'-cyclic-nucleotide 3'-phosphodiesterase [CNPase], adenomatous polyposis coli [APC], platelet-derived growth factor receptor alpha [PDGFR-α], oligodendrocyte marker O4 [O4], oligodendrocyte transcription factor [Olig-2], and myelin basic protein [MBP]) were analyzed at 7 and 28 days.

Results—

The BDNF-treated animals showed less functional deficit at 28 days after treatment than the controls (
P
<0.05). Although T2-MRI did not show differences in lesion size at 7 and 28 days between groups, diffusion tensor imaging tractography analysis revealed significantly better tract connectivity at 28 days in the BDNF group than in the controls (
P
<0.05). Increased proliferation of oligodendrocyte progenitors was observed in treated animals at 7 days (
P
<0.05). Finally, the levels of white matter repair markers (A2B5, CNPase, and O4 at 7 days; Olig-2 and MBP at 28 days) were higher in the BDNF group than in the controls (
P
<0.05).

Conclusions—

BDNF administration exerted better functional outcome, oligodendrogenesis, remyelination, and fiber connectivity than controls in rats subjected to subcortical damage in ischemic stroke.
White Matter Microstructural Damage in Small Vessel Disease Is Associated With Montreal Cognitive Assessment But Not With Mini Mental State Examination Performances
Authors: Pasi Marco , Salvadori Emilia , Poggesi Anna , Ciolli Laura , Del Bene Alessandra , Marini Sandro , Nannucci Serena , Pescini Francesca , Valenti Raffaella , Ginestroni Andrea , Toschi Nicola , Diciotti Stefano , Mascalchi Mario , Inzitari Domenico , Pantoni Leonardo
Published: November 2014

Background and Purpose—

Montreal Cognitive Assessment (MoCA) has been proposed as a screening tool in vascular cognitive impairment. Diffusion tensor imaging is sensitive to white matter microstructural damage. We investigated if diffusion tensor imaging-derived indices are more strongly associated with performances on MoCA or on the widely used mini mental state examination in patients with mild cognitive impairment and small vessel disease.

Methods—

Mild cognitive impairment patients with moderate/severe degrees of white matter hyperintensities on MRI were enrolled. Lacunar infarcts, cortical atrophy, medial temporal lobe atrophy and median values of mean diffusivity and fractional anisotropy of the cerebral white matter were studied and correlated with cognitive tests performances.

Results—

Seventy-six patients (mean age 75.1±6.8 years, mean years of education 8.0±4.3) were assessed. In univariate analyses, a significant association of both MoCA and mini mental state examination scores with age, education, cortical atrophy, and medial temporal lobe atrophy was found, whereas mean diffusivity and fractional anisotropy were associated with MoCA. In partial correlation analyses, adjusting for all demographic and neuroimaging variables, both mean diffusivity and fractional anisotropy were associated only with MoCA (mean diffusivity:
r
= −0.275,
P
=0.023; fractional anisotropy:
r
=0.246,
P
=0.043).

Conclusions—

In patients with mild cognitive impairment and small vessel disease, diffusion tensor imaging-measured white matter microstructural damage is more related to MoCA than mini mental state examination performances. MoCA is suited for the cognitive screening of patients with small vessel disease.
Association of the transcobalamin II gene 776C→G polymorphism with Alzheimer’s type dementia: dependence on the 5, 10-methylenetetrahydrofolate reductase 1298A→C polymorphism genotype
Authors: Cascalheira José F , Gonçalves Mónica , Barroso Madalena , Castro Rita , Palmeira Manuela , Serpa André , Dias-Cabral Ana C , Domingues Fernanda C , Almeida Sofia
Published: November 2014

Background

Decreased serum concentrations of vitamin B12 are associated with Alzheimer’s type dementia. The transcobalamin II gene (TCN2) 776C→G polymorphism affects transcobalamin II function as a carrier of vitamin B12 and might modify its availability. The association of the TCN2 776C→G polymorphism with Alzheimer’s type dementia is unclear and was investigated in the present study.

Methods

Case–control study including 27 individuals diagnosed with Alzheimer’s type dementia and 28 healthy controls. Serum concentrations of vitamin B12, homocysteine and other analytes were determined and the presence of TCN2 776C→G and 5, 10-methylenetetrahydrofolate reductase 1298A→C polymorphisms genotypes was ascertained by polymerase chain reaction–restriction fragment length polymorphism.

Results

Serum concentrations of vitamin B12 were lower while those of homocysteine were higher in patients than in controls ( P < 0.05). The frequency of individuals carrying at least one 5, 10-methylenetetrahydrofolate reductase 1298C allele was higher (59% versus 32%) while frequency of individuals harbouring at least one TCN2 776G allele was lower (58% versus 86%) in patients than in controls ( P < 0.05). Univariate logistic regression showed negative association of TCN2 776CG genotype with Alzheimer’s type dementia (OR = 0.17 versus CC genotype, P < 0.02). Multivariate logistic regression identified TCN2 776C→G polymorphism as independent predictor of Alzheimer’s type dementia together with higher concentrations of homocysteine, cholesterol and uric acid and lower concentrations of oestradiol. Association of TCN2 776C→G polymorphism with Alzheimer’s type dementia was observed for individuals carrying the 5,10-methylenetetrahydrofolate reductase 1298AA genotype but not the AC or CC genotypes, indicating interaction between the two polymorphisms.

Conclusions

The TCN2 776C→G polymorphism is negatively associated with Alzheimer’s type dementia, suggesting a protective role against the disease in subjects with the 5, 10-methylenetetrahydrofolate reductase 1298AA genotype.
Leonard Woolf and the book in the jungle
Authors: Manocha Nisha
Published: November 2014

This article considers the representation of the book in Leonard Woolf’s The Village in the Jungle (1913). The depiction of the book or the act of writing in the colonial context as an “event” — inspiring awe or scepticism in the illiterate native or painfully/pleasantly reminiscent of the colonial administrator’s life at “home” — is certainly not a fictional scene exclusive to Woolf. However, differently from his contemporaries, Woolf responds to the book in colonial Sri Lanka not as shorthand for modernity, but as colonial fetish. A century since its publication, it is possible — and perhaps profitable — to discuss The Village in the Jungle beyond its marked affiliations or stark disassociations with the fictions of Woolf’s peers including Rudyard Kipling, Joseph Conrad, E. M. Forster, and William Butler Yeats to name a few; rather, we can afford to take the longer view of his work. By way of gleaning particular insight into Woolf’s treatment of the book in the jungle, this article will invoke the fiction of Nigerian writer Chinua Achebe, staunch anti-imperialist and also fierce critic of post-independence corruption, whose novels Things Fall Apart (1958) and Arrow of God (1964) were published in the final decade of Woolf’s life. Woolf’s affiliations with Achebe might therefore be referenced as an index of the radicality of his anti-colonial sympathies.
What Kinds of Value Motives Guide People in Their Moral Attitudes? The Role of Personal and Prescriptive Values at the Culture Level and Individual Level
Authors: Vauclair Christin-Melanie , Fischer Ronald , Ferreira Maria Cristina , Guerra Valeschka , Hößler Ulrich , Karabati Serdar , de Carvalho Filho Moises Kirk , Porto Juliana B. , Reyes Melissa Lopez , Rytkönen Jenni , Spieß Erika
Published: November 2014

Opinions about moralized issues are arguably one of the most difficult issues in interpersonal dialogues given that they can result in intolerance and prejudicial behavior toward those with divergent moral beliefs. Recent research has shown that moral attitudes vary not only depending on the individual’s characteristics but also as a function of culture. Individuals from individualistic-oriented cultures exhibit more lenient judgments toward moralized issues than those from collectivistic-oriented cultures. What is unclear to date is what kinds of cultural value motives underlie these attitudes—Are they driven only by intrinsic value motives (personal values) or also by extrinsic value motives (prescriptive values in the form of societal expectations about what should be valued)? The cultural press to conform is arguably stronger if moral attitudes are predicted by the latter. Participants from eight countries ( N = 1,456) responded to a questionnaire containing a modified version of the Schwartz Value Survey assessing personal and prescriptive values. The results showed that personal value ratings of openness-to-change versus conservation at the culture and individual levels were predictive of individuals’ moral attitudes consistent with previous findings. Prescriptive value ratings of openness-to-change versus conservation also predicted individuals’ moral attitudes, but only at the aggregated culture level. This suggests that the prescriptive values concept is a truly group-level phenomenon and that attitudes toward moralized issues are guided by cultural values with normative qualities. We discuss the implications for intercultural contact situations.