bluuebunny/crossref_metadata_2025 huggingface dataset:
Scenario Analysis on the Benefits of Multi-National Cooperation for the Development of a Common Nuclear Energy System Based on PWR and LFR Fleets
Authors: Ciotti Marco , Manzano Jorge L. , Kuznetsov Vladimir , Fesenko Galina , Ferroni Luisa , Giannetti Fabio
Published: November 2014

Financial aspects, environmental concerns and non-favorable public opinion are strongly conditioning the deployment of new Nuclear Energy Systems across Europe. Nevertheless, new possibilities are emerging to render competitive electricity from Nuclear Power Plants (NPPs) owing to two factors: the first one, which is the fast growth of High Voltage lines interconnecting the European countries’ national electrical grids, this process being triggered by huge increase of the installed intermittent renewable electricity sources (Wind and PV); and the second one, determined by the carbon-free constraints imposed on the base load electricity generation. The countries that due to public opinion pressure can’t build new NPPs on their territory may find it profitable to produce base load nuclear electricity abroad, even at long distances, in order to comply with the European dispositions on the limitation of the CO2 emissions. In this study the benefits from operating at multinational level with the deployment of a fleet of PWRs and subsequently, at a proper time, the one of Lead Fast Reactors (LFRs) are analyzed. The analysis performed involves Italy (a country with a current moratorium on nuclear power on spite that its biggest utility operates NPPs abroad), and the countries from South East and Central East Europe potentially looking for introduction or expansion of their nuclear power programmes. According to the predicted evolution of their Gross Domestic Product (GDP) a forecast of the electricity consumption evolution for the present century is derived with the assumption that a certain fraction of it will be covered by nuclear electricity. In this context, evaluated are material balances for the front and the back end of nuclear fuel cycle associated with the installed nuclear capacity. A key element of the analysis is the particular type of LFR assumed in the scenario, characterized by having a fuel cycle where only fission products and the reprocessing losses are sent for disposition and natural or depleted uranium is added to fuel in each reprocessing cycle. Such LFR could be referred to as “adiabatic reactor”. Owing to introduction of such reactors a substantive reduction in uranium consumption and final disposal requirements can be achieved. Finally, the impacts of the LFR and the economy of scale in nuclear fuel cycle on the Levelized Cost of Electricity (LCOE) are being evaluated, for scaling up from a national to a multinational dimension, illustrating the benefits potentially achievable through cooperation among countries.
Heat Transfer and Fluid Flow Characteristics of One Side Heated Vertical Rectangular Channel Inserting Copper Wire
Authors: Takeda Tetsuaki , Funatani Shumpei
Published: November 2014

In the Very High Temperature Reactor (VHTR) which is a next generation nuclear reactor system, ceramics and graphite are used as a fuel coating material and a core structural material, respectively. Even if the depressurization accident occurs and the reactor power goes up instantly, the temperature of the core will change slowly. This is because the thermal capacity of the core is so large. Therefore, the VHTR system can passively remove the decay heat of the core by natural convection and radiation from the surface of the reactor pressure vessel (RPV). The objective of this study is to not only investigate heat transfer characteristics of natural convection of a one-side heated vertical channel inserting the porous materials with high porosity but also develop the passive cooling system for the Very-High-Temperature Reactor (VHTR). An experiment was carried out using the one-side heated vertical rectangular channel. In order to obtain the heat transfer and fluid flow characteristics of the vertical channel inserting porous material, we have also carried out a numerical analysis using a commercial CFD code. This paper describes thermal performances of the one-side heated vertical rectangular channel inserting copper wire with high porosity.
Preliminary Results on the Coupling of a Three-Dimensional Lead Fast Reactor Model and a One-Dimensional External Loop
Authors: Cerroni Daniele , Cervone Antonio , Meloni Paride , Polidori Massimiliano , Manservisi Sandro
Published: November 2014

An accurate three-dimensional simulation of all the components of the primary circuit of a LFR (Lead Fast Reactor) cannot be performed with the current computational power. One strategy to deal with such complex systems is to adopt a multi-scale approach, where different models and geometric representations are introduced for different parts of the reactor. This paper presents a preliminary assessment of a methodology developed in the framework of the FEM-LCORE code to simulate an accident scenario where natural circulation plays a key role in the heat removal.
AP1000® Plant Application of Defense in Depth
Authors: Schulz Terry L. , Gorgemans Julie
Published: November 2014

The AP1000 plant is an 1100-MWe pressurized water reactor (PWR) with passive safety features and extensive plant simplifications that enhance construction, operation, maintenance and safety. One of the key design approaches in the AP1000 plant design is to use passive features to mitigate design basis accidents. Active defense-in-depth (DiD) features provide investment protection, reduce the demands on the passive features and support the Probabilistic Risk Assessment (PRA). The passive features are classified as safety-related in the United States. The active DiD features are classified as nonsafety-related (with supplemental requirements) in the United States. The AP1000 plant design has also incorporated a standardization approach, which together with the level of safety achieved by the passive safety features, results in a plant design that can be applied to different geographical regions with varying regulatory standards and utility expectations without major changes.

This paper will discuss the approach taken to defining DiD in the AP1000 plant and the effectiveness of that approach. It will also address the capability of the AP1000 plant to meet deterministic DiD guidelines such as the ones in application in the UK or described in the Western European Nuclear Regulators’ Association (WENRA) safety objectives for new plants.
Loss-of-Flow-Accidents (LOFA) Study for 100 MW IPWR
Authors: Yin Shasha , Gao Liang , Tian Wenxi , Zhang Yapei , Qiu Suizheng , Su Guanghui
Published: November 2014

The inherent system safety of the 100 MW integral pressurized water reactor (IPWR) can be improved by placing the core, the efficient once-through steam generators and the main coolant pumps in the reactor pressure vessel, and omitting some large pipes and valves in the primary coolant system which can prevent the occurrence of large break loss of coolant accident and reduce the possibility of core melt accident. The application of the passive safety systems simplifies the structures of IPWR and improves the economy of the reactor. In case of accidents, the primary coolant system establishes natural circulation to take the core decay heat away by passive safety systems using gravity and other natural driving forces, thereby enhancing the safety and reliability of the system IPWR. It’s of great significance to establish reasonable and correctable models, including the primary coolant system model, the second loop model and passive core cooling system model, to study thermal-hydraulic phenomena under steady state, transient state and accident conditions.

Based on transient safety analysis program RELAP5/MOD3.4, 100 MW IPWR system was simulated. A series of models of reactor coolant system and passive safety systems were established. The main system models are composed of primary coolant system model, part of second loop model, passive safety injection system model and passive residual heat removal system model. The primary coolant system model includes core, lower plenum, downcomer, region of steam generators, upper plenum, riser, pressurizer, and surge line; the second loop model includes the main feed water line, the steam line, and steam generator tubes; passive safety injection system model includes core makeup tank, accumulator, automatic depressurization system, direct vessel injection line; and passive residual heat removal system model includes passive residual heat removal heat exchanger in containment refueling water storage tank. Based on the established models, the steady state was debugged with the RELAP5 input card.

Steady state calculation was performed and the results agree well with designed values, which verifies the validity of the model and the input card. Using the steady state results as initial conditions, transient calculation was performed. Typical accidents (loss of main water accident) were calculated, which were relieved by auxiliary feedwater system (AFWS) and passive residual heat removal system (PRHR SYSTEM). The results, obtained from AFWS and PRHR SYSTEM, were contrasted and process of accident and thermal-hydraulic phenomena were analyzed according to transient calculation results. The transient calculation results showed that the integral PWR system and the passive safety system model can provide a reference for IPWR transient safety analysis.
Automated, Highly Accurate Verification of RELAP5-3D
Authors: Mesina George L. , Aumiller David L. , Buschman Francis X.
Published: November 2014

Computer programs that analyze light water reactor safety solve complex systems of governing, closure and special process equations to model the underlying physics. In addition, these programs incorporate many other features and are quite large. RELAP5-3D[1] has over 300,000 lines of coding for physics, input, output, data management, user-interaction, and post-processing. For software quality assurance, the code must be verified and validated before being released to users. Verification ensures that a program is built right by checking that it meets its design specifications. Recently, there has been an increased importance on the development of automated verification processes that compare coding against its documented algorithms and equations and compares its calculations against analytical solutions and the method of manufactured solutions[2]. For the first time, the ability exists to ensure that the data transfer operations associated with timestep advancement/repeating and writing/reading a solution to a file have no unintended consequences. To ensure that the code performs as intended over its extensive list of applications, an automated and highly accurate verification method has been modified and applied to RELAP5-3D. Furthermore, mathematical analysis of the adequacy of the checks used in the comparisons is provided.
LES of an Isothermal High Reynolds Number Turbulent Round Jet
Authors: Salkhordeh Sasan , Mazumdar Sagnik , Landfried D. Tyler , Jana Anirban , Kimber Mark L.
Published: November 2014

Round turbulent jets have fundamental relevance in various engineering applications and are also of practical interest in the lower plenum of the High Temperature Gas-Cooled Reactors (HTGR). In the direction of developing an experimentally validated computational model for the lower plenum flow, a Large Eddy Simulation (LES) of an isothermal high Reynolds number confined jet has been studied. The enclosure within which the jet is confined has been selected large enough so that the results can be compared with well-known experimental studies available in the literature. The Sub-Grid Scale (SGS) model chosen within the LES framework is a variant of the dynamic Smagorinsky model. The effect of inlet flow profile and turbulent fluctuations on the evolution of the jet have been analyzed in detail. The mesh distribution was found to play a vital role in the magnitude and profile of the Reynolds stresses throughout the computational domain. Additionally, it is critically important to properly specify the turbulent fluctuations at the jet inlet in order to accurately predict key near field characteristics such as the potential core length. We perform a separate discrete eddy simulation of the flow in the nozzle upstream of the jet inlet to accurately determine the inlet turbulent fluctuations. The LES results of this study include both first order statistics (mean velocity field) and second order statistics (components of the Reynolds stresses). For each of these quantities, excellent agreement is obtained between our LES predictions and experimental measurements. This research lays the groundwork needed to develop a high-fidelity computational model of the complex mixing flow in the HTGR lower plenum.
The Effect of Coupling the ARI3SG Filter Model With the MELCOR Code: A Re-Assessment of a SGTR Meltdown Sequence
Authors: Herranz Luis E. , López Claudia
Published: November 2014

The risk relevance of meltdown SGTR scenarios lies in the potential direct release of fission products to the environment from a degrading core without passing through containment (i.e., containment bypass). Given the lack of knowledge a decade ago, no credit has been traditionally given to any retention at the secondary side of the steam generator. Nonetheless, more than 10 years of research, through projects like EU-SGTR, ARTIST and ARTIST-II, have demonstrated that retention would occur even in the worst case, when water level is below the tube breach and no fission product can be scrubbed by water.

The ARI3SG model was developed to estimate the aerosol retention around the breach nearby (i.e., break stage). Based on a semi-empirical filter approach, ARI3SG was validated against an ad-hoc database and a theoretical correlation depending on particle Reynolds and Stokes non-dimensional numbers, was derived. By implementing such a correlation through the filter model in MELCOR 2.1 and by using a control function to describe the particle retention efficiency in the break stage, an analysis of a meltdown SGTR sequence has been conducted and the results compared to those obtained for the same postulated scenario when ARI3SG contribution is not considered.

This paper presents the results of such analysis in terms of the mass fraction released to the environment and discusses difficulties found when using the MELCOR filter component to introduce the ARI3SG correlation. All in all, the outcome from this study is the confirmation that a substantial retention might be achieved at the break stage (up to around 70% of incoming mass), whenever particle aggregates entering the secondary side of the steam generator have densities around or higher than 2000 kg/m3 and their cohesive forces among primary particles prevent their massive fragmentation when colliding with tubes and/or undergo shear stress.

This work is framed in the collaboration agreement with CSN for investigation on severe accidents (CSNAS).
Uncertainties in Predictions by System Thermal-Hydraulic Codes: The CASUALIDAD Method
Authors: Petruzzi A. , D’Auria F.
Published: November 2014

The present paper deals with the description of the salient features of three independent approaches for estimating uncertainties associated with predictions of complex system codes. The 1st approach is the “standard” one and the most used at the industrial level: it is based upon the selection of input uncertain parameters, on assigning related ranges of variations and, possibly, PDF (Probability Density Functions) and on performing a suitable number of code runs to get the combined effect of variation on the results. In the 2nd approach the uncertainty derives from the comparison between relevant measured data and results of corresponding code calculations. The 3rd approach is based on the Bayesian inference technique and on the availability of experimental data by which computer model predictions can be improved and the ranges of variation of (in theory) ‘all’ input parameters can be characterized. More details are provided in respect with the third approach that has been named CASUALIDAD (Code with the capability of Adjoint Sensitivity and Uncertainty AnaLysis by Internal Data ADjustment and assimilation).
Comparison of Oxidation Kinetics of Nitrite-Oxidizing Bacteria: Nitrite Availability as a Key Factor in Niche Differentiation
Authors: Nowka Boris , Daims Holger , Spieck Eva
Published: November 2014

Nitrification has an immense impact on nitrogen cycling in natural ecosystems and in wastewater treatment plants. Mathematical models function as tools to capture the complexity of these biological systems, but kinetic parameters especially of nitrite-oxidizing bacteria (NOB) are lacking because of a limited number of pure cultures until recently. In this study, we compared the nitrite oxidation kinetics of six pure cultures and one enrichment culture representing three genera of NOB (
Nitrobacter
,
Nitrospira
,
Nitrotoga
). With half-saturation constants (

K
m

) between 9 and 27 μM nitrite,
Nitrospira
bacteria are adapted to live under significant substrate limitation.
Nitrobacter
showed a wide range of lower substrate affinities, with

K
m

values between 49 and 544 μM nitrite. However, the advantage of
Nitrobacter
emerged under excess nitrite supply, sustaining high maximum specific activities (
V
max
) of 64 to 164 μmol nitrite/mg protein/h, contrary to the lower activities of
Nitrospira
of 18 to 48 μmol nitrite/mg protein/h. The
V
max
(26 μmol nitrite/mg protein/h) and

K
m

(58 μM nitrite) of “
Candidatus
Nitrotoga arctica” measured at a low temperature of 17°C suggest that
Nitrotoga
can advantageously compete with other NOB, especially in cold habitats. The kinetic parameters determined represent improved basis values for nitrifying models and will support predictions of community structure and nitrification rates in natural and engineered ecosystems.
Occurrence of Antimicrobial-Resistant Escherichia coli and Salmonella enterica in the Beef Cattle Production and Processing Continuum
Authors: Schmidt John W. , Agga Getahun E. , Bosilevac Joseph M. , Brichta-Harhay Dayna M. , Shackelford Steven D. , Wang Rong , Wheeler Tommy L. , Arthur Terrance M.
Published: November 2014

Specific concerns have been raised that third-generation cephalosporin-resistant (3GC
r
)
Escherichia coli
, trimethoprim-sulfamethoxazole-resistant (COT
r
)
E. coli
, 3GC
r
Salmonella enterica
, and nalidixic acid-resistant (NAL
r
)
S. enterica
may be present in cattle production environments, persist through beef processing, and contaminate final products. The prevalences and concentrations of these organisms were determined in feces and hides (at feedlot and processing plant), pre-evisceration carcasses, and final carcasses from three lots of fed cattle (
n
= 184). The prevalences and concentrations were further determined for strip loins from 103 of the carcasses. 3GC
r
Salmonella
was detected on 7.6% of hides during processing and was not detected on the final carcasses or strip loins. NAL
r
S. enterica
was detected on only one hide. 3GC
r
E. coli
and COT
r
E. coli
were detected on 100.0% of hides during processing. Concentrations of 3GC
r
E. coli
and COT
r
E. coli
on hides were correlated with pre-evisceration carcass contamination. 3GC
r
E. coli
and COT
r
E. coli
were each detected on only 0.5% of final carcasses and were not detected on strip loins. Five hundred and 42 isolates were screened for extraintestinal pathogenic
E. coli
(ExPEC) virulence-associated markers. Only two COT
r
E. coli
isolates from hides were ExPEC, indicating that fed cattle products are not a significant source of ExPEC causing human urinary tract infections. The very low prevalences of these organisms on final carcasses and their absence on strip loins demonstrate that current sanitary dressing procedures and processing interventions are effective against antimicrobial-resistant bacteria.
High Levels of Antimicrobial Resistance among Escherichia coli Isolates from Livestock Farms and Synanthropic Rats and Shrews in the Mekong Delta of Vietnam
Authors: Nhung N. T. , Cuong N. V. , Campbell J. , Hoa N. T. , Bryant J. E. , Truc V. N. T. , Kiet B. T. , Jombart T. , Trung N. V. , Hien V. B. , Thwaites G. , Baker S. , Carrique-Mas J.
Published: November 2014

In Mekong Delta farms (Vietnam), antimicrobials are extensively used, but limited data are available on levels of antimicrobial resistance (AMR) amongEscherichia coliisolates. We performed a structured survey of AMR inE. coliisolates (n= 434) from 90 pig, chicken, and duck farms. The results were compared with AMR amongE. coliisolates (n= 234) from 66 small wild animals (rats and shrews) trapped on farms and in forests and rice fields. The isolates were susceptibility tested against eight antimicrobials.E. coliisolates from farmed animals were resistant to a median of 4 (interquartile range [IQR], 3 to 6) antimicrobials versus 1 (IQR, 1 to 2) among wild mammal isolates (P< 0.001). The prevalences of AMR among farmed species isolates (versus wild animals) were as follows: tetracycline, 84.7% (versus 25.6%); ampicillin, 78.9% (versus 85.9%); trimethoprim-sulfamethoxazole, 52.1% (versus 18.8%); chloramphenicol, 39.9% (versus 22.5%); amoxicillin-clavulanic acid, 36.6% (versus 34.5%); and ciprofloxacin, 24.9% (versus 7.3%). The prevalence of multidrug resistance (MDR) (resistance against three or more antimicrobial classes) among pig isolates was 86.7% compared to 66.9 to 72.7% among poultry isolates. After adjusting for host species, MDR was ∼8 times greater among isolates from wild mammals trapped on farms than among those trapped in forests/rice fields (P< 0.001). Isolates were assigned to unique profiles representing their combinations of susceptibility results. Multivariable analysis of variance indicated that AMR profiles from wild mammals trapped on farms and those from domestic animals were more alike (R2range, 0.14 to 0.30) thanE. coliisolates from domestic animals and mammals trapped in the wild (R2range, 0.25 to 0.45). The results strongly suggest that AMR on farms is a key driver of environmental AMR in the Mekong Delta.
Exposure to sodium channel-inhibiting drugs and cancer survival: protocol for a cohort study using the QResearch primary care database
Authors: Fairhurst Caroline , Watt Ian , Martin Fabiola , Bland Martin , Brackenbury William J
Published: November 2014

Introduction

Metastasis from solid tumours is associated with significant morbidity and mortality, and is the leading cause of cancer-related deaths. Voltage-gated sodium channels (VGSCs) are drug targets for the treatment of epilepsy. VGSCs are also present in cancer cells, where they regulate metastatic cell behaviours, including cellular movement and invasion. Treating cancer cells with the VGSC-inhibiting anticonvulsant phenytoin reduces cellular invasion and migration. Together, these suggest that VGSCs may be useful targets for inhibiting metastasis. The purpose of this study is to test the hypothesis that use of VGSC-inhibiting drugs will reduce metastasis, and therefore increase survival time in patients with cancer.

Methods and analysis

A cohort study based on primary care data from the QResearch database will include patients with one of the three common tumours: breast, bowel and prostate. The primary outcome will be overall survival from the date of cancer diagnosis. Cox proportional hazards regression will be used to compare the survival of patients with cancer taking VGSC-inhibiting drugs (including anticonvulsants and class I antiarrhythmic agents) with patients with cancer not exposed to these drugs, adjusting for age and sex. Exposure to VGSC-inhibiting drugs will be defined as having at least one prescription for these drugs prior to cancer diagnosis. High and low exposure groups will be identified based on the length of use. A number of sensitivity and secondary analyses will be conducted.

Ethics and dissemination

The protocol has been independently peer-reviewed and approved by the QResearch Scientific Board. The project has also been approved by the University of York Ethical Review Process. The results will be presented at international conferences and published in an open access peer-reviewed journal, in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria.
Development and testing of an objective structured clinical exam (OSCE) to assess socio-cultural dimensions of patient safety competency
Authors: Ginsburg Liane R , Tregunno Deborah , Norton Peter G , Smee Sydney , de Vries Ingrid , Sebok Stefanie S , VanDenKerkhof Elizabeth G , Luctkar-Flude Marian , Medves Jennifer
Published: November 2014

Background

Patient safety (PS) receives limited attention in health professional curricula. We developed and pilot tested four Objective Structured Clinical Examination (OSCE) stations intended to reflect socio-cultural dimensions in the Canadian Patient Safety Institute's Safety Competency Framework.

Setting and participants

18 third year undergraduate medical and nursing students at a Canadian University.

Methods

OSCE cases were developed by faculty with clinical and PS expertise with assistance from expert facilitators from the Medical Council of Canada. Stations reflect domains in the Safety Competency Framework (ie, managing safety risks, culture of safety, communication). Stations were assessed by two clinical faculty members. Inter-rater reliability was examined using weighted κ values. Additional aspects of reliability and OSCE performance are reported.

Results

Assessors exhibited excellent agreement (weighted κ scores ranged from 0.74 to 0.82 for the four OSCE stations). Learners’ scores varied across the four stations. Nursing students scored significantly lower (p<0.05) than medical students on three stations (nursing student mean scores=1.9, 1.9 and 2.7; medical student mean scores=2.8, 2.9 and 3.5 for stations 1, 2 and 3, respectively where 1=borderline unsatisfactory, 2=borderline satisfactory and 3=competence demonstrated). 7/18 students (39%) scored below ‘borderline satisfactory’ on one or more stations.

Conclusions

Results show (1) four OSCE stations evaluating socio-cultural dimensions of PS achieved variation in scores and (2) performance on this OSCE can be evaluated with high reliability, suggesting a single assessor per station would be sufficient. Differences between nursing and medical student performance are interesting; however, it is unclear what factors explain these differences.
Does henna impact pulse oximetry results?
Authors: Zolfaghari Mitra , Moradi Majd Parisa , Behesht Aeen Fatemeh , Mohseni Ali Reza , Azimi Ahangari Khadijeh , Haghani Hamid
Published: November 2014

Objective

To evaluate the effects of henna on the results of pulse oximetry in healthy women.

Methods

100 young women (20–60 years of age) were recruited. The Iranian original red henna was used to colour the index finger of THE non-dominant hand; the middle finger of the same hand was the control. Blood oxygen saturation was simultaneously measured by two calibrated pulse oximeters.

Result

Henna did not affect pulse oximetry measurement of oxygen saturation. There was no statistically significant difference between the control and the henna dyed fingers.

Conclusions

Henna is not likely to change the accuracy of oxygen saturation measured by pulse oximeter.

Clinical trial registration

20120906159N20.
Three-dimensional numerical simulation by upscaling of gas migration through engineered and geological barriers for a deep repository for radioactive waste
Authors: Ahusborde E. , Amaziane B. , Jurak M.
Published: November 2014

This paper presents the results of a benchmark study that compares a number of numerical models applied to a specific problem in the context of hydrogen flow and transport in a nuclear waste repository. The processes modelled are two-phase (water and hydrogen) immiscible compressible two-component transient flow in a heterogeneous porous medium under isothermal conditions. The three-dimensional (3D) model represents a module of a repository for high-level waste in a clay host rock. An upscaling technique and a vertex-centred finite-volume method are employed to yield very accurate solutions. Since the full range of results required in the benchmark is too large to be displayed in this paper, we focus on the evolution of the pressures, the saturations, the fluxes and the comparison of the numerical results with the other participants. A homemade C++ upscaling code and the parallel multiphase flow simulator DuMu
X
have been adopted for this study.
Gas-pressure-induced integrity of salt formations
Authors: Popp Till , Minkley Wolfgang , Wiedemann Michael , Salzer Klaus
Published: November 2014

Besides other host rocks, rock salt formations are considered for the long-term storage of radioactive waste to exclude any threat to the biosphere. This means that the host-rock's integrity has to be guaranteed during construction, operation and in the post-closure phase of a repository. Gas-transport properties are key issues in the long-term assessment of the storage of high-level radioactive or toxic waste in salt formations. In this context, the impacts of disturbance induced by the excavation of the underground facilities and long-term effects during recompaction of the excavation disturbed zone (EDZ) are important items but in the past significant progress has been made. However, significant gas quantities may be generated in the long term (e.g. due to anaerobic corrosion, if humidity is present), resulting in a time-dependent pressure build-up that may affect the barrier integrity if the acting minimal stress is exceeded. The objective of this paper is to review the current understanding of the gas-transport properties in a salt environment at increased gas pressures associated with a radioactive waste repository. This knowledge has mainly been developed by laboratory work and fieldwork over the last decade.
Recent progress in research on molecular mechanisms of autophagy in the heart
Authors: Maejima Yasuhiro , Chen Yun , Isobe Mitsuaki , Gustafsson Åsa B. , Kitsis Richard N. , Sadoshima Junichi
Published: November 2014

Dysregulation of autophagy, an evolutionarily conserved process for degradation of long-lived proteins and organelles, has been implicated in the pathogenesis of human disease. Recent research has uncovered pathways that control autophagy in the heart and molecular mechanisms by which alterations in this process affect cardiac structure and function. Although initially thought to be a nonselective degradation process, autophagy, as it has become increasingly clear, can exhibit specificity in the degradation of molecules and organelles, such as mitochondria. Furthermore, it has been shown that autophagy is involved in a wide variety of previously unrecognized cellular functions, such as cell death and metabolism. A growing body of evidence suggests that deviation from appropriate levels of autophagy causes cellular dysfunction and death, which in turn leads to heart disease. Here, we review recent advances in understanding the role of autophagy in heart disease, highlight unsolved issues, and discuss the therapeutic potential of modulating autophagy in heart disease.
Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib
Authors: Nijhof Inger S. , Groen Richard W.J. , Noort Willy A. , van Kessel Berris , de Jong-Korlaar Regina , Bakker Joost , van Bueren Jeroen J.L. , Parren Paul W.H.I. , Lokhorst Henk M. , van de Donk Niels W.C.J. , Martens Anton C.M. , Mutis Tuna
Published: November 2014

Purpose: Novel therapeutic agents have significantly improved the survival of patients with multiple myeloma. Nonetheless, the prognosis of patients with multiple myeloma who become refractory to the novel agents lenalidomide and bortezomib is very poor, indicating the urgent need for new therapeutic options for these patients. The human CD38 monoclonal antibody daratumumab is being evaluated as a novel therapy for multiple myeloma. Prompted with the encouraging results of ongoing clinical phase I/II trials, we now addressed the potential value of daratumumab alone or in combination with lenalidomide or bortezomib for the treatment of lenalidomide- and bortezomib-refractory patients.

Experimental Design: In ex vivo assays, mainly evaluating antibody-dependent cell-mediated cytotoxicity, and in an in vivo xenograft mouse model, we evaluated daratumumab alone or in combination with lenalidomide or bortezomib as a potential therapy for lenalidomide- and bortezomib-refractory multiple myeloma patients.

Results: Daratumumab induced significant lysis of lenalidomide/bortezomib-resistant multiple myeloma cell lines and of primary multiple myeloma cells in the bone marrow mononuclear cells derived from lenalidomide- and/or bortezomib-refractory patients. In these assays, lenalidomide but not bortezomib, synergistically enhanced daratumumab-mediated multiple myeloma lysis through activation of natural killer cells. Finally, in an in vivo xenograft model, only the combination of daratumumab with lenalidomide effectively reduced the tumorigenic growth of primary multiple myeloma cells from a lenalidomide- and bortezomib-refractory patient.

Conclusions: Our results provide the first preclinical evidence for the benefit of daratumumab plus lenalidomide combination for lenalidomide- and bortezomib-refractory patients. Clin Cancer Res; 21(12); 2802–10. ©2014 AACR.

See related commentary by Laubach and Richardson, p. 2660
A First-in-Human Phase I Study of MORAb-004, a Monoclonal Antibody to Endosialin in Patients with Advanced Solid Tumors
Authors: Diaz Luis A. , Coughlin Christina M. , Weil Susan C. , Fishel Jean , Gounder Mrinal M. , Lawrence Susan , Azad Nilofer , O'Shannessy Daniel J. , Grasso Luigi , Wustner Jason , Ebel Wolfgang , Carvajal Richard D.
Published: November 2014

Purpose: Endosialin (TEM-1, CD248) is a protein expressed on the surface of activated mesenchymal cells, including certain subsets of tumors. Preclinical models suppressing endosialin function have shown antitumor activity. A humanized monoclonal antibody, MORAb-004, was engineered to target endosialin and is the first agent in clinical development for this mesenchymal cell target.

Experimental Design: This first-in-human, open-label, phase I study recruited patients with treatment-refractory solid tumors. MORAb-004 was administered intravenously once weekly in 4-week cycles. Objectives included determination of the safety of multiple infusions of MORAb-004, identification of the maximum tolerated dose (MTD), pharmacokinetic modeling, detection of any anti-human antibody response, and assessment of objective radiographic response to therapy.

Results: Thirty-six patients were treated at 10 dose levels of MORAb-004, ranging from 0.0625 to 16 mg/kg. Drug-related adverse events were primarily grade 1–2 infusion toxicities. Dose-limiting toxicity of grade 3 vomiting was observed at 16 mg/kg. Eighteen of 32 evaluable patients across all doses achieved disease stability, with minor radiographic responses observed in 4 patients (pancreatic neuroendocrine, hepatocellular, and sarcoma tumor types). Pharmacokinetics showed MORAb-004 accumulation beginning at 4 mg/kg and saturable elimination beginning at 0.25 mg/kg. Exposure increased in a greater-than-dose-proportional manner with terminal half-life increasing proportionally with dose. The MTD was identified as 12 mg/kg.

Conclusions: Preliminary antitumor activity was observed. Safety profile, pharmacokinetics, and early antitumor activity suggest that MORAb-004 is safe at doses up to 12 mg/kg and should be studied further for efficacy. Clin Cancer Res; 21(6); 1281–8. ©2014 AACR.
The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model
Authors: Scott Katherine A. , Dalgleish Angus G. , Liu Wai M.
Published: November 2014

High-grade glioma is one of the most aggressive cancers in adult humans and long-term survival rates are very low as standard treatments for glioma remain largely unsuccessful. Cannabinoids have been shown to specifically inhibit glioma growth as well as neutralize oncogenic processes such as angiogenesis. In an attempt to improve treatment outcome, we have investigated the effect of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) both alone and in combination with radiotherapy in a number of glioma cell lines (T98G, U87MG, and GL261). Cannabinoids were used in two forms, pure (P) and as a botanical drug substance (BDS). Results demonstrated a duration- and dose-dependent reduction in cell viability with each cannabinoid and suggested that THC-BDS was more efficacious than THC-P, whereas, conversely, CBD-P was more efficacious than CBD-BDS. Median effect analysis revealed all combinations to be hyperadditive [T98G 48-hour combination index (CI) at FU50, 0.77–1.09]. Similarly, pretreating cells with THC-P and CBD-P together for 4 hours before irradiation increased their radiosensitivity when compared with pretreating with either of the cannabinoids individually. The increase in radiosensitivity was associated with an increase in markers of autophagy and apoptosis. These in vitro results were recapitulated in an orthotopic murine model for glioma, which showed dramatic reductions in tumor volumes when both cannabinoids were used with irradiation (day 21: 5.5 ± 2.2 mm3 vs. 48.7 ± 24.9 mm3 in the control group; P < 0.01). Taken together, our data highlight the possibility that these cannabinoids can prime glioma cells to respond better to ionizing radiation, and suggest a potential clinical benefit for glioma patients by using these two treatment modalities. Mol Cancer Ther; 13(12); 2955–67. ©2014 AACR.
Seasonal variation in the reproductive tract of the Indian flying fox, Pteropus giganteus (Brünnich, 1782)
Authors: Noureen Sajida , Sajid Nadeem Muhammad , Azhar Beg Mirza , Anwar Maqsood
Published: November 2014

Seasonal variation in the reproductive tract of Pteropus giganteus was studied at 13 sites of the Pothwar Plateau and Islamabad Capital Territory. Ninety-three dead specimens were collected from roosts, orchards and home-based small cultivations of fruit trees. In males, seasonal differences in testis length, testis width, cauda epididymidis length and penis length were recorded. Positive correlations were found between body weight, body length and all parameters of male reproductive tract. Significant monthly variations in testes conditions (viz. flaccid and turgid) were observed. In females, seasonal variation in reproductive tract weight, ovary length, ovary width, uterus length and uterus width were seen. In females, a strong relationship of body weight with total body length and female reproductive tract parameters were found. In flying foxes’ population of Pothwar, first mating was observed in December-January and second in June-July, suggesting two mating seasons in winter and summer.
Article 9.2 of the Aarhus Convention and eu Law
Authors: Darpö Jan
Published: November 2014

One important means for the implementation of the third pillar of the Aarhus Convention into eu law is the provisions on access to justice in the eia Directive (2011/92). The case-law of the cjeu on those provisions has developed rapidly in the last couple of years. This body of cases has given the concept “access to justice in environmental decision-making” a new meaning and improved the understanding of the requirement for judicial protection under eu environmental law. The aim of this article is to highlight this development and discuss a couple of key issues on access to justice. First, the relationship between “direct effect” and the individuals “rights” and the principles of effectiveness and judicial protection according to eu law is analysed. Thereafter, the meaning of “substantive and procedural legality” and the distinction between general and personal interests in relation to individual’s standing are discussed. The next issue concerns the role of environmental non-governmental organisations. Finally, the concept “courts or tribunals” in environmental decision-making procedures is considered.
Subordination in 15th- and 16th-Century Judeo-Arabic
Authors: Wagner Esther-Miriam
Published: November 2014

Judeo-Arabic sources from the 15th and 16th centuries are of great interest for research into subordinate syntax, as they are written in a repertoire that echoes the Classical Arabic elements of Medieval Judeo-Arabic as much as the colloquial forms of Late Judeo-Arabic. The most interesting phenomena concern the adverbial clauses, which show a great variation of adverbial connectives. It is also notable that compounds of prepositions and relativizers or complementizers appear to have become very popular, whereas few of the inherited non-prepositional Classical Arabic adverbial connectives occur. This article also raises the possibility that adverbial clauses may have only developed in the course of the codification of the Semitic languages, and perhaps of languages in general. Relative and complement clauses in the 15th- and 16th-century sources are less conspicuous, but in relative clauses, the form ʾan, homophonous with the complementizer and originating from constructions using thetanwīn, may occur as relativizer after indefinite antecedent. A noteworthy point regarding complement clauses is the lack of asyndetical constructions as compared with earlier Judeo-Arabic documentary material.
Judeo-Arabic Dialects in North Africa as Communal Languages: Lects, Polylects, and Sociolects
Authors: Chetrit Joseph
Published: November 2014

The study aims to present a comprehensive analysis of the North African Judeo-Arabic dialects in their internal diversity and in their communal use in daily interaction as well as in specialized genres of oral and written discourse. Internal diversity pertains to the various daily and elaborated genres of discourse and types of texts that developed in Jewish communities from the sixteenth century, generating different lects, polylects, and archilects in poetry, in journalism, and in daily interaction; combinations of lects constitute the repertories of three distinct communal sociolects: rabbinic, males,’ and females’ sociolects. Internal diversity also includes the changing linguistic Arabic matrix and the external components it integrated and which hybridized the dialects: Hebrew-Aramaic, Berber, Turkish, and Romance (Castilian, Portuguese, Italian, French). Three oral texts illustrating various Judeo-Arabic lects are presented and discussed.
The Judeo-Spanish Language of R. Moses Almosnino in Light of a Newly Discovered Manuscript of His Treatise on the Astrolabe
Authors: Sheynin Hayim Y.
Published: November 2014

Spanish he used in his literary writings. This article lists the distinctive features of Almosnino’s language and shows that it can be classified as early Judeo-Spanish rooted in mid-fifteenth-century Castilian. Some facts of Almosnino’s biography also testify to this end. Beside traditional linguistic analysis, the new sociophilological approach in research on Jewish languages is used to demonstrate that Almosnino’s language belongs to a Jewish variety of Spanish.
Touch-Screen Technology for the Dynamic Display of 2D Spatial Information Without Vision: Promise and Progress
Authors: Klatzky Roberta L. , Giudice Nicholas A. , Bennett Christopher R. , Loomis Jack M.
Published: November 2014

Many developers wish to capitalize on touch-screen technology for developing aids for the blind, particularly by incorporating vibrotactile stimulation to convey patterns on their surfaces, which otherwise are featureless. Our belief is that they will need to take into account basic research on haptic perception in designing these graphics interfaces. We point out constraints and limitations in haptic processing that affect the use of these devices. We also suggest ways to use sound to augment basic information from touch, and we include evaluation data from users of a touch-screen device with vibrotactile and auditory feedback that we have been developing, called a vibro-audio interface.
The Effect of Extended Sensory Range via the EyeCane Sensory Substitution Device on the Characteristics of Visionless Virtual Navigation
Authors: Maidenbaum Shachar , Levy-Tzedek Shelly , Chebat Daniel Robert , Namer-Furstenberg Rinat , Amedi Amir
Published: November 2014

Mobility training programs for helping the blind navigate through unknown places with a White-Cane significantly improve their mobility. However, what is the effect of new assistive technologies, offering more information to the blind user, on the underlying premises of these programs such as navigation patterns?

We developed the virtual-EyeCane, a minimalistic sensory substitution device translating single-point-distance into auditory cues identical to the EyeCane’s in the real world. We compared performance in virtual environments when using the virtual-EyeCane, a virtual-White-Cane, no device and visual navigation. We show that the characteristics of virtual-EyeCane navigation differ from navigation with a virtual-White-Cane or no device, and that virtual-EyeCane users complete more levels successfully, taking shorter paths and with less collisions than these groups, and we demonstrate the relative similarity of virtual-EyeCane and visual navigation patterns. This suggests that additional distance information indeed changes navigation patterns from virtual-White-Cane use, and brings them closer to visual navigation.
Assessment of Sea Ice Albedo Radiative Forcing and Feedback over the Northern Hemisphere from 1982 to 2009 Using Satellite and Reanalysis Data
Authors: Cao Yunfeng , Liang Shunlin , Chen Xiaona , He Tao
Published: November 2014

The decreasing surface albedo caused by continuously retreating sea ice over Arctic plays a critical role in Arctic warming amplification. However, the quantification of the change in radiative forcing at top of atmosphere (TOA) introduced by the decreasing sea ice albedo and its feedback to the climate remain uncertain. In this study, based on the satellite-retrieved long-term surface albedo product CLARA-A1 (Cloud, Albedo, and Radiation dataset, AVHRR-based, version 1) and the radiative kernel method, an estimated 0.20 ± 0.05 W m−2 sea ice radiative forcing (SIRF) has decreased in the Northern Hemisphere (NH) owing to the loss of sea ice from 1982 to 2009, yielding a sea ice albedo feedback (SIAF) of 0.25 W m−2 K−1 for the NH and 0.19 W m−2 K−1 for the entire globe. These results are lower than the estimate from another method directly using the Clouds and the Earth’s Radiant Energy System (CERES) broadband planetary albedo. Further data analysis indicates that kernel method is likely to underestimate the change in all-sky SIRF because all-sky radiative kernels mask too much of the effect of sea ice albedo on the variation of cloudy albedo. By applying an adjustment with CERES-based estimate, the change in all-sky SIRF over the NH was corrected to 0.33 ± 0.09 W m−2, corresponding to a SIAF of 0.43 W m−2 K−1 for NH and 0.31 W m−2 K−1 for the entire globe. It is also determined that relative to satellite surface albedo product, two popular reanalysis products, ERA-Interim and MERRA, severely underestimate the changes in NH SIRF in melt season (May–August) from 1982 to 2009 and the sea ice albedo feedback to warming climate.