Large Safety Margin Research Articles

Criticality safety analysis for GNS IQ® – The Integrated Quiver System for damaged fuel

Abstract The phase-out of nuclear energy in Germany has triggered the demand for a comprehensive solution to dispose of damaged fuel rods, normally remaining in the fuel pond until the final shutdown of the NPP. In order to establish a disposal concept for damaged fuel rods suitable for the needs of German utilities, GNS has developed a first of its kind solution, the Integrated Quiver System for Damaged Fuel (GNS IQ®), which can be loaded into the transport and storage casks of the CASTOR® family also by GNS. The GNS IQ® features a robust yet simple design with a high mechanical stability, a reliable leak tightness and large safety margins for future requirements on safety analysis. It can be easily adapted to a large variety of different damaged fuel rods and tailored to the specific needs of the customer. The quiver is adaptable e.g. in length and diameter for use in other types of transport and storage casks and is applicable in other countries as well. The paper gives a general overview of the disposal concept and provides a description of the Integrated Quiver System for Damaged Fuel with the focus on criticality safety assessment.

Review and performance of the Dose Profiler, a particle therapy treatments online monitor

Particle therapy (PT) can exploit heavy ions (such as He, C or O) to enhance the treatment efficacy, profiting from the increased Relative Biological Effectiveness and Oxygen Enhancement Ratio of these projectiles with respect to proton beams. To maximise the gain in tumor control probability a precise online monitoring of the dose release is needed, avoiding unnecessary large safety margins surroundings the tumor volume accounting for possible patient mispositioning or morphological changes with respect to the initial CT scan. The Dose Profiler (DP) detector, presented in this manuscript, is a scintillating fibres tracker of charged secondary particles (mainly protons) that will be operating during the treatment, allowing for an online range monitoring. Such monitoring technique is particularly promising in the context of heavy ions PT, in which the precision achievable by other techniques based on secondary photons detection is limited by the environmental background during the beam delivery. Developed and built at the SBAI department of “La Sapienza”, within the INSIDE collaboration and as part of a Centro Fermi flagship project, the DP is a tracker detector specifically designed and planned for clinical applications inside a PT treatment room. The DP operation in clinical like conditions has been tested with the proton and carbon ions beams of Trento proton-therapy center and of the CNAO facility. In this contribution the detector performances are presented, in the context of the carbon ions monitoring clinical trial that is about to start at the CNAO centre.

Comparison of the usefulness of a targeted temperature management protocol before and after modification: A single-centre retrospective study

Background: After the targeted temperature management (TTM) trial in 2014, guidelines for cardiac arrest recommend maintaining a target temperature between 32 °C and 36 °C after return of spontaneous circulation (ROSC). We established an original TTM protocol that included maintaining a temperature of 35 °C for our institute, as this temperature provides a large safety margin for temperature variation and is expected to reduce the comorbidity with TTM. This is a single-centre retrospective study that assessed the usefulness of the new 35 °C TTM protocol in comparison with the conventional 34 °C or 36 °C protocol.

A Stochastic Range Estimation Algorithm for Electric Vehicles Using Traffic Phase Classification

Limited range and charging infrastructure leads to range anxiety of electric vehicle drivers. Current range estimation algorithms are deemed unreliable and large safety margins are reserved to prevent the risk of stranding. Range estimation in general depends on two factors: current battery energy content and the energy consumption forecast on the route to destination. This paper aims at improving the latter by enhancing the forecast with a notion of uncertainty. The prediction algorithm itself learns from driver and traffic data in a training set to generate accurate, driver-individual energy consumption forecasts. Thereby, a central part of the algorithm is the explicit evaluation of the traffic situation by classifying the traffic phases. With the help of this methodology, individual forecasts can be made more precise since they are highly dependent on surrounding traffic. To demonstrate the validity of the algorithms, the performance is evaluated using real test drive data comprising multiple drivers. On the basis of the performance evaluation, both the superiority of stochastic algorithms over deterministic predictions and the improvement of predictive performance by evaluating explicit traffic phases can be shown. Implementing the proposed methodology in modern day electric vehicles could reduce range anxiety and ultimately increase acceptance of electric mobility worldwide.

Large branch and leaf hydraulic safety margins in subtropical evergreen broadleaved forest.

As a global biodiversity hotspot, the subtropical evergreen broadleaved forest (SEBF) in southern China is strongly influenced by the humid monsoon climate, with distinct hot-wet and cool-dry seasons. However, the hydraulic strategies of this forest are not well understood. Branch and leaf hydraulic safety margins (HSMbranch and HSMleaf, respectively), as well as seasonal changes in predawn and midday leaf water potential (Ψpd and Ψmd), stomatal conductance (Gs), leaf to sapwood area ratio (AL/AS) and turgor loss point (Ψtlp), were examined for woody species in a mature SEBF. For comparison, we compiled these traits of tropical dry forests (TDFs) and Mediterranean-type woodlands (MWs) from the literature because they experience a hot-dry season. We found that on average, SEBF showed larger HSMbranch and HSMleaf than TDF and MW. During the dry season, TDF and MW species displayed a significant decrease in Ψpd and Ψmd. However, SEBF species showed a slight decrease in Ψpd but an increase in Ψmd. Similar to TDF and MW species, Gs was substantially lower in the dry season for SEBF species, but this might be primarily because of the low atmospheric temperature (low vapor pressure deficit). On the other hand, AL/AS and Ψtlp were not significant different between seasons for any SEBF species. Most SEBF species had leaves that were more resistant to cavitation than branches. Additionally, species with stronger leaf-to-branch vulnerability segmentation tended to have smaller HSMleaf but larger HSMbranch. Our results suggest that SEBF is at low hydraulic risk under the current climate.

Independent root-cause analysis of contributing factors, including dismantling of 2 duodenoscopes, to investigate an outbreak of multidrug-resistant Klebsiella pneumoniae

Worldwide, an increasing number of duodenoscope-associated outbreaks are reported. The high prevalence rate of contaminated duodenoscopes puts patients undergoing ERCP at risk of exogenous transmission of microorganisms. The contributing factors of the duodenoscope design to contamination are not well understood. This article reports on the investigation after the outbreak of a multidrug-resistant Klebsiella pneumoniae (MRKP) related to 2 Olympus TJF-Q180V duodenoscopes. We conducted a contact patient screening and microbiologic laboratory database search. Reprocessing procedures were audited, and both duodenoscopes were fully dismantled to evaluate all potential contamination factors. Outcomes were reviewed by an experienced independent expert. In total, 102 patients who had undergone an ERCP procedure from January to August 2015 were invited for screening. Cultures were available of 81 patients, yielding 27 MRKP-infected or -colonized patients. Ten patients developed an MRKP-related active infection. The 2 duodenoscopes had attack rates (the number of infected or colonized cases/number of exposed persons) of 35% (17/49) and 29% (7/24), respectively. Identical MRKP isolates were cultured from channel flushes of both duodenoscopes. The review revealed 4 major abnormalities: miscommunication about reprocessing, undetected damaged parts, inadequate repair of duodenoscope damage, and duodenoscope design abnormalities, including the forceps elevator, elevator lever, and instrumentation port sealing. Outbreaks are associated with a combination of factors, including duodenoscope design issues, repair issues, improper cleaning, and systemic monitoring of contamination. To eliminate future duodenoscope-associated infections, a multipronged approach is required, including clear communication by all parties involved, a reliable servicing market, stringent surveillance measures, and eventually new duodenoscope designs and reprocessing procedures with a larger margin of safety.

Accuracy of robot-assisted versus optical frameless navigated stereoelectroencephalography electrode placement in children.

OBJECTIVE The aim of this study was to compare the accuracy of optical frameless neuronavigation (ON) and robot-assisted (RA) stereoelectroencephalography (SEEG) electrode placement in children, and to identify factors that might increase the risk of misplacement. METHODS The authors undertook a retrospective review of all children who underwent SEEG at their institution. Twenty children were identified who underwent stereotactic placement of a total of 218 electrodes. Six procedures were performed using ON and 14 were placed using a robotic assistant. Placement error was calculated at cortical entry and at the target by calculating the Euclidean distance between the electrode and the planned cortical entry and target points. The Mann-Whitney U-test was used to compare the results for ON and RA placement accuracy. For each electrode placed using robotic assistance, extracranial soft-tissue thickness, bone thickness, and intracranial length were measured. Entry angle of electrode to bone was calculated using stereotactic coordinates. A stepwise linear regression model was used to test for variables that significantly influenced placement error. RESULTS Between 8 and 17 electrodes (median 10 electrodes) were placed per patient. Median target point localization error was 4.5 mm (interquartile range [IQR] 2.8–6.1 mm) for ON and 1.07 mm (IQR 0.71–1.59) for RA placement. Median entry point localization error was 5.5 mm (IQR 4.0–6.4) for ON and 0.71 mm (IQR 0.47–1.03) for RA placement. The difference in accuracy between Stealth-guided (ON) and RA placement was highly significant for both cortical entry point and target (p < 0.0001 for both). Increased soft-tissue thickness and intracranial length reduced accuracy at the target. Increased soft-tissue thickness, bone thickness, and younger age reduced accuracy at entry. There were no complications. CONCLUSIONS RA stereotactic electrode placement is highly accurate and is significantly more accurate than ON. Larger safety margins away from vascular structures should be used when placing deep electrodes in young children and for trajectories that pass through thicker soft tissues such as the temporal region. ABBREVIATIONS CTA = CT angiography; IQR = interquartile range; MEG = magnetoencephalography; ON = optical frameless neuronavigation; RA = robot-assisted; SEEG = stereoelectroencephalography.

Determination of limiting values of 1H spin-spin relaxation time to assess lifetime of thermally aged acrylonitrile butadiene rubber

We propose a method to determine the limiting value of 1H spin–spin relaxation time (T2) for assessing the lifetime of thermally aged acrylonitrile butadiene rubber (NBR) parts. So far, it has been difficult to determine the limiting values of T2 without performing other experiments such as mechanical property measurements and air tightness tests. We exposed two types of NBR diaphragm sheets to air at 100 °C for up to 7540 h and 6000 h, respectively. After that, we tested their air-tightness and we measured T2 of the virgin and aged diaphragms. To evaluate the temperature dependence of T2, T2 measurements were performed at 20, 40, and 60 °C. Additionally, we observed the 13C Nuclear Magnetic Resonance (NMR) spectra, toluene swelling ratio, acetone soluble fraction, and glass transition temperature for only one type of the diaphragm sheets. The diaphragm aged for 7540 h had lost sealability, and all the results indicated that this was caused by the degradation of NBR. The 13C NMR spectra clearly revealed that the degradation of NBR proceeded in three stages: self-cross-linking reactions in the initial stage, concurrent reactions of cross-linking and molecular chain scission in the second stage, and an increased number of reactions of cross-linking and molecular chain scission in the final stage. The results of the T2 measurements showed that T2 is useful not only to evaluate the complicated degradation behavior quantitatively, but also to determine the different limiting values of T2 itself corresponding to large and small safety margins. Finally, we demonstrated that the temperature dependence of T2 is an effective parameter for quantitatively predicting the ultimate lifetime at each aging temperature with no safety margin for various thermally aged NBR rubber sheets.

ADVANCED TECHNOLOGIES FOR HOIST UNITS SERVICE LIFE INCREASING

The operating experience of hoist units for underground and overhaul of wells in the fields of the Bashneft oil campaign and their technical maintenance at the departments of technological transport have shown that, upon expiration of their service life, they are written off as scrap metal. For the reliability of sufficient residual safety margin and maintainability of hoisting units by the end of service life, certain manufacturers examined each unit separately by type of work when performing scheduled preventive maintenance schedules for the period from 2013 to 2018 in a specialized workshop of the oil company Bashneft. Analysis of the repair of individual parts and assemblies during the implementation of the schedule of preventive repair shows that the hoisting units for the most part have a large margin of safety. It can be confirmed the reliability of the large residual margin of safety and maintainability of the masts of the hoisting units that have worked out their factory life. The advanced technologies in the field of heat treatment and spraying with carbide powders of the mating working surfaces of the parts (in the design of the winch braking mechanism) of the hoisting unit have been changed. Particular attention is paid to mast construction elements that are subject to cyclic loads, corrosive effects (the mast post area at the wellhead) and even shock loads. Based on the results of an in-depth analysis of wear and its causes, using non-destructive testing technologies for parts and assemblies, appropriate technologies for restoration of unit parts are selected, such as chemical-thermal heat treatment (nitriding) in electric shaft furnaces, gas-thermal spraying with hard-alloy wear-resistant powders.

Safety margin characterization for high power fueled experiments

The updated safety basis of the Advanced Test Reactor (ATR) has specific criteria for experiments that are cooled by the primary coolant. It requires that during a Condition 2 transient (where flow coastdown is typically the most limiting), the Critical Heat Flux ratio (CHFR) is greater than 2.0 after consideration of several power multipliers. This safety criteria is often overly conservative for fueled experiments and restricts the acceptance of experiments. In the updated safety basis, a provision for a stochastic approach is included. In this study, coupled Dakota-RELAP5 and RAVEN-RELAP5 are used to propagate uncertainties. The objective of this study is to provide a quantitative basis for utilizing the provisions in the ATR experiment safety criteria.Three different fueled experiments, MP-1, FSP-1, and AFIP-6 are considered. RELAP5 models for each experiment are used to simulate the flow coastdown transient. Several thermal-hydraulic correlations are assessed to determine the Onset of Significant Voiding (OSV), Onset of Flow Instability (OFI), and Critical Heat Flux (CHF). The OSV and OFI correlations considered indicate that there is a large safety margin. The CHF correlations also indicate that there is a moderate to large safety margin. The high mass flux of the experiments exceed the Look-up Table (LUT) correlation range. This results in an artificially restricted prediction of CHF value. A high mass flux modifier was implemented to improve LUT applicability. Due to the specifications of the experiments considered, the correlations must be applicable to higher mass flux ranges. It was also found that, often, the conventional CHFR >2.0 criterion is not met. However, the statistical CHFR margin (μ−3σ>1.2) is met. This result suggests that new criteria, while maintaining adequate safety margins, can be used to expand the operating envelope of high power fueled experiments at ATR. The Pearson ranking indicates that the power level and mass flux have the largest impact on the CHFR and OFI predictions. If a reduction of uncertainty in predictions is sought, the factors affecting fuel experiment fission power should be prioritized for scrutiny, followed by the mass flow rate.

Novel Tetrahydrobenzo [b] Thiophene Compounds Exhibit Anticancer Activity through Enhancing Apoptosis and Inhibiting Tyrosine Kinase.

Developing new chemotherapeutic agents with molecular targets, larger margin of safety against normal cells and low cost is the target many scientists try to achieve. The present study was undertaken to investigate the anticancer activity of a novel series of thiophene compounds and the molecular mechanisms associated. A series of novel heterocyclic compounds including pyrimidine derivatives (2, 3, 4, 5 8, 11, 12, 13, 14, and 15), thiophene derivatives (6, 7, and 10) and oxoisothiazolidine derivative (9) was synthesized from 4,5,6,7- tetrahydrobenzo[b] thiophene (1). The newly synthesized derivatives along with the parent compound were evaluated for their anticancer activity against human HepG2, MCF7 and HCT116 cell lines and compared to doxorubicin as a reference drug. Compound 7 was very selective in targeting only the colon cells. Compounds 1, 5, and 12 showed strong cytotoxic activities against the 3 cell lines at 6-16 µM without any apparent toxicity to the normal fibroblasts WI-38. They had DNA affinity at 29-36 µM. The three compounds enhanced apoptosis to varying degrees elevating the expression of Bax, caspase 9 and caspase 3 in HepG2. Compound 5 was the most potent analogue and was superior to the standard drug used in upregulating the apoptotic genes and inhibiting tyrosine kinase at 1 µM. The IC50 value for compound 5 against TK was 296 nM. Taken together, this study presents some thiophene scaffolds as auspicious hits for further optimization as specific antiproliferative agents against cancer cells and promising tyrosine kinase inhibitors at nanomolar concentrations.

Impact of uncertainties on the safety performances of the LBE-XADS concept nuclear reactor

Abstract The demonstration of large operative safety margins is the fundamental requirement for the transition of new generation nuclear reactors from the early concept phase to the initial industrial design one. In order to do so, it is necessary to perform a thorough characterization of the uncertainties affecting the models used for describing the physical behavior of the reactors and to quantify their impact on the safety performances of the plant, typically in terms of the probability of occurrence of deviations from the nominal, or design, operative conditions, often referred to as failure probabilities (reliability analysis). Conceptually, this problem can be solved by framing the problem within a stochastic setting and propagating the uncertainties, represented by suitable probability distributions, by resorting to sampling-based, Monte Carlo (MC) schemes. However, the high reliability of these plants and the complexity of the computer codes used to model their behavior are such that standard MC approaches would require prohibitive computational times. Further computational issues then arise due to the fact that the stochastic models adopted, i.e., the probability distributions, are, in turn, affected by uncertainties, typically related to the inference process adopted to estimate their relevant parameters, so that the estimates of the failure probabilities also become uncertain, with potentially significant impacts on any safety-based decision making process. In this context, the objective of this work is that of providing an innovative computational tool for efficiently performing Sobol-based global reliability sensitivity analysis that allows to satisfactorily quantify the impact of these additional uncertainties on the safety performances of innovative nuclear reactors concepts. The method exploits an original adaptive surrogate modeling with MC variance based techniques, in order to reduce the computational efforts while maintaining sufficient degrees of accuracy. The resulting algorithm is demonstrated with reference to a real innovative nuclear reactor concept, i.e., the Lead Bismuth Eutectic eXperimental Accelerator Driven System (LBE-XADS) reactor. The results of the analysis show the potentiality of the method, offering important insights on the robustness of the concept reactor safety design and suggesting possible paths of improvement, at acceptable computational times.

Structural Qualification of a Developed GFRP-Reinforced Concrete Bridge Barrier using Ultimate Load Testing

Corrosion of reinforcing steel bars is the main factor affecting durability and service life of steel-reinforced bridge barriers in North America. The use of glass fiber reinforcing polymer (GFRP) bars as non-corrosive material has emerged as an innovative solution to corrosion related problems. A recent cost-effective design of PL-3 bridge barrier was developed at Ryerson University incorporating high-modulus GFRP bars with headed ends. An experimental program was conducted to investigate the load carrying capacity of the developed barrier wall. A 40-m long barrier was constructed and tested at four different locations to investigate its structural behavior, crack pattern and ultimate strength when subjected to the equivalent static loading simulating vehicle impact. Experimental results were compared with the design values specified in the Canadian Highway Bridge Design Code. Experimental findings showed a large margin of safety for the proposed GFRP-reinforced barriers. The failure pattern due to transversal loading the longitudinal barrier over 2400 mm length was initiated by a trapezoidal flexural crack pattern at front face of the barrier, followed by punching shear failure at the transverse load location. Comparison between the available punching shear equations in the literature and the punching shear failure developed in the barrier wall was conducted.

Elucidating the hydraulic vulnerability of the longest-lived Southern Hemisphere conifer to aridification

Drier climatic conditions will be the future scenario in many regions worldwide, including southern South America. Few studies have characterized the ecophysiological vulnerability of the endemic tree species that inhabit this area, to climate change. In this study we assessed the hydraulic vulnerability of the longest-lived tree of the Southern Hemisphere, Fitzroya cupressoides, focusing on adult trees and saplings from two highly disturbed populations: the Coastal Range (AC) and Central Depression (FN) of southern Chile, which represent contrasting site conditions. This, as a basis for the design of conservation strategies to safeguard the persistence of these endangered forests in a drier future. We assessed water potentials (WP) throughout a growing season, their relationships with environmental conditions, as well as leaf and stem (branch) traits and hydraulic safety margins. Despite that the studied summer was the second driest in the last seven decades, minimum WP were not that negative (−1.3 to −1.5 MPa); which could be partly explained by a high leaf capacitance in this species. Adult trees and saplings from both sites did not significantly differ in their WP at turgor loss point, and their associated leaf safety margins, which were relatively low in all cases. However, they significantly differed in the xylem WP causing a 50% loss of stem conductivity (P50): adults AC: −5.14, saplings AC: −2.53, adults FN: −3.71, and saplings FN: −3.87 MPa. These values led to a relatively large stem safety margin (SSM) in most cases, and their variation was not explained neither by wood density, nor by tracheid size changes. Moreover, there appears to be an ontogenic adjustment in the more restrictive site AC, which was not seen in FN. Within the continuum of species strategies to cope with water stress, Fitzroya has features of the two ends of the continuum: tissues with large SSM, and tissues that sustain milder operation pressures through capacitance. Although Fitzroya appears to be relatively resistant to water scarcity, saplings from AC, seem to be the most vulnerable to the aridification trend in southern Chile. Moreover, future drying could become a significant extra threat to the highly endangered Central Depression population. Conservation actions are urgently needed to secure the future of Fitzroya forests in southern Chile.

Fatigue properties and material characteristics of additively manufactured AlSi10Mg – Effect of the contour parameter on the microstructure, density, residual stress, roughness and mechanical properties

Additive Manufacturing (AM) is in general seen as a game changing technology. In particular for the space industry, it seems a promising tool for the constant strive towards increasing performance and reducing the cost of space missions. The layer-wise approach allows an increased design freedom and optimisation. Current space applications are designed with a large safety margin since the AM process generates imperfections in the material, which can lower the mechanical properties. A profound understanding on the one hand of the link between process parameters and final properties, and on the other hand of the influence of possible imperfections on mechanical properties still requires more research and can result in a further design and performance optimisation. With this aim, this study characterised the fatigue behaviour of AlSi10Mg processed via AM and the influence of the process parameters, and possible resulting imperfections, on fatigue behaviour. First of all, the influence of building direction, platform temperature, powder layer thickness, surface finish and heat treatment on the fatigue properties was verified. Results showed that there is a direct correlation between the process parameters and the fatigue properties of AlSi10Mg parts, having received the same post processing. Observations indicate that changing the parameters influences the defect population characteristics, determining the fatigue life. In addition, the different surface finishing methods have, as expected, a strong impact on the fatigue behaviour of AM AlSi10Mg materials. Interestingly, vibratory polished specimens produced without contour parameter endured on average a larger amount of cycles to failure than specimens produced with contour parameter. Therefore, the dimensions, roughness, hardness, microstructure, defect population and residual stresses were verified for these two different scanning strategies to look for an explanation for this behaviour. The samples without contour showed lower surface roughness and higher compressive residual stresses in the load direction, potentially explaining the higher number of sustained cycles to failure. Overall, this study showed that an optimised combination of process parameters and surface finish can improve fatigue performance, without the need for machining of the AM parts.

AMPA receptor modulators selective for the accessory protein TARP‐g8

BackgroundThe α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) subtype of ionotropic glutamate receptors mediates the majority of fast synaptic transmission within the mammalian brain. The ubiquitous expression of the primary subunits of AMPA receptors (AMPARs), and the lack of pharmacological selectivity amongst them, preclude regional or neuronal subtype specificity. In vivo, AMPARs comprise a variety of accessory proteins. Of particular interest, TARP‐γ8 is highly expressed in the hippocampus, a region of the brain implicated in several psychiatric and neurological disorders.MethodsWe used high‐throughput screening to discover compounds that selectively modulate AMPARs containing TARP‐γ8. Subsequent medicinal chemistry efforts were used to improve potency and pharmacokinetics of the hits. Assays were developed to measure target occupancy and functional effects of the compounds in vivo.ResultsThese compounds possess a novel mechanism‐of‐action consistent with a partial attenuation of the interaction between the TARP and the pore‐forming subunits of the channel. Lead molecules with oral bioavailability and high brain penetration allowed demonstration of a strong relationship between pharmacokinetics and pharmacodynamics. The compounds show anticonvulsant and anxiolytic profiles in rodent. Molecules in this class provide large safety margins in preclinical species relative to non‐specific AMPAR antagonists due to the improved regional specificity of TARP‐γ8 modulators.ConclusionsAMPAR modulators selective for TARP‐γ8 have the potential to be novel treatments for anxiety/depression, bipolar disorder, temporal lobe epilepsy, and/or prodromal schizophrenia. This project also represents proof‐of‐concept for pharmacological targeting of accessory proteins and small‐molecule modulation of protein‐protein interactions.Support or Funding InformationAuthors are employees of Janssen R &amp; D, LLCThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Leak-before-break analyses of PWR and BWR piping concerning size effects

Components of primary circuit piping of light water reactor (LWR) plants fulfil high safety requirements. Beside prevention against any damage, cracking, and leaking, pipes are especially designed to exclude double-ended ruptures, which may cause a high loss of coolant. One option in this strategy, supported by regulations and standards in several countries, is the leak-before-break (LBB) behavior: a crack-like leakage should be detected before it becomes a break.Evidently, many factors influence the LBB behavior of a specific piping section. Material properties, plant operation parameters, assumed accident scenarios and the local geometry determine the result of a LBB analysis as well as the associated safety margins. Therefore, an analysis is traditionally done case by case, and site by site, according to the applicable standard.In this article, typical components of pressure water reactor (PWR) and boiling water reactor (BWR) primary circuits are examined, and their LBB behavior is investigated. The German standard (KTA) and the US approach (U.S.NRC) are compared. The quantitative results are obtained with the GRS codes PROST and WinLeck, which include different methods for fracture assessment and leak rate calculation. A clear trend concerning the pipe size is found, resulting in large safety margins for large-diameter piping.

Serum Lipid and Protein Changes in Healthy Dyslipidemic Subjects Given a Selective Inhibitor of p70 S6 Kinase-1.

The safety, pharmacokinetic, and pharmacodynamic effects of LY2584702, a selective inhibitor for p70 S6 serine/threonine protein kinase-1, were evaluated in healthy dyslipidemic volunteers. LY2584702 was tolerated well as a monotherapy and dose-dependently reduced low-density lipoprotein cholesterol and triglycerides by up to 60% and 50%, respectively, without significantly changing high-density lipoprotein cholesterol levels in plasma. LY2584702 also dose-dependently decreased factor V activity. Alanine aminotransferase elevations were noted in 2 subjects when LY2584702 was given with atorvastatin. We suspect that the formation of 4-aminopyrazolo[3,4-d]pyrimidine (4-APP) during metabolism may have contributed to some of the adverse effects of LY2584702, and the contribution of 4-APP to the pharmacology merits further investigation. Although clinical investigation of LY2584702 has been terminated because of hepatotoxicity risk, we suggest that a selective inhibitor of p70 S6 serine/threonine protein kinase-1 with a larger margin of safety and without the possibility of being metabolized to 4-APP may be useful in the treatment of dyslipidemia.

Stress levels and failure modes of tantalum-clad tungsten targets at ISIS

The ISIS spallation neutron source operates two tantalum-clad targets. Efforts to understand the operating conditions and lifetime limiting factors of these targets are ongoing, driven in part by premature failures of several recent TS2 targets. The Hot Isostatic Press (HIP) process used in target manufacturing is thought to introduce large residual stresses, particularly in the tantalum cladding. In addition, the pre-stressed target materials are subjected to cyclic proton beam heating and irradiation damage during operation. Manufacturing and beam-induced stresses were simulated using finite element analysis. The residual stress simulation results appear largely consistent with the findings from recent neutron diffraction measurements on an ISIS target plate. Simulations of the beam induced cyclic stress in the target, together with the available tantalum fatigue data, indicate that there is a large safety margin on the material fatigue limit and that a fatigue failure in the ISIS target cladding is therefore unlikely.

Development of high-performance energy absorption component based on the structural design and nanocrystallization

Over the past decades, to meet the ever-increasing energy-saving and environmental-friendly needs, light-weight vehicles, e.g., electric cars, have been widely advocated. Due to significant deterioration in the capability of energy dissipation, crashworthiness enhancement becomes again the most critical issue for the light-weighted vehicles. However, the design based on conventional structure has been more difficult, and the employment of high-strength materials induces much higher cost. To achieve both large safety margin and low cost, this study implemented both material enhancement and structure optimization in the energy absorber design. Since most light-weight structures involve thin-walled frames, the surface mechanical attrition treatment (SMAT), able to induce nanostructures in metals for strength enhancement without sacrificing ductility, is the perfect choice. Based on the structure of energy absorber, SMAT technology was intensively improved to take full advantage of the excellent performance of the advanced steel material and fulfill real-life application. Structure optimization was also explored through extensive experiments and numerical simulations. The final products was examined by real tests, and the results revealed that it was lighter, stronger and have high-safety impact levels compared to similar products on the present market as expected.