bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermal–hydraulic–mechanical (THM) behaviour of a large-scale in situ heating experiment during cooling and dismantling
Authors: Sánchez M. , Gens A. , Guimarães L. 
Published: October 2012

A geological disposal facility for high-level radioactive waste (HLW) encompasses both natural (host rock) and (generally clay-based) engineered barriers. Many processes can influence, either positively or negatively, the effectiveness of the safety functions of isolation and retardation. This paper focuses on the analysis of a large-scale heating test when subjected to cooling and subsequent partial dismantling. The experiment reproduces the conditions of an HLW repository at full scale under realistic conditions. Key thermal, hydraulic, and mechanical (THM) variables, such as temperature, relative humidity, stresses, and fluid pressures, were measured in the clay barrier and surrounding rock. The experimental observations recorded during the cooling down and clay barrier excavation are analyzed in light of a fully coupled THM finite element formulation. This analysis has provided the opportunity to explore the behaviour of the clay and natural barriers under conditions very relevant for the repository performance but not analyzed previously. Overall, the model predictions are quite satisfactory when compared against experimental observations. Furthermore, model predictions for a period of 20 years, including the transient phase induced by the partial dismantling, are also presented. This additional analysis has allowed a better understanding of the effect of thermal gradient on long-term clay hydration.
Stabilization of a railway embankment using electrokinetic geosynthetics
Authors: Lamont-Black John , Hall Jean A. , Glendinning Stephanie , White Chris P. , Jones Colin J. F. P. 
Published: October 2012

Abstract

A trial was conducted on a Victorian embankment to evaluate the use of electrokinetic geosynthetics for embankment stabilization. The embankment had been constructed by end tipping London Clay fill onto unprepared ground and has a history of instability. Ground investigations indicated a core of firm material underlain by softened embankment fill and alluvium and overlain by softened material towards the ground surface. The slope was treated to a maximum of depth of 7 m using electrokinetic geosynthetics and electrokinetic soil nails. Over a period of 42 days, electrokinetic treatment forced water out of the ground by raising it >4 m above the initial groundwater level such that discharge from activated electrokinetic prefabricated vertical drains (ePVDs) was >25 times that of control drains. Cation exchange processes were active as part of the treatment and correlated with reductions in plasticity and shrinkage. Overall DC power consumption was approximately 11.5 kWh m
−3
of soil treated. Post treatment boreholes demonstrated that the soft material beneath the embankment had become firm and exhibited apparent improvements in both undrained and drained strength parameters. Pull-out tests on electrokinetic soil nails demonstrated an improvement in the bond strength of the nails by an average of 263%. Inclinometer data showed a significant reduction of movement tending to zero after treatment.
Measuring and mitigating the environmental impact of earthworks and other geotechnical processes
Authors: O'Riordan Nick , Phear Alan 
Published: October 2012

Abstract
Considerable progress has been made in the assessment, management and maintenance of existing earthworks and in the selection of methods of construction of new earthworks. Techniques involving multi-criteria analysis, carbon-footprinting and life cycle assessment of competing schemes provide transparent methodologies for use in environmental impact assessment.

This review paper provides examples of use of the various techniques, and in particular concentrates on areas of innovation including:

reuse of excavated tunnel spoil

methods of ground treatment to minimise earthwork impact (e.g.
in-situ
soil strengthening, green walls etc).

combining performance-based design, under environmental load cases such as earthquake and flood, with carbon footprint and cost analyses
Spanish technical regulation for road construction
Authors: Dapena E. , Parrilla A. 
Published: October 2012

Abstract

The new
Technical Regulation for Road Construction
(PG3) has applied in Spain since 2002 and governs execution of all the highways, expressways and motorways run by State Administration.

The most important aspects introduced in this regulation in terms of the construction of fills are (1) extending the characteristics of the fill material to use as large a quantity as possible of the excavated ground
in situ
and to keep the amount sent to dump sites to a minimum; (2) to set up standards to regulate finished fills; and (3) to define a new type of random or quarry-run fill consisting of materials with a grading between earth and rock fill that were not in the earlier PG3 regulation.

The new PG3 regulation refers to the construction of earth, rock and random fills, and pays particular attention to the placement, installation and the relevant control of the methods involved. In the case of earth fills, the control method involves fixing some preliminary characteristics for the soils to be used in fills, determined by laboratory tests, whereas for random and rock fills, the control consists of first creating test fills through which the previously established compaction procedure is accepted or modified. For random and rock fills, the control of the finished fill requires dividing the layers into set-sized sections and running tests on predetermined strips. The regulation also defines the criterion for acceptance or rejection of the zone being tested.
The PI3K/AKT/mTOR Pathway as a Therapeutic Target in Endometrial Cancer
Authors: Slomovitz Brian M. , Coleman Robert L. 
Published: October 2012

Abstract
Endometrial cancer is the most common gynecologic malignancy in the United States. Overactivation of the PI3K/AKT/mTOR pathway, a signaling pathway that plays an important role in cellular growth and survival, has recently been implicated in endometrial cancer pathogenesis, and as such, inhibition of the PI3K/AKT/mTOR pathway is of therapeutic interest. Preclinical and clinical studies are proving useful in elucidating the antitumor effects of different PI3K/AKT/mTOR pathway inhibitors, and in defining which patient populations these inhibitors might be most effective in. For example, an increasing amount of preclinical data suggest that loss of PTEN or genetic alteration of PIK3CA may be indicators of sensitivity to PI3K/AKT/mTOR pathway inhibition, while activating KRAS mutations may predict resistance. In the latter case, combined inhibition of the RAS/RAF/MEK and PI3K/AKT/mTOR pathways has been suggested as a therapeutic strategy. In addition, the PI3K/AKT/mTOR pathway has been implicated in conferring resistance to conventional therapies, and so PI3K/AKT/mTOR pathway inhibitors in combination with hormonal and/or cytotoxic agents are being evaluated. In conclusion, preclinical models are providing insights into the antitumor activity of PI3K/AKT/mTOR pathway inhibition, and are helping define patient populations most likely to benefit from these therapies. Clinical validation of these findings is ongoing. Clin Cancer Res; 18(21); 5856–64. ©2012 AACR.
Ethacrynic Acid and a Derivative Enhance Apoptosis in Arsenic Trioxide–Treated Myeloid Leukemia and Lymphoma Cells: The Role of Glutathione S-Transferase P1-1
Authors: Wang Rui , Liu Changda , Xia Lijuan , Zhao Guisen , Gabrilove Janice , Waxman Samuel , Jing Yongkui 
Published: October 2012

Abstract
Purpose: Arsenic trioxide (ATO) as a single agent is used for treatment of acute promyelocytic leukemia (APL) with minimal toxicity, but therapeutic effect of ATO in other types of malignancies has not been achieved. We tested whether a combination with ethacrynic acid (EA), a glutathione S-transferase P1-1 (GSTP1-1) inhibitor, and a reactive oxygen species (ROS) inducer will extend the therapeutic effect of ATO beyond APL.
Experimental Design: The combined apoptotic effects of ATO plus ethacrynic acid were tested in non-APL leukemia and lymphoma cell lines. The role of ROS, GSTP1-1, glutathione (GSH), and Mcl-1 in apoptosis was determined. The selective response to this combination of cells with and without GSTP1-1 expression was compared.
Results: ATO/EA combination synergistically induced apoptosis in myeloid leukemia and lymphoma cells. This treatment produced high ROS levels, activated c-jun-NH2-kinase (JNK), and reduced Mcl-1 protein. This led to the decrease of mitochondrial transmembrane potential, release of cytochrome c, and subsequently, to activation of caspase-3 and -9. Induction of apoptosis in leukemia and lymphoma cells expressing GSTP1-1 required high ethacrynic acid concentrations to be combined with ATO. Silencing of GSTP1 in leukemia cells sensitized them to ATO/EA–induced apoptosis. In a subgroup of B-cell lymphoma, which does not express GSTP1-1, lower concentrations of ethacrynic acid and its more potent derivative, ethacrynic acid butyl-ester (EABE), decreased intracellular GSH levels and synergistically induced apoptosis when combined with ATO.
Conclusion: B-cell lymphoma cells lacking GSTP1-1 are more sensitive than myeloid leukemia cells to ATO/EA–induced apoptosis. Clin Cancer Res; 18(24); 6690–701. ©2012 AACR.
Translating the Therapeutic Potential of AZD4547 in FGFR1-Amplified Non–Small Cell Lung Cancer through the Use of Patient-Derived Tumor Xenograft Models
Authors: Zhang Jingchuan , Zhang Lin , Su Xinying , Li Ming , Xie Liang , Malchers Florian , Fan ShuQiong , Yin XiaoLu , Xu YanPing , Liu Kunji , Dong Zhengwei , Zhu Guanshan , Qian Ziliang , Tang Lili , Zhan Ping , Ji Qunsheng , Kilgour Elaine , Smith Paul D. , Brooks A. Nigel , Thomas Roman K. , Gavine Paul R. 
Published: October 2012

Abstract
Purpose: To investigate the incidence of FGFR1 amplification in Chinese non–small cell lung cancer (NSCLC) and to preclinically test the hypothesis that the novel, potent, and selective fibroblast growth factor receptor (FGFR) small-molecule inhibitor AZD4547 will deliver potent antitumor activity in NSCLC FGFR1–amplified patient-derived tumor xenograft (PDTX) models.
Experimental Design: A range of assays was used to assess the translational relevance of FGFR1 amplification and AZD4547 treatment including in vitro lung cell line panel screening and pharmacodynamic (PD) analysis, FGFR1 FISH tissue microarray (TMA) analysis of Chinese NSCLC (n = 127), and, importantly, antitumor efficacy testing and PD analysis of lung PDTX models using AZD4547.
Results: The incidence of FGFR1 amplification within Chinese patient NSCLC tumors was 12.5% of squamous origin (6 of 48) and 7% of adenocarcinoma (5 of 76). AZD4547 displayed a highly selective profile across a lung cell line panel, potently inhibiting cell growth only in those lines harboring amplified FGFR1 (GI50 = 0.003–0.111 μmol/L). AZD4547 induced potent tumor stasis or regressive effects in four of five FGFR1-amplified squamous NSCLC PDTX models. Pharmacodynamic modulation was observed in vivo, and antitumor efficacy correlated well with FGFR1 FISH score and protein expression level.
Conclusions: This study provides novel epidemiologic data through identification of FGFR1 gene amplification in Chinese NSCLC specimens (particularly squamous) and, importantly, extends the clinical significance of this finding by using multiple FGFR1-amplified squamous lung cancer PDTX models to show tumor stasis or regression effects using a specific FGFR inhibitor (AZD4547). Thus, the translational science presented here provides a strong rationale for investigation of AZD4547 as a therapeutic option for patients with squamous NSCLC tumors harboring amplification of FGFR1. Clin Cancer Res; 18(24); 6658–67. ©2012 AACR.
The Tropical Precipitation Response to Orbital Precession
Authors: Merlis Timothy M. , Schneider Tapio , Bordoni Simona , Eisenman Ian 
Published: October 2012

AbstractOrbital precession changes the seasonal distribution of insolation at a given latitude but not the annual mean. Hence, the correlation of paleoclimate proxies of annual-mean precipitation with orbital precession implies a nonlinear rectification in the precipitation response to seasonal solar forcing. It has previously been suggested that the relevant nonlinearity is that of the Clausius–Clapeyron relationship. Here it is argued that a different nonlinearity related to moisture advection by the atmospheric circulation is more important. When perihelion changes from one hemisphere’s summer solstice to the other’s in an idealized aquaplanet atmospheric general circulation model, annual-mean precipitation increases in the hemisphere with the brighter, warmer summer and decreases in the other hemisphere, in qualitative agreement with paleoclimate proxies that indicate such hemispherically antisymmetric climate variations. The rectification mechanism that gives rise to the precipitation changes is identified by decomposing the perturbation water vapor budget into “thermodynamic” and “dynamic” components. Thermodynamic changes (caused by changes in humidity with unchanged winds) dominate the hemispherically antisymmetric annual-mean precipitation response to precession in the absence of land–sea contrasts. The nonlinearity that enables the thermodynamic changes to affect annual-mean precipitation is a nonlinearity of moisture advection that arises because precession-induced seasonal humidity changes correlate with the seasonal cycle in low-level convergence. This interpretation is confirmed using simulations in which the Clausius–Clapeyron relationship is explicitly linearized. The thermodynamic mechanism also operates in simulations with an idealized representation of land, although in these simulations the dynamic component of the precipitation changes is also important, adding to the thermodynamic precipitation changes in some latitudes and offsetting it in others.
The Reversibility of Sea Level Rise
Authors: Bouttes N. , Gregory J. M. , Lowe J. A. 
Published: October 2012

Abstract
During the last century, global climate has been warming, and projections indicate that such a warming is likely to continue over coming decades. Most of the extra heat is stored in the ocean, resulting in thermal expansion of seawater and global mean sea level rise. Previous studies have shown that after CO2 emissions cease or CO2 concentration is stabilized, global mean surface air temperature stabilizes or decreases slowly, but sea level continues to rise. Using idealized CO2 scenario simulations with a hierarchy of models including an AOGCM and a step-response model, the authors show how the evolution of thermal expansion can be interpreted in terms of the climate energy balance and the vertical profile of ocean warming. Whereas surface temperature depends on cumulative CO2 emissions, sea level rise due to thermal expansion depends on the time profile of emissions. Sea level rise is smaller for later emissions, implying that targets to limit sea level rise would need to refer to the rate of emissions, not only to the time integral. Thermal expansion is in principle reversible, but to halt or reverse it quickly requires the radiative forcing to be reduced substantially, which is possible on centennial time scales only by geoengineering. If it could be done, the results indicate that heat would leave the ocean more readily than it entered, but even if thermal expansion were returned to zero, the geographical pattern of sea level would be altered. Therefore, despite any aggressive CO2 mitigation, regional sea level change is inevitable.
Simulation of Spaced Antenna Wind Retrieval Performance on an X-Band Active Phased Array Weather Radar
Authors: Venkatesh V. , Frasier S. J. 
Published: October 2012

Abstract
Spaced antenna baseline wind retrievals, in conjunction with traditional Doppler measurements, are a potential means of fine angular resolution weather radar wind vector retrieval. A spaced antenna implementation on an X-band active phased array architecture is investigated via Monte Carlo simulations of the backscattered electric fields at the antenna array. Several retrieval methods are exercised on the data produced by the simulator. Parameters of the X-band spaced-antenna design are then optimized. Benefiting from the parametric fitting procedure inherent in the time domain slope at zero lag and full correlation analysis, the study finds both of these algorithms to be more immune to thermal noise than the spectral retrieval algorithms investigated. With appropriately chosen baselines, these time domain algorithms are shown to perform adequately for 5-dB SNR and above. The study also shows that the Gaussian slope at zero lag (G-SZL) algorithm leads to more robust estimates over a wider range of beamwidths than the Gaussian full correlation analysis (G-FCA) algorithm. The predicted performance of the X-band array is compared to a similar spaced antenna implementation on the S-band National Weather Radar Testbed (NWRT). Since the X-band signal decorrelates more rapidly (relative to S band), the X-band array accumulates more independent samples, thereby obtaining lower retrieval uncertainty. However, the same rapid decorrelation also limits the maximum range of the X-band array, as the pulse rate must be sufficiently high to sample the cross-correlation function. It also limits the range of tolerable turbulence velocity within the resolution cell.
Synoptic-Scale Environments of Predecessor Rain Events Occurring East of the Rocky Mountains in Association with Atlantic Basin Tropical Cyclones*
Authors: Moore Benjamin J. , Bosart Lance F. , Keyser Daniel , Jurewicz Michael L. 
Published: October 2012

Abstract
The synoptic-scale environments of predecessor rain events (PREs) occurring to the east of the Rocky Mountains in association with Atlantic basin tropical cyclones (TCs) are examined. PREs that occurred during 1988–2010 are subjectively classified based upon the synoptic-scale upper-level flow configuration within which the PRE develops, with a focus on the following: 1) the position of the jet streak relative to the TC, 2) the position of the jet streak relative to trough and ridge axes, and 3) the positions of trough and ridge axes relative to the PRE and to the TC. Three categories were identified from this classification procedure: “jet in ridge,” “southwesterly jet,” and “downstream confluence.” PRE-relative composite analysis for each category reveals that, consistent with previous studies, PREs typically occur near a low-level baroclinic zone, beneath the equatorward entrance region of an upper-level jet streak, and in the presence of a stream of water vapor from a TC. Despite these common characteristics, key differences exist among the three PRE categories related to the phasing of a TC with the synoptic-scale flow and to the interactions between a TC and its environment. Brief case studies of PREs associated with TC Rita (2005), TC Wilma (2005), and TC Ernesto (2006) are presented as specific examples of the three PRE categories.
The association between suicide and the utilization of mental health services in South Tirol, Italy: A psychological autopsy study
Authors: Giupponi Giancarlo , Pycha Roger , Innamorati Marco , Lamis Dorian A , Schmidt Evelyn , Conca Andreas , Kapfhammer Hans Peter , Lester David , Girardi Paolo , Pompili Maurizio 
Published: October 2012

Aims: The aim of the present study was to investigate potential differences between suicide decedents who had contact with a psychologist or psychiatrist before committing suicide and those individuals who had not had previous contact with a mental health professional prior to ending their lives. Methods: Psychological autopsy interviews ( N = 396) were conducted for individuals who died by suicide between 1997 and 2007 in South Tirol, Italy. Results: The study found that suicide decedents known to mental health professionals were more frequently women and more frequently unemployed or with unstable employment. These decedents were significantly more likely than those unknown to mental health professionals to have a family history of mental illness, one or more past suicide attempts, and more frequent substance abuse, and likely to have frequent alcohol abuse. They more often had visited a physician in the last four weeks before dying and more frequently complained about psychological symptoms. In the prediction of group membership, individuals whom were known to mental health professionals prior to their suicidal act were 3 times more likely to have a family history of mental illness, 5.8 times more likely to have one past suicide attempt, 9.7 times more likely to have two or more past suicide attempts and 3.5 times more likely to have visited a physician in the four weeks prior to their death. Conclusion: Our findings indicate that suicide decedents who had contact with mental health services can be distinguished from those who were not known to mental health professionals.
In silico predictive studies of mAHR congener binding using homology modelling and molecular docking
Authors: Panda Roshni , Cleave A Suneetha Susan , Suresh PK 
Published: October 2012

The aryl hydrocarbon receptor (AHR) is one of the principal xenobiotic, nuclear receptor that is responsible for the early events involved in the transcription of a complex set of genes comprising the CYP450 gene family. In the present computational study, homology modelling and molecular docking were carried out with the objective of predicting the relationship between the binding efficiency and the lipophilicity of different polychlorinated biphenyl (PCB) congeners and the AHR in silico. Homology model of the murine AHR was constructed by several automated servers and assessed by PROCHECK, ERRAT, VERIFY3D and WHAT IF. The resulting model of the AHR by MODWEB was used to carry out molecular docking of 36 PCB congeners using PatchDock server. The lipophilicity of the congeners was predicted using the XLOGP3 tool. The results suggest that the lipophilicity influences binding energy scores and is positively correlated with the same. Score and Log P were correlated with r = +0.506 at p = 0.01 level. In addition, the number of chlorine (Cl) atoms and Log P were highly correlated with r = +0.900 at p = 0.01 level. The number of Cl atoms and scores also showed a moderate positive correlation of r = +0.481 at p = 0.01 level. To the best of our knowledge, this is the first study employing PatchDock in the docking of AHR to the environmentally deleterious congeners and attempting to correlate structural features of the AHR with its biochemical properties with regards to PCBs. The result of this study are consistent with those of other computational studies reported in the previous literature that suggests that a combination of docking, scoring and ranking organic pollutants could be a possible predictive tool for investigating ligand-mediated toxicity, for their subsequent validation using wet lab-based studies.