bluuebunny/crossref_metadata_2025 huggingface dataset:
An evidence-based guide to the selection of sequential therapies in metastatic renal cell carcinoma
Authors: Sun Maxine , Shariat Shahrokh F. , Trinh Quoc-Dien , Meskawi Malek , Bianchi Marco , Hansen Jens , Abdollah Firas , Perrotte Paul , Karakiewicz Pierre I.
Published: December 2012

Targeted therapies have introduced a paradigm shift in the management of metastatic renal cell carcinoma. Currently, four molecules (sunitinib, pazopanib, bevacizumab plus interferon, temsirolimus) are considered in first-line therapy, and three other molecules for second, or subsequent lines of therapy (everolimus, axitinib, sorafenib). In addition, other molecules and sequencing schemes are being tested in ongoing phase II/III studies. We conducted a systematic review using PubMed and several other databases up to December 2011 of prospective and retrospective studies on treatment management of metastatic renal cell carcinoma using targeted therapies, with a special focus on use of sequential treatment. Based on phase III data, the optimal sequencing scheme for patients with clear cell or even non-clear cell histological subtype appears to consist of sunitinib, followed by axitinib, followed by everolimus. Subsequent treatment options rely on lower evidence studies and could consist of fourth-line sorafenib or sunitinib rechallenge. Such therapies would qualify as last recourse options. In another context, temsirolimus may be used in patients who fulfill the Memorial Sloan-Kettering Cancer Center poor risk criteria or who have poor performance status. We conclude that in the current setting, sequential therapy represents the cornerstone of effective management of metastatic renal cell carcinoma.
Predicting Browsers and Purchasers of Hotel Websites
Authors: Wu Edmond H. C. , Law Rob , Jiang Brianda
Published: December 2012

A study of the online browsing and purchasing habits of some 1,400 outbound travelers in Hong Kong demonstrates the analytical power of weight-of-evidence (WOE) data mining. The WOE approach allows analysts to identify and transform the variables with the most predictive power regarding the likelihood of tourists’ online preferences and decisions. The study found that just over one-third of the respondents browsed hotel-related websites, and about half of those browsers had booked a room on those sites. Browsers in Hong Kong tended to be young, well educated, and well traveled. Those who used the hotel websites for purchases were, of course, part of the browser group, and were likewise relatively well educated. However, one unexpected variable set off those who used the websites for a hotel purchase, the length of their most recent trip. One possible reason is that long-haul tourists want to be sure of their accommodations, or this may reflect hotels’ free-night offers. The convenient use of model-based customer segmentation and decision rules would help hospitality practitioners effectively manage their marketing resources and activities, and enhance information-based marketing strategies to attract target customers.
Osteogenic differentiation of human dental pulp stem cells on β-tricalcium phosphate/poly (l-lactic acid/caprolactone) three-dimensional scaffolds
Authors: Khanna-Jain Rashi , Mannerström Bettina , Vuorinen Annukka , Sándor George KB , Suuronen Riitta , Miettinen Susanna
Published: December 2012

Functional tissue engineering for bone augmentation requires the appropriate combination of biomaterials, mesenchymal stem cells, and specific differentiation factors. Therefore, we investigated the morphology, attachment, viability, and proliferation of human dental pulp stem cells cultured in xeno-free conditions in human serum medium seeded on β-tricalcium phosphate/poly(l-lactic acid/caprolactone) three-dimensional biomaterial scaffold. Additionally, osteogenic inducers dexamethasone and vitamin D3 were compared to achieve osteogenic differentiation. Dental pulp stem cells cultured in human serum medium maintained their morphology; furthermore, cells attached, remained viable, and increased in cell number within the scaffold. Alkaline phosphatase staining showed the osteogenic potential of dental pulp stem cells under the influence of osteogenic medium containing vitamin D3 or dexamethasone within the scaffolds. Maintenance of dental pulp stem cells for 14 days in osteogenic medium containing vitamin D3 resulted in significant increase in osteogenic markers as shown at mRNA level in comparison to osteogenic medium containing dexamethasone. The results of this study show that osteogenic medium containing vitamin D3 osteo-induced dental pulp stem cells cultured in human serum medium within β-tricalcium phosphate/poly(l-lactic acid/caprolactone) three-dimensional biomaterial, which could be directly translated clinically.
Langerhans cell homeostasis in mice is dependent on mTORC1 but not mTORC2 function
Authors: Kellersch Bettina , Brocker Thomas
Published: December 2012

The PI3K/Akt/mTOR pathway has emerged as a critical regulator of dendritic cell (DC) development and function. The kinase mTOR is found in 2 distinct complexes, mTORC1 and mTORC2. In this study, we show that mTORC1 but not mTORC2 is required for epidermal Langerhans cell (LC) homeostasis. Although the initial seeding of the epidermis with LCs is not affected, the lack of mTORC1 activity in DCs by conditional deletion of Raptor leads to a progressive loss of LCs in the skin of mice. Ablation of mTORC2 function by deletion of Rictor results in a modest reduction of LCs in skin draining lymph nodes. In young mice Raptor-deficient LCs show an increased tendency to leave the skin, leading to a higher frequency of migratory DCs in skin draining lymph nodes, indicating that the loss of LCs results from enhanced migration. LCs lacking Raptor are smaller and display reduced expression of Langerin, E-cadherin, β-catenin, and CCR7 but unchanged levels of MHC-II, ruling out enhanced spontaneous maturation. Ki-67 and annexin V stainings revealed a faster turnover rate and increased apoptosis of Raptor-deficient LCs, which might additionally affect the preservation of the LC network. Taken together our results show that the homeostasis of LCs strictly depends on mTORC1.
Abnormal properties of red blood cells suggest a role in the pathophysiology of Gaucher disease
Authors: Franco Melanie , Collec Emmanuel , Connes Philippe , van den Akker Emile , Billette de Villemeur Thierry , Belmatoug Nadia , von Lindern Marieke , Ameziane Nejma , Hermine Olivier , Colin Yves , Le Van Kim Caroline , Mignot Cyril
Published: December 2012

Gaucher disease (GD) is a lysosomal storage disorder caused by glucocerebrosidase deficiency. It is notably characterized by splenomegaly, complex skeletal involvement, ischemic events of the spleen and bones, and the accumulation of Gaucher cells in several organs. We hypothesized that red blood cells (RBCs) might be involved in some features of GD and studied the adhesive and hemorheologic properties of RBCs from GD patients. Hemorheologic analyses revealed enhanced blood viscosity, increased aggregation, and disaggregation threshold of GD RBCs compared with control (CTR) RBCs. GD RBCs also exhibited frequent morphologic abnormalities and lower deformability. Under physiologic flow conditions, GD RBCs adhered more strongly to human microvascular endothelial cells and to laminin than CTR. We showed that Lu/BCAM, the unique erythroid laminin receptor, is overexpressed and highly phosphorylated in GD RBCs, and may play a major role in the adhesion process. The demonstration that GD RBCs have abnormal rheologic and adhesion properties suggests that they may trigger ischemic events in GD, and possibly phagocytosis by macrophages, leading to the appearance of pathogenic Gaucher cells.
Acute pressure on the sciatic nerve results in rapid inhibition of the wide dynamic range neuronal response
Authors: Wang Wenxue , Tan Wei , Luo Danping , Lin Jianhua , Yu Yaoqing , Wang Qun , Zhao Wangyeng , Wu Buling , Chen Jun , He Jiman
Published: December 2012

Background

Acute pressure on the sciatic nerve has recently been reported to provide rapid short-term relief of pain in patients with various pathologies. Wide dynamic range (WDR) neurons transmit nociceptive information from the dorsal horn to higher brain centers. In the present study, we examined the effect of a 2-min application of sciatic nerve pressure on WDR neuronal activity in anesthetized male Sprague–Dawley rats.

Results

Experiments were carried out on 41 male Sprague–Dawley albino rats weighing 160–280 grams. Dorsal horn WDR neurons were identified on the basis of characteristic responses to mechanical stimuli applied to the cutaneous receptive field. Acute pressure was applied for 2 min to the sciatic nerve using a small vascular clip. The responses of WDR neurons to three mechanical stimuli applied to the cutaneous receptive field were recorded before, and 2, 5 and 20 min after cessation of the 2-min pressure application on the sciatic nerve. Two-min pressure applied to the sciatic nerve caused rapid attenuation of the WDR response to pinching, pressure and brushing stimuli applied to the cutaneous receptive field. Maximal attenuation of the WDR response to pinching and pressure was noted 5 min after release of the 2-min pressure on the sciatic nerve. The mean firing rate decreased from 31.7±1.7 Hz to 13±1.4 Hz upon pinching (p < 0.001), from 31.2±2.3 Hz to 10.9±1.4 Hz (p < 0.001) when pressure was applied, and from 18.9±1.2 Hz to 7.6±1.1 Hz (p < 0.001) upon brushing. Thereafter, the mean firing rates gradually recovered.

Conclusions

Our results indicate that acute pressure applied to the sciatic nerve exerts a rapid inhibitory effect on the WDR response to both noxious and innocuous stimuli. Our results may partially explain the rapid analgesic effect of acute sciatic nerve pressure noted in clinical studies, and also suggest a new model for the study of pain.
Peroxiredoxin 6 promotes upregulation of the prion protein (PrP) in neuronal cells of prion-infected mice
Authors: Wagner Wibke , Reuter Andreas , Hüller Petra , Löwer Johannes , Wessler Silja
Published: December 2012

Background

It has been widely established that the conversion of the cellular prion protein (PrPC) into its abnormal isoform (PrPSc) is responsible for the development of transmissible spongiform encephalopathies (TSEs). However, the knowledge of the detailed molecular mechanisms and direct functional consequences within the cell is rare. In this study, we aimed at the identification of deregulated proteins which might be involved in prion pathogenesis.

Findings

Apolipoprotein E and peroxiredoxin 6 (PRDX6) were identified as upregulated proteins in brains of scrapie-infected mice and cultured neuronal cell lines. Downregulation of PrP gene expression using specific siRNA did not result in a decrease of PRDX6 amounts. Interestingly, selective siRNA targeting PRDX6 or overexpression of PRDX6 controlled PrPC and PrPSc protein amounts in neuronal cells.

Conclusions

Besides its possible function as a novel marker protein in the diagnosis of TSEs, PDRX6 represents an attractive target molecule in putative pharmacological intervention strategies in the future.
Inactivation of Chikungunya virus by 1,5 iodonapthyl azide
Authors: Sharma Anuj , Gupta Paridhi , Maheshwari Radha K
Published: December 2012

Background

Chikungunya virus (CHIKV) is an arthropod borne alphavirus of the family Togaviridae. CHIKV is a reemerging virus for which there is no safe prophylactic vaccine. A live attenuated strain of CHIKV, CHIK181/25, was previously demonstrated to be highly immunogenic in humans, however, it showed residual virulence causing transient arthralgia.

Findings

In this study, we demonstrate the complete inactivation of CHIKV181/25 by 1,5 iodonapthyl azide (INA). No cytopathic effect and virus replication was observed in cells infected with the INA-inactivated CHIKV. However, a reduction in the INA-inactivated CHIK virus-antibody binding capacity was observed by western blot analysis.

Conclusion

INA completely inactivated CHIKV and can further be explored for developing an inactivated-CHIKV vaccine.
Comparative study of sulfite pretreatments for robust enzymatic saccharification of corn cob residue
Authors: Bu Lingxi , Xing Yang , Yu Hailong , Gao Yuxia , Jiang Jianxin
Published: December 2012

Background

Corn cob residue (CCR) is a kind of waste lignocellulosic material with enormous potential for bioethanol production. The moderated sulphite processes were used to enhance the hydrophily of the material by sulfonation and hydrolysis. The composition, FT-IR spectra, and conductometric titrations of the pretreated materials were measured to characterize variations of the CCR in different sulfite pretreated environments. And the objective of this study is to compare the saccharification rate and yield of the samples caused by these variations.

Results

It was found that the lignin in the CCR (43.2%) had reduced to 37.8%, 38.0%, 35.9%, and 35.5% after the sulfite pretreatment in neutral, acidic, alkaline, and ethanol environments, respectively. The sulfite pretreatments enhanced the glucose yield of the CCR. Moreover, the ethanol sulfite sample had the highest glucose yield (81.2%, based on the cellulose in the treated sample) among the saccharification samples, which was over 10% higher than that of the raw material (70.6%). More sulfonic groups and weak acid groups were produced during the sulfite pretreatments. Meanwhile, the ethanol sulfite treated sample had the highest sulfonic group (0.103 mmol/g) and weak acid groups (1.85 mmol/g) in all sulfite treated samples. In FT-IR spectra, the variation of bands at 1168 and 1190 cm-1 confirmed lignin sulfonation during sulfite pretreatment. The disappearance of the band at 1458 cm-1 implied the methoxyl on lignin had been removed during the sulfite pretreatments.

Conclusions

It can be concluded that the lignin in the CCR can be degraded and sulfonated during the sulfite pretreatments. The pretreatments improve the hydrophility of the samples because of the increase in sulfonic group and weak acid groups, which enhances the glucose yield of the material. The ethanol sulfite pretreatment is the best method for lignin removal and with the highest glucose yield.
Disease activity and cognition in rheumatoid arthritis: an open label pilot study
Authors: Raftery Graham , He Jiabao , Pearce Ruth , Birchall Daniel , Newton Julia L , Blamire Andrew M , Isaacs John D
Published: December 2012

Introduction

We hypothesised that fatigue in rheumatoid arthritis (RA) is related to TNF-alpha induced dysregulation of cerebral blood flow. Our objectives were to assess fatigue, cognitive function and cerebral blood flow before and after initiation of anti-TNF treatment.

Methods

In a pilot study, 15 patients initiating treatment with adalimumab were assessed for fatigue using a visual analogue scale (FACIT-F), cognitive function using a panel of psychometric tests and regional cerebral blood flow using MR perfusion imaging.

Results

Patients improved clinically after anti-TNF therapy in terms of DAS28 and FACIT-F. Furthermore significant improvements were documented in full scale, verbal and performance IQ following therapy. There was a non-significant trend towards reduced cerebral perfusion in both grey and white matter, and fatigue at 3 months correlated with cerebral blood flow in white (p = 0.014) and grey (p = 0.005) matter.

Conclusions

We demonstrate for the first time a significant improvement in cognitive function following effective treatment of RA. Although we observed minor reductions in cerebral blood flow, and a correlation between cerebral blood flow and fatigue, a larger, controlled study would be required to affirm a causal relationship.
Positron Emission Tomography/Computed Tomography Identification of Clear Cell Renal Cell Carcinoma: Results From the REDECT Trial
Authors: Divgi Chaitanya R. , Uzzo Robert G. , Gatsonis Constantine , Bartz Roman , Treutner Silke , Yu Jian Qin , Chen David , Carrasquillo Jorge A. , Larson Steven , Bevan Paul , Russo Paul
Published: December 2012

Purpose

A clinical study to characterize renal masses with positron emission tomography/computed tomography (PET/CT) was undertaken.

Patients and Methods

This was an open-label multicenter study of iodine-124 (124I) -girentuximab PET/CT in patients with renal masses who were scheduled for resection. PET/CT and contrast-enhanced CT (CECT) of the abdomen were performed 2 to 6 days after intravenous 124I-girentuximab administration and before resection of the renal mass(es). Images were interpreted centrally by three blinded readers for each imaging modality. Tumor histology was determined by a blinded central pathologist. The primary end points—average sensitivity and specificity for clear cell renal cell carcinoma (ccRCC)—were compared between the two modalities. Agreement between and within readers was assessed.

Results

124I-girentuximab was well tolerated. In all, 195 patients had complete data sets (histopathologic diagnosis and PET/CT and CECT results) available. The average sensitivity was 86.2% (95% CI, 75.3% to 97.1%) for PET/CT and 75.5% (95% CI, 62.6% to 88.4%) for CECT (P = .023). The average specificity was 85.9% (95% CI, 69.4% to 99.9%) for PET/CT and 46.8% (95% CI, 18.8% to 74.7%) for CECT (P = .005). Inter-reader agreement was high (κ range, 0.87 to 0.92 for PET/CT; 0.67 to 0.76 for CECT), as was intrareader agreement (range, 87% to 100% for PET/CT; 73.7% to 91.3% for CECT).

Conclusion

This study represents (to the best of our knowledge) the first clinical validation of a molecular imaging biomarker for malignancy. 124I-girentuximab PET/CT can accurately and noninvasively identify ccRCC, with potential utility for designing best management approaches for patients with renal masses.
Phase II and Biomarker Study of the Dual MET/VEGFR2 Inhibitor Foretinib in Patients With Papillary Renal Cell Carcinoma
Authors: Choueiri Toni K. , Vaishampayan Ulka , Rosenberg Jonathan E. , Logan Theodore F. , Harzstark Andrea L. , Bukowski Ronald M. , Rini Brian I. , Srinivas Sandy , Stein Mark N. , Adams Laurel M. , Ottesen Lone H. , Laubscher Kevin H. , Sherman Laurie , McDermott David F. , Haas Naomi B. , Flaherty Keith T. , Ross Robert , Eisenberg Peter , Meltzer Paul S. , Merino Maria J. , Bottaro Donald P. , Linehan W. Marston , Srinivasan Ramaprasad
Published: December 2012

Purpose

Foretinib is an oral multikinase inhibitor targeting MET, VEGF, RON, AXL, and TIE-2 receptors. Activating mutations or amplifications in MET have been described in patients with papillary renal cell carcinoma (PRCC). We aimed to evaluate the efficacy and safety of foretinib in patients with PRCC.

Patients and Methods

Patients were enrolled onto the study in two cohorts with different dosing schedules of foretinib: cohort A, 240 mg once per day on days 1 through 5 every 14 days (intermittent arm); cohort B, 80 mg daily (daily dosing arm). Patients were stratified on the basis of MET pathway activation (germline or somatic MET mutation, MET [7q31] amplification, or gain of chromosome 7). The primary end point was overall response rate (ORR).

Results

Overall, 74 patients were enrolled, with 37 in each dosing cohort. ORR by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 was 13.5%, median progression-free survival was 9.3 months, and median overall survival was not reached. The presence of a germline MET mutation was highly predictive of a response (five of 10 v five of 57 patients with and without germline MET mutations, respectively). The most frequent adverse events of any grade associated with foretinib were fatigue, hypertension, gastrointestinal toxicities, and nonfatal pulmonary emboli.

Conclusion

Foretinib demonstrated activity in patients with advanced PRCC with a manageable toxicity profile and a high response rate in patients with germline MET mutations.
A Unique Tradition of Materialism in Japan: Osugi Sakae, Tosaka Jun, and Uno Kozo
Authors: Endo Katsuhiko
Published: December 2012

This article closely examines the very “ambiguity” of Osugi Sakae's “philosophy of labor movement” in relation to the ongoing “street fighting” in Japan and elsewhere. In doing so, it attempts to reveal the significance of his work in today's context. On the one hand, Osugi's thought has provided the philosophical underpinning for the quasi-autonomous, middle-class movement that formed the consensus for Japan's prewar empire, or Osaka Ishi No Kai (Association for Osaka Restoration), that is making a loud noise in Japan right now. On the other hand, however, as the article argues, it also teaches us how to criticize it and, more important, how to extend and intensify the kind of autonomy that has recently emerged everywhere from Tahrir Square in Cairo to the streets around the Diet building in Tokyo. Investigating the several concepts found in his text, such as “feeling,” “desire,” “labor-power (or power of action),” and “autonomy,” the article tries to draw a clear line between these two conflicting aspects and extract the “center of possibility” of this very unique thinker/activist's work. Those whom I call “Osugi Children” from Uno Kozo and Tosaka Jun to Gilles Deleuze and Harry Harootunian help us do so, but it is ultimately the voices of the women on the streets from Ito Noe to Muto Ruiko that lead this journey of ours.
Heterotopic ossificans in chronic venous insufficiency: a new consideration for clinical, aetiology, anatomy and pathophysiology staging
Authors: Cafasso D E , Bowen D K , Kinkennon S A , Stanbro M D , Kellicut D C
Published: December 2012

Objectives:

Heterotopic ossification is defined as the abnormal formation of true bone within extraskeletal soft tissues. It may be associated with a variety of clinical conditions, but is most frequently seen with musculoskeletal trauma, neurologic injury or genetic abnormalities. It has also been described in patients with chronic venous insufficiency; however, it often goes underdiagnosed due to chronic ulceration that masks exam findings. To date, few reports of heterotopic ossification due to chronic venous disease exist within the literature with the most recent dating back to the 1970s.

Methods:

We present a case study of a man presenting with extensive leg ulceration and a history of chronic venous insufficency. He had a large non-healing venous stasis ulcer of the left lower extremity with extensive heterotopic ossification discovered intraoperatively.

Results:

The patient was managed with serial wound debridement, innovative woundcare and eventual split thickness skin grafting that achieved limb salvage despite the complexity of his wound.

Conclusions:

Our discussion focuses on the epidemiology, pathophysiology, diagnostic work-up and management of heterotopic ossification in the setting of chronic venous insufficiency. We propose that heterotopic ossification be included in any future modifications of the clinical, aetiology, anatomy and pathophysiology system classification as a complication of chronic venous disease.
Implementation of a fast-track-pathway including analgo-sedation with local anaesthesia for outpatient varicose vein surgery: a cohort study
Authors: Licker M , Brandao-Farinelli E , Cartier V , Gemayel G , Christenson J T
Published: December 2012

Objective

To evaluate the clinical and economical impact of a fast-track anaesthesia protocol in the management of primary varicose vein (VV) surgery.

Methods

Over a 10-month period (from 1 December 2009 to 30 September 2011), all patients eligible for open VV surgery ( N = 176) were enrolled in a fast-track clinical pathway including titrated analgo-sedation combined with local anaesthesia. This fast-track cohort was compared with a historical cohort undergoing similar procedures and receiving general anaesthesia (GA) or spinal anaesthesia (SA) (between 1 December 2009 to 30 September 2011, N = 200). The length of stay in the operating facilities and postoperative recovery areas were reported and hospital costs were estimated. In addition, the occurrence of adverse events and unplanned hospital admission were compared between the two consecutive periods.

Results

Patients characteristics and surgical procedure were not different in the two cohorts. After implementation of the fast-track pathway, the incidence of postoperative adverse events decreased from 41% to 2.3%, with no need for overnight hospital stay (0% versus 7%). The reduction in anaesthesia-controlled time (-47%) and in postoperative recovery time (-61%) were associated with an increased operating capacity (1 extra case per day) and with substantial cost-savings (mean reduction of €312 per case, P < 0.001).

Conclusions

Implementation of a fast-track pathway for outpatient VV surgery was successful, safe and efficient. Analgo-sedation combined with infiltrative anaesthesia (instead of GA or SA) contributed to increase the operating capacity and to reduce the workload of nursing personnel.
Italy: Renewables Policy as a Barrier to Energy Innovation
Authors: Standish Dominic
Published: December 2012

Italy's limited natural energy reserves, high dependency on imports and enormous user costs provide an opportunity to innovate. Yet the 2008–2011 Italian government failed to uphold its legislation permitting construction of innovative nuclear reactors. As this government's popularity dwindled, subsidising low-risk renewable projects appeared more popular, especially for solar installations. European and Italian subsidies for Italian renewable energy encouraged the more widespread application of existing technologies, rather than innovation. During 2012, Italy's technocratic government has debated a new energy law, which will continue incentives for low-capacity, renewable and low-risk energy projects, although with reduced subsidies. The new law will not support serious technological innovation to boost energy production, reduce import dependency or defray high costs. Instead, this paper recommends expanding hydro-electric power, exploiting shale gas, constructing more large-scale solar installations, equipping coal-fired power plants with carbon capture and storage, and building at least four nuclear European Pressurised Reactors.
Not Too Smart an Innovation: Britain's Plans to Switch Consumers to Smart Electricity and Gas Meters
Authors: Thomas Stephen D.
Published: December 2012

The high cost of meeting peak demand for electricity could be reduced if demand could be smoothed. Growth in the use of intermittent, renewable sources of energy will reinforce the need to be able reduce demand when necessary. “Smart” meters for electricity and gas could meet this need, and, by 2018, plans exist for all UK households to have them. However, the UK government's cost-benefit analyses of smart meters for electricity make little mention of their most powerful capability: To set prices in real time, so that consumers pay high prices when supply is tight. Without this, the benefits of smart meters may not be enough to repay the huge cost of their installation. Officialdom's silence on time-of-day pricing means that its impact on poor consumers is not addressed. With smart meters for gas, the case for introduction, even with time-of-day pricing, is equally unconvincing.
Energy Innovation and Avoiding Policy Complexity: The Air Capture Approach
Authors: Fox Timothy A.
Published: December 2012

Access to secure and affordable energy has underpinned the rise of civilisations since human history began. When such sources become threatened with unavailability, societies that attempt to meet the challenge by adding increasing levels of sociopolitical complexity to energy policy find themselves in a state of decline. When an era of this type presents itself, the need is for innovation, not complexity. In our current epoch of rapidly growing energy demand and increased environmental risk from continued fossil fuel usage, the international political community has reacted not by innovating, but by adding complexity. This paper argues that, through the harnessing of market forces, the removal of carbon dioxide from the atmosphere offers a way to unlock innovative approaches to maintaining access to affordable energy. It concludes that governments should learn lessons from history and adopt this paradigm shift in thinking, so as to meet global energy aspirations while reducing environmental risk.
Solving Inverse Structural Reliability Problem Using Artificial Neural Networks and Small-Sample Simulation
Authors: Lehký David , Novák Drahomír
Published: December 2012

A new general inverse reliability analysis approach based on artificial neural networks is proposed. An inverse reliability analysis is a problem of obtaining design parameters corresponding to a specified reliability (reliability index or theoretical failure probability). Design parameters can be deterministic or they can be associated with random variables. The aim is to generally solve not only single design parameter cases but also multiple parameter problems with given multiple reliability constraints. Inverse analysis is based on the coupling of a stochastic simulation of the Monte Carlo type (the small-sample simulation method Latin hypercube sampling) and an artificial neural network. The validity and efficiency of this approach is shown using numerical examples with single as well as multiple reliability constraints and with single as well as multiple design parameters, and with independent basic random variables as well as random variables with prescribed statistical correlations.
Experimental Investigations of Stochastic Control of Randomly Base-Excited Structures
Authors: Li Jie , Mei Zhen , Chen Jianbing , Peng Yongbo
Published: December 2012

A series of numerical simulations and experimental verifications on vibration control of structures subjected to earthquake excitations have been conducted. In most existing researches, only several ground motions at different levels are considered, and the efficacy of vibration suppression is usually denoted by the reduction of peak responses. In this paper, a complete shaking-table test on a controlled structured is carried out, in which the randomness inherent in the earthquake ground motions was considered. The representative time histories of ground accelerations, as the base excitation, are generated employing the stochastic ground motion model. The stochastic response analyses of the experimental structures with and without control are conducted, respectively, based on various criteria, including peak responses, RMS responses and PDFs of responses. Experimental results indicate that the seismic performance of the test structure with magnetorheological (MR) dampers is significantly improved compared with that of the uncontrolled structure. The investigation on PDFs of the stochastic responses with control system is very important to better understand the structural performance.
Effect of Second Order Analysis on the Drift Reliability of Steel Buildings
Authors: Baji H. , Ronagh H.R. , Shayanfar M.A. , Barkhordari M.A.
Published: December 2012

Serviceability limit state is an important limit state in the reliability analysis of building structures. One of the serviceability limit states to consider in the design is the lateral displacement or drift check. Due to the uncertainties in the cross-sectional dimensions and the mechanical properties of materials, the lateral drift of structures is a random variable. Second order effects also amplify the lateral displacements and are a function of gravity loads and lateral displacements. In this study, the drift reliability of steel frames and the effects of second order analysis are investigated using geometric nonlinear analysis and Monte Carlo Simulation technique. Results show that for the drift limit state that does not include P–Δ effect, reliability indices do not depend on return period of the load cmbination, the wind to gravity load ratio or the drift limits. On the other hands, for the limit state in which P–Δ effect is incorporated, in low wind to gravity range, the reliability indices are sensitive, and could change dramatically. The limit state that does not have the P–Δ effect is the lower bound of load combination with 50 year return period, but is the upper bound for the other load combination with 20 year return period. Furthermore, the value of drift limit affects the reliability indices for the limit states that include P–Δ effect.
Deflection Reliability Analysis of PSC Box-Girder Bridge under High-Speed Railway Loads
Authors: Guo Tong , Liu Tie , Li Aiqun
Published: December 2012

A high-speed railway (HSR) construction boom has been observed in China during the past few years, in which prestressed concrete (PSC) box-girders are widely used for HSR bridges. Concerns have been raised regarding the long-term deflection of girders under the combined actions of concrete creep, shrinkage, and tendon relaxation, since the time-variant deflection significantly undermines the safety of high-speed trains. This paper presents the time-variant deflection reliability analysis of an existing HSR PSC box-girder bridge, in which a hybrid method, consisting of the response surface (RS) method, the finite element (FE) method and the checking point method (i.e., the JC method), is used. The pre-and post-cracking behaviors of the thin-walled box girder are described by using composite degenerated shell elements with the smeared cracking model and the Hordijk's tension softening relation. In particular, the CEB-FIP model for creep and shrinkage is applied in the finite-element (FE) analyses. By using the probabilistic sensitivity analyses, random variables that significantly affect the time-variant deflection are selected for the reliability calculation. It is found that the deflection reliabilities are high in the early stage of bridge service but decrease rapidly during the first 10 to 20 service years. Higher speed limits result in a significant decrease in deflection reliability indices, which may fall below the target value prior to the expected service life. The proposed methodologies can be used in the design optimization, speed control and making rational maintenance or repair strategies for HSR PSC bridges.
VOF Simulations of Countercurrent Gas-Liquid Flow in a PWR Hot Leg
Authors: Murase Michio , Utanohara Yoichi , Kinoshita Ikuo , Yanagi Chihiro , Takata Takashi , Yamaguchi Akira , Tomiyama Akio
Published: December 2012

In order to evaluate flow patterns and CCFL (countercurrent flow limitation) characteristics in a PWR hot leg under reflux condensation, numerical simulations have been done using a two-fluid model and a VOF (volume of fluid) method implemented in the CFD software, FLUENT6.3.26. The two-fluid model gave good agreement with CCFL data under low pressure conditions but did not give good results under high pressure steam-water conditions. On the other hand, the VOF method gave good agreement with CCFL data for tests with a rectangular channel but did not give good results for calculations in a circular channel. Therefore, in this paper, the computational grid and schemes were improved in the VOF method, numerical simulations were done for steam-water flows at 1.5 MPa under PWR full-scale conditions with the diameter of 0.75 m, and the calculated results were compared with the UPTF data at 1.5 MPa. As a result, the calculated flow pattern was found to be similar to the flow pattern observed in small-scale air-water tests, and the calculated CCFL characteristics agreed well with the UPTF data at 1.5 MPa except in the region of a large steam volumetric flux.
Dynamic Modeling Strategy for Flow Regime Transition in Gas-Liquid Two-Phase Flows
Authors: Wang Xia , Sun Xiaodong , Doup Benjamin , Zhao Haihua
Published: December 2012

In modeling gas-liquid two-phase flows, the concept of flow regimes has been widely used to characterize the global interfacial structure of the flows. Nearly all constitutive relations that provide closures to the interfacial transfers in two-phase flow models, such as the two-fluid model, are flow regime dependent. Current nuclear reactor safety analysis codes, such as RELAP5, classify flow regimes using flow regime maps or transition criteria that were developed for steady-state, fully-developed flows. As two-phase flows are dynamic in nature, it is important to model the flow regime transitions dynamically to more accurately predict the two-phase flows. The present work aims to develop a dynamic modeling strategy to determine flow regimes in gas-liquid two-phase flows through introduction of interfacial area transport equations (IATEs) within the framework of a two-fluid model. The IATE is a transport equation that models the interfacial area concentration by considering the creation of the interfacial area, fluid particle (bubble or liquid droplet) disintegration, boiling and evaporation, and the destruction of the interfacial area, fluid particle coalescence and condensation. For flow regimes beyond bubbly flows, a two-group IATE has been proposed, in which bubbles are divided into two groups based on their size and shapes, namely group-1 and group-2 bubbles. A preliminary approach to dynamically identify the flow regimes is discussed, in which discriminators are based on the predicted information, such as the void fraction and interfacial area concentration. The flow regime predicted with this method shows good agreement with the experimental observations.
Earthquake Engineering – Reconnaissance and Assessment of Existing Buildings
Authors: Gebbeken N. , Braun M. , Hachmann T. , Yilmaz H.
Published: December 2012

Most existing built infrastructure, especially historical monuments, has not been designed in accordance with earthquake resistant standards. Earthquake engineering as a specific field of science and practice has only been developed over the past fifty years. Therefore, many buildings across the globe need to be inspected and to be assessed in order to determine their resistance against earthquakes based on today's knowledge. Based on safety standards and a risk assessment, the earthquake engineer provides information to the owner as to use the building in the future in order to fulfill economic as well as safety demands. This paper outlines the inspection procedure, defines the methodology of reconnaissance on site and describes the subsequent assessment of buildings from the practical point of view.
Finite Element Analysis of 3-D Problems of Deformation and Failure of Masonry under Explosive Loading
Authors: Bazhenov Valentin Georgiyevich , Kibetz Alexader Ivanovich , Kruszka Leopold
Published: December 2012

A finite-element procedure is developed for solving three-dimensional non-steady problems of deformation and fracture of brickwork reinforced by composite plates, including rigid and soft layers.
Experimental Modeling of Extreme Hydrodynamic Forces on Structural Models
Authors: Al-Faesly Taofiq , Palermo Dan , Nistor Ioan , Cornett Andrew
Published: December 2012

This paper presents the results of a comprehensive experimental program focused on the impact of extreme hydrodynamic forces on structural models generated by a turbulent hydraulic bore. The parameters investigated include: (1) bore depth-time history; (2) initial flume-bed conditions (dry bed versus wet); and (3) damping effect of mitigation walls on the hydrodynamic forces. At impact, the maximum inundation (bore) depths varied between 250 mm and 450 mm and the bore front velocity ranged from 2.6 m/s to 5.0 m/s. High-speed video recordings of the bore-structural model interaction were captured simultaneously with the base shear force-, pressure-, base overturning moment-, and top lateral displacement-time histories experienced by the structural models. Three force components were identified in the bore-induced force-time histories: impulsive, run-up (transient hydrodynamic force), and quasi-steady hydrodynamic. The impulsive or run-up force was the maximum force component experienced by the structural models under initial dry-bed flume conditions; while for the initial wet-bed flume condition, the run-up force component was the maximum force. The effect of 100 mm and 150 mm low-height mitigation walls inclined at angles of 45° or 90°, which were installed at distances of 305 mm or 915 mm upstream from the structural model, was also investigated. The angle of inclination of the mitigation walls, its location relative to the structural model, and its cross-sectional shape all influence the base shear force- and base overturning moment-time histories. The base shear forces in the direction of the flow measured during experimental testing were greater than those estimated using the Federal Emergency Management Agency (FEMA) document P646, while the Structural Design Method of Buildings for Tsunami Resistance (SMBTR) overestimated the base shear forces.
Enhancing Leisure Experiences Post Traumatic Brain Injury: A Pilot Study
Authors: Carbonneau Hélène , Martineau Éric , Andre Melanie , Dawson Deirdre
Published: December 2012

Up to 90% of people with severe traumatic brain injury (TBI) report dissatisfaction with the status of their leisure participation and/or social integration. Yet, there are virtually no studies that have investigated the benefits of interventions that target leisure specifically for this population. The purpose of this study was to determine whether the Leisure Education Program (Carbonneau, Fontaine, & Lussier, 2006) designed to assist people with stroke to engage in meaningful leisure activities, build leisure self-efficacy and promote general wellbeing would have similar benefits for survivors of TBI. We recruited three community-dwelling survivors of TBI to participate in a 10-week leisure program. All three participants reported some benefit in leisure satisfaction and self-efficacy. This extended to improvements in general wellbeing and health-related quality of life for two of the three. These findings suggest that further investigations into the benefits of leisure education for adults with TBI should be conducted.
Jung Ji-Woo's Happy End: Modernity, Masculinity, and Murder
Authors: Childs Cynthia
Published: December 2012

In a brilliant and enigmatic film, Happy End, director Jung Ji-woo has indexed all of these themes: shifting gender hierarchies, the valorization of aggressive masculinity, the establishment of a modern national identity, and the social uncertainties of a faltering economy. Happy End
is a film clearly situated within the significant political, economic, and social events of the period within which it was made.
On Western Critiques of Chinese Film
Authors: Browne Nick
Published: December 2012

In the following article, Nick Browne examines the numerous achievements in Chinese film production over the last 25 years, and examines the cultural significance of the emerging field of academic criticism.
History, Memory, Nostalgia: Rewriting Socialism in Chinese Cinema and Television Drama
Authors: Lu Sheldon
Published: December 2012

This study will focus on a cluster of new films and television dramas that revisit and rewrite the history of Chinese socialism from a different point of view in light of the capitalist frenzy of commercialism and commodification in contemporary post-socialist China. It seems that it
is only possible after some 20 years, after the historical wounds and traumas have been largely healed, that a new critical distance can be reached in regard to the past. Socialism during the 1950s-1970s conveniently signifies the values and ideals that are putatively absent today—idealism,
egalitarianism, self-sacrifice, and innocence. The critique of the present consumer society thus comes in the form of nostalgia for the past in contemporary Chinese cinema.
Release of macrophage migration inhibitory factor by neuroendocrine-differentiated LNCaP cells sustains the proliferation and survival of prostate cancer cells
Authors: Tawadros Thomas , Alonso Florian , Jichlinski Patrice , Clarke Noel , Calandra Thierry , Haefliger Jacques-Antoine , Roger Thierry
Published: December 2012

The acquisition of neuroendocrine (NE) characteristics by prostate cancer (PCa) cells is closely related to tumour progression and hormone resistance. The mechanisms by which NE cells influence PCa growth and progression are not fully understood. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in oncogenic processes, and MIF serum levels correlate with aggressiveness of PCa. Here, we investigated the regulation and the functional consequences of MIF expression during NE transdifferentiation of PCa cells. NE differentiation (NED) of LNCaP cells, initiated either by increasing intracellular levels of cAMP or by culturing cells in an androgen-depleted medium, was associated with markedly increased MIF release. Yet, intracellular MIF protein and mRNA levels andMIFgene promoter activity decreased during NED of LNCaP cells, suggesting that NED favours MIF release despite decreasing MIF synthesis. Adenoviral-mediated forced MIF expression in NE-differentiated LNCaP cells increased cell proliferation without affecting the expression of NE markers. Addition of exogenous recombinant MIF to LNCaP and PC-3 cells stimulated the AKT and ERK1/2 signalling pathways, the expression of genes involved in PCa, as well as proliferation and resistance to paclitaxel and thapsigargin-induced apoptosis. Altogether, these data provide evidence that increased MIF release during NED in PCa may facilitate cancer progression or recurrence, especially following androgen deprivation. Thus, MIF could represent an attractive target for PCa therapy.
Mitotic Exit and Separation of Mother and Daughter Cells
Authors: Weiss Eric L
Published: December 2012

Productive cell proliferation involves efficient and accurate splitting of the dividing cell into two separate entities. This orderly process reflects coordination of diverse cytological events by regulatory systems that drive the cell from mitosis into G1. In the budding yeast Saccharomyces cerevisiae, separation of mother and daughter cells involves coordinated actomyosin ring contraction and septum synthesis, followed by septum destruction. These events occur in precise and rapid sequence once chromosomes are segregated and are linked with spindle organization and mitotic progress by intricate cell cycle control machinery. Additionally, critical parts of the mother/daughter separation process are asymmetric, reflecting a form of fate specification that occurs in every cell division. This chapter describes central events of budding yeast cell separation, as well as the control pathways that integrate them and link them with the cell cycle.
Mammalian Developmental Genetics in the Twentieth Century
Authors: Artzt Karen
Published: December 2012

This Perspectives is a review of the breathtaking history of mammalian genetics in the past century and, in particular, of the ways in which genetic thinking has illuminated aspects of mouse development. To illustrate the power of that thinking, selected hypothesis-driven experiments and technical advances are discussed. Also included in this account are the beginnings of mouse genetics at the Bussey Institute, Columbia University, and The Jackson Laboratory and a retrospective discussion of one of the classic problems in developmental genetics, the T/t complex and its genetic enigmas.