bluuebunny/crossref_metadata_2025 huggingface dataset:
The Consequences of Emotional Labor for Public Sector Workers and the Mitigating Role of Self-Efficacy
Authors: Sloan Melissa M.
Published: October 2012

Emotional labor that requires workers to suppress their truly felt emotions and create a fake emotional display has negative consequences for workers including psychological distress and lowered job satisfaction. This type of emotional labor, called surface acting, is often necessary in public service work. In an effort to identify ways to reduce the harmful effects of emotional labor for workers, this research further specifies the relationship between emotional labor and worker well-being using data from a large sample of public service workers working in a variety of occupations ( n = 1,395). The analyses test a mediator and moderators of the relationship between emotional labor and worker well-being. The findings suggest that surface acting emotional labor is harmful to workers because it increases feelings of self-estrangement. In addition, a worker’s sense of self-efficacy in emotional labor performance is shown to reduce the negative effects of surface acting.
(Re)enchanting geography? The nature of being critical and the character of critique in human geography
Authors: Woodyer Tara , Geoghegan Hilary
Published: October 2012

Enchantment is a term frequently used by human geographers to express delight, wonder or that which cannot be simply explained. However, it is a concept that has yet to be subject to sustained critique, specifically how it can be used to progress geographic thought and praxis. This paper makes sense of, and space for, the unintelligibility of enchantment in order to encourage a less repressed, more cheerful way of engaging with the geographies of the world. We track back through our disciplinary heritage to explore how geographers have employed enchantment as a force through which the world inspires affective attachment. We review the terrain of the debate surrounding recent geographical engagements with enchantment, focusing on the nature of being critical and the character of critique in human geography, offering a new ‘enchanted’ stance to our geographical endeavours. We argue that the moment of enchantment has not passed with the current challenging climate; if anything, it is more pressing.
Charitable Estate Planning as Visualized Autobiography
Authors: James Russell N. , O’Boyle Michael W.
Published: October 2012

This first ever functional magnetic resonance imaging (fMRI) analysis of charitable bequest decision making found increased activation in the precuneus and lingual gyrus of the brain compared to charitable giving and volunteering decisions. Greater lingual gyrus activation was also associated with increased propensity to make a charitable bequest. Previous studies have shown that activation of these brain regions is related to taking an outside perspective of one’s self, recalling the recent death of a loved one, and recalling vivid autobiographical memories across one’s life. We propose that bequest decision making is analogous to visualizing the final chapter in one’s autobiography and that fund-raisers may do well to emphasize donors’ autobiographical connections with the charity. Due to inherent mortality salience, people may resist creating this final chapter but, once engaged, may seek to leave an enduring legacy.
Fatigue life and reliability evaluation for dental implants based on computer simulation and limited test data
Authors: Tsai Yuo-Tern , Wang Kuo-Shong , Woo Jeng-Chung
Published: October 2012

Dental implants have been extensively utilized on edentulous patients for many years. The fatigue life of dental implants is critical for them being approved to use in human body because they are within the area of biomedicine. To perform a preliminary investigation of fatigue life of dental implants, this article reports a method of fatigue life estimation based on the combination of computer simulation and limited test data. The method is developed based on a probabilistic form of fatigue life given according to the properties of material fatigue strength. The procedure is carried out by shifting of the regression line (representing the fatigue–life curve) to the desired value of the probability of occurrence. Computer simulation includes both stress analysis and life estimation which are done using the ANSYS software. This estimation model offers a method for fatigue life evaluation and yields the life distribution in respect to the scatter of the cyclic properties of dental implants. Furthermore, the reliability of lifetime is calculated based on the probabilistic form. The purposes of this study are to predict fatigue life using a small amount of testing data and to provide a risk assessment for dental implants in use.
Maternal Education as a Determinant of Neonatal Mortality in Bangladesh
Authors: Kamal S.M. Mostafa
Published: October 2012

This study aims to investigate the effect of maternal education on neonatal mortality in Bangladesh using data from the nationally representative 2007 Bangladesh Demographic and Health Survey. Both bivariate and multivariate statistical analyses were used to assess the relationship between neonatal mortality and contextual factors focusing on maternal education. The prevalence of neonatal mortality was 37/1,000. The statistical analyses yielded quantitatively important and reliable estimates of neonatal death. The sequential multivariate logistic regression analyses yielded strong significant negative association between maternal education and neonatal mortality. Maternal age, religion, birth order and antenatal care seeking are also important determinants of neonatal death. Programmes should be undertaken to improve female education in Bangladesh for a better chance of satisfying important factors that can improve infant survival, such as the quality of infant feeding, household sanitation and adequate use of preventive and curative health services.
Causal Model of Oral Health Care Expenditure in the Surveyed Households of Dharwad, Karnataka State, India: A Structural Equation Modelling Approach
Authors: Javali S.B.
Published: October 2012

The purpose of this study is to examine the contributory relationships among factors determining demand of oral health care by utilizing the applications of structural equation modelling (SEM). A systematic random sample of 1,381 persons was interviewed from 280 households, in which 208 persons were reported with various oral health problems during reference period of study, and data were collected through direct personal interview method. The causal relationships were established by SEM method using SPSS and AMOS statistical software. All factors have significant positive relationship with oral health care (p < 0.05), except the distance of care from the residence (in km) and total number of living persons in the household have a significant negative relationship with oral health care (p < 0.05). The SEM fitted to the oral health care data adequately. The results indicated that the age of sick person, duration of illness episode (in days) and the total number of visits made to source of health care during the reference period had significant effect on oral health care expenditure (p < 0.05).

The duration of illness episode (in days) and the total number of visits made to source of health care during the reference period are the main contributors to oral health care expenditure in surveyed households of Dharwad, Karnataka, India. It is proposed that to meet the increase the demand for health care, efforts should be made to reduce the duration of illness, the distance travelled by the sick person or patient and also, the number of visits to health care providers.
Association of Smoking Status With Quality of Life in a Cross-sectional Population-Based Sample of Iranian Adults
Authors: Toghianifar Nafiseh , Najafian Jamshid , Pooya Arash , Rabiei Katayoun , Eshrati Babak , Anaraki Jafar , Sarrafzadegan Nizal
Published: October 2012

This study aimed to examine the association between smoking status and quality of life (QOL) in a population-based sample of Iranian adults. The study used data from the Isfahan Healthy Heart Program (IHHP). A total of 5830 participants were included. They were categorized as current, former, or never smokers. QOL was evaluated using the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF), Persian version. Data entry was performed using SPSS (SPSS Inc, Chicago, IL) software version 13.0. QOL was associated with marital status ( P = .014), education ( P = .001), occupation ( P = .007), and income ( P < .000) among current smokers. After adjusting for sociodemographic characteristics, smoking decreased QOL among current (odds ratio [OR] = 0.98; 95% confidence interval [CI] = 0.97-0.99) and past (OR = 0.97; 95%CI = 0.95-0.98) smokers relative to never smokers. QOL is lower among Iranian current and past smokers, and the relation is independent of underlying sociodemographic factors.
Family Case Conceptualization and Medical Conditions
Authors: Sperry Len
Published: October 2012

Developing accurate case conceptualizations is increasingly expected of counselors today, particularly when working with couples and families dealing with a medical condition. Described here are the reasons for the increasing role of case conceptualization in counseling practice, the components of a case conceptualization, and an introduction to family case conceptualization. A case example illustrates this kind of case conceptualization with a family dealing with a serious medical condition.
Treatment With Low-dose Atorvastatin, Losartan, and Their Combination Increases Expression of Vasoactive-Related Genes in Rat Aortas
Authors: Lunder Mojca , Drevenšek Gorazd , Černe Darko , Marc Janja , Janić Miodrag , Šabovič Mišo
Published: October 2012

Recently it has been shown that statins and angiotensin receptor blockers (ARBs) at low doses express beneficial pleiotropic vascular effects. We aimed to explore whether these drugs at low doses induce the expression of vasoactive-related genes. Sixty adult Wistar rats were treated with low-dose atorvastatin (2 mg/kg), low-dose losartan (5 mg/kg), their combination or saline daily for 4, 6, or 8 weeks. Expression of the vasoactive-related genes endothelin receptor type A ( EDNRA), endothelial nitric oxide synthase 3 ( NOS3), inducible nitric oxide synthase 2 ( NOS2), and angiotensin II receptor type 1 ( AGTRL1a) was measured in isolated thoracic aortas. Expression of EDNRA gradually decreased, the lowest values being obtained after 8 weeks (low-dose atorvastatin, losartan [1.6- and 1-7-fold vs controls, respectively; both P < .05], and the combination [2.3-fold vs control, P < .001]). The highest values of NOS3 were obtained after 6 weeks (low-dose atorvastatin, losartan, and their combination, 3.1-fold, P < .01; 3.4-fold, P < .001; and 3.6-fold, P < .001 vs controls, respectively) and then declined after 8 weeks. The combination was more effective in inducing total NOS3 expression when compared to the separate drugs (1.4-fold; P < .05). Importantly, expression of NOS3 was associated with increased plasma NO levels and positively correlated with thoracic aorta relaxation. No changes in expression of NOS2 and AGTRL1a were observed. We showed that low-dose atorvastatin or losartan and especially their combination increases the expression of NOS3 and decreases the expression of EDNRA. These findings are valuable in explaining the effectiveness of the “low-dose pharmacological approach” for improvement in arterial function.
Active tendon control of a Geiger dome
Authors: Ouni Mohamed Hechmi El , Kahla Nabil Ben
Published: October 2012

This paper investigates the nonlinear modeling of a smart tensegrity structure of Geiger’s type with active damping using pairs of displacement actuator and force sensor, collocated at the lower end of strings and/or struts. A control strategy based on decentralized collocated integral force feedback is employed. A linear model is first used to optimize the number and the location of the active tendons. A geometric nonlinear dynamic procedure is then used for the analysis of the response of the structure with and without active control. An incremental-iterative solution based on a Newmark direct integration method and a modified Newton–Raphson scheme is adopted for solving the nonlinear equation of motion. For high excitations, the nonlinear dynamic behavior of the smart cable dome is observed and damping is successfully added to the system. The responses with and without control of particular modes are studied in frequency and time domains. The results obtained indicate that the active control strategy presented in this paper is adequate for vibration attenuation of Geiger domes.
Random vibration control of a hydraulic shaking table
Authors: Guan Guang-Feng , Wang Hai-Tao , Xiong Wei
Published: October 2012

A multi-input multi-output (MIMO) random vibration control method is proposed for a multi-axis hydraulic shaking table system to replicate the reference power spectral density (PSD). Kinematics analysis is presented to reduce cross-coupling between the axes of the hydraulic shaking table. The time histories generated by time domain randomization in conventional MIMO random vibration control have spectral leakage between the frequency resolutions. The drive signal PSD is used in the proposed control method to design a linear time-invariant system. Circular convolution is then proposed to implement the designed system and convert the PSD to time histories with white noise. Experimental results obtained in step response and two-axis PSD replication show the effectiveness of the proposed control method.
Giving content to new politics
Authors: Båtstrand Sondre
Published: October 2012

The concept of New Politics is rarely translated into actual political measures differentiated from measures of Old Politics. This article presents a new approach to the categorization of policy measures as either leftist or rightist on an Old Politics or New Politics dimension. The approach is tested on climate policies expressed in the electoral manifestos of four Norwegian parties considered to be representative of the Old Left, Old Right, New Left or New Right. The analysis suggests that it is possible to incorporate actual politics in the hypothesis on New Politics. The article’s main contribution is theoretical rather than empirical, but evidence is presented that points to New Politics as an addition to Old Politics, rather than as a replacement or New Politics being absorbed by Old Politics.
Negotiating gender equality in development organizations:The role of agency in the institutionalization of new norms and practices
Authors: Porter Fenella
Published: October 2012

This article considers how, in the context of development, the negotiation of meanings and individual values can create a crucial link between an awareness of gender relations and actual changes in the norms and practices of an organization. I use the concept of institutional agency to question whether as gendered individuals, development practitioners can challenge how development organizations go about their work? Or whether we are all trapped in a ‘meta structure’ of norms, practices and meanings that ultimately block both our own agency and the changes we are trying to bring about?
Infrastructural violence: Introduction to the special issue
Authors: Rodgers Dennis , O’Neill Bruce
Published: October 2012

This introduction lays out some of the theoretical underpinnings of the notion of ‘infrastructural violence’. We begin by considering infrastructure as an ethnographically graspable manifestation, before then moving on to highlight how broader processes of marginalization, abjection and disconnection often become operational and sustainable in contemporary cities through infrastructure. We then show how the concept of ‘infrastructural violence’ can nuance our analyses of the relations between people and things that converge daily in urban life to the detriment of marginalized actors, while also proposing a normative reflexivity that can provide a concrete means through which to talk, imagine and build towards greater regimes of quality and collective benefit. Finally, we conclude with a summary of each of the contributions to this special issue.
A visual analytics process for maritime response, resource allocation and risk assessment
Authors: Malik Abish , Maciejewski Ross , Jang Yun , Oliveros Silvia , Yang Yang , Maule Ben , White Matthew , Ebert David S
Published: October 2012

In this paper, we present our collaborative work with the U.S. Coast Guard’s Ninth District and Atlantic Area Commands, in which we develop a visual analytics system to analyze historic response operations and assess the potential risks in the maritime environment associated with the hypothetical allocation of Coast Guard resources. The system includes linked views and interactive displays that enable the analysis of trends, patterns, and anomalies among the U.S. Coast Guard search and rescue (SAR) operations and their associated sorties. Our system allows users to determine the change in risks associated with closing certain stations in terms of response time and potential lives and property lost. It also allows users to determine which stations are best suited to assuming control of the operations previously handled by the closed station. We provide maritime risk assessment tools that allow analysts to explore Coast Guard coverage for SAR operations and identify regions of high risk. The system also enables a thorough assessment of all SAR operations conducted by each Coast Guard station in the Great Lakes region. Our system demonstrates the effectiveness of visual analytics in analyzing risk within the maritime domain and is currently being used by analysts at the Coast Guard Atlantic Area.
Repair and Regeneration of Skin Injury by Transplanting Microparticles Mixed With Wharton’s Jelly and MSCs From the Human Umbilical Cord
Authors: Zhang Yajing , Hao Haojie , Liu Jiejie , Fu Xiaobing , Han Weidong
Published: October 2012

The prognosis for extensive and deep skin injury is not satisfactory because of scar formation and the loss of normal function and skin appendages. Several novel therapies for skin repair and regeneration have emerged. Currently, stem cell–based therapies are attractive candidates in regenerative medicine to treat skin injuries. Human umbilical cord Wharton’s jelly–derived mesenchymal stem cells (hUC-MSCs) have become a unique, accessible, and noncontroversial source of regeneration in medicine. The aim of this study was to explore a new strategy for treating skin wounds. A mixture of hUC-MSCs, Wharton’s jelly, and skin microparticles were transplanted to 10-mm diameter, full-thickness, middorsal, excisional skin wounds of mice. After 7 days, the tissue sections were sampled for reconstruction analysis and histological examination. After transplantation, there was a remarkable development of newborn skin and its appendages. We could see newly generated layers of epidermis, sebaceous glands, hair follicle, and sweat glands clearly. This innovative strategy could be very promising and may significantly increase the quality of repair and regeneration of skin in injuries.
The Unraveling of Support for Authoritarianism
Authors: Stein Elizabeth A.
Published: October 2012

This work examines the dynamic relationship among elites, media, and the public during authoritarian rule. Using Brazil’s military regime (1964–85), it investigates whether changing press censorship influenced public support for military rule during the period of political liberalization. This paper uses the exposure-resistance model of opinion formation, in which a person’s probability of supporting a position depends first on her probability of exposure to and reception of an elite cue advocating that position, and secondarily on the probability that she resists that position once exposed. Her likelihood of exposure to and reception of elite cues increases with her attention to news media and the extent of her political awareness; her odds of accepting the positions advocated by elites depends on her political ideology and her critical capacity to evaluate the content and source of the cue. Using three public opinion surveys carried out between 1972 and 1982, and an analysis of newspaper content during the dictatorship, this research demonstrates that censored media convinced Brazilians to support military rule initially, only later during political liberalization, to expose them to increasingly critical coverage of the regime, convincing many to abandon their support for the regime.
Meis1 preserves hematopoietic stem cells in mice by limiting oxidative stress
Authors: Unnisa Zeenath , Clark Jason P. , Roychoudhury Jayeeta , Thomas Elizabeth , Tessarollo Lino , Copeland Neal G. , Jenkins Nancy A. , Grimes H. Leighton , Kumar Ashish R.
Published: October 2012

The transcription factor Meis1 is expressed preferentially in hematopoietic stem cells (HSCs) and overexpressed in certain leukemias. However, the functions of Meis1 in hematopoiesis remain largely unknown. In the present study, we found that Meis1 is required for the maintenance of hematopoiesis under stress and over the long term, whereas steady-state hematopoiesis was sustained in the absence of Meis1 in inducible knock-out mice. BM cells of Meis1-deficient mice showed reduced colony formation and contained significantly fewer numbers of long-term HSCs, which exhibited loss of quiescence. Further, we found that Meis1 deletion led to the accumulation of reactive oxygen species in HSCs and decreased expression of genes implicated in hypoxia response. Finally, reactive oxygen species scavenging by N-acetyl cysteine or stabilization of hypoxia signaling by knockdown of the von-Hippel-Lindau (VHL) protein led to reversal of the effects of Meis1 deletion. The results of the present study demonstrate that Meis1 protects and preserves HSCs by restricting oxidative metabolism.
Small sizes and indolent evolutionary dynamics challenge the potential role of P2RY8-CRLF2–harboring clones as main relapse-driving force in childhood ALL
Authors: Morak Maria , Attarbaschi Andishe , Fischer Susanna , Nassimbeni Christine , Grausenburger Reinhard , Bastelberger Stephan , Krentz Stefanie , Cario Gunnar , Kasper David , Schmitt Klaus , Russell Lisa J. , Pötschger Ulrike , Stanulla Martin , Eckert Conny , Mann Georg , Haas Oskar A. , Panzer-Grümayer Renate
Published: October 2012

The P2RY8-CRLF2 fusion defines a particular relapse-prone subset of childhood acute lymphoblastic leukemia (ALL) in Italian Association of Pediatric Hematology and Oncology Berlin-Frankfurt-Münster (AIEOP-BFM) 2000 protocols. To investigate whether and to what extent different clone sizes influence disease and relapse development, we quantified the genomic P2RY8-CRLF2 fusion product and correlated it with the corresponding CRLF2 expression levels in patients enrolled in the BFM-ALL 2000 protocol in Austria. Of 268 cases without recurrent chromosomal translocations and high hyperdiploidy, representing approximately 50% of all cases, 67 (25%) were P2RY8-CRLF2 positive. The respective clone sizes were ≥ 20% in 27% and < 20% in 73% of them. The cumulative incidence of relapse of the entire fusion-positive group was clone size independent and significantly higher than that of the fusion-negative group (35% ± 8% vs 13% ± 3%, P = .008) and primarily confined to the non–high-risk group. Of 22 P2RY8-CRLF2–positive diagnosis/relapse pairs, only 4/8 had the fusion-positive dominant clone conserved at relapse, whereas none of the original 14 fusion-positive small clones reappeared as the dominant relapse clone. We conclude that the majority of P2RY8-CRLF2–positive clones are small at diagnosis and virtually never generate a dominant relapse clone. Our findings therefore suggest that P2RY8-CRLF2–positive clones do not have the necessary proliferative or selective advantage to evolve into a disease-relevant relapse clone.
Characterization of methionine oxidation and methionine sulfoxide reduction using methionine-rich cysteine-free proteins
Authors: Liang Xinwen , Kaya Alaattin , Zhang Yan , Le Dung Tien , Hua Deame , Gladyshev Vadim N
Published: October 2012

Background

Methionine (Met) residues in proteins can be readily oxidized by reactive oxygen species to Met sulfoxide (MetO). MetO is a promising physiological marker of oxidative stress and its inefficient repair by MetO reductases (Msrs) has been linked to neurodegeneration and aging. Conventional methods of assaying MetO formation and reduction rely on chromatographic or mass spectrometry procedures, but the use of Met-rich proteins (MRPs) may offer a more streamlined alternative.

Results

We carried out a computational search of completely sequenced genomes for MRPs deficient in cysteine (Cys) residues and identified several proteins containing 20% or more Met residues. We used these MRPs to examine Met oxidation and MetO reduction by in-gel shift assays and immunoblot assays with antibodies generated against various oxidized MRPs. The oxidation of Cys-free MRPs by hydrogen peroxide could be conveniently monitored by SDS-PAGE and was specific for Met, as evidenced by quantitative reduction of these proteins with Msrs in DTT- and thioredoxin-dependent assays. We found that hypochlorite was especially efficient in oxidizing MRPs. Finally, we further developed a procedure wherein antibodies made against oxidized MRPs were isolated on affinity resins containing same or other oxidized or reduced MRPs. This procedure yielded reagents specific for MetO in these proteins, but proved to be ineffective in developing antibodies with broad MetO specificity.

Conclusion

Our data show that MRPs provide a convenient tool for characterization of Met oxidation, MetO reduction and Msr activities, and could be used for various aspects of redox biology involving reversible Met oxidation.
Resolvin D1 reverses chronic pancreatitis-induced mechanical allodynia, phosphorylation of NMDA receptors, and cytokines expression in the thoracic spinal dorsal horn
Authors: Quan-Xin Feng , Fan Feng , Xiang-Ying Feng , Shu-Jun Li , Shi-Qi Wang , Zhao-Xu Liu , Xu-Jie Zhang , Qing-Chuan Zhao , Wei Wang
Published: October 2012

Background

We previously reported that immune activation in the spinal dorsal horn contributes to pain induced by chronic pancreatitis (CP). Targeting immune response in the CNS may provide effective treatments for CP-induced pain. Recent findings demonstrate that resolvin D1 (RvD1) can potently dampen inflammatory pain. We hypothesized that intrathecal injection of RvD1 may inhibit pain of CP.

Methods

Rat CP model was built through intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS). All the rats were divided into three groups: TNBS, sham, and naïve controls and were further divided for intrathecal RvD1 administration. Pain behavior of rats was tested with von Frey filaments. Anxiety-like behavior and free locomotor and exploration of rats were evaluated by open field test and elevated plus maze. Pancreatic histology was evaluated with hematoxylin and eosin staining. Phosphorylation of NMDA receptor and expression of inflammatory cytokines were examined with Western blot, real-time RT-PCR and ELISA.

Results

Behavioral study indicated that compared to the vehicle control, RvD1 (100 ng/kg) significantly decreased TNBS-induced mechanical allodynia at 2 h after administration (response frequencies: 49.2 ± 3.7% vs 71.3 ± 6.1%), and this effect was dose-dependent. Neither CP nor RvD1 treatment could affect anxiety-like behavior. CP or RvD1 treatment could not affect free locomotor and exploration of rats. Western blot analysis showed that compared with that of naïve group, phosphorylated NR1 (pNR1) and pNR2B in TNBS rats were significantly increased in the spinal cord (pNR1: 3.87±0.31 folds of naïve control, pNR2B: 4.17 ± 0.24 folds of naïve control). Compared to vehicle control, 10 ng/kg of RvD1 could significantly block expressions of pNR1 (2.21 ± 0.26 folds of naïve) and pNR2B (3.31 ± 0.34 folds of naïve). Real-time RT-PCR and ELISA data showed that RvD1 (10 ng/kg) but not vehicle could significantly block expressions of TNF-alpha, IL-1beta and IL-6. In addition, RvD1 did not influence pain behavior, NMDA receptor phosphorylation or cytokines production in sham-operated rats.

Conclusions

These data highly suggest that RvD1 could be a novel and effective treatment for CP-induced chronic pain.
Corkscrew angiopathy of intracranial vessels in a young stroke patient: a case report
Authors: Alurkar Anand , Karanam Lakshmi Sudha P , Oak Sagar P
Published: October 2012

Introduction

We present a rare finding of a ‘corkscrew appearance’ of the distal cerebral vessels in a young Asian woman who presented with acute stroke.

Case presentation

A 32-year-old Asian woman presented with a 3-month history of recurrent right-sided transient ischemic attacks. Her clinical workup and brain imaging results were normal. A digital subtraction angiogram revealed an abnormal corkscrew appearance of all intracranial distal vessels. She was discharged on a single antiplatelet drug. She had no further transient ischemic attacks on clinical follow-up. A digital subtraction angiogram performed 1 year later revealed no changes in the appearance of these vessels.

Conclusion

To the best of our knowledge no similar previous reports exist in the literature. The present report describes a unique case of an unusual corkscrew appearance of the distal intracranial vessels. However, the underlying etiology in the present case remains unknown.
Construction of a novel selection system for endoglucanases exhibiting carbohydrate-binding modules optimized for biomass using yeast cell-surface engineering
Authors: Nakanishi Akihito , Bae Jungu , Kuroda Kouichi , Ueda Mitsuyoshi
Published: October 2012

To permit direct cellulose degradation and ethanol fermentation, Saccharomyces cerevisiae BY4741 (Δ
sed1) codisplaying 3 cellulases (Trichoderma reesei endoglucanase II [EG], T. reesei cellobiohydrolase II [CBH], and Aspergillus aculeatus β-glucosidase I [BG]) was constructed by yeast cell-surface engineering. The EG used in this study consists of a family 1 carbohydrate-binding module (CBM) and a catalytic module. A comparison with family 1 CBMs revealed conserved amino acid residues and flexible amino acid residues. The flexible amino acid residues were at positions 18, 23, 26, and 27, through which the degrading activity for various cellulose structures in each biomass may have been optimized. To select the optimal combination of CBMs of EGs, a yeast mixture with comprehensively mutated CBM was constructed. The mixture consisted of yeasts codisplaying EG with mutated CBMs, in which 4 flexible residues were comprehensively mutated, CBH, and BG. The yeast mixture was inoculated in selection medium with newspaper as the sole carbon source. The surviving yeast consisted of RTSH yeast (the mutant sequence of CBM: N18R, S23T, S26S, and T27H) and wild-type yeast (CBM was the original) in a ratio of 1:46. The mixture (1 RTSH yeast and 46 wild-type yeasts) had a fermentation activity that was 1.5-fold higher than that of wild-type yeast alone in the early phase of saccharification and fermentation, which indicates that the yeast mixture with comprehensively mutated CBM could be used to select the optimal combination of CBMs suitable for the cellulose of each biomass.
A BCL2 promoter polymorphism rs2279115 is not associated with BCL2 protein expression or patient survival in breast cancer patients
Authors: Searle Claire J , Brock Ian W , Cross Simon S , Balasubramanian Sabapathy P , Reed Malcolm W R , Cox Angela
Published: October 2012

The B-cell CLL/lymphoma 2 (BCL2) gene family encodes pro- and anti-apoptotic proteins that are critical regulators of programmed cell death. Higher levels of BCL2 expression in breast tumours have been shown to be an independent prognostic factor for improved survival from breast cancer. The promoter single nucleotide polymorphism (SNP) rs2279115 has been associated with both BCL2 expression and patient survival. The aim of this study was to attempt to replicate these observations in a cohort of 1015 UK women with breast cancer, and to compare genotype frequencies in cases and controls. In this study, 1015 breast cancer cases and 1034 control subjects were genotyped for the rs2279115 SNP by 5’ nuclease PCR. Paraffin embedded tumour tissue for 342 case subjects was assembled into tissue microarrays, and the level of expression of BCL2 was established by immunohistochemistry. Kaplan Meier survival curves and Cox Proportional Hazards models were used to examine the effect of genotype on patient survival. The effect of SNP genotype on tumour BCL2 protein levels and breast cancer susceptibility was assessed by logistic regression. In this study higher BCL2 expression was significantly associated with improved survival from breast cancer (p = 0.015), in keeping with previous reports. The SNP rs2279115 was not found to be associated with tumour expression of BCL2, (p = 0.77), and neither was it associated with case/control status (p = 0.25). There was no significant association between the SNP and overall survival (p = 0.75). In conclusion, we found that higher tumour BCL2 expression is associated with improved survival from breast cancer, in keeping with previous studies. However, in contrast to a previous report, the promoter SNP rs2279115 was not associated with BCL2 expression or overall survival from breast cancer.
Randomized Phase II Study of Bortezomib, Thalidomide, and Dexamethasone With or Without Cyclophosphamide As Induction Therapy in Previously Untreated Multiple Myeloma
Authors: Ludwig Heinz , Viterbo Luisa , Greil Richard , Masszi Tamas , Spicka Ivan , Shpilberg Ofer , Hajek Roman , Dmoszynska Anna , Paiva Bruno , Vidriales María-Belén , Esteves Graca , Stoppa Anne Marie , Robinson Don , Ricci Deborah , Cakana Andrew , Enny Christopher , Feng Huaibao , van de Velde Helgi , Harousseau Jean-Luc
Published: October 2012

Purpose

Bortezomib-thalidomide-dexamethasone (VTD) is an effective induction therapy in multiple myeloma (MM). This phase II, noncomparative study sought to determine whether addition of cyclophosphamide to this regimen (VTDC) could further increase efficacy without compromising safety.

Patients and Methods

Patients age 18 to 70 years with previously untreated, measurable MM, who were eligible for high-dose chemotherapy–autologous stem-cell transplantation (HDCT-ASCT), were randomly assigned to bortezomib 1.3 mg/m2, thalidomide 100 mg, and dexamethasone 40 mg, with (n = 49) or without (n = 49) cyclophosphamide 400 mg/m2for four 21-day cycles, followed by HDCT-ASCT. The primary end point was postinduction combined rate of near-complete response (nCR) or better (including complete response [CR] with normalized serum κ:λ free light chain ratio, CR, and nCR).

Results

Postinduction, 51% (VTD) and 44% (VTDC) of patients achieved combined CR/nCR, with bone marrow–confirmed CR in 29% and 31%, overall response rates of 100% and 96%, respectively, and very good partial response or better rates of 69% per arm. Post–HDCT-ASCT, combined CR/nCR rates were 85% (VTD) and 77% (VTDC). In all, 35% (VTD) and 27% (VTDC) of patients were negative for minimal residual disease (MRD) during induction and postinduction. Three-year overall survival was 80% (both arms). Grade 3 to 4 adverse events (AEs) and serious AEs were observed in 47% and 22% (VTD) and 57% and 41% (VTDC) of patients, respectively. The primary health-related quality of life end point (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 [EORTC QLQ-C30] Global Health score) steadily increased with VTD during induction and reached a clinically relevant difference post-transplantation versus baseline.

Conclusion

Both VTD and VTDC are highly active induction regimens producing high combined CR/nCR and MRD-negative rates; however, VTDC was associated with increased toxicity and suggestion of transient decreases in Global Health score, without an increase in activity.
Biallelic ATM Inactivation Significantly Reduces Survival in Patients Treated on the United Kingdom Leukemia Research Fund Chronic Lymphocytic Leukemia 4 Trial
Authors: Skowronska Anna , Parker Anton , Ahmed Gulshanara , Oldreive Ceri , Davis Zadie , Richards Sue , Dyer Martin , Matutes Estella , Gonzalez David , Taylor A. Malcolm R. , Moss Paul , Thomas Peter , Oscier David , Stankovic Tatjana
Published: October 2012

Purpose

The prognostic significance of ATM mutations in chronic lymphocytic leukemia (CLL) is unclear. We assessed their impact in the context of a prospective randomized trial.

Patients and Methods

We analyzed the ATM gene in 224 patients treated on the Leukemia Research Fund Chronic Lymphocytic Leukemia 4 (LRF-CLL4) trial with chlorambucil or fludarabine with and without cyclophosphamide. ATM status was analyzed by denaturing high-performance liquid chromatography and was related to treatment response, survival, and the impact of TP53 alterations for the same patient cohort.

Results

We identified 36 ATM mutations in 33 tumors, 16 with and 17 without 11q deletion. Mutations were associated with advanced disease stage and involvement of multiple lymphoid sites. Patients with both ATM mutation and 11q deletion showed significantly reduced progression-free survival (median, 7.4 months) compared with those with ATM wild type (28.6 months), 11q deletion alone (17.1 months), or ATM mutation alone (30.8 months), but survival was similar to that in patients with monoallelic (6.7 months) or biallelic (3.4 months) TP53 alterations. This effect was independent of treatment, immunoglobulin heavy chain variable gene (IGHV) status, age, sex, or disease stage. Overall survival for patients with biallelic ATM alterations was also significantly reduced compared with those with ATM wild type or ATM mutation alone (median, 42.2 v 85.5 v 77.6 months, respectively).

Conclusion

The combination of 11q deletion and ATM mutation in CLL is associated with significantly shorter progression-free and overall survival following first-line treatment with alkylating agents and purine analogs. Assessment of ATM mutation status in patients with 11q deletion may influence the choice of subsequent therapy.
Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group
Authors: Womer Richard B. , West Daniel C. , Krailo Mark D. , Dickman Paul S. , Pawel Bruce R. , Grier Holcombe E. , Marcus Karen , Sailer Scott , Healey John H. , Dormans John P. , Weiss Aaron R.
Published: October 2012

Purpose

Chemotherapy with alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide cycles and primary tumor treatment with surgery and/or radiation therapy constitute the usual approach to localized Ewing sarcoma in North America. We tested whether chemotherapy intensification through interval compression could improve outcome.

Patients and Methods

This was a prospective, randomized controlled trial for patients younger than 50 years old with newly diagnosed localized extradural Ewing sarcoma. Patients assigned to standard and intensified treatment were to begin chemotherapy cycles every 21 and 14 days, respectively, provided an absolute neutrophil count greater than 750 × 106/L and a platelet count greater than 75 × 109/L. Patients received vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1.2 g/m2) alternating with ifosfamide (9 g/m2) and etoposide (500 mg/m2) for 14 cycles, with filgrastim (5 mg/kg per day; maximum, 300 mg) between cycles. Primary tumor treatment (surgery, radiation, or both) was to begin at week 13 (after four cycles in the standard arm and six cycles in the intensified arm). The primary end point was event-free survival (EFS). The study is registered at ClinicalTrials.gov (identifier: NCT00006734).

Results

Five hundred eighty-seven patients were enrolled and randomly assigned, and 568 patients were eligible, with 284 patients in each regimen. For all cycles, the median cycle interval for standard treatment was 21 days (mean, 22.45 days); for intensified treatment, the median interval was 15 days (mean, 17.29 days). EFS at a median of 5 years was 65% in the standard arm and 73% in the intensified arm (P = .048). The toxicity of the regimens was similar.

Conclusion

For localized Ewing sarcoma, chemotherapy administered every 2 weeks is more effective than chemotherapy administered every 3 weeks, with no increase in toxicity.
Rituximab Maintenance Therapy After Autologous Stem-Cell Transplantation in Patients With Relapsed CD20+ Diffuse Large B-Cell Lymphoma: Final Analysis of the Collaborative Trial in Relapsed Aggressive Lymphoma
Authors: Gisselbrecht Christian , Schmitz Norbert , Mounier Nicolas , Singh Gill Devinder , Linch David C. , Trneny Marek , Bosly Andre , Milpied Noel J. , Radford John , Ketterer Nicolas , Shpilberg Ofer , Dührsen Ulrich , Hagberg Hans , Ma David D. , Viardot Andreas , Lowenthal Ray , Brière Josette , Salles Gilles , Moskowitz Craig H. , Glass Bertram
Published: October 2012

Purpose

The standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL) is salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT). The impact of maintenance rituximab after ASCT is not known.

Patients and Methods

In total, 477 patients with CD20+ DLBCL who were in their first relapse or refractory to initial therapy were randomly assigned to one of two salvage regimens. After three cycles of salvage chemotherapy, the responding patients received high-dose chemotherapy followed by ASCT. Then, 242 patients were randomly assigned to either rituximab every 2 months for 1 year or observation.

Results

After ASCT, 122 patients received rituximab, and 120 patients were observed only. The median follow-up time was 44 months. The 4-year event-free survival (EFS) rates after ASCT were 52% and 53% for the rituximab and observation groups, respectively (P = .7). Treatment with rituximab was associated with a 15% attributable risk of serious adverse events after day 100, with more deaths (six deaths v three deaths in the observation arm). Several factors affected EFS after ASCT (P < .05), including relapsed disease within 12 months (EFS: 46% v 56% for relapsed disease after 12 months), secondary age-adjusted International Prognostic Index (saaIPI) more than 1 (EFS: 37% v 61% for saaIPI < 1), and prior treatment with rituximab (EFS: 47% v 59% for no prior rituximab). A significant difference in EFS between women (63%) and men (46%) was also observed in the rituximab group. In the Cox model for maintenance, the saaIPI was a significant prognostic factor (P < .001), as was male sex (P = .01).

Conclusion

In relapsed DLBCL, we observed no difference between the control group and the rituximab maintenance group and do not recommend rituximab after ASCT.
Eph/ephrin signalling during development
Authors: Klein Rüdiger
Published: October 2012

Eph receptors and their membrane-tethered ligands have important functions in development. Trans interactions of Eph receptors with ephrins at cell-cell interfaces promote a variety of cellular responses, including repulsion, attraction and migration. Eph-ephrin signalling can be bi-directional and controls actin cytoskeleton dynamics, thereby leading to changes in cellular shape. This article provides an overview of the general structures and signalling mechanisms, and of typical developmental functions along with cell biological principles.
Intercellular calcium signaling in a gap junction-coupled cell network establishes asymmetric neuronal fates in C. elegans
Authors: Schumacher Jennifer A. , Hsieh Yi-Wen , Chen Shiuhwei , Pirri Jennifer K. , Alkema Mark J. , Li Wen-Hong , Chang Chieh , Chuang Chiou-Fen
Published: October 2012

The C. elegans left and right AWC olfactory neurons specify asymmetric subtypes, one default AWCOFF and one induced AWCON, through a stochastic, coordinated cell signaling event. Intercellular communication between AWCs and non-AWC neurons via a NSY-5 gap junction network coordinates AWC asymmetry. However, the nature of intercellular signaling across the network and how individual non-AWC cells in the network influence AWC asymmetry is not known. Here, we demonstrate that intercellular calcium signaling through the NSY-5 gap junction neural network coordinates a precise 1AWCON/1AWCOFF decision. We show that NSY-5 gap junctions in C. elegans cells mediate small molecule passage. We expressed vertebrate calcium-buffer proteins in groups of cells in the network to reduce intracellular calcium levels, thereby disrupting intercellular communication. We find that calcium in non-AWC cells of the network promotes the AWCON fate, in contrast to the autonomous role of calcium in AWCs to promote the AWCOFF fate. In addition, calcium in specific non-AWCs promotes AWCON side biases through NSY-5 gap junctions. Our results suggest a novel model in which calcium has dual roles within the NSY-5 network: autonomously promoting AWCOFF and non-autonomously promoting AWCON.
Screening for haemoglobinopathies on cord blood: laboratory and clinical experience
Authors: Wolff Fleur , Cotton Frédéric , Gulbis Béatrice
Published: October 2012

Objectives

Blood from the umbilical cord (cord blood) is screened for haemoglobinopathies in several neonatal screening programmes, as well as before banking as a source of stem cells. We investigated the pre-analytical and analytical aspects of neonatal screening for haemoglobinopathies on liquid cord blood using the Sebia Haemoglobin kit. We give an interpretation of the results as well as a proposed scheme for reporting of the results.

Methods

A neonatal screening programme on liquid cord blood has been performed in all labour wards in Brussels since 1994. Using that material, the screening methods of isoelectric focusing and capillary zone electrophoresis were compared using 962 cord blood samples. From December 2008 to December 2010, 47,388 neonatal samples were analysed by capillary electrophoresis as the first-line method for neonatal screening. High-performance liquid chromatography was used as the second-line method.

Results

Capillary zone electrophoresis on liquid cord blood enabled the detection of all clinically significant haemoglobin variants, significant levels of Hb Bart's, and β-thalassaemia major. Among the 47,388 neonatal samples tested, 362 (0.7%) were suspected to be contaminated with maternal blood, but no diagnostic error was reported retrospectively for a major haemoglobinopathy. Recommendations for the interpretation and reporting of results of neonatal screening for haemoglobinopathies using the Sebia Haemoglobin kit are proposed.

Conclusions

A routine capillary electrophoresis kit adapted to neonatal screening and liquid cord blood is reliable for screening for haemoglobinopathies. It enables early detection and reporting of all major haemoglobinopathies and most minor ones. It also enables use of a simple scheme to report the results.