bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Test Design With Rule-Based Item Generation
Authors: Geerlings Hanneke , van der Linden Wim J. , Glas Cees A. W.
Published: December 2012

Optimal test-design methods are applied to rule-based item generation. Three different cases of automated test design are presented: (a) test assembly from a pool of pregenerated, calibrated items; (b) test generation on the fly from a pool of calibrated item families; and (c) test generation on the fly directly from calibrated features defining the item families. The last two cases do not assume any item calibration under a regular response theory model; instead, entire item families or critical features of them are assumed to be calibrated using a hierarchical response model developed for rule-based item generation. The test-design models maximize an expected version of the Fisher information in the test and control critical attributes of the test forms through explicit constraints. Results from a study with simulated response data highlight both the effects of within-family item-parameter variability and the severity of the constraint sets in the test-design models on their optimal solutions.
Women’s Work and Family Balance: The Scope for Equal Opportunity Programmes in India
Authors: Palanivel R.V. , Sinthuja M.
Published: January 2013

This article aims to assess the ability of formal equal employment opportunity (EEO) programmes and workplace agreement making in India to facilitate work and family balance for women workers. Using documentary analysis and semi-structured interviews in six Indian organisations that are required to develop formal EEO programmes, it is found that formal EEO programmes and agreement making are limited in their ability to promote work and family-friendly arrangements at the workplace. Informal arrangements and managerial discretion remain important in realising work and care balance. The article highlights thus that formal mechanisms alone cannot achieve effective work and care reconciliation for women workers, mainly because they are built upon limited minimum requirements, are voluntary and are dependent upon bargaining processes at the workplace.
Freedom? Nothingness? Time? Fluxus and the Laboratory of Ideas
Authors: Friedman Ken
Published: January 2013

At the 50-year anniversary of Fluxus, Ken Friedman looks back on the activities and achievements of a laboratory for art, architecture, design, and music. This article examines the political and economic context of the 1950s against which Fluxus emerged to become the most radical and experimental art project of the 1960s, thoroughly international in structure, with women as well as men in central roles. The article examines the hermeneutical interface of life and art through 12 Fluxus ideas: globalism, the unity of art and life, intermedia, experimentalism, chance, playfulness, simplicity, implicativeness, exemplativism, specificity, presence in time, and musicality.
Eating me up inside
Authors: Wilkinson Laura L. , Rowe Angela C. , Heath Georgina H.
Published: January 2013

Recent research has shown that attachment anxiety (a model of interpersonal relationships characterised by a fear of abandonment) is a good predictor of disinhibited eating and, in turn, body mass index. However, this association has yet to be explored within an eating episode. The present study investigated the effect of priming attachment security and attachment anxiety on food intake. Normal weight participants ( N = 21) were primed with security and anxiety on separate occasions and given ad libitum access to a snack food. Priming anxiety led to a significantly higher food intake than priming security ( p = .016). We suggest that participants consumed more food in response to the anxious prime in an attempt to manage the resulting feelings of insecurity. These results provide behavioural evidence for a link between attachment anxiety and disinhibited eating.
Acting Out
Authors: Holmgren Beth
Published: December 2012

In the turbulent context of interwar Polish politics, a period bookended by the right-wing nationalists’ repression of an ethnically heterogeneous state, several popular high-quality cabarets persisted in Warsaw even as they provoked and defied the nationalists’ harsh criticism. In their best, most influential incarnation, Qui pro Quo (1919–1932) and its successors, these literary cabarets violated the right’s value system through their shows’ insistent metropolitan focus, their stars’ role-modeling of immoral behavior and parodic impersonation, and their companies’ explicitly Jewish–Gentile collaboration. In the community of the cabaret, which was even more bohemian and déclassé than that of the legitimate theater, the social and ethnic antagonisms of everyday Warsaw society mattered relatively little. Writers and players bonded with each other, above all, in furious pursuit of fun, fortune, celebrity, artistic kudos, and putting on a hit show. This analysis details how the contents and stars of Qui pro Quo challenged right-wing values. Its shows advertised the capital as a sumptuous metropolis as well as a home to an eccentric array of plebeian and underworld types, including variations on the cwaniak warszawski enacted by comedian Adolf Dymsza. Its chief female stars—Zula Pogorzelska, Mira Zimińska, and Hanna Ordonówna—incarnated big-city glamour and sexual emancipation. Its recurring Jewish characters—Józef Urstein’s Pikuś and Kazimierz Krukowski’s Lopek—functioned as modern-day Warsaw’s everymen, beleaguered and bedazzled as they assimilated to city life. Qui pro Quo’s popular defense against an exclusionary nationalism showcased collaborative artistry and diverse, charismatic stars.
Aerodynamic braking device for high-speed trains: Design, simulation and experiment
Authors: Jianyong Zuo , Mengling Wu , Chun Tian , Ying Xi , Zhuojun Luo , Zhongkai Chen
Published: January 2013

This paper proposes the design of an aerodynamic braking device for a high-speed train. The design is based on the parameters of the high-speed train and the working principles of airplane wings. The proposed device is a unidirectional opening model driven by hydraulics. The prototype uses hard-wired signals to transmit braking commands on eight levels. The important characteristics of the device include a synchronous action and a fault-oriented security design. Its functions include service braking, gradual braking, emergency braking and self-checking. Simulation results show that deceleration in the high-speed zone between 250 and 500 km/h can be improved by between 8 and 60%. When the train runs at 500 km/h, the braking deceleration rate can be improved by 0.12 m/s2. The simulation results are found to agree with wind tunnel test results. The braking characteristics are also investigated using a test bed, which mimics the aerodynamic load exerted on the prototype when the train is running between 0 and 550 km/h. It is clearly demonstrated that the proposed principle of the aerodynamic braking system is feasible and its design scheme is reasonable. The aerodynamic braking device can survive a 50,000 N aerodynamic load, and the time taken to achieve the maximum braking capacity, which is the time taken to take the brake panel from its closed position of −5° to the maximum angle of 75°, is less than 3 s. The proposed prototype therefore offers an important step in the design of practical systems.
Moral distress in nursing
Authors: Burston Adam S , Tuckett Anthony G
Published: December 2012

Moral distress has been widely reviewed across many care contexts and among a range of disciplines. Interest in this area has produced a plethora of studies, commentary and critique. An overview of the literature around moral distress reveals a commonality about factors contributing to moral distress, the attendant outcomes of this distress and a core set of interventions recommended to address these. Interventions at both personal and organizational levels have been proposed. The relevance of this overview resides in the implications moral distress has on the nurse and the nursing workforce: particularly in regard to quality of care, diminished workplace satisfaction and physical health of staff and increased problems with staff retention.
An institutional perspective on the development of Canada’s first public accounts
Authors: Baker Ron , Rennie Morina D
Published: December 2012

This study examines the Dominion of Canada’s first accounting system from the perspective of institutional theory. We find that Canada’s first accounting system was a continuation of an institution-building process begun earlier in the former Province of Canada. We argue that the political upheaval associated with the dissolution of one political jurisdiction and the creation of a new country created conditions conducive to institutional persistence rather than change, and that persistence was supported by continuity of the legislation and important agents that bridged the organizational discontinuity created by the confederation event.
Family Health Nursing
Authors: Martin Paul , Duffy Tim , Johnston Brian , Banks Pauline , Harkess-Murphy Eileen , Martin Colin R.
Published: January 2013

The European Family Health Nursing Project is a revitalized World Health Organization initiative led by the University of the West of Scotland. Partner countries include Armenia, Austria, Germany, Italy, Poland, Portugal, Romania, Slovenia, and Spain. European Union Lifelong Learning funding was received in 2011 to facilitate a consistency of approach in the development of a definition of family health nursing, required core competencies and capabilities, and consequent education and training requirements. Global health challenges have informed the development of the project: increasingly aging populations, the increasing incidence in noncommunicable diseases that are currently the main cause of death, and the significant progress made in the way health systems have developed to meet the demands in relation to access and equality of health services. Governments and policy makers should develop a health workforce based on the principles of teamwork and interdisciplinarity while recognizing the core contribution of the “specialist generalist” role in the primary care setting.
Modeling and predicting performance of high performance computing applications on hardware accelerators
Authors: Meswani Mitesh R. , Carrington Laura , Unat Didem , Snavely Allan , Baden Scott , Poole Stephen
Published: December 2012

Hybrid-core systems speedup applications by offloading certain compute operations that can run faster on hardware accelerators. However, such systems require significant programming and porting effort to gain a performance benefit from the accelerators. Therefore, prior to porting it is prudent to investigate the predicted performance benefit of accelerators for a given workload. To address this problem we present a performance-modeling framework that predicts the application performance rapidly and accurately for hybrid-core systems. We present predictions for two full-scale HPC applications—HYCOM and Milc. Our results for two accelerators (GPU and FPGA) show that gather/scatter and stream operations can speedup by as much as a factor of 15 and overall compute time of Milc and HYCOM improve by 3.4% and 20%, respectively. We also show that in order to benefit from the accelerators, 70% of the latency of data transfer time between the CPU and the accelerators needs to be overcome.
Applications of the streamed storage format for sparse matrix operations
Authors: Guo Dahai , Gropp William
Published: January 2013

The streamed storage format for sparse matrices showed good performance improvement for sparse matrix and vector multiply (SpMV) compared with compressed sparse row (CSR) and block CSR (BCSR) formats, particularly on IBM Power processors. We extend the format to exploit single instruction multiple data (SIMD) instructions in order to utilize the vector unit, and discuss how the streamed formats perform on the Power7 processor, which is the first eight-core chip from IBM. The streamed format is then applied to two more operations of sparse matrices, successive over-relaxation (SOR) iteration sweeps and incomplete lower and upper (ILU) triangular solvers. Basic solvers are developed for them in the high-performance computing (HPC) package PETSc. Test results on the IBM Power7 processor show that the SIMD instructions improve the performance of the streamed storage format on SpMV. The format also accelerates SOR iteration sweeps and ILU matrix solvers, compared with the traditional BCSR format used in PETSc.
Self-Congruity and Functional Congruity in Brand Loyalty
Authors: Kang Juhee , Tang Liang , Lee Ju Yup
Published: January 2013

This study used image congruity theory to understand customer loyalty in name-brand coffee shops in Korea. The authors developed and tested a structural model that links image congruity (self-congruity and functional congruity) and brand loyalty components (cognitive, affective, and conative loyalty). The elaboration likelihood model was used to understand the information processing underlying the structural model. The results showed that self-congruity significantly influences both cognitive and affective loyalty in the central route of persuasion. Functional congruity significantly influences cognitive loyalty in the peripheral route of communication. This study suggests promotional strategies for the marketers of name-brand coffee shops in Korea.
Symbolic meanings and e-learning in the workplace: The case of an intranet-based training tool
Authors: Michalski Marina P
Published: January 2013

This article contributes to the debate on work-based e-learning, by unpacking the notion of ‘the learning context’ in a case where the mediating tool for training also supports everyday work. Users’ engagement with the information and communication technology tool is shown to reflect dynamic interactions among the individual, peer group, organizational and institutional levels. Also influential are professionals’ values and identity work, alongside their interpretations of espoused and emerging symbolic meanings. Discussion draws on pedagogically informed studies of e-learning and the wider organizational learning literature. More centrally, this article highlights the instrumentality of symbolic interactionism for e-learning research and explores some of the framework’s conceptual resources as applied to organizational analysis and e-learning design.
Analysis of externally pressurized multirecess conical hybrid journal bearing system using micropolar lubricant
Authors: Rajput Arvind K , Sharma Satish C
Published: January 2013

This article describes an analytical study to demonstrate the influence of micropolar lubricant on a four-pocket conical hybrid journal bearing system compensated with membrane restrictor. The modified Reynolds equation has been derived using Eringen’s theory of micropolar fluids with usual assumptions in cylindrical coordinates. The finite element modeling of the modified Reynolds equation has been made using Galerkin’s technique. The variation of bearing characteristics parameters for both Newtonian and micropolar lubricated bearings have been plotted with respect to radial load parameter for the chosen values of semi-cone angles, coupling number, characteristic length, and membrane compliance. The numerically simulated results indicate that micropolar lubricated bearing provides enhanced performance vis-à-vis Newtonian lubricated bearing.
Social control and trust in the New Zealand environmental movement
Authors: O’Brien Thomas
Published: January 2013

Escalating concern regarding environmental issues has resulted in an increase in the number and scope of environmental movements internationally. The diversity and proactive nature of these movements has put pressure on public (state) actors to address challenges and engage with movement actors. Engagement is not universally positive and can lead to attempts to disrupt or subvert challenging movements. This article examines the impact of perceived state subversion on trust within the New Zealand environmental movement through the alleged use of spies. The analysis finds that short-term emotional reactions within the movement that led to questioning of relationships were outweighed by longer-term pragmatic view about the need to maintain collective action.
A comparison of efficacy and safety of an ezetimibe/simvastatin combination compared with other intensified lipid-lowering treatment strategies in diabetic patients with symptomatic cardiovascular disease
Authors: Rosen Jeffrey B , Jimenez Jose G , Pirags Valdis , Vides Hella , Hanson Mary E , Massaad Rachid , McPeters Gail , Brudi Philippe , Triscari Joseph
Published: January 2013

The low-density lipoprotein cholesterol (LDL-C) lowering efficacy of switching to ezetimibe/simvastatin (EZ/S) 10/20 mg versus doubling the run-in statin dose (to simvastatin 40 mg or atorvastatin 20 mg) or switching to rosuvastatin 10 mg in subjects with cardiovascular disease (CVD) and diabetes was assessed. Endpoints included percentage change in LDL-C and percentage of patients achieving LDL-C <70 mg/dL. Significantly greater reductions in LDL-C occurred when switching to EZ/S versus statin doubling in the overall population and in subjects treated with simvastatin 20 mg or atorvastatin 10 mg (all p < 0.001). The LDL-C reduction was numerically greater when switching to EZ/S versus switching to rosuvastatin ( p = 0.060). Significantly more subjects reached LDL-C <70 mg/dL with EZ/S (54.5%) versus statin doubling (27.0%) or rosuvastatin (42.5%) in the overall population (all p < 0.001) and within each stratum (all p < 0.001). Switching to EZ/S provided significantly greater reductions in LDL-C versus statin doubling and significantly greater achievement of LDL-C targets versus statin doubling or switching to rosuvastatin.
The Impact of a Student-Driven Social Marketing Campaign on College Student Alcohol-Related Beliefs and Behaviors
Authors: Thompson Erika Beseler , Heley Frank , Oster-Aaland Laura , Stastny Sherri Nordstrom , Crawford Elizabeth Crisp
Published: January 2013

Researchers examined a student-driven campaign intended to reduce high-risk drinking at a Midwestern, public research university in the United States. The campaign was implemented as part of a comprehensive social marketing effort to address high-risk drinking. Efforts employed on campus addressed various aspects of the marketing mix, including product, price, place, and promotion through late-night alcohol-free activities, increased enforcement, a substance abuse mentoring program, and the student-driven promotional campaign. Outcome measures of the campaign evaluation included assessing the effectiveness of promotional materials in prompting student visits to the campaign website and assessing the impact on students’ reported drinking-related beliefs and behaviors. Following extensive formative research, student developers designed campaign promotional materials that incorporated socially relevant images and messages to enhance students’ confidence related to making simple, low-risk decisions about drinking. Evaluation included an anonymous survey sent to a stratified random sample of undergraduate students. Responses were gathered regarding student demographics, appeal of promotional materials, self-reported drinking patterns, and whether the campaign impacted students’ reflections on drinking or beliefs and behaviors concerning their own alcohol consumption. Study results indicate online and interactive promotional materials (i.e., Facebook page and campaign video) increased the likelihood of student visits to the website, and students exposed to the website reported increased confidence and use of techniques to reduce alcohol-related harm. Use of socially relevant messages and online or interactive campaign components appear to be promising when implementing campaigns to address college student high-risk drinking.
Evolutionarily Stable Strategies in Sports Contests
Authors: Grossmann Martin
Published: January 2013

Most articles on sports economics presume the well-known Nash equilibrium concept. In this article, however, we apply evolutionary game theory in a sports-contest model. If clubs follow evolutionarily stable strategies (ESS), then ESS generate greater investments and smaller profits than predicted by Nash’s strategies, independent of whether a club is win-maximizing or profit-maximizing. Overdissipation of the rent is possible for Nash strategies and for ESS.
Measurement of Competitive Balance in Conference and Divisional Tournament Design
Authors: Lenten Liam J. A.
Published: January 2013

The conference and divisional system has long been a staple part of tournament design in the major pro-sports leagues of North America. This popular but highly rigid system determines on how many occasions all bilateral pairings of teams play each other during the season. Despite the virtues of this system, it necessitates removing the biases it generates in the set of win ratios from the regular season standings prior to calculating within-season measures of competitive balance. This article applies a modified version of a recent model, an extension that is generalizable to any unbalanced schedule design in professional sports leagues worldwide, to correct for this inherent bias for the NFL over the seasons 2002-2011, the results of which suggest the NFL is even more competitively balanced than thought previously.
Interpersonal Psychotherapy Informed Treatment for Avoidant Personality Disorder With Subsequent Depression
Authors: Gilbert Sarah E. , Gordon Kristina C.
Published: December 2012

This is a single-case study of a young woman with avoidant personality disorder (APD) and subsequent depression, worry, lack of motivation, feelings of inadequacy, and nonassertive behaviors in her romantic relationship and professional career. Treatment was informed by interpersonal psychotherapy (IPT) for depression and also utilized assertiveness skills training. The client’s self-confidence was tracked daily, using a subjective self-report measure, and the completion of personality and symptom assessment measures before treatment (Phase A) and during the termination stage of treatment. Simulation Modeling Analysis for Time Series evaluated the change in levels of self-confidence across baseline, active treatment (Phase B), and termination (Phase C). In addition, reliable change was assessed using a comparison of Minnesota Multiphasic Personality Inventory 2–Restructured Form and Symptom Checklist-90–Revised results from baseline and Phase C. The patient experienced symptom improvement in self-confidence, somatic complaints, stress and worry, anxiety, and depression, suggesting that IPT techniques may be useful in the treatment of APD.
Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex
Authors: Gao Chong , Dimitrov Todor , Yong Kol Jia , Tatetsu Hiro , Jeong Ha-won , Luo Hongbo R. , Bradner James E. , Tenen Daniel G. , Chai Li
Published: January 2013

Key Points

The SALL4/NuRD/PTEN pathway is important for acute myeloid leukemogenesis. Targeting AML can be achieved by blocking the interaction between transcription factor SALL4 and the epigenetic NuRD complex.
Circulating CD34+ progenitor cell frequency is associated with clinical and genetic factors
Authors: Cohen Kenneth S. , Cheng Susan , Larson Martin G. , Cupples L. Adrienne , McCabe Elizabeth L. , Wang Ying A. , Ngwa Julius S. , Martin Roderick P. , Klein Rachael J. , Hashmi Basma , Ge Yin , O'Donnell Christopher J. , Vasan Ramachandran S. , Shaw Stanley Y. , Wang Thomas J.
Published: January 2013

Key Points

CD34+ progenitor cell frequency is reduced in older subjects, and is influenced by environmental factors such as smoking and statin use. CD34+ progenitor cell frequency is highly heritable and associated with common genetic variants at several loci.
Comparison of primary human cytotoxic T-cell and natural killer cell responses reveal similar molecular requirements for lytic granule exocytosis but differences in cytokine production
Authors: Chiang Samuel C. C. , Theorell Jakob , Entesarian Miriam , Meeths Marie , Mastafa Monika , Al-Herz Waleed , Frisk Per , Gilmour Kimberly C. , Ifversen Marianne , Langenskiöld Cecilia , Machaczka Maciej , Naqvi Ahmed , Payne Jeanette , Perez-Martinez Antonio , Sabel Magnus , Unal Ekrem , Unal Sule , Winiarski Jacek , Nordenskjöld Magnus , Ljunggren Hans-Gustaf , Henter Jan-Inge , Bryceson Yenan T.
Published: January 2013

Key Points

Compared with cytotoxic T cells, NK cells share mechanisms for lytic granule release but more stringently control cytokine production. Analysis of CD57bright cytotoxic T-cell function may prove useful in the diagnosis of primary immunodeficiencies.
The role of chromatin modifiers in normal and malignant hematopoiesis
Authors: Butler Jill S. , Dent Sharon Y. R.
Published: January 2013

Complex developmental processes such as hematopoiesis require a series of precise and coordinated changes in cellular identity to ensure blood homeostasis. Epigenetic mechanisms help drive changes in gene expression that accompany the transition from hematopoietic stem cells to terminally differentiated blood cells. Genome-wide profiling technologies now provide valuable glimpses of epigenetic changes that occur during normal hematopoiesis, and genetic mouse models developed to investigate the in vivo functions of chromatin-modifying enzymes clearly demonstrate significant roles for these enzymes during embryonic and adult hematopoiesis. Here, we will review the basic science aspects of chromatin modifications and the enzymes that add, remove, and interpret these epigenetic marks. This overview will provide a framework for understanding the roles that these molecules play during normal hematopoiesis. Moreover, many chromatin-modifying enzymes are involved in hematologic malignancies, underscoring the importance of establishing and maintaining appropriate chromatin modification patterns to normal hematology.
Bif-1 haploinsufficiency promotes chromosomal instability and accelerates Myc-driven lymphomagenesis via suppression of mitophagy
Authors: Takahashi Yoshinori , Hori Tsukasa , Cooper Timothy K. , Liao Jason , Desai Neelam , Serfass Jacob M. , Young Megan M. , Park Sungman , Izu Yayoi , Wang Hong-Gang
Published: January 2013

Key Points

Bif-1 acts as a haploinsufficient tumor suppressor in Myc-induced lymphomagenesis. Bif-1 plays a key role in mitophagy to maintain chromosome stability.
Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα) in chronic hypoxia- and antigen-mediated pulmonary vascular remodeling
Authors: Angelini Daniel J , Su Qingning , Yamaji-Kegan Kazuyo , Fan Chunling , Skinner John T , Poloczek Andre , El-Haddad Hazim , Cheadle Chris , Johns Roger A
Published: January 2013

Background

Both chronic hypoxia and allergic inflammation induce vascular remodeling in the lung, but only chronic hypoxia appears to cause PH. We investigate the nature of the vascular remodeling and the expression and role of hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα) in explaining this differential response.

Methods

We induced pulmonary vascular remodeling through either chronic hypoxia or antigen sensitization and challenge. Mice were evaluated for markers of PH and pulmonary vascular remodeling throughout the lung vascular bed as well as HIMF expression and genomic analysis of whole lung.

Results

Chronic hypoxia increased both mean pulmonary artery pressure (mPAP) and right ventricular (RV) hypertrophy; these changes were associated with increased muscularization and thickening of small pulmonary vessels throughout the lung vascular bed. Allergic inflammation, by contrast, had minimal effect on mPAP and produced no RV hypertrophy. Only peribronchial vessels were significantly thickened, and vessels within the lung periphery did not become muscularized. Genomic analysis revealed that HIMF was the most consistently upregulated gene in the lungs following both chronic hypoxia and antigen challenge. HIMF was upregulated in the airway epithelial and inflammatory cells in both models, but only chronic hypoxia induced HIMF upregulation in vascular tissue.

Conclusions

The results show that pulmonary vascular remodeling in mice induced by chronic hypoxia or antigen challenge is associated with marked increases in HIMF expression. The lack of HIMF expression in the vasculature of the lung and no vascular remodeling in the peripheral resistance vessels of the lung is likely to account for the failure to develop PH in the allergic inflammation model.
Astaxanthin protects against MPP+-induced oxidative stress in PC12 cells via the HO-1/NOX2 axis
Authors: Ye Qinyong , Huang Bixia , Zhang Xiaodong , Zhu Yuangui , Chen Xiaochun
Published: December 2012

Background

Although the etiology of PD remains unclear, increasing evidence has shown that oxidative stress plays an important role in its pathogenesis and that of other neurodegenerative disorders. NOX2, a cytochrome subunit of NOX, transports electrons across the plasma membrane to generate ROS, leading to physiological and pathological processes. Heme oxygenase-1 (HO-1) can be rapidly induced by oxidative stress and other noxious stimuli in the brain or other tissues. Astaxanthin (ATX), a carotenoid with antioxidant properties, is 100–1000 times more effective than vitamin E. The present study investigated the neuroprotective effects of ATX on MPP+-induced oxidative stress in PC12 cells.

Results

MPP+ significantly decreased MTT levels in a concentration-dependent manner. Hemin, SnPPIX and ATX didn’t exhibit any cytotoxic effects on PC12 cells. Pretreatment with ATX (5, 10, 20 μM), caused intracellular ROS production in the MPP+ group to decrease by 13.06%, 22.13%, and 27.86%, respectively. MPP+ increased NOX2, NRF2 and HO-1 protein expression compared with control (p < 0.05). Co-treatment with hemin or ATX suppressed NOX2 expression (p < 0.01), and greatly increased NRF2 and HO-1 expression (p < 0.01). MPP+ treatment up-regulated both NOX2 (p < 0.01) and HO-1 (p < 0.01) mRNA levels. Co-treatment with hemin or ATX significantly increased HO-1 mRNA levels (p < 0.01), and decreased NOX2 mRNA levels (p < 0.01). MPP+ increased NOX2 and HO-1 expression with considerable fluorescence extending out from the perinuclear region toward the periphery; this was attenuated by DPI. Co-treatment with hemin or ATX significantly up-regulated HO-1 expression and decreased NOX2 expression with considerable fluorescence intensity (stronger than the control and MPP+ groups).

Conclusions

ATX suppresses MPP+-induced oxidative stress in PC12 cells via the HO-1/NOX2 axis. ATX should be strongly considered as a potential neuroprotectant and adjuvant therapy for patients with Parkinson’s disease.
Inter- and intra-observer reliability of clinical movement-control tests for marines
Authors: Monnier Andreas , Heuer Joachim , Norman Kjell , Äng Björn O
Published: December 2012

Background

Musculoskeletal disorders particularly in the back and lower extremities are common among marines. Here, movement-control tests are considered clinically useful for screening and follow-up evaluation. However, few studies have addressed the reliability of clinical tests, and no such published data exists for marines. The present aim was therefore to determine the inter- and intra-observer reliability of clinically convenient tests emphasizing movement control of the back and hip among marines. A secondary aim was to investigate the sensitivity and specificity of these clinical tests for discriminating musculoskeletal pain disorders in this group of military personnel.

Methods

This inter- and intra-observer reliability study used a test-retest approach with six standardized clinical tests focusing on movement control for back and hip. Thirty-three marines (age 28.7 yrs, SD 5.9) on active duty volunteered and were recruited. They followed anin-vivoobservation test procedure that covered both low- and high-load (threshold) tasks relevant for marines on operational duty. Two independent observers simultaneously rated performance as “correct” or “incorrect” following a standardized assessment protocol. Re-testing followed 7–10 days thereafter. Reliability was analysed using kappa (κ) coefficients, while discriminative power of the best-fitting tests for back- and lower-extremity pain was assessed using a multiple-variable regression model.

Results

Inter-observer reliability for the six tests was moderate to almost perfect with κ-coefficients ranging between 0.56-0.95. Three tests reached almost perfect inter-observer reliability with mean κ-coefficients > 0.81. However, intra-observer reliability was fair-to-moderate with mean κ-coefficients between 0.22-0.58. Three tests achieved moderate intra-observer reliability with κ-coefficients > 0.41. Combinations of one low- and one high-threshold test best discriminated prior back pain, but results were inconsistent for lower-extremity pain.

Conclusions

Our results suggest that clinical tests of movement control of back and hip are reliable for use in screening protocols using several observers with marines. However, test-retest reproducibility was less accurate, which should be considered in follow-up evaluations. The results also indicate that combinations of low- and high-threshold tests have discriminative validity for prior back pain, but were inconclusive for lower-extremity pain.
Impact of unlinked deaths and coding changes on mortality trends in the Swiss National Cohort
Authors: Schmidlin Kurt , Clough-Gorr Kerri M , Spoerri Adrian , Egger Matthias , Zwahlen Marcel ,   for the Swiss National Cohort
Published: January 2013

Background

Results of epidemiological studies linking census with mortality records may be affected by unlinked deaths and changes in cause of death classification. We examined these issues in the Swiss National Cohort (SNC).

Methods

The SNC is a longitudinal study of the entire Swiss population, based on the 1990 (6.8 million persons) and 2000 (7.3 million persons) censuses. Among 1,053,393 deaths recorded 1991–2007 5.4% could not be linked using stringent probabilistic linkage. We included the unlinked deaths using pragmatic linkages and compared mortality rates for selected causes with official mortality rates. We also examined the impact of the 1995 change in cause of death coding from version 8 (with some additional rules) to version 10 of the International Classification of Diseases (ICD), using Poisson regression models with restricted cubic splines. Finally, we compared results from Cox models including and excluding unlinked deaths of the association of education, marital status, and nationality with selected causes of death.

Results

SNC mortality rates underestimated all cause mortality by 9.6% (range 2.4% - 17.9%) in the 85+ population. Underestimation was less pronounced in years nearer the censuses and in the 75–84 age group. After including 99.7% of unlinked deaths, annual all cause SNC mortality rates were reflecting official rates (relative difference between −1.4% and +1.8%). In the 85+ population the rates for prostate and breast cancer dropped, by 16% and 21% respectively, between 1994 and 1995 coincident with the change in cause of death coding policy. For suicide in males almost no change was observed. Hazard ratios were only negligibly affected by including the unlinked deaths. A sudden decrease in breast (21% less, 95% confidence interval: 12% - 28%) and prostate (16% less, 95% confidence interval: 7% - 23%) cancer mortality rates in the 85+ population coincided with the 1995 change in cause of death coding policy.

Conclusions

Unlinked deaths bias analyses of absolute mortality rates downwards but have little effect on relative mortality. To describe time trends of cause-specific mortality in the SNC, accounting for the unlinked deaths and for the possible effect of change in death certificate coding was necessary.
Detection of a common chimeric transcript between human chromosomes 7 and 16
Authors: Fang Wenwen , Wei Yong , Kang Yibin , Landweber Laura F
Published: December 2012

Interchromosomal chimeric RNA molecules are often transcription products from genomic rearrangement in cancerous cells. Here we report the computational detection of an interchromosomal RNA fusion between ZC3HAV1L and CHMP1A from RNA-seq data of normal human mammary epithelial cells, and experimental confirmation of the chimeric transcript in multiple human cells and tissues. Our experimental characterization also detected three variants of the ZC3HAV1L-CHMP1A chimeric RNA, suggesting that these genes are involved in complex splicing. The fusion sequence at the novel exon-exon boundary, and the absence of corresponding DNA rearrangement suggest that this chimeric RNA is likely produced by trans-splicing in human cells.

Reviewers

This article was reviewed by Rory Johnson (nominated by Fyodor Kondrashov); Gal Avital and Itai Yanai
Automated compound classification using a chemical ontology
Authors: Bobach Claudia , Böhme Timo , Laube Ulf , Püschel Anett , Weber Lutz
Published: December 2012

Background

Classification of chemical compounds into compound classes by using structure derived descriptors is a well-established method to aid the evaluation and abstraction of compound properties in chemical compound databases. MeSH and recently ChEBI are examples of chemical ontologies that provide a hierarchical classification of compounds into general compound classes of biological interest based on their structural as well as property or use features. In these ontologies, compounds have been assigned manually to their respective classes. However, with the ever increasing possibilities to extract new compounds from text documents using name-to-structure tools and considering the large number of compounds deposited in databases, automated and comprehensive chemical classification methods are needed to avoid the error prone and time consuming manual classification of compounds.

Results

In the present work we implement principles and methods to construct a chemical ontology of classes that shall support the automated, high-quality compound classification in chemical databases or text documents. While SMARTS expressions have already been used to define chemical structure class concepts, in the present work we have extended the expressive power of such class definitions by expanding their structure-based reasoning logic. Thus, to achieve the required precision and granularity of chemical class definitions, sets of SMARTS class definitions are connected by OR and NOT logical operators. In addition, AND logic has been implemented to allow the concomitant use of flexible atom lists and stereochemistry definitions. The resulting chemical ontology is a multi-hierarchical taxonomy of concept nodes connected by directed, transitive relationships.

Conclusions

A proposal for a rule based definition of chemical classes has been made that allows to define chemical compound classes more precisely than before. The proposed structure-based reasoning logic allows to translate chemistry expert knowledge into a computer interpretable form, preventing erroneous compound assignments and allowing automatic compound classification. The automated assignment of compounds in databases, compound structure files or text documents to their related ontology classes is possible through the integration with a chemical structure search engine. As an application example, the annotation of chemical structure files with a prototypic ontology is demonstrated.
Ray-based gridded tomography for tilted transversely isotropic media
Authors: Wang Xiaoxiang , Tsvankin Ilya
Published: January 2013

Reflection tomography in the migrated domain can help reconstruct heterogeneous, anisotropic velocity fields needed for accurate depth imaging of complex geologic structures. The presence of anisotropy, however, increases the uncertainty in velocity analysis and typically requires a priori constraints on the model parameters. Here, we develop a 2D P-wave tomographic algorithm for heterogeneous transversely isotropic media with a tilted symmetry axis (TTI) and investigate the conditions necessary for stable estimation of the symmetry-direction velocity [Formula: see text] and the anisotropy parameters [Formula: see text] and [Formula: see text]. The model is divided into rectangular cells, and the parameters [Formula: see text], [Formula: see text], [Formula: see text], and the tilt [Formula: see text] of the symmetry axis are defined at the grid points. To increase the stability of the inversion, the symmetry axis is set orthogonal to the imaged reflectors, with the tilt interpolated inside each layer. The iterative migration velocity analysis involves efficient linearized parameter updating designed to minimize the residual moveout in image gathers for all available reflection events. The moveout equation in the depth-migrated domain includes a nonhyperbolic term that describes long-offset data, which are particularly sensitive to [Formula: see text]. Synthetic tests for models with a “quasi-factorized” TTI syncline (i.e., [Formula: see text] and [Formula: see text] are constant inside the anisotropic layer) and a TTI thrust sheet demonstrate that stable parameter estimation requires either strong smoothness constraints or additional information from walkaway VSP (vertical seismic profiling) traveltimes. If the model is quasi-factorized with a linear spatial variation of [Formula: see text], it may be possible to obtain the interval TTI parameters just from long-spread reflection data.
Neural development is dependent on the function of specificity protein 2 in cell cycle progression
Authors: Liang Huixuan , Xiao Guanxi , Yin Haifeng , Hippenmeyer Simon , Horowitz Jonathan M. , Ghashghaei H. Troy
Published: January 2013

Faithful progression through the cell cycle is crucial to the maintenance and developmental potential of stem cells. Here, we demonstrate that neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs) employ a zinc-finger transcription factor specificity protein 2 (Sp2) as a cell cycle regulator in two temporally and spatially distinct progenitor domains. Differential conditional deletion of Sp2 in early embryonic cerebral cortical progenitors, and perinatal olfactory bulb progenitors disrupted transitions through G1, G2 and M phases, whereas DNA synthesis appeared intact. Cell-autonomous function of Sp2 was identified by deletion of Sp2 using mosaic analysis with double markers, which clearly established that conditional Sp2-null NSCs and NPCs are M phase arrested in vivo. Importantly, conditional deletion of Sp2 led to a decline in the generation of NPCs and neurons in the developing and postnatal brains. Our findings implicate Sp2-dependent mechanisms as novel regulators of cell cycle progression, the absence of which disrupts neurogenesis in the embryonic and postnatal brain.
De novoDNA methylation of endogenous retroviruses is shaped by KRAB-ZFPs/KAP1 and ESET
Authors: Rowe Helen M. , Friedli Marc , Offner Sandra , Verp Sonia , Mesnard Daniel , Marquis Julien , Aktas Tugce , Trono Didier
Published: January 2013

Endogenous retroviruses (ERVs) undergo de novo DNA methylation during the first few days of mammalian embryogenesis, although the factors that control the targeting of this process are largely unknown. We asked whether KAP1 (KRAB-associated protein 1) is involved in this mechanism because of its previously defined role in maintaining the silencing of ERVs through the histone methyltransferase ESET and histone H3 lysine 9 trimethylation. Here, we demonstrate that introduced ERV sequences are sufficient to direct rapid de novo methylation of a flanked promoter in embryonic stem (ES) cells. This mechanism requires the presence of an ERV sequence-recognizing KRAB zinc-finger protein (ZFP) and both KAP1 and ESET. Furthermore, this process can also take place on a strong cellular promoter and leads to methylation signatures that are subsequently maintained in vivo throughout embryogenesis. Finally, we show that methylation of ERVs residing in the genome is affected by knockout of KAP1 in early embryos. KRAB-ZFPs, KAP1 and ESET are thus likely to be responsible for the early embryonic instatement of stable epigenetic marks at ERV-containing loci.
Temporal coherency between receptor expression, neural activity and AP-1-dependent transcription regulatesDrosophilamotoneuron dendrite development
Authors: Vonhoff Fernando , Kuehn Claudia , Blumenstock Sonja , Sanyal Subhabrata , Duch Carsten
Published: January 2013

Neural activity has profound effects on the development of dendritic structure. Mechanisms that link neural activity to nuclear gene expression include activity-regulated factors, such as CREB, Crest or Mef2, as well as activity-regulated immediate-early genes, such as fos and jun. This study investigates the role of the transcriptional regulator AP-1, a Fos-Jun heterodimer, in activity-dependent dendritic structure development. We combine genetic manipulation, imaging and quantitative dendritic architecture analysis in a Drosophila single neuron model, the individually identified motoneuron MN5. First, Dα7 nicotinic acetylcholine receptors (nAChRs) and AP-1 are required for normal MN5 dendritic growth. Second, AP-1 functions downstream of activity during MN5 dendritic growth. Third, using a newly engineered AP-1 reporter we demonstrate that AP-1 transcriptional activity is downstream of Dα7 nAChRs and Calcium/calmodulin-dependent protein kinase II (CaMKII) signaling. Fourth, AP-1 can have opposite effects on dendritic development, depending on the timing of activation. Enhancing excitability or AP-1 activity after MN5 cholinergic synapses and primary dendrites have formed causes dendritic branching, whereas premature AP-1 expression or induced activity prior to excitatory synapse formation disrupts dendritic growth. Finally, AP-1 transcriptional activity and dendritic growth are affected by MN5 firing only during development but not in the adult. Our results highlight the importance of timing in the growth and plasticity of neuronal dendrites by defining a developmental period of activity-dependent AP-1 induction that is temporally locked to cholinergic synapse formation and dendritic refinement, thus significantly refining prior models derived from chronic expression studies.
Plasticity in Dnmt3L-dependent and -independent modes of de novo methylation in the developing mouse embryo
Authors: Guenatri Mounia , Duffié Rachel , Iranzo Julian , Fauque Patricia , Bourc'his Déborah
Published: January 2013

A stimulatory DNA methyltransferase co-factor, Dnmt3L, has evolved in mammals to assist the process of de novo methylation, as genetically demonstrated in the germline. The function of Dnmt3L in the early embryo remains unresolved. By combining developmental and genetic approaches, we find that mouse embryos begin development with a maternal store of Dnmt3L, which is rapidly degraded and does not participate in embryonic de novo methylation. A zygotic-specific promoter of Dnmt3l is activated following gametic methylation loss and the potential recruitment of pluripotency factors just before implantation. Importantly, we find that zygotic Dnmt3L deficiency slows down the rate of de novo methylation in the embryo by affecting methylation density at some, but not all, genomic sequences. Dnmt3L is not strictly required, however, as methylation patterns are eventually established in its absence, in the context of increased Dnmt3A protein availability. This study proves that the postimplantation embryo is more plastic than the germline in terms of DNA methylation mechanistic choices and, importantly, that de novo methylation can be achieved in vivo without Dnmt3L.