bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of enhanced curving forces on the behaviour of canted ballasted track
Authors: Priest Jeffery A , Powrie William , Le Pen Louis , Mak Patric , Burstow Mark C
Published: September 2012

The performance of railway ballast depends not only on the characteristics of the ballast itself but also the magnitude, frequency and number of axle loads imposed by the trains running on the track it supports. Recent trends towards more frequent and faster trains have highlighted some potential limitations of ballasted railway track. In particular, the introduction of tilting trains on the UK West Coast Main Line, which allowed train operating speeds to be increased over much of the route, has coincided with the sporadic occurrence of localized areas of ballast migration. This phenomenon involves ballast particles moving from the high side of a canted section of track to the low side, exposing the sleeper ends on the high (outer) side of the curve, reducing the lateral resistance of the track and therefore increasing maintenance requirements.

This paper reports the results of an investigation carried out to try to identify the underlying mechanism responsible for this behaviour. Measurements of sleeper end displacements under the passage of trains were made at two locations which had experienced ballast migration. Analysis of the measured data together with numerical modelling of the forces imposed on the track structure suggest that the increased speed and typical axle loads of the tilting trains result in larger lateral forces and larger rotation of the sleeper (in the vertical plane) than for a train consisting of a locomotive plus trailing vehicle, as was previously used on the route. It is hypothesized that this leads in turn to a slow but progressive movement of the ballast down the slope of the canted track. However, given the highly localized nature of the ballast migration sites, other factors such as an irregular sub-base stiffness and ballast depth may also contribute to the phenomenon and further work is required to determine the combinations of circumstances that may trigger this effect.
Impact of superelevation deficiencies on the loading pattern of railway sleepers
Authors: Sadeghi Javad , Shoja Hafiz
Published: September 2012

Although the loads transferred from a rail to a sleeper and from the sleeper to the ballast have been thoroughly investigated in the literature, little attention has been paid to the influence of superelevation deficiency (SED) on the loading pattern of the sleeper. A thorough field investigation into the effects of SED on the mechanical behavior of railway sleepers was carried out in this research. For this purpose, several load cells were installed above and beneath a sleeper in order to record the loads transferred from the rail to the sleeper and from the sleeper to the ballast, for a railway track with various SED levels. The results obtained were analyzed and a mathematical model for the loading pattern on the sleeper was developed. This model is a function of axle load, train speed, sleeper length and SED. Application of the proposed model in the design of sleepers indicates that SED can have a considerable impact on the sleeper design parameters. Consequently, the sleeper design method can be improved by adding correction factors to the conventional formulation of sleeper bending moments.
Basic Characteristics of Simultaneous Color Contrast Revisited
Authors: Ekroll Vebjørn , Faul Franz
Published: September 2012

In this article, we present evidence supporting the hypothesis that the local mechanism of simultaneous color contrast is the same as the mechanism responsible for the crispening effect and the gamut expansion effect. A theoretically important corollary of this hypothesis is that the basic characteristics of simultaneous contrast are at odds with traditional laws. First, this hypothesis implies that the direction of the simultaneous contrast effect in color space is given by the vector from surround to target and not—as traditionally assumed—by the hue complementary to that of the surround. Second, it implies that the size of the simultaneous contrast effect depends on the difference between the target and surround colors in a way that challenges Kirschmann’s fourth law. The widespread belief in the traditional laws, we argue, is due to the confounding influence of temporal adaptation.
A new system design method for space launch vehicles
Authors: Wu Kui , Wang Xiaojun , Gu Lixiang , Yan Xiu-Tian
Published: September 2012

A new system design and information modelling method based on a classification of comprehensive information models called four primitives is presented for the design and development of new generation of space launch vehicles, taking advantages of the latest technologies of information modelling of systems. Through an extensive investigation of vast amount of information generated during the design processes of launch vehicles in this research, the information of a design system is classified into four-primitive model or information domains, namely, product information, design process, simulation models and design problems. Based on this classification, a new design method based on four-primitive models is proposed, by which a launch vehicle system design process consists of two phases: meta-design phase and design phase. Furthermore, five steps are generated as a generic procedure to tackle the whole design process, and these include requirement decomposition and mapping, design information modelling, structuring of design pattern, execution of design pattern and utilization of design results. The proposed design method has been validated by applying the method in a design and comparing its key design performance measurement including launch capacity as case study validation examples of the research work.
Public judgment on science expenditure in the national budget of Japan: An experimental approach to examining the effects of unpacking science
Authors: Yokoyama Hiromi M. , Nakayachi Kazuya
Published: September 2012

How does the public assess an appropriate financial allocation to science promotion? This article empirically examined the subadditivity effect in the judgment of budgetary allocation. Results of the first experiment showed that the ratio of the national budget allocated for science promotion by participants increased when science was decomposed into more specific categories compared to when it was presented as “science promotion” alone. Consistent with these findings, results of the second experiment showed that the allotment ratio to science promotion decreased when the number of other expenditure items increased. Meanwhile, the third experiment revealed that in the case of a budgetary cutback, the total amount taken from science promotion greatly increased when science was decomposed into subcategories. The subadditivity effect and increase in the total allotment ratio by unpacking science promotion was confirmed by these three experiments not only on budgetary allocation but also on budgetary cutback.
Between equity, efficiency and redistribution: An analysis of revealed allocation criteria of regional public investment in Greece
Authors: Monastiriotis Vassilis , Psycharis Yannis
Published: September 2012

As the debt crisis in Europe continues to unfold, renewed attention is placed increasingly on public (and private) investment as a vehicle for reigniting growth and counterbalancing the austerity effects of fiscal consolidation policies. Nowhere is this more urgent, or salient, than in Greece. However, there is remarkably little research, at least in that country, examining the criteria under which public investment is allocated across functional categories and across space. This article offers an extensive analysis of the spatial and functional allocation of public investment in Greece over a 33-year period and for various political-economic sub-periods. It examines the prevalence of criteria relating to redistribution, efficiency and equity; the temporal stability and functional complementarity of the observed allocations; and the extent of specialisation, concentration and clustering. Our results offer little evidence of regional or functional targeting, the exploitation of synergies and scale effects (efficiency), or the pursuit of objectives related to equity or redistribution. This raises serious questions about the efficacy of past public investment allocations in Greece and, with the expected increase in funding emanating from the EU, highlights the need for (re)defining the priorities and criteria for the spatial and functional allocation of public investments in the future.
Influence of submission form characteristics on clinical information received in biopsy accession
Authors: Brannick Erin M. , Zhang Jianying , Zhang Xiaoli , Stromberg Paul C.
Published: September 2012

Clinical information supplied to diagnostic laboratories through biopsy submission forms is crucial to accurate, timely diagnosis and to clinicopathologic correlation between microscopic findings and the clinical condition of the patient. The current study attempts to quantify the prevalence of deficient and inadequate submissions in veterinary biopsy service and to determine whether form characteristics, such as the open or closed nature of the form and the presence of specific prompts, influence reporting of essential case information. The hypotheses of this study are, first, that deficient and inadequate biopsy submissions do occur in veterinary medicine and, second, that open-type biopsy submission forms elicit quantitatively and qualitatively more complete case information overall, and in specific content areas, compared to closed-type biopsy submission forms. Three percent of submissions reviewed were information deficient, devoid of information beyond patient signalment, and more than 88% of forms supplied inadequate clinical information in at least 1 key content area. Both form type and specific prompts significantly influenced reporting of important clinical information. This study demonstrates the need and lays the foundation for informational completeness research in veterinary medicine.
Understanding the Special Olympics Debate From Lifeworld and System Perspectives
Authors: Counsell Shelly , Agran Martin
Published: September 2012

Keith Storey outlined a comprehensive overview examining the pros and cons of Special Olympics and the unintended negative consequences for participants. In conclusion, he briefly summarized three options on how to respond to Special Olympics: (a) make no change, (b) reform the current structure but keep the basic conditions of Special Olympics, or (c) discontinue or replace Special Olympics with programs designed to promote more inclusive recreational leisure situations. The purpose of this article is to employ Habermas’s theory of communicative action relative to the issues and concerns outlined by Storey into this framework to increase the understanding of the Special Olympics as a movement and a system. Newly gained insights from this investigation reveal a conceptual/philosophical disconnect between (a) the Special Olympics as a meritocratic deficit-based system according to the 1960s Liberal Egalitarian lifeworld view of people with disabilities and (b) the current lifeworld view of empowerment for persons with disabilities as promoted by researchers, scholars, and educators needed to achieve socially valuable lifestyles (social justice). The Special Olympics’ antiquated deficit lifeworld view has largely resulted in outdated program practices that run counter to the current empowered lifeworld view of integrated recreational living.
Playing With a Concept
Authors: Smrt Diana Lazarova , Nelson Reed Elliot
Published: September 2012

Using a toy construction set, we introduce to students the job characteristics model in a fun and engaging way. The activity not only describes the theoretical variables of the model but also allows students to (a) experience the dynamic interaction among these variables and (b) gain a better, hands-on understanding of the model. The exercise progresses through three stages where participants are gradually exposed to different manipulations of the variables in the job characteristics model. The exercise can be conducted in one quick-paced 75-minute class session.
Constructing Climate Change in the Americas
Authors: Zamith Rodrigo , Pinto Juliet , Villar Maria Elena
Published: September 2012

This study examined the portrayal of climate change in four national newspapers from Argentina, Brazil, Colombia, and the United States. The results indicated that leading media in Brazil and the United States highlighted the policy progress being made to mitigate climate change and presented the issue in economic terms, whereas coverage in Argentina and Colombia portrayed the issue as being urgent and emphasized the catastrophic consequences of climate change. The findings are consistent with previous work indicating a lack of focus on scientific controversy from non-U.S. media and present implications for comparative studies examining nuances in international coverage of climate change.
Design, Development, and Formative Evaluation of a Smartphone Application for Recording and Monitoring Physical Activity Levels
Authors: Kirwan Morwenna , Duncan Mitch J. , Vandelanotte Corneel , Mummery W. Kerry
Published: September 2012

Objectives. Limited research exists addressing the development of health-related smartphone apps, a new and potentially effective health promotion delivery strategy. This article describes the development and formative evaluation of a smartphone app associated with a physical activity promotion website. Methods. A combination of qualitative and quantitative techniques (performance measures, direct observation, and subjective participant preferences) were implemented during two usability testing sessions (pre- and postmodification) while participants were completing tasks using the app. Results. Design improvements to the app resulted in a reduction in the problems experienced and a decrease in the time taken to complete tasks. Four usability themes emerged from the data: design, feedback, navigation, and terminology. Conclusion. This study demonstrates the relevance of usability testing to the design and modification of a smartphone app related to a health promotion website. This study resulted in an app with much higher usability, which might increase usage and maintenance of health behavior change in the long term. Practical implications. This study demonstrates the need for formative evaluation in health-related smartphone apps. Attention should be given to basic design principles as well as feedback, navigation, and terminology in order to ensure utility and ease of use of future smartphone app designs.
Training Paraprofessionals to Facilitate Social Interactions Between Children With Autism and Their Typically Developing Peers
Authors: Feldman Eileen Klein , Matos Rosy
Published: September 2012

To support children with autism in inclusive classrooms, schools are increasingly utilizing paraprofessionals. However, research suggests that paraprofessionals often lack sufficient training and may inadvertently hinder the social interactions between children with disabilities and their peers. This study used a multiple baseline across participants design to empirically investigate whether paraprofessionals could learn to implement social facilitation procedures based on Pivotal Response Treatment. Results indicated that the paraprofessionals learned to utilize the social facilitation procedures with fidelity and generalized the techniques to untrained activities. Furthermore, once the paraprofessionals met the fidelity criteria, decreases in hovering and uninvolved behavior and increases in social facilitation and monitoring were observed. Likewise, the reciprocal social behavior of the children with autism increased rapidly.
Evaluation of thermo-mechanical behavior and stress intensity factor of titania-filled zinc–aluminium alloy composites
Authors: Patnaik Amar , Mamatha TG , Biswas Sandhyarani , Redhewall Amit Kumar , Kumar Sunand
Published: September 2012

Experimental investigation and finite element analysis model has been developed to study the physical, mechanical, thermal and thermo-mechanical behavior of titania (TiO2) (0, 4, 8 and 12 wt%) filled zinc–aluminium (ZA-27) alloy composite materials fabricated by stir casting techniques. The experimental thermal conductivity are measured and compared with both theoretical and finite element analysis model results. The error between experimental-Hasselman & Johnson model and experimental-finite element simulation for 4 wt% of TiO2-filled composite is 2.43% and 0.81% while for 8 wt% of TiO2-filled composite is 2.60% and 1.73% and for 12 wt% of TiO2-filled composite is 11% and 1.9% respectively in longitudinal direction. Similarly, in transverse direction the error lies between experimental-Hamilton & Crosser model and experimental-finite elemet simulation for 4 wt% of TiO2-filled composite is 2.62%, 3.19%, while for 8 wt% of TiO2-filled composite is 1.42%, 1.45% and for 12 wt% of TiO2-filled composite is 5.76% and 3.64%, respectively. The thermo-mechanical characteristics of the particulate-filled alloy composites are investigated in the temperature range of 80–400 ℃ with the single cantilever technique using dynamic mechanical analyzer. The composites with 12 wt% of TiO2 filled has been observed to exhibit superior thermo-mechanical response with highest energy dissipation/damping ability accompanied with a constant storage modulus without any substantial decay till 125 ℃. Finally, the stress intensity factor for all the particulate-filled composites is studied experimentally and compared with finite element method results. The results obtained from this analysis facilitate to understand the fracture propagation in the composites.
Marketplace public radio and news routines reconsidered: Between structures and agents
Authors: Usher Nikki
Published: September 2012

This article is based on a five-month in-depth ethnographic study of Marketplace, a US public radio business news show. While older news ethnographies have tended to focus more on organizational explanations for newswork, this article adds to a growing body of literature that shows the nuanced relationship between individuals and organizations. Using Giddens’ structuration as a framework, this article argues that structures such as time and organizational identity limit agency, but that journalists are more purposive actors than they are given credit. Agency can most clearly shape structure when new technology is introduced.
On children as syncretic natives: Disrupting and moving beyond normative binaries
Authors: Souto-Manning Mariana
Published: September 2012

Historically, US schools have failed multicultural and multilingual children of colour and marginalized expansive conceptualizations of home and community literacy practices. Given the importance of fully inclusive education, this article seeks to understand the ways in which young multilingual and multicultural children take up issues of educational success and inclusion through translinguistic oral narratives. Through the analysis of a representative narrative authored by an Afro-Latino boy within the context of an afterschool programme, I introduce the notion of children as syncretic natives, intentionally and skilfully navigating within and across normative binaries set up by teachers who often occupy the role of syncretic immigrants. Because of a lack of support through professional development, teacher education and/or the ideologies promoted in school systems, many teachers tend to stick to a menu of known pedagogical practices and tools, taking on the role of syncretic immigrants as they implement and enforce normative binaries as opposite and exclusionary educational practices. As syncretic natives, children tend to engage in the creation of new practices, which move beyond traditional normative binaries. Findings indicate incoherencies in the construction of normative educational binaries and what counts as educational success. Implications point to the need for teachers to learn how to disrupt and move beyond normative binaries in order to see the brilliant syncretic practices of young children from multicultural and multilingual backgrounds, thus fashioning more fully inclusive curricula and teaching with the acknowledgement and recognition that children are syncretic natives who bring knowledge and expertise that can greatly enrich classroom opportunities for them to learn and grow.
‘Veil’ and the politics of community exhibiting: some thoughts from Glasgow
Authors: Munro Ealasaid
Published: September 2012

This paper is broadly concerned with community engagement as a facet of museum practice. The paper offers a reading of a community exhibition entitled Curious, held at St Mungo’s Museum of Religious Life and Art in the city of Glasgow. I take the reader on a tour of the exhibition, offering insights into its form and function. I show how community exhibitions can pose challenges to traditional museum practice by disrupting taken-for-granted assumptions about curatorial authority, and I emphasize both the range of meanings that can be attached to museum objects and the radical potential of including non-expert knowledge in the creation of displays and exhibitions. I also argue, however, that community exhibitions may be understood as poor relations to traditionally curated exhibits, and that curatorial authority is still key to the production of museum displays.
Identifying Health Promotion Needs Among Prison Staff in Three English Prisons
Authors: Woodall James
Published: September 2012

Prisons are seen as a (temporary) home and community for offenders, yet they also have a dual role as a workplace for prison staff. This article explores how the “healthy settings” philosophy, commonly used in schools, applies in the prison environment. The article explores the concept of the health-promoting prison from the perspective of prison staff using semistructured interviews in three English prisons. Data were analyzed using Attride-Stirling’s thematic network approach. The findings indicate that working in a prison can be highly stressful and can have a negative impact on physical and mental health. Staff perceived that the focus of health promotion efforts was in many cases exclusively focused on prisoners, and many suggested that prison staff needs were being overlooked. The article argues that the theory and practice of a health-promoting prison have developed rapidly in recent years but still lag behind developments in other organizations. The article suggests that health promotion policy and practice in prison settings may need to be reconfigured to ensure that the needs of all those who live and work there are recognized.
Relevance of Motion-Related Assessment Metrics in Laparoscopic Surgery
Authors: Oropesa Ignacio , Chmarra Magdalena K. , Sánchez-González Patricia , Lamata Pablo , Rodrigues Sharon P. , Enciso Silvia , Sánchez-Margallo Francisco M. , Jansen Frank-Willem , Dankelman Jenny , Gómez Enrique J.
Published: September 2012

Introduction. Motion metrics have become an important source of information when addressing the assessment of surgical expertise. However, their direct relationship with the different surgical skills has not been fully explored. The purpose of this study is to investigate the relevance of motion-related metrics in the evaluation processes of basic psychomotor laparoscopic skills and their correlation with the different abilities sought to measure. Methods. A framework for task definition and metric analysis is proposed. An explorative survey was first conducted with a board of experts to identify metrics to assess basic psychomotor skills. Based on the output of that survey, 3 novel tasks for surgical assessment were designed. Face and construct validation was performed, with focus on motion-related metrics. Tasks were performed by 42 participants (16 novices, 22 residents, and 4 experts). Movements of the laparoscopic instruments were registered with the TrEndo tracking system and analyzed. Results. Time, path length, and depth showed construct validity for all 3 tasks. Motion smoothness and idle time also showed validity for tasks involving bimanual coordination and tasks requiring a more tactical approach, respectively. Additionally, motion smoothness and average speed showed a high internal consistency, proving them to be the most task-independent of all the metrics analyzed. Conclusion. Motion metrics are complementary and valid for assessing basic psychomotor skills, and their relevance depends on the skill being evaluated. A larger clinical implementation, combined with quality performance information, will give more insight on the relevance of the results shown in this study.
In-vivo confirmation of the use of the dart thrower’s motion during activities of daily living
Authors: Brigstocke G.H.O. , Hearnden A. , Holt C. , Whatling G.
Published: September 2012

The dart thrower’s motion is a wrist rotation along an oblique plane from radial extension to ulnar flexion. We report an in-vivo study to confirm the use of the dart thrower’s motion during activities of daily living. Global wrist motion in ten volunteers was recorded using a three-dimensional optoelectronic motion capture system, in which digital infra-red cameras track the movement of retro-reflective marker clusters. Global wrist motion has been approximated to the dart thrower’s motion when hammering a nail, throwing a ball, drinking from a glass, pouring from a jug and twisting the lid of a jar, but not when combing hair or manipulating buttons. The dart thrower’s motion is the plane of global wrist motion used during most activities of daily living. Arthrodesis of the radiocarpal joint instead of the midcarpal joint will allow better wrist function during most activities of daily living by preserving the dart thrower’s motion.
Ethical Issues in Sports Medicine
Authors: Greenfield Bruce H. , West Charles Robert
Published: September 2012

Ethical issues present a challenge for health care professionals working with athletes of sports teams. Health care professionals—including the team physician, the physical therapist, and the athletic trainer—are faced with the challenge of returning an athlete to competition as quickly as possible but as safely as possible. Conflicts of interest arise due to conflicting obligations of the team physician to the athlete and other members of the sports organization, including coaches and the team owner. The multiple stakeholders involved in sports teams challenge the traditional notion of confidentiality and autonomy. The aims of this article are to explicate the ethics of sports medicine, highlight the ethical issues, and provide some strategies and suggestions for ethical decision making.
Reliability of a New Stabilized Dynamometer System for the Evaluation of Hip Strength
Authors: Tourville Timothy W. , Smith Helen C. , Shultz Sandra J. , Vacek Pamela M. , Slauterbeck James R. , Johnson Robert J. , Beynnon Bruce D.
Published: September 2012

Background:

Hip strength is associated with numerous orthopaedic and neuromuscular injuries and/or pathologies and may be assessed with a variety of anatomic testing positions and techniques. Isokinetic dynamometers are generally too cumbersome and intricate for efficient use in mass screenings (for prognostic studies of risk for injury) as well as with special populations. The reliability of isometric testing devices has demonstrated varied reliability, generally examining only 1 or 2 motions of the hip and reporting values of force, not torque. Consequently, there is a need for an efficient hip strength-testing device to quantify torque that tests subjects in 1 anatomic position, while evaluating multiple hip motions.

Hypothesis:

Evaluation of supine hip abduction, adduction, flexion, and extension torque using a new stabilized dynamometer system will produce good to excellent intra- and interexaminer reliability results.

Study Design:

A blinded, randomized, repeated-measures study design was used in this descriptive laboratory investigation.

Methods:

Supine isometric hip flexion, extension, abduction, and adduction torques were evaluated with a cage-stabilized dynamometer in 19 collegiate and professional-level ice hockey athletes by 2 investigators at 3 time intervals. Inter- and intrarater reliability was assessed.

Results:

Supine hip flexion, extension, abduction, and adduction torque was performed with good to excellent inter- and intrarater reliability (intraclass correlation coefficients ranging from 0.74 to 0.92 and 0.78 to 0.92, respectively) for all motions tested.

Conclusions:

We have developed an isometric hip strength-testing device that can be assembled around an examination table to efficiently and reliably evaluate torque developed for multiple motions of the hip.

Clinical Relevance:

This device and testing protocol may be used to efficiently evaluate hip strength in numerous settings; it allows decreased subject burden and increased comfort (which may be important following an injury in case-control investigations); and it may be well tolerated when testing athletes as well as special populations in the clinical setting.
Glenohumeral Joint Injections
Authors: Gross Christopher , Dhawan Aman , Harwood Daniel , Gochanour Eric , Romeo Anthony
Published: September 2012

Context:

Intra-articular injections into the glenohumeral joint are commonly performed by musculoskeletal providers, including orthopaedic surgeons, family medicine physicians, rheumatologists, and physician assistants. Despite their frequent use, there is little guidance for injectable treatments to the glenohumeral joint for conditions such as osteoarthritis, adhesive capsulitis, and rheumatoid arthritis.

Evidence Acquisition:

We performed a comprehensive review of the available literature on glenohumeral injections to help clarify the current evidence-based practice and identify deficits in our understanding. We searched MEDLINE (1948 to December 2011 [week 1]) and EMBASE (1980 to 2011 [week 49]) using various permutations of intra-articular injections AND ( corticosteroid OR hyaluronic acid) and ( adhesive capsulitis OR arthritis).

Results:

We identified 1 and 7 studies that investigated intra-articular corticosteroid injections for the treatment of osteoarthritis and adhesive capsulitis, respectively. Two and 3 studies investigated the use of hyaluronic acid in osteoarthritis and adhesive capsulitis, respectively. One study compared corticosteroids and hyaluronic acid injections in the treatment of osteoarthritis, and another discussed adhesive capsulitis.

Conclusion:

Based on existing studies and their level of evidence, there is only expert opinion to guide corticosteroid injection for osteoarthritis as well as hyaluronic acid injection for osteoarthritis and adhesive capsulitis.
Risk Factors for Hip Fracture in Japanese Older Adults
Authors: Yamashita Takashi , Bailer A. John
Published: September 2012

Risk factors for hip fracture in Japanese older populations are understudied compared with Western countries arguably due to the relatively lower prevalence rates in Japan. Nationally representative data from the Nihon University Japanese Longitudinal Study of Aging were analyzed using logistic regression to examine possible risk factors of hip fractures, separately for older women ( n = 2,859) and older men ( n = 2,108). Results showed that older Japanese women with difficulty bending their knees (OR = 1.9), with diabetes (OR = 1.7 times), and/or with more activity of daily living limitations (OR = 1.1) had higher risks of hip fracture. Older Japanese men with difficulty bending their knees (OR = 2.6), who use more external prescription drugs (OR = 1.9), and with cancer (OR = 2.0 times) had higher risks of hip fracture. Further considerations of gender- and culture-specific factors along with the identified risk factors may provide insights into future intervention programs for hip fracture in Japanese older populations.
Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells
Authors: Tian Ze , Zhao Jian-jun , Tai Yu-Tzu , Amin Samir B. , Hu Yiguo , Berger Allison J. , Richardson Paul , Chauhan Dharminder , Anderson Kenneth C.
Published: September 2012

miRs play a critical role in tumor pathogenesis as either oncogenes or tumor-suppressor genes. However, the role of miRs and their regulation in response to proteasome inhibitors in multiple myeloma (MM) is unclear. In the current study, miR profiling in proteasome inhibitor MLN2238-treated MM.1S MM cells shows up-regulation of miR33b. Mechanistic studies indicate that the induction of miR33b is predominantly via transcriptional regulation. Examination of miR33b in patient MM cells showed a constitutively low expression. Overexpression of miR33b decreased MM cell viability, migration, colony formation, and increased apoptosis and sensitivity of MM cells to MLN2238 treatment. In addition, overexpression of miR33b or MLN2238 exposure negatively regulated oncogene PIM-1 and blocked PIM-1 wild-type, but not PIM-1 mutant, luciferase activity. Moreover, PIM-1 overexpression led to significant abrogation of miR33b- or MLN2238-induced cell death. SGI-1776, a biochemical inhibitor of PIM-1, triggered apoptosis in MM. Finally, overexpression of miR33b inhibited tumor growth and prolonged survival in both subcutaneous and disseminated human MM xenograft models. Our results show that miR33b is a tumor suppressor that plays a role during MLN2238-induced apoptotic signaling in MM cells, and these data provide the basis for novel therapeutic strategies targeting miR33b in MM.
Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke
Authors: Gelderblom Mathias , Weymar Anna , Bernreuther Christian , Velden Joachim , Arunachalam Priyadharshini , Steinbach Karin , Orthey Ellen , Arumugam Thiruma V. , Leypoldt Frank , Simova Olga , Thom Vivien , Friese Manuel A. , Prinz Immo , Hölscher Christoph , Glatzel Markus , Korn Thomas , Gerloff Christian , Tolosa Eva , Magnus Tim
Published: September 2012

The devastating effect of ischemic stroke is attenuated in mice lacking conventional and unconventional T cells, suggesting that inflammation enhances tissue damage in cerebral ischemia. We explored the functional role of αβ and γδ T cells in a murine model of stroke and distinguished 2 different T cell–dependent proinflammatory pathways in ischemia-reperfusion injury. IFN-γ produced by CD4+ T cells induced TNF-α production in macrophages, whereas IL-17A secreted by γδ T cells led to neutrophil recruitment. The synergistic effect of TNF-α and IL-17A on astrocytes resulted in enhanced secretion of CXCL-1, a neutrophil chemoattractant. Application of an IL-17A–blocking antibody within 3 hours after stroke induction decreased infarct size and improved neurologic outcome in the murine model. In autoptic brain tissue of patients who had a stroke, we detected IL-17A–positive lymphocytes, suggesting that this aspect of the inflammatory cascade is also relevant in the human brain. We propose that selective targeting of IL-17A signaling might provide a new therapeutic option for the treatment of stroke.
Disentangling evolutionary signals: conservation, specificity determining positions and coevolution. Implication for catalytic residue prediction
Authors: Teppa Elin , Wilkins Angela D , Nielsen Morten , Buslje Cristina Marino
Published: September 2012

Background

A large panel of methods exists that aim to identify residues with critical impact on protein function based on evolutionary signals, sequence and structure information. However, it is not clear to what extent these different methods overlap, and if any of the methods have higher predictive potential compared to others when it comes to, in particular, the identification of catalytic residues (CR) in proteins. Using a large set of enzymatic protein families and measures based on different evolutionary signals, we sought to break up the different components of the information content within a multiple sequence alignment to investigate their predictive potential and degree of overlap.

Results

Our results demonstrate that the different methods included in the benchmark in general can be divided into three groups with a limited mutual overlap. One group containing real-value Evolutionary Trace (rvET) methods and conservation, another containing mutual information (MI) methods, and the last containing methods designed explicitly for the identification of specificity determining positions (SDPs): integer-value Evolutionary Trace (ivET), SDPfox, and XDET. In terms of prediction of CR, we find using a proximity score integrating structural information (as the sum of the scores of residues located within a given distance of the residue in question) that only the methods from the first two groups displayed a reliable performance. Next, we investigated to what degree proximity scores for conservation, rvET and cumulative MI (cMI) provide complementary information capable of improving the performance for CR identification. We found that integrating conservation with proximity scores for rvET and cMI achieved the highest performance. The proximity conservation score contained no complementary information when integrated with proximity rvET. Moreover, the signal from rvET provided only a limited gain in predictive performance when integrated with mutual information and conservation proximity scores. Combined, these observations demonstrate that the rvET and cMI scores add complementary information to the prediction system.

Conclusions

This work contributes to the understanding of the different signals of evolution and also shows that it is possible to improve the detection of catalytic residues by integrating structural and higher order sequence evolutionary information with sequence conservation.
Diversity and evolution of multiple orc/cdc6-adjacent replication origins in haloarchaea
Authors: Wu Zhenfang , Liu Hailong , Liu Jingfang , Liu Xiaoqing , Xiang Hua
Published: September 2012

Background

While multiple replication origins have been observed in archaea, considerably less is known about their evolutionary processes. Here, we performed a comparative analysis of the predicted (proved in part)orc/cdc6-associated replication origins in 15 completely sequenced haloarchaeal genomes to investigate the diversity and evolution of replication origins in halophilic Archaea.

Results

Multipleorc/cdc6-associated replication origins were predicted in all of the analyzed haloarchaeal genomes following the identification of putative ORBs (origin recognition boxes) that are associated withorc/cdc6genes. Five of these predicted replication origins inHaloarcula hispanicawere experimentally confirmed via autonomous replication activities. Strikingly, several predicted replication origins inH. hispanicaandHaloarcula marismortuiare located in the distinct regions of their highly homologous chromosomes, suggesting that these replication origins might have been introduced as parts of new genomic content. A comparison of the origin-associated Orc/Cdc6 homologs and the corresponding predicted ORB elements revealed that the replication origins in a given haloarchaeon are quite diverse, while different haloarchaea can share a few conserved origins. Phylogenetic and genomic context analyses suggested that there is an original replication origin (oriC1) that was inherited from the ancestor of archaea, and several other origins were likely evolved and/or translocated within the haloarchaeal species.

Conclusion

This study provides detailed information about the diversity of multipleorc/cdc6-associated replication origins in haloarchaeal genomes, and provides novel insight into the evolution of multiple replication origins in Archaea.
Computational identification of transcriptionally co-regulated genes, validation with the four ANT isoform genes
Authors: Dupont Pierre-Yves , Guttin Audrey , Issartel Jean-Paul , Stepien Georges
Published: September 2012

Background

The analysis of gene promoters is essential to understand the mechanisms of transcriptional regulation required under the effects of physiological processes, nutritional intake or pathologies. In higher eukaryotes, transcriptional regulation implies the recruitment of a set of regulatory proteins that bind on combinations of nucleotide motifs. We developed a computational analysis of promoter nucleotide sequences, to identify co-regulated genes by combining several programs that allowed us to build regulatory models and perform a crossed analysis on several databases. This strategy was tested on a set of four human genes encoding isoforms 1 to 4 of the mitochondrial ADP/ATP carrier ANT. Each isoform has a specific tissue expression profile linked to its role in cellular bioenergetics.

Results

From their promoter sequence and from the phylogenetic evolution of these ANT genes in mammals, we constructed combinations of specific regulatory elements. These models were screened using the full human genome and databases of promoter sequences from human and several other mammalian species. For each of transcriptionally regulated ANT1, 2 and 4 genes, a set of co-regulated genes was identified and their over-expression was verified in microarray databases.

Conclusions

Most of the identified genes encode proteins with a cellular function and specificity in agreement with those of the corresponding ANT isoform. Our in silico study shows that the tissue specific gene expression is mainly driven by promoter regulatory sequences located up to about a thousand base pairs upstream the transcription start site. Moreover, this computational strategy on the study of regulatory pathways should provide, along with transcriptomics and metabolomics, data to construct cellular metabolic networks.
Modified endoscopic submucosal dissection with enucleation for treatment of gastric subepithelial tumors originating from the muscularis propria layer
Authors: Chu Yin-Yi , Lien Jau-Min , Tsai Ming-Hung , Chiu Cheng-Tang , Chen Tse-Ching , Yang Kuo-Ching , Ng Soh-Ching
Published: September 2012

Background

Gastric subepithelial tumors are usually asymptomatic and observed incidentally during endoscopic examination. Although most of these tumors are considered benign, some have a potential for malignant transformation, particularly those originating from the muscularis propria layer. For this type of tumor, surgical resection is the standard treatment of choice. With recent advent of endoscopic resection techniques and devices, endoscopic submucosal dissection (ESD) has been considered as an alternative way of treatment. The aim of this study is to demonstrate the feasibility of a modified ESD technique with enucleation for removal of gastric subepithelial tumors originating from the muscularis propria layer, and to evaluate its efficacy and safety.

Methods

From November 2009 to May 2011, a total of 16 patients received a modified ESD with enucleation for their subepithelial tumors. All tumors were smaller than 5 cm and originated from the muscularis propria layer of the stomach, as shown by endoscopic ultrasonography (EUS). The procedure was conducted with an insulated-tip knife 2. Patient’s demographics, tumor size and pathological diagnosis, procedure time, procedure-related complication, and treatment outcome were reviewed.

Results

Fifteen of the sixteen tumors were successful complete resection. The mean tumor size measured by EUS was 26.1 mm (range: 20–42 mm). The mean procedure time was 52 minutes (range: 30–120 minutes). Endoscopic features of the 4 tumors were pedunculated and 12 were sessile. Their immunohistochemical diagnosis was c-kit (+) stromal tumor in 14 patients and leiomyoma in 2 patients. There was no procedure-related perforation or overt bleeding. During a mean follow up duration of 14.8 months (range: 6–22 months), there was no tumor recurrence or metastasis.

Conclusions

Using a modified ESD with enucleation for treatment of gastric subepithelial tumors originating from the muscularis propria layer and larger than 2 cm, complete resection can be successfully performed without serious complication. It is a safe and effective alternative to surgical therapy for these tumors of 2 to 5 cm in size.
High yield of culture-based diagnosis in a TB-endemic setting
Authors: Demers Anne-Marie , Verver Suzanne , Boulle Andrew , Warren Robin , van Helden Paul , Behr Marcel A , Coetzee David
Published: September 2012

Background

In most of the world, microbiologic diagnosis of tuberculosis (TB) is limited to microscopy. Recent guidelines recommend culture-based diagnosis where feasible.

Methods

In order to evaluate the relative and absolute incremental diagnostic yield of culture-based diagnosis in a high-incidence community in Cape Town, South Africa, subjects evaluated for suspected TB had their samples processed for microscopy and culture over a 21 month period.

Results

For 2537 suspect episodes with 2 smears and 2 cultures done, 20.0% (508) had at least one positive smear and 29.9% (760) had at least one positive culture. One culture yielded 1.8 times more cases as 1 smear (relative yield), or an increase of 12.0% (absolute yield). Based on the latter value, thenumber of culturesneeded todiagnose (NND) one extra case of TB was 8, compared to 19 if second specimens were submitted for microscopy.

Conclusion

In a high-burden setting, the introduction of culture can markedly increase TB diagnosis over microscopy. The concept of number needed to diagnose can help in comparing incremental yield of diagnosis methods. Although new promising diagnostic molecular methods are being implemented, TB culture is still the gold standard.
A missense founder mutation in VLDLR is associated with Dysequilibrium Syndrome without quadrupedal locomotion
Authors: Ali Bassam R , Silhavy Jennifer L , Gleeson Matthew J , Gleeson Joseph G , Al-Gazali Lihadh
Published: September 2012

Background

Dysequilibrium syndrome is a genetically heterogeneous condition that combines autosomal recessive, nonprogressive cerebellar ataxia with mental retardation. The condition has been classified into cerebellar ataxia, mental retardation and disequilibrium syndrome types 1 (CAMRQ1), 2 (CAMRQ2) and 3 (CAMRQ3) and attributed to mutations in VLDLR, CA8 and WDR81 genes, respectively. Quadrupedal locomotion in this syndrome has been reported in association with mutations in all three genes.

Methods

SNP mapping and candidate gene sequencing in one consanguineous Omani family from the United Arab Emirates with cerebellar hypoplasia, moderate mental retardation, delayed ambulation and truncal ataxia was used to identify the mutation. In a second unrelated consanguineous Omani family, massively parallel exonic sequencing was used.

Results

We identified a homozygous missense mutation (c.2117 G > T, p.C706F) in the VLDLR gene in both families on a shared affected haplotype block.This is the first reported homozygous missense mutation in VLDLR and it occurs in a highly conserved residue and predicted to be damaging to protein function.

Conclusions

We have delineated the phenotype associated with dysequilibrium syndrome in two Omani families and identified the first homozygous missense pathogenic mutation in VLDLR gene with likely founder effect in the southeastern part of the Arabian Peninsula.