bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel differential frequency micro-gyroscope
Authors: Nayfeh Ali H , Abdel-Rahman Eihab M , Ghommem Mehdi
Published: July 2013

We present a frequency-domain method to measure angular speeds using electrostatic micro-electro-mechanical system actuators. Towards this end, we study a single-axis gyroscope made of a micro-cantilever and a proof-mass coupled to two fixed electrodes. The gyroscope possesses two orthogonal axes of symmetry and identical flexural mode shapes along these axes. We develop the equations of motion describing the coupled bending modes in the presence of electrostatic and Coriolis forces. Furthermore, we derive a consistent closed-form higher-order expression for the natural frequencies of the coupled flexural modes. The closed-form expression is verified by comparing its results to those obtained from numerical integration of the equations of motion. We find that rotations around the beam axis couple each pair of identical bending modes to produce a pair of global modes. They also split their common natural frequency into a pair of closely spaced natural frequencies. We propose the use of the difference between this pair of frequencies, which is linearly proportional to the speed of rotation around the beam axis, as a detector for the angular speed.
Shape memory alloy-based adaptive-passive dynamic vibration absorber for vibration control in piping applications
Authors: Mani Yuvaraja , Senthilkumar Mouleeswaran
Published: July 2013

A dynamic vibration absorber (DVA) can be used as an effective vibration control device. It is essentially a secondary mass, attached to an original system via a spring and damper. The natural frequency of the DVA is tuned such that it coincides with the frequency of unwanted vibration in the original system. This results in absorption of the inertial energy transferred from the primary structure. This work aims at developing an adaptive-passive dynamic vibration absorber with the help of shape memory alloy (SMA) springs in order to attenuate the vibration for a range of excitation frequencies. In this paper, the unique property of SMAs temperature-dependent Young’s modulus has been used to change the stiffness of the spring actively to control the vibration. Experiments were carried out with an SMA-based dynamic vibration absorber to study the effect of reduction in amplitude of vibration of a cantilever structure. A microcontroller-based control system has been developed for timely actuation of SMA and to supply optimum current to the SMA springs connected in parallel. The experimental results show that the SMA-based dynamic vibration absorber is more effective in reducing the amplitude of vibration for a wider frequency range. The developed SMA-based DVA is used to damp out the vibration in piping applications. The effectiveness of adaptive-passive DVA in controlling the vibration for a range of excitation frequencies was proved.
Adaptive vibration control for MEMS vibratory gyroscope using backstepping sliding mode control
Authors: Xin Mingyuan , Fei Juntao
Published: July 2013

In this paper, an adaptive backstepping sliding mode control approach is proposed to control the MEMS triaxial gyroscope. An adaptive backstepping controller that can compensate the system nonlinearities is incorporated into the sliding mode control scheme in the Lyapunov framework. First, a robust backstepping control system incorporated with sliding mode control technique is designed. Then, an adaptive law is derived to estimate the upper bound value of the lumped uncertainty in the backstepping sliding mode control. With the adaptive backstepping sliding mode controller, the chattering in control efforts can be obviously reduced. Numerical simulation is provided to verify the effectiveness of the proposed scheme.
Children’s Encounters With Things
Authors: Jones Liz
Published: July 2013

This article draws on work around matter and the material in order to examine how (extra)ordinary “things” are used to (re)produce formulaic and predictable performances within the context of an early years classroom. Using ethnographic data I focus on a series of encounters where oscillations between (in)animate objects and the child work at schooling the body. I also note how the “work” of things constitutes a point of tension where on the one hand they are implicated in discourses of normalization yet simultaneously work at “othering.” The article also argues that despite their coercive propensities children’s relationships with and through material things can open up possibilities for dislocating sedimented pedagogical practices where “something else” becomes possible.
Exploring Values, Drivers, and Barriers as Antecedents of Implementing Responsible Tourism
Authors: Carasuk Raviv , Becken Susanne , Hughey Kenneth F. D.
Published: July 2013

There is a worldwide growing interest in what factors lead tourism businesses to behave more responsibly. Three organizational values and four drivers of change are widely regarded as the key factors. This research seeks to understand the linkages between these values and drivers, and the related importance of barriers and facilitators. To elicit information, semistructured interviews were conducted with senior management of 24 New Zealand Responsible Tourism Qualmark scheme–accredited businesses. Businesses motivated by altruistic values rarely report external drivers, they were more likely to be gold accredited and they reported implementation of more costly and long-term responsible tourism measures. In contrast, businesses motivated by legitimacy and competitiveness values demonstrated strong linkages to the external drivers of business environment and economic advantage, and they interpreted responsible tourism as a business opportunity. Their accreditation was typically at the lower levels of silver and bronze, and they referred to a wide range of barriers that prevented them from implementing more extensive measures. Using the theory of planned behavior to integrate the factors and thereby explain intentions and responsible behavior, this research will help to improve accreditation schemes and target businesses more effectively to become involved.
EvalPartners
Authors: Kosheleva Natalia , Segone Marco
Published: July 2013

In many less developed democracies Voluntary Organizations for Professional Evaluation (VOPEs) face the challenges of low demand for evaluation and the resulting low economic capacity of national evaluation communities. The VOPE model that evolved in well-developed democracies is not directly applicable under these circumstances, so a new model has to be developed. EvalPartners Initiative, launched in 2012 by the International Organization for Cooperation in Evaluation and UNICEF with support of international donors, seeks to facilitate the development of this new model by building a global community of national VOPEs able to effectively influence policy makers and public opinion to promote evaluation as the basis for evidence-based policy. EvalPartners activities include: (a) facilitation of peer-to-peer collaborations among VOPEs; (b) development of a toolkit on VOPE institutional capacity; (c) generation of new knowledge on VOPE operation; (d) promotion of enabling environment for evaluation; (e) promotion of equity-focused and gender-responsive evaluation.
Bridging the vocabulary gap for EFL medical undergraduates: The establishment of a medical word list
Authors: Hsu Wenhua
Published: July 2013

This study created a medical word list (MWL) to bridge the gap between non-technical and technical vocabulary. The researcher compiled a corpus containing 155 textbooks across 31 medical subject areas from e-book databases (totaling 15 million running words) and examined the range and frequency of words outside the most frequent 3,000-word families along the British National Corpus scale. To reach 98% lexical coverage for adequate comprehension of medical texts, 595 of the most frequently-occurring word families in the corpus were ultimately chosen and formed the MWL, and these accounted for 10.72% of the tokens in the medical textbooks under study. Excluding highly-specialized medical terms of Greek/Latin sources, the MWL encompasses various sub-technical and lay-technical vocabularies. It is suggested that with the help of free online concordancers, medical teachers can raise their students’ awareness of the commonly-used medical words reported in this study by incorporating concordance data into teaching materials, thereby consolidating the vocabulary knowledge acquired from the MWL. For medical novices, the present MWL provides a window to the medical register.
The role of maternity dress consumption in shaping the self and identity during the liminal transition of pregnancy
Authors: Ogle Jennifer Paff , Tyner Keila E. , Schofield-Tomschin Sherry
Published: July 2013

The present interpretive work explores the consumption experiences of pregnant women transitioning to mother roles, focusing specifically upon the consumption of maternity dress, which has not been previously considered within the context of liminal consumption. Of particular interest were if and how the consumption of maternity dress may shape the self during the liminal transition of pregnancy. Findings revealed that consumption of maternity dress during pregnancy both complicated and supported participants’ embodied experiences as liminal, pregnant selves and their transition to motherhood. Three overarching themes were identified and reflect the ways in which participants’ consumption practices were tightly bound with their identities, which, in turn, represented a repertoire of possible selves that often diverged from the participants’ current identities. Specifically, the three emergent themes included: (1) maternity dress consumption representing disruption in the ‘Woman I Am Most of the Time,’ (2) maternity dress consumption to affirm one’s new identity as ‘Pregnant/Expectant Mother,’ and (3) maternity dress consumption to maintain continuity in the ‘Woman I Am Most of the Time.’ Findings also underscored that consumption during liminality is complex, both inciting and relieving ambivalence during role transition.
Motherhood in utero: Consuming away anxiety
Authors: Theodorou Eleni , Spyrou Spyros
Published: July 2013

This article focuses on examining and understanding the way motherhood and babyhood are constituted in the midst of cultural practice and particularly though consumption as a fundamental and constitutive element of modern-day definitions and understandings of motherhood and babyhood. More specifically, the article focuses on how middle-class first-time (to be) Greek Cypriot mothers acquire a sense of motherhood and simultaneously construct notions of babyhood as their pregnancies unfold; how the experience of pregnancy is lived and perceived by expectant mothers as a state of anxiety and a condition of risk; and, finally, how all these processes are mediated by consumption broadly conceived. Findings of this qualitative study show that the experience of pregnancy for these women was associated with feelings of acute anxiety for the amelioration of which they engaged in a variety of consumptive practices, especially medically related, which served to further institute consumption as a constitutive element of ‘motherhood proper’.
Creativity and Human Resource Development
Authors: Joo Baek-Kyoo (Brian) , McLean Gary N. , Yang Baiyin
Published: July 2013

A focus on creativity has increased in the last two decades due to the turbulent changes in the business environment, the fierce competition in the global market, and the knowledge-based economy that has made jobs more complex and mobile. This article discusses the history and transition of creativity research based on three perspectives of creativity: personal characteristics, contextual perspectives, and integrative perspectives. This article also reviews the extant empirical studies that have been published from 2001 to 2012. Furthermore, to stimulate more rigorous creativity research in human resource development (HRD), this article provides a conceptual framework integrating personal factors and contextual factors such as organizational, social/group, and job contexts. Finally, theoretical implications and recommendations for future creativity research in HRD are discussed.
Obstacles to Success in the Workplace for People With Disabilities
Authors: Kulkarni Mukta , Lengnick-Hall Mark L.
Published: July 2013

Our objectives in this article were to summarize research relevant to obstacles that people with disabilities face in the workplace and to identify directions for future research on the topic. We included review, theoretical, and empirical articles in management journals and those in psychology or rehabilitation journals if they had clear workplace implications. We argue that obstacles identified in prior research may only partially reflect organizational reality. This is because of the heavy reliance on laboratory studies, which we urge researchers to replicate in organizational settings. A better understanding of obstacles will lead to more evidence-based solutions for human resource development (HRD) practitioners to create a less exclusionary workplace wherein all employees are provided opportunities to use their talent.
Integrity
Authors: Noelliste Mirlenda
Published: July 2013

Human Resource Development (HRD) incorporates an ethical paradigm to evaluate the standards of behavior that inform Human Resource (HR) practice. HRD professionals who stress principles of ethics and integrity as guidelines promote and foster an environment conducive to building productive teams and socially responsible organizations. However, integrity has been so diversely defined that the role of HRD practitioners as guardians of ethical conduct remains obscure. Meanwhile, ethical scandals continue to challenge organizations globally and the cognitive hurdles to behaving with integrity remain unknown. Thus, it is the purpose of this article to direct scholarly attention to the construct of integrity from an intrapersonal perspective and the pivotal role that it plays in the ethical decision-making process of the individual. Specifically, this article identifies, defines, and distinguishes various types of integrity for the purpose of proposing models of alignment and incongruencies. Recommendations for HR theory, research, and practice are generated.
Illustrating Relevance, Questioning Norms, and Creating Space
Authors: Collins Joshua C.
Published: July 2013

Scholarly dialogue in HRD (Human Resource Development) has become gradually more accepting of essential conversations regarding equity and social justice in research. However, much work remains in bridging the gaps between this scholarship and the practice of HRD. One way to create change is through teaching, as the ways in which we choose to educate students of HRD inevitably shapes the future of the field. In reflecting on one of my own works, “Identity matters: A critical exploration of lesbian, gay, and bisexual identity and leadership in HRD,” it occurred to me that even well-meaning and skilled instructors could struggle to incorporate its ideas into the dialogue in their classrooms and research. Thus, the purpose of this essay is to use “Identity Matters” as an explicatory example in discussing how emerging critical perspectives could be taught.
Quality of Life Following Component Separation Versus Standard Open Ventral Hernia Repair for Large Hernias
Authors: Klima David A. , Tsirline Victor B. , Belyansky Igor , Dacey Kristian T. , Lincourt Amy E. , Kercher Kent W. , Heniford B. Todd
Published: July 2013

Introduction. Component separation (CS) has become a viable alternative to repair large ventral defects when the fascia cannot be reapproximated. However, the impact of transecting the external oblique to facilitate closure of the abdomen on quality of life (QOL) has yet to be investigated. The study goal was to investigate QOL and outcomes after standard open ventral hernia repair (OVHR) versus CS for large ventral hernias. Study design. Prospective data for all CSs were reviewed and compared with matched OVHR controls. All defects were 100 to 1000 cm2 in size and repaired with mesh. Comorbidities, complications, outcomes, and Carolinas Comfort Scale (CCS) scores, were reviewed. Results. Seventy-four CS patients were compared with 154 patients undergoing standard OVHR with similar defect sizes. Age (56.7±13.0 vs 54.7 ± 12.3 years, P = .26), defect sizes (299 ± 160 vs 304 ± 210cm2, P = .87), and BMI (32.7 ± 6.9 vs 34.2 ± 9.0 kg/m2, P = .26) were similar in both groups, respectively. There were no differences in major postoperative complications (P = .22), mesh infections (P = 1.00), wound infections (P = .07), or hernia recurrence (P = .09), but wound breakdown increased after CS (10% vs 1%, P < .001) as did seroma interventions (15% vs 4%, P = .005). Postoperative CCS scores were similar at 1 month (P = .82) and 1 year (P = .14). Conclusions. In the first comparative study of its kind, it is found that patient undergoing CS with mesh reinforcement had equal short- and long-term QOL outcomes compared with similar patients who underwent standard OVHR. Whereas wound breakdown and seroma formation are higher, the overall complication, mesh infection, and recurrence rates are similar.
Toward Greater Production Diversity
Authors: Johnson Robin S.
Published: July 2013

Commercial video game studios erect boundaries through the organization of work that tends to discourage the production of a diverse range of games. This article adds to the scholarship on the production of video games by examining gender and other boundaries in the way work is organized at a U.S. commercial studio. Video games are a result of social conditions in a distinct organizational culture. Changing these conditions to allow for gender and other types of diverse organizational structures can impact the role of video games for the broader culture. The organization of work was analyzed through teamwork and the physical layout of the office space in relation to external customer relations and internal departmental organization. Additionally, the article examines how gender is engaged within these organizational dynamics. These factors contribute to an environment that enables game employees with a certain disposition to affectively invest in boundary maintenance.
Wither Mario Factory?
Authors: O'Donnell Casey
Published: July 2013

This article examines the role that game development tools have in the design and creation of video games. It does so through the lens of a series of patents by Nintendo that outlined the technological foundations for a truly (co)creative production platform for games. Game development tools shape and are shaped by the kinds of games they are used to produce as well as the underlying technologies of game consoles. The roles, sites, and means by which users are allowed to or encouraged to engage with (co)creative tools significantly impacts the kinds of interventions users may make. The article makes the argument that tools, like Mario Factory, form a technological foundation for (co)creation, participatory design, and convergence at a level that differs significantly from the current forms.
Performance and Inflammation Outcomes are Predicted by Different Facets of SES Under Stereotype Threat
Authors: John-Henderson Neha A. , Rheinschmidt Michelle L. , Mendoza-Denton Rodolfo , Francis Darlene D.
Published: July 2013

We experimentally tested whether negative stereotypes linked to lower socioeconomic status (SES), in addition to impairing academic performance (Croizet & Claire, 1998), instigate inflammation processes that are implicated in numerous disease processes. In Study 1, verbal test performance and activation of inflammation processes (measured by levels of an inflammatory protein, Interleukin-6 [IL-6]) varied as a function of SES and test framing (i.e., diagnostic vs. nondiagnostic of intellectual ability), with low SES students underperforming and exhibiting greater IL-6 production in the “diagnostic” condition. In Study 2, students expected their verbal exam performance to be compared to peers of higher or lower SES. Low SES students in the upward comparison condition displayed the greatest inflammatory response and worst test performance. Across both studies, different facets of SES predicted vulnerability to negative outcomes, such that low early life SES predicted heightened inflammation responses, while low current SES predicted impaired academic performance.
Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000)
Authors: Radford John , Davies Andrew , Cartron Guillaume , Morschhauser Franck , Salles Gilles , Marcus Robert , Wenger Michael , Lei Guiyuan , Wassner-Fritsch Elisabeth , Vitolo Umberto
Published: July 2013

Key Points

Obinutuzumab is a novel type II anti-CD20 monoclonal antibody under early-stage clinical investigation. Obinutuzumab plus CHOP or FC has an acceptable safety profile and is effective in relapsed/refractory follicular lymphoma.
HLA specificities are related to development and prognosis of diffuse large B-cell lymphoma
Authors: Alcoceba Miguel , Sebastián Elena , Marín Luis , Balanzategui Ana , Sarasquete M. Eugenia , Chillón M. Carmen , Jiménez Cristina , Puig Noemí , Corral Rocío , Pardal Emilia , Grande Carlos , Bello José Luis , Albo Carmen , de la Cruz Fátima , Panizo Carlos , Martín Alejandro , González-Barca Eva , Caballero M. Dolores , San Miguel Jesús F. , García-Sanz Ramón , González Marcos
Published: July 2013

Key Points

DLBCL patients carrying the HLA-B44 supertype have a worse progression-free and overall survival after R-CHOP-like treatment. The HLA-DRB1*01 allele increases the risk of DLBCL development.
Development of gene therapy for blood disorders: an update
Authors: Nienhuis Arthur W.
Published: July 2013

This review addresses the current status of gene therapy for immunodeficiencies, chronic granulomatous disease, suicide gene therapy for graft-versus-host disease, viral infections, malignant hematologic disorders, hemophilia, and the hemoglobin disorders. New developments in vector design have fostered improved expression as well as enhanced safety, particularly of integrating retroviral vectors. Several immunodeficiencies have been treated successfully by stem cell–targeted, retroviral-mediated gene transfer with reconstitution of the immune system following infusion of the transduced cells. In a trial for hemophilia B, long-term expression of human FIX has been observed following adeno-associated viral vector–mediated gene transfer into the liver. This approach should be successful in treating any disorder in which liver production of a specific protein is therapeutic.
Genomics analysis of potassium channel genes in songbirds reveals molecular specializations of brain circuits for the maintenance and production of learned vocalizations
Authors: Lovell Peter V , Carleton Julia B , Mello Claudio V
Published: July 2013

Background

A fundamental question in molecular neurobiology is how genes that determine basic neuronal properties shape the functional organization of brain circuits underlying complex learned behaviors. Given the growing availability of complete vertebrate genomes, comparative genomics represents a promising approach to address this question. Here we used genomics and molecular approaches to study how ion channel genes influence the properties of the brain circuitry that regulates birdsong, a learned vocal behavior with important similarities to human speech acquisition. We focused on potassium (K-)Channels, which are major determinants of neuronal cell excitability.

Starting with the human gene set of K-Channels, we used cross-species mRNA/protein alignments, and syntenic analysis to define the full complement of orthologs, paralogs, allelic variants, as well as novel loci not previously predicted in the genome of zebra finch (Taeniopygia guttata). We also compared protein coding domains in chicken and zebra finch orthologs to identify genes under positive selective pressure, and those that contained lineage-specific insertions/deletions in functional domains. Finally, we conducted comprehensive in situ hybridizations to determine the extent of brain expression, and identify K-Channel gene enrichments in nuclei of the avian song system.

Results

We identified 107 K-Channel finch genes, including 6 novel genes common to non-mammalian vertebrate lineages. Twenty human genes are absent in songbirds, birds, or sauropsids, or unique to mammals, suggesting K-Channel properties may be lineage-specific. We also identified specific family members with insertions/deletions and/or high dN/dS ratios compared to chicken, a non-vocal learner. In situ hybridization revealed that while most K-Channel genes are broadly expressed in the brain, a subset is selectively expressed in song nuclei, representing molecular specializations of the vocal circuitry.

Conclusions

Together, these findings shed new light on genes that may regulate biophysical and excitable properties of the song circuitry, identify potential targets for the manipulation of the song system, and reveal genomic specializations that may relate to the emergence of vocal learning and associated brain areas in birds.
Abnormal activity of default mode network in GERD patients
Authors: Sun Huihui , Chen Ying , Zhao Xiaohu , Wang Xiangbin , Jiang Yuanxi , Wu Ping , Tang Yinhan , Meng Qingwei , Xu Shuchang
Published: July 2013

Background

Abnormal processing of esophageal sensation at the level of the central nervous system has been proven to be involved in gastroesophageal reflux disease (GERD). However, most studies were focused on the possible functions of perceptual processing related network during task status, little attention has been paid to default mode network, which has been manifested to be important in the pathogenesis of many diseases. In our study, we compared the brain activity characteristic in GERD patients with the healthy subjects (HS) at baseline, looking for whether activities of default mode network were abnormal in GERD patients and attempting to identify their possible roles in GERD. In present study, fractional amplitude of low-frequency fluctuation was adopted to detect the brain activities at baseline. Group-level analyses were conducted by one-sample t test within groups (voxel thresholds were p < 0.001 and cluster level >42, corrected P < 0.05) and independent-samples t test between groups (p < 0.01 and cluster level >90, corrected P < 0.05) using SPM5.

Results

The predominant activity area in both groups mainly located in default mode network such as medial superior frontal gyrus, precuneus, posterior cingulate gyrus, etc. However, the activities of precuneus and posterior cingulate gyrus were significantly lower in GERD patients than those in the HS.

Conclusions

The activities of precuneus and posterior cingulate gyrus of default mode network in GERD patients were significantly lower compared to the HS, suggesting abnormal activities of brain regions in default mode network may be involved in pathophysiology of GERD symptom generation.
The dual targeting ability of type II NAD(P)H dehydrogenases arose early in land plant evolution
Authors: Xu Lin , Law Simon R , Murcha Monika W , Whelan James , Carrie Chris
Published: July 2013

Background

Type II NAD(PH) dehydrogenases are located on the inner mitochondrial membrane of plants, fungi, protists and some primitive animals. However, recent observations have been made which identify several Arabidopsis type II dehydrogenases as dual targeted proteins. Targeting either mitochondria and peroxisomes or mitochondria and chloroplasts.

Results

Members of the ND protein family were identified in various plant species. Phylogenetic analyses and subcellular targeting predictions were carried out for all proteins. All ND proteins from three model plant species Arabidopsis, rice and Physcomitrella were cloned as N- and C-terminal GFP fusions and subcellular localisations were determined. Dual targeting of plant type II dehydrogenases was observed to have evolved early in plant evolution and to be widespread throughout different plant species. In all three species tested dual targeting to both mitochondria and peroxisomes was found for at least one NDA and NDB type protein. In addition two NDB type proteins from Physcomitrella were also found to target chloroplasts. The dual targeting of NDC type proteins was found to have evolved later in plant evolution.

Conclusions

The functions of type II dehydrogenases within plant cells will have to be re-evaluated in light of this newly identified subcellular targeting information.
Risk factors of recurrence and life-threatening complications for patients hospitalized with chronic suppurative osteomyelitis of the jaw
Authors: Chen Lin , Li Tangxin , Jing Wei , Tang Wei , Tian Weidong , Li Cai , Liu Lei
Published: July 2013

Background

Clinically, recurrence and life-threatening complications are challenging problems for chronic suppurative osteomyelitis of the jaw (CSOJ), but there is no quantitative analysis or report about the causes of or risk factors for the two problems to date. Doctors identify the causes or risk factors only through clinical experience. We performed a retrospective study of 322 patients with CSOJ to quantificationally analysed the risk factors for the abovementioned two problems by logistic regression analysis.

Methods

A retrospective study of 322 patients hospitalized with CSOJ was performed. The socio-demographic and clinical characteristics were recorded. The risk factors for the above two problems were analyzed by logistic regression analysis. Frequency and percentage were used to indicate descriptive research factors. A univariate logistic regression analysis was performed to calculate the odds ratio (OR) and to identify independent risk factors. The independent risk factors were further identified by multivariate logistic regression analysis.

Results

An age from 6–12 years or > 65 years, pre-admission antibiotic administration, a lesion at the mandibular ramus, concurrent maxillofacial space infection (MSI), and conservation of pathogenic teeth were found to be risk factors for recurrence. An age > 65 years, admission temperature > 39 degree Celsius, admission white blood cell (WBC) count >15×109/L, pre-admission antibiotic administration, concurrent MSI, pre-existing diabetes, and respiratory difficulty were found to be risk factors for life-threatening complications.

Conclusions

The results indicate that doctors should remain mindful of the risk factors listed above, and the management of CSOJ should be increasingly aggressive when the above risk factors are present, especially when the lesion is located at the mandibular ramus. In addition, pathogenic teeth must be extracted, and antibiotics should be administered properly.

Trial registration

Clinicaltrials.gov (NCT01670422)
Crosslinking and mass spectrometry suggest that the isolated NTD domain dimer of Moloney murine leukemia virus integrase adopts a parallel arrangement in solution
Authors: Henriquez Daniel R , Zhao Caifeng , Zheng Haiyan , Arbildua José J , Acevedo Mónica L , Roth Monica J , Leon Oscar
Published: July 2013

Background

Retroviral integrases (INs) catalyze the integration of viral DNA in the chromosomal DNA of the infected cell. This reaction requires the multimerization of IN to coordinate a nucleophilic attack of the 3’ ends of viral DNA at two staggered phosphodiester bonds on the recipient DNA. Several models indicate that a tetramer of IN would be required for two-end concerted integration. Complementation assays have shown that the N-terminal domain (NTD) of integrase is essential for concerted integration, contributing to the formation of a multimer through protein-protein interaction. The isolated NTD of Mo-MLV integrase behave as a dimer in solution however the structure of the dimer in solution is not known.

Results

In this work, crosslinking and mass spectrometry were used to identify regions involved in the dimerization of the isolated Mo-MLV NTD. The distances between the crosslinked lysines within the monomer are in agreement with the structure of the NTD monomer found in 3NNQ. The intermolecular crosslinked peptides corresponding to Lys 20-Lys 31, Lys 24-Lys 24 and Lys 68-Lys 88 were identified. The 3D coordinates of 3NNQ were used to derive a theoretical structure of the NTD dimer with the suite 3D-Dock, based on shape and electrostatics complementarity, and filtered with the distance restraints determined in the crosslinking experiments.

Conclusions

The crosslinking results are consistent with the monomeric structure of NTD in 3NNQ, but for the dimer, in our model both polypeptides are oriented in parallel with each other and the contacting areas between the monomers would involve the interactions between helices 1 and helices 3 and 4.
Development and evaluation of a de-identification procedure for a case register sourced from mental health electronic records
Authors: Fernandes Andrea C , Cloete Danielle , Broadbent Matthew TM , Hayes Richard D , Chang Chin-Kuo , Jackson Richard G , Roberts Angus , Tsang Jason , Soncul Murat , Liebscher Jennifer , Stewart Robert , Callard Felicity
Published: July 2013

Background

Electronic health records (EHRs) provide enormous potential for health research but also present data governance challenges. Ensuring de-identification is a pre-requisite for use of EHR data without prior consent. The South London and Maudsley NHS Trust (SLaM), one of the largest secondary mental healthcare providers in Europe, has developed, from its EHRs, a de-identified psychiatric case register, the Clinical Record Interactive Search (CRIS), for secondary research.

Methods

We describe development, implementation and evaluation of a bespoke de-identification algorithm used to create the register. It is designed to create dictionaries using patient identifiers (PIs) entered into dedicated source fields and then identify, match and mask them (with ZZZZZ) when they appear in medical texts. We deemed this approach would be effective, given high coverage of PI in the dedicated fields and the effectiveness of the masking combined with elements of a security model. We conducted two separate performance tests i) to test performance of the algorithm in masking individual true PIs entered in dedicated fields and then found in text (using 500 patient notes) and ii) to compare the performance of the CRIS pattern matching algorithm with a machine learning algorithm, called the MITRE Identification Scrubber Toolkit – MIST (using 70 patient notes – 50 notes to train, 20 notes to test on). We also report any incidences of potential breaches, defined by occurrences of 3 or more true or apparent PIs in the same patient’s notes (and in an additional set of longitudinal notes for 50 patients); and we consider the possibility of inferring information despite de-identification.

Results

True PIs were masked with 98.8% precision and 97.6% recall. As anticipated, potential PIs did appear, owing to misspellings entered within the EHRs. We found one potential breach. In a separate performance test, with a different set of notes, CRIS yielded 100% precision and 88.5% recall, while MIST yielded a 95.1% and 78.1%, respectively. We discuss how we overcome the realistic possibility – albeit of low probability – of potential breaches through implementation of the security model.

Conclusion

CRIS is a de-identified psychiatric database sourced from EHRs, which protects patient anonymity and maximises data available for research. CRIS demonstrates the advantage of combining an effective de-identification algorithm with a carefully designed security model. The paper advances much needed discussion of EHR de-identification – particularly in relation to criteria to assess de-identification, and considering the contexts of de-identified research databases when assessing the risk of breaches of confidential patient information.
Methodological approaches to help unravel the intracellular metabolome of Bacillus subtilis
Authors: Meyer Hanna , Weidmann Hendrikje , Lalk Michael
Published: July 2013

Background

Bacillus subtilis (B. subtilis) has become widely accepted as a model organism for studies on Gram-positive bacteria. A deeper insight into the physiology of this prokaryote requires advanced studies of its metabolism. To provide a reliable basis for metabolome investigations, a validated experimental protocol is needed since the quality of the analytical sample and the final data are strongly affected by the sampling steps. To ensure that the sample analyzed precisely reflects the biological condition of interest, outside biases have to be avoided during sample preparation.

Results

Procedures for sampling, quenching, extraction of metabolites, cell disruption, as well as metabolite leakage were tested and optimized for B. subtilis. In particular the energy status of the bacterial cell, characterized by the adenylate energy charge, was used to evaluate sampling accuracy. Moreover, the results of the present study demonstrate that the cultivation medium can affect the efficiency of the developed sampling procedure.

Conclusion

The final workflow presented here allows for the reproducible and reliable generation of physiological data. The method with the highest qualitative and quantitative metabolite yield was chosen, and when used together with complementary bioanalytical methods (i.e., GC-MS, LC-MS and 1H-NMR) provides a solid basis to gather information on the metabolome of B. subtilis.
Importance of leptin signaling and signal transducer and activator of transcription-3 activation in mediating the cardiac hypertrophy associated with obesity
Authors: Leifheit-Nestler Maren , Wagner Nana-Maria , Gogiraju Rajinikanth , Didié Michael , Konstantinides Stavros , Hasenfuss Gerd , Schäfer Katrin
Published: July 2013

Background

The adipokine leptin and its receptor are expressed in the heart, and leptin has been shown to promote cardiomyocyte hypertrophy in vitro. Obesity is associated with hyperleptinemia and hypothalamic leptin resistance as well as an increased risk to develop cardiac hypertrophy and heart failure. However, the role of cardiac leptin signaling in mediating the cardiomyopathy associated with increased body weight is unclear, in particular, whether it develops subsequently to cardiac leptin resistance or overactivation of hypertrophic signaling pathways via elevated leptin levels.

Methods

The cardiac phenotype of high-fat diet (HFD)-induced obese wildtype (WT) mice was examined and compared to age-matched genetically obese leptin receptor (LepR)-deficient (LepRdb/db) or lean WT mice. To study the role of leptin-mediated STAT3 activation during obesity-induced cardiac remodeling, mice in which tyrosine residue 1138 within LepR had been replaced with a serine (LepRS1138) were also analyzed.

Results

Obesity was associated with hyperleptinemia and elevated cardiac leptin expression in both diet-induced and genetically obese mice. Enhanced LepR and STAT3 phosphorylation levels were detected in hearts of obese WT mice, but not in those with LepR mutations. Moreover, exogenous leptin continued to induce cardiac STAT3 activation in diet-induced obese mice. Although echocardiography revealed signs of cardiac hypertrophy in all obese mice, the increase in left ventricular (LV) mass and diameter was significantly more pronounced in LepRS1138 animals. LepRS1138 mice also exhibited an increased activation of signaling proteins downstream of LepR, including Jak2 (1.8-fold), Src kinase (1.7-fold), protein kinase B (1.3-fold) or C (1.6-fold). Histological analysis of hearts revealed that the inability of leptin to activate STAT3 in LepRdb/db and LepRS1138 mice was associated with reduced cardiac angiogenesis as well as increased apoptosis and fibrosis.

Conclusions

Our findings suggest that hearts from obese mice continue to respond to elevated circulating or cardiac leptin, which may mediate cardioprotection via LepR-induced STAT3 activation, whereas signals distinct from LepR-Tyr1138 promote cardiac hypertrophy. On the other hand, the presence of cardiac hypertrophy in obese mice with complete LepR signal disruption indicates that additional pathways also play a role.
Simulation of normal and pathological gaits using a fusion knowledge strategy
Authors: Martínez Fabio , Cifuentes Christian , Romero Eduardo
Published: July 2013

Background

Gait distortion is the first clinical manifestation of many pathological disorders. Traditionally, the gait laboratory has been the only available tool for supporting both diagnosis and prognosis, but under the limitation that any clinical interpretation depends completely on the physician expertise. This work presents a novel human gait model which fusions two important gait information sources: an estimated Center of Gravity (CoG) trajectory and learned heel paths, by that means allowing to reproduce kinematic normal and pathological patterns. The CoG trajectory is approximated with a physical compass pendulum representation that has been extended by introducing energy accumulator elements between the pendulum ends, thereby emulating the role of the leg joints and obtaining a complete global gait description. Likewise, learned heel paths captured from actual data are learned to improve the performance of the physical model, while the most relevant joint trajectories are estimated using a classical inverse kinematic rule. The model is compared with standard gait patterns, obtaining a correlation coefficient of 0.96. Additionally,themodel simulates neuromuscular diseases like Parkinson (phase 2, 3 and 4) and clinical signs like the Crouch gait, case in which the averaged correlation coefficient is 0.92.
MORPH-PRO: a novel algorithm and web server for protein morphing
Authors: Castellana Natalie E , Lushnikov Andrey , Rotkiewicz Piotr , Sefcovic Natasha , Pevzner Pavel A , Godzik Adam , Vyatkina Kira
Published: July 2013

Background

Proteins are known to be dynamic in nature, changing from one conformation to another while performing vital cellular tasks. It is important to understand these movements in order to better understand protein function. At the same time, experimental techniques provide us with only single snapshots of the whole ensemble of available conformations. Computational protein morphing provides a visualization of a protein structure transitioning from one conformation to another by producing a series of intermediate conformations.

Results

We present a novel, efficient morphing algorithm,Morph-Probased on linear interpolation. We also show that apart from visualization, morphing can be used to provide plausible intermediate structures. We test this by using the intermediate structures of a c-Jun N-terminal kinase (JNK1) conformational change in a virtual docking experiment. The structures are shown to dock with higher score to known JNK1-binding ligands than structures solved using X-Ray crystallography. This experiment demonstrates the potential applications of the intermediate structures in modeling or virtual screening efforts.

Conclusions

Visualization of protein conformational changes is important for characterization of protein function. Furthermore, the intermediate structures produced by our algorithm are good approximations to true structures. We believe there is great potential for these computationally predicted structures in protein-ligand docking experiments and virtual screening. TheMorph-Proweb server can be accessed athttp://morph-pro.bioinf.spbau.ru.
Dysphagia caused by focal guttural pouch mycosis: mononeuropathy of the pharyngeal ramus of the vagal nerve in a 20-year-old pony mare
Authors: Eichentopf Annemarie , Snyder Alice , Recknagel Stephan , Uhlig Albrecht , Waltl Veronika , Schusser Gerald Fritz
Published: July 2013

A 20-year-old pony mare was presented to the equine hospital with a ten-day history of dysphagia, regurgitation and coughing. An obstruction of the oesophagus was excluded via endoscopy, but the proximal oesophagus appeared to be distended and circular contractions were missing. A guttural pouch endoscopy revealed a single, black-mottled plaque on the pharyngeal ramus of the vagus nerve in the left guttural pouch, causing a local swelling of this nerve. The pharyngeal ramus seemed to be atrophic distal to the lesion. A biopsy was taken from the lesion and histopathological findings proved the reasonable suspicion of a guttural pouch mycosis with a high degree of purulent-necrotic inflammation and invasion of fungal hyphae. There were no signs of neoplasia, such as melanoma. Daily guttural pouch irrigations with a clotrimazole emulsion (20 g Canesten®Gyn4solved in 500 ml water), led to a good recovery of the mucosa above the nerve. Periodic endoscopic examination of the left guttural pouch showed that local thickening and distal atrophy of this pharyngeal ramus did not improve, neither did the clinical symptoms. Due to progressive weight loss, acute respiratory distress and aspiration pneumonia, the 20-year-old pony mare unfortunately had to be euthanized three weeks after discharge. This case report emphasizes the enormous importance of a single nerve for the realization of the swallowing process. The one-sided loss of function of the pharyngeal branch of the vagal nerve cannot be compensated neither by the remaining ipsilateral nerves nor by the contralateral normal functioning glossopharyngeal and vagal nerves and thus inevitably leads to severe dysphagia.
Versican is upregulated in circulating monocytes in patients with systemic sclerosis and amplifies a CCL2-mediated pathogenic loop
Authors: Masuda Ayako , Yasuoka Hidekata , Satoh Takashi , Okazaki Yuka , Yamaguchi Yukie , Kuwana Masataka
Published: July 2013

Introduction

Altered phenotypes of circulating monocytes of patients with systemic sclerosis (SSc) have been reported, but the role of these alterations in the pathogenesis of SSc remains unclear. This study was undertaken to identify molecules that are preferentially expressed by SSc monocytes, and to investigate the roles of these molecules in the pathogenic process of SSc.

Methods

We analyzed circulating CD14+ monocytes isolated from 36 patients with SSc and 32 healthy control subjects. The monocytes' gene expression profiles were assessed by Oligo GEArray® (SABiosciences, Frederic, MA, USA) and semiquantitative or quantitative PCR; their protein expression was evaluated in culture supernatants of unstimulated monocytes by immunoblotting or ELISA, and by immunocytostaining. Monocyte chemoattractant activity of CCL2 was assessed in a TransWell® system (Corning Incorporated, Corning, NY, USA) in the presence or absence of chondroitin sulfate (CS).

Results

A step-wise approach to profiling gene expression identified that versican and CCL2 were upregulated in SSc monocytes. Subsequent analysis of proteins expressed in monocyte culture supernatants confirmed enhanced production of versican and CCL2 in SSc monocytes compared with control monocytes. CCL2 bound to CS chains of versican and colocalized with versican in the monocytes' Golgi apparatus. Finally, CCL2 had a greater ability to mediate monocyte migration when bound to CS chains, because this binding provided efficient formation of CCL2 gradients and protection from protease attack.

Conclusion

Circulating monocytes with elevated versican and CCL2 levels may contribute to the fibrotic process in a subset of SSc patients by amplifying a positive feedback loop consisting of versican, CCL2, and the influx of monocytes.