bluuebunny/crossref_metadata_2025 huggingface dataset:
Buffeting mitigation using carbon nanotube composites: a feasibility study
Authors: Yuan Jie , Allegri Giuliano , Scarpa Fabrizio
Published: October 2012

The article describes a feasibility study to assess the use of nanotubes-based composites to mitigate tail buffeting. The buffeting of a representative business jet rudder is considered as case study. The baseline rudder configuration consists in a sandwich structure with honeycomb core and carbon/epoxy IM7/8552 skins. The damping characteristics of the baseline rudder configuration are compared to those achieved employing constrained layer Al/3M467 skin patches, and those obtained by dispersing multi-walled carbon nanotubes in the baseline carbon/epoxy material. The loads applied to the rudder during flight are obtained by airworthiness standards. Static and dynamic finite element analyses of the rudder under flight loads are carried out to evaluate the structural response at two different temperatures, −40 ℃ and +30 ℃. IM7/8552/MWNT with 1.5 wt% nanofiller is shown to have the best overall performance for the case study considered here, with the potential of outperforming conventional constrained layer patches for buffeting mitigation.
Bilingualism Enriches the Poor
Authors: Engel de Abreu Pascale M. J. , Cruz-Santos Anabela , Tourinho Carlos J. , Martin Romain , Bialystok Ellen
Published: October 2012

This study explores whether the cognitive advantage associated with bilingualism in executive functioning extends to young immigrant children challenged by poverty and, if it does, which specific processes are most affected. In the study reported here, 40 Portuguese-Luxembourgish bilingual children from low-income immigrant families in Luxembourg and 40 matched monolingual children from Portugal completed visuospatial tests of working memory, abstract reasoning, selective attention, and interference suppression. Two broad cognitive factors of executive functioning—representation (abstract reasoning and working memory) and control (selective attention and interference suppression)—emerged from principal component analysis. Whereas there were no group differences in representation, the bilinguals performed significantly better than did the monolinguals in control. These results demonstrate, first, that the bilingual advantage is neither confounded with nor limited by socioeconomic and cultural factors and, second, that separable aspects of executive functioning are differentially affected by bilingualism. The bilingual advantage lies in control but not in visuospatial representational processes.
Strategic HR Integration and Proactive Communication during M&A: A Study of Indian Bank Mergers
Authors: Bhaskar A. Uday , Bhal Kanika T. , Mishra Bijaya
Published: October 2012

Research in the past has documented the use of strategic human resources (HR) integration and proactive communication as best practices in mergers and acquisitions (M&A) to deliver the expected synergy out of a combination (merger or acquisition). The failure of majority of M&A deals has been attributed to improper handling of HR issues and lack of a thorough understanding of the merger/acquisition context by the acquiring management. This study was initiated to understand how proactive communication and strategic integration of HR issues improves the chances of deal success. Based on data collected through field interviews with managers of two bank mergers in India, it was concluded that strategic employee communication, appropriate changes in the performance management system and a compensation structure with cutting edge strategic HR practices paved the way for successful integration and merger success in one of the cases studied.
Aircel: Distribution Challenges
Authors: Mukherjee Jaydeep , Gupta Amit , Pande Bhavesh
Published: October 2012

The case is about the marketing challenge faced by the Head of the Delhi/NCR circle of Aircel Ltd, a telecom company in India. In Delhi circle, the company had achieved a commendable share of users in just two years, but they also had the lowest average revenue per user (ARPU) among the telecom majors. Both the achievement of user base and failure to get adequate ARPU could, in some way, be attributed to the type of distribution channel and end consumers they attracted due to their late entry in the Delhi circle. The company was attempting to change its customer strategy to henceforth focus on the quality of customers rather than the number of customers. It was also planning to implement a strategy of bundling handsets with the connection, based on the research finding that such customers were likely to have a greater ARPU. The dilemmas presented were the impact of the change in the customer strategy on the distribution channel and its motivation. The case deals with the choices to be made and how to make the changes necessary to implement the marketing strategy through the well-established distribution system.
Microelectromechanical system cantilever-based frequency doublers
Authors: Basu Joydeep , Bhattacharyya Tarun K
Published: October 2012

Microelectromechanical system based on-chip resonators offer great potential for high-frequency signal processing circuits such as reference oscillators and filters. This is due to their exceptional features such as small size, large frequency–quality factor product, integrability with CMOS integrated circuits, low power consumption, low-cost batch fabrication, and so on. A capacitively transduced cantilever beam resonator is one such popular microelectromechanical resonator topology. In this article, the inherent square-law nonlinearity of the voltage-to-force transfer function of a cantilever resonator’s capacitive transducer has been employed for the realization of frequency doubling effect. Using this concept, frequency doubling of input signals of 500 kHz to1 MHz and 227.5 kHz to 455 kHz have been experimentally demonstrated for two cantilever beams of length 51.75 and 76.75 µm, respectively. The microelectromechanical system cantilevers have been fabricated with polysilicon using the PolyMUMPs surface micromachining process, and their testing has been performed using laser Doppler vibrometry. The test results obtained are in reasonable compliance with the analytical and CoventorWare finite element simulation results. The high efficiency demonstrated by the cantilever frequency doubler makes it a promising choice for signal generation at high frequencies.
Hybrid modal damping identification for bladed disks and blisks
Authors: Holland Darren E , Epureanu Bogdan I
Published: October 2012

Current damping identification methodologies typically require measurements of complex eigenvalues, complex eigenvectors, and the applied force. Also, these methods can be sensitive to measurement noise. Most importantly, only a few current methods can be used for regions of high modal density. Thus, the work herein utilizes the frequency response of a system to identify modal damping in regions of (low and) high modal density. This method does not require knowledge of the absolute forcing, rather only the relative forcing is needed. Results are presented for a mistuned blisk, and the proposed method is compared with an alternative damping identification technique.
Ipilimumab for advanced melanoma: A pharmacologic perspective
Authors: Trinh Van Anh , Hagen Brenda
Published: October 2012

Ipilimumab, a fully human anti-CTLA-4 antibody, has been approved for the treatment of unresectable or metastatic melanoma based on its survival benefit demonstrated in randomized phase III studies. The current approved dosing schedule of ipilimumab is 3 mg/kg as a 90-min intravenous infusion every 3 weeks for a total of 4 doses. The immune-mediated mechanism of action of ipilimumab can result in tumor response patterns that may differ from those observed with conventional chemotherapy; therefore, revised response criteria to fully capture the spectrum of responses have been developed and are being prospectively validated. The safety profile of ipilimumab also reflects its mechanism of action and is characterized by immune-related adverse events. Although most of these events are mild, tolerable and reversible, high-grade immune-related adverse events have been observed in 15% of patients and can be potentially life-threatening if not managed appropriately. Guidelines for the management of these events emphasize thorough patient education, vigilant monitoring and prompt intervention with corticosteroids when appropriate. Ongoing research, including evaluation of ipilimumab in the adjuvant setting, investigation of its use in combination with other agents and assessment of alternative doses, will help optimize and expand the use of this innovative treatment.
Risky Sexual Behavior Among College Students With ADHD
Authors: Huggins Suzanne Perrigue , Rooney Mary E. , Chronis-Tuscano Andrea
Published: October 2012

Objective: This study examined the extent to which ADHD was associated with risky sexual behaviors (RSBs) in a sample of 92 undergraduates with ( n = 44) and without ( n = 48) ADHD. Mother–child relationship quality was examined as a potential moderator. Method: We conducted comprehensive assessments for ADHD and comorbid conditions and collected measures of RSB and mother–child relationship quality. Results: Female students with ADHD were least likely to use condoms than males overall and females without ADHD. An interaction between ADHD and mother–child relationship quality accounted for significant variance in the number of past-year sexual partners, such that a high-quality relationship was protective only for students with ADHD. No other significant associations were found between ADHD and RSB. Conclusion: Results suggest that female college students with ADHD are at risk for unprotected sex. Moreover, a positive mother–child relationship may be protective for college students with ADHD in relation to RSB.
Stormwater Programs
Authors: Grigg Neil S.
Published: October 2012

Urban stormwater programs provide mandated and discretionary public services of convenience, security, and environmental enhancement. Due to their increasing complexity and funding needs, they have become more complex to organize and finance. Competing visions for them are common and how communities value these services creates a challenge to measure effectiveness and levy charges. Usually, two organizational models compete, the tax-supported public works model and the fee-based utility model. Taxpayer revolts led to the utility model, which creates new revenue streams and has been widely accepted but not universally. State laws provide the legal structure for stormwater finance, and research showed the utility model to be accepted commonly in the West Coast and Mountain regions, in Florida and along the southern part of the East Coast, as well as in parts of the Central region of the United States. The public works model is prevalent in much of the Northeast, the noncoastal Southeast, and parts of the Central region, where programs vary from state-to-state. Prospects for stormwater programs indicate more experiments with program organization and finance as communities seek to balance responsibilities. The competing views of stormwater program organization and finance s will join larger issues of local government roles in solving social and environmental problems and outcomes will be a bellwether of commitment to sustainable and livable communities.
Suspected muscarinic mushroom intoxication in a cat
Authors: Herreria-Bustillo Vicente J , Saiz-Alvarez Rocio , Jasani Shailen
Published: October 2012

A 3-year-old domestic shorthair cat was witnessed ingesting mushrooms and developed signs of muscarine intoxication. After stabilisation and treatment with atropine the cat recovered well and was discharged from hospital in 2 days. This report describes the features and successful management of this unusual toxicosis in cats.
The Children’s Health and Activity Modification Program (C.H.A.M.P.)
Authors: Pearson Erin S , Irwin Jennifer D , Burke Shauna M
Published: October 2012

To date, there is a paucity of qualitative research examining the influence of community-based interventions for childhood obesity on the participants themselves. This study explored the experiences of children who participated in the Children’s Health and Activity Modification Program (C.H.A.M.P.), a four-week day camp for children with obesity aged 8–14, in order to uncover key program elements for positive behavior change. Following the intervention, children ( n = 36) participated in focus groups where they were asked about their experiences pertaining to physical activity and nutrition, what it was like to be part of a team, and how they felt about themselves. Findings revealed that participants perceived C.H.A.M.P. as helpful (e.g. in making healthier food choices, being more active, and feeling more confident and self-aware). This pilot study offers unique insights into the perspectives of children with obesity. Results are discussed with respect to future program development and research for childhood obesity treatment.
Children in an adult world
Authors: Ekra Else Mari Ruberg , Blaaka Gunnhild , Korsvold Tora , Gjengedal Eva
Published: October 2012

Hospital conditions for children have changed dramatically over the last decades. Until recently, hospitalised children were left without their parents in an environment that was not adapted to children. In the period 1950–1980, hospitalised children did not have a voice. The aim of this Norwegian study was to use adult memories of childhood hospitalisation to investigate the influences of the hospital environment on the experiences of children. The study had a qualitative design and used a hermeneutic phenomenological approach. Twelve adults who were 5½ to 12 years old when they were first hospitalised with type 1 diabetes were interviewed. The participants described their hospital stays as representing a life in an adult world. They encountered an unfamiliar place where it was challenging to be abandoned in an adult hospital community with a serious and exhausting illness. The results underscore the need to incorporate children’s perspectives to achieve a ‘child friendly’ environment in the hospital. Thirty years later there still may be a tension between the adults’ responsibility to protect children and the children’s own right to participation in decision-making. To understand current practices, it is important to know our historical past.
Children’s conceptions of their parent’s lung transplant
Authors: Fulbrook Paul , Leisfield Trish , Wiggins Kay
Published: October 2012

There has been no research that has investigated the psychosocial impact on children whose parents have undergone a lung transplant. The aim of this qualitative study was to describe children’s concerns and understandings of their parent’s transplant surgery. Artwork was used as a creative medium to enable children to portray their experiences in a safe, non-threatening environment. This was used as a visual primer for follow-up interviews. All children expressed similar and complementary views about uncertainty and anxiety, separation, disruption to family life, their desire for normality, and the importance of social support. Differences were evident in the way that some children managed well by adapting to the changing situations, whereas others tended towards avoidance. The findings provide several themes that may be used as a framework for family support and counselling by nurses, social workers, and other healthcare professionals who are caring for patients and their families during the transplant process.
Plassein: On the fluid mobility of place and urban qualities in planning
Authors: Bylund Jonas
Published: October 2012

What could the addition of a variegated spatial approach contribute to planning studies? Planning studies, by and large, rely on Euclidean space as a ‘reality’ to be planned. However, Euclidean space may only be one of many spaces enacted in planning practice. Thus, this article proposes that most urban planning practice features at least a severe spatial imaginative challenge to our understanding of it. First, there is the problem of how to manage at a distance, which is solved by a translation and hence mobilization of place. Second, there is the problem of how mobilized place is done ex situ, which suggests that it must become somewhat fluid and be translated into plassein. These features are discussed in light of brief empirical illustrations drawn from a study of urban waterfront redevelopment in Swedish cities. In concluding the argument, a note is made on the relevance of plassein with a suggestion that fluidity is a requirement for achieving democracy in planning practices.
Characterization of sky scanner measurements based on CIE and ISO standard CIE S 011/2003
Authors: Kobav MB , Bizjak G , Dumortier D
Published: October 2012

The aim of this paper is to present a complete analysis of the sky luminance distribution data measured with a sky scanner at the International Daylight Measurement Program station in Lyon. Besides presentation of the sky luminance distribution, we also derive the CIE sky type based on the CIE S 011/2003 standard. The CIE sky type is based on gradation and indicatrix functions. Determination of the gradation and indicatrix group is based on the calculation of luminance ratio between two elements on every almucantar. Since there are six gradation and six indicatrix groups, we have 36 combinations but only 15 of them are listed in the CIE standard. Since some of combinations are really rare, we provide a table to show how to allocate 36 combinations to 15 standard CIE sky types. At the end of the paper, we present frequencies of occurrence of CIE sky types in Lyon.
Effect of dissipation on free convective flow of a non-Newtonian nanofluid in a porous medium with gyrotactic microorganisms
Authors: Uddin Mohammad J , Khan Waqar A , Ismail Ahmad I
Published: October 2012

This study is devoted to investigate the influences of viscous dissipation on free convective boundary layer flow of a non-Newtonian power law nanofluid over an isothermal vertical flat plate embedded in a porous medium. The present model contains both nanoparticles and gyrotactic microorganisms. The governing partial differential equations are converted to ordinary differential equations using suitable similarity transformations. The effects of nanofluid and bioconvection parameters on the dimensionless velocity, temperature, concentration of nanoparticles, and density of motile microorganisms as well as on the rate of heat transfer, nanoparticle volume fraction, and the rate of density of motile microorganism are investigated. The present results show that the nanofluid and bioconvection parameters have strong effects on the flow, heat and mass transfer, and motile microorganism characteristics.
Targeted approach to metastatic colorectal cancer: what comes beyond epidermal growth factor receptor antibodies and bevacizumab?
Authors: Troiani Teresa , Martinelli Erika , Morgillo Floriana , Capasso Anna , Nappi Anna , Sforza Vincenzo , Ciardiello Fortunato
Published: October 2012

The prognosis of patients with cancer remains poor in spite of the advances obtained in recent years with new therapeutic agents, new approaches in surgical procedures and new diagnostic methods. The discovery of a plethora of cellular targets and the rational generation of selective targeting agents has opened an era of new opportunities and extraordinary challenges. The specificity of these agents renders them capable of specifically targeting the inherent abnormalities of cancer cells, potentially resulting in less toxicity than traditional nonselective cytotoxics. Among the many new types of rationally designed agents are therapeutics targeting various strategic facets of growth signal transduction, malignant angiogenesis, survival, metastasis and cell-cycle regulation. The evaluation of these agents is likely to require some changes from the traditional drug development paradigms to realize their full potential. Inhibition of the epidermal growth factor receptor and the vascular endothelial growth factor have provided proof of principle that disruption of signal cascades in patients with colorectal cancer has therapeutic potential. This experience has also taught us that resistance to such rationally developed targeted therapeutic strategies is common. In this article, we review the role of signal transduction in colorectal cancer, introduce promising molecular targets, and outline therapeutic approaches under development.
Assessment of T-dependent and T-independent immune responses in cattle using a B cell ELISPOT assay
Authors: Grant Clare FJ , Lefevre Eric A , Carr B Veronica , Prentice Helen , Gubbins Simon , Pollard Andrew J , Charreyre Catherine , Charleston Bryan
Published: October 2012

Understanding the mechanisms that maintain protective antibody levels after immunisation is important for vaccine design. In this study, we have determined the kinetics of plasma and memory B cells detectable in the blood of cattle immunised with model T-dependent or T-independent antigens. Immunisation with the T-D antigen resulted in an expansion of TNP-specific plasma cells post-TNP primary and booster immunisations, which was associated with increased titres of TNP-specific IgG antibodies. Although no TNP-specific memory B cells were detected in the T-D group following the primary immunisation, we detected an increase in the number of TNP-specific memory B cells post-TNP boost. In contrast, no TNP-specific plasma or memory B cells were detected after primary or secondary immunisation with the T-I antigen. We then investigated if immunisation with a third party antigen (tetanus toxin fragment C, TTC) would result in a bystander stimulation and increase the number of TNP-specific plasma and memory B cells in the T-D and/or T-I group. TTC immunisation in the T-D group resulted in a small increase in the number of TNP-specific plasma cells post-TTC primary immunisation and boost, and in an increase in the number of TNP-specific memory B cells post-TTC boost. This bystander effect was not observed in the animals previously immunised with the T-I antigen. In conclusion, the present study characterised for the first time the B cell response in cattle to immunisation with T-D and T-I antigens and showed that bystander stimulation of an established T-D B cell memory response may occur in cattle.
Identical fracture patterns in combat vehicle blast injuries due to improvised explosive devices; a case series
Authors: Commandeur Joris , Derksen Robert Jan , MacDonald Damian , Breederveld Roelf
Published: October 2012

Background

In November 2008, a surgical team from the Red Cross Hospital Beverwijk, the Netherlands, was deployed in Afghanistan for three months to attend in the army hospital of Kandahar.

During their stay, four incidents of armored personnel carriers encountering an improvised explosive device were assessed. In each incident, two soldiers were involved, whose injuries were strikingly similar.

Case presentation

The described cases comprise paired thoracic vertebral fractures, radial neck fractures, calcaneal fractures and talar fractures. Moreover, the different types of blast injury are mentioned and related to the injuries described in our series. Acknowledging the different blast mechanisms is important for understanding possible injury patterns.

Conclusion

From this case series, as well as the existing literature on injury patterns caused by blast injuries, it seems appropriate to pay extra attention to bodily areas that were injured in other occupants of the same vehicle. Obviously, the additional surveillance for specific injuries should be complementary to the regular trauma work-up (e.g., ATLS).
Targeting SPARC by lentivirus-mediated RNA interference inhibits cervical cancer cell growth and metastasis
Authors: Chen Jie , Shi Dehuan , Liu Xiaoyan , Fang Shuang , Zhang Jie , Zhao Yueran
Published: October 2012

Background

Secreted protein acidic and rich in cysteine (SPARC), a calcium-binding matricellular glycoprotein, is implicated in the progressions of some cancers. However, no information has been available to date regarding the function of SPARC in cervical cancer cell growth and metastasis.

Methods

In this study, we isolated and established high invasive subclones and low invasive subclones from human cervical cancer cell lines HeLa and SiHa by the limited dilution method. Real-time q-RT-PCR, Western Blot and ICC were performed to investigate SPARC mRNA and protein expressions in high invasive subclones and low invasive subclones. Then lentivirus vector with SPARC shRNA was constructed and infected the highly invasive subclones. Real-time q-RT-PCR, Western Blot and ICC were also performed to investigate the changes of SPARC expression after viral infection. In functional assays, effects of SPARC knockdown on the biological behaviors of cervical cancer cells were investigated. The mechanisms of SPARC in cervical cancer proliferation, apoptosis and invasion were also researched.

Results

SPARC was over-expressed in the highly invasive subclones compared with the low invasive subclones. Knockdown of SPARC significantly suppressed cervical cancer cell proliferation, and induced cell cycle arrest at the G1/G0 phase through the p53/p21 pathway, also caused cell apoptosis accompanied by the decreased ratio of Bcl-2/Bax, and inhibited cell invasion and metastasis accompanied by down-regulated MMP2 and MMP9 expressions and up-regulated E-cadherin expression.

Conclusion

SPARC is related to the invasive phenotype of cervical cancer cells. Knockdown of SPARC significantly suppresses cervical cancer cell proliferation, induces cell apoptosis and inhibits cell invasion and metastasis. SPARC as a promoter improves cervical cancer cell growth and metastasis.
Confidence in the efficacy and safety of dietary supplements among United States active duty army personnel
Authors: Carvey Christina E , Farina Emily K , Lieberman Harris R
Published: October 2012

Background

United States Army Soldiers regularly use dietary supplements (DS) to promote general health, enhance muscle strength, and increase energy, but limited scientific evidence supports the use of many DS for these benefits. This study investigated factors associated with Soldiers’ confidence in the efficacy and safety of DS, and assessed Soldiers’ knowledge of federal DS regulatory requirements.

Methods

Between 2006 and 2007, 990 Soldiers were surveyed at 11 Army bases world-wide to assess their confidence in the effectiveness and safety of DS, knowledge of federal DS regulations, demographic characteristics, lifestyle-behaviors and DS use.

Results

A majority of Soldiers were at least somewhat confident that DS work as advertised (67%) and thought they are safe to consume (71%). Confidence in both attributes was higher among regular DS users than non-users. Among users, confidence in both attributes was positively associated with rank, self-rated diet quality and fitness level, education, and having never experienced an apparent DS-related adverse event. Fewer than half of Soldiers knew the government does not require manufacturers to demonstrate efficacy, and almost a third incorrectly believed there are effective pre-market federal safety requirements for DS.

Conclusions

Despite limited scientific evidence supporting the purported benefits and safety of many popular DS, most Soldiers were confident that DS are effective and safe. The positive associations between confidence and DS use should be considered when developing DS-related interventions or policies. Additionally, education to clarify Soldiers’ misperceptions about federal DS safety and efficacy regulations is warranted.
Importance of glycolysis and oxidative phosphorylation in advanced melanoma
Authors: Ho Jonhan , de Moura Michelle Barbi , Lin Yan , Vincent Garret , Thorne Stephen , Duncan Lyn M , Hui-Min Lin , Kirkwood John M , Becker Dorothea , Van Houten Bennett , Moschos Stergios J
Published: October 2012

Serum lactate dehydrogenase (LDH) is a prognostic factor for patients with stage IV melanoma. To gain insights into the biology underlying this prognostic factor, we analyzed total serum LDH, serum LDH isoenzymes, and serum lactate in up to 49 patients with metastatic melanoma. Our data demonstrate that high serum LDH is associated with a significant increase in LDH isoenzymes 3 and 4, and a decrease in LDH isoenzymes 1 and 2. Since LDH isoenzymes play a role in both glycolysis and oxidative phosphorylation (OXPHOS), we subsequently determined using tissue microarray (TMA) analysis that the levels of proteins associated with mitochondrial function, lactate metabolism, and regulators of glycolysis were all elevated in advanced melanomas compared with nevic melanocytes. To investigate whether in advanced melanoma, the glycolysis and OXPHOS pathways might be linked, we determined expression of the monocarboxylate transporters (MCT) 1 and 4. Analysis of a nevus-to-melanoma progression TMA revealed that MCT4, and to a lesser extend MCT1, were elevated with progression to advanced melanoma. Further analysis of human melanoma specimens using the Seahorse XF24 extracellular flux analyzer indicated that metastatic melanoma tumors derived a large fraction of energy from OXPHOS. Taken together, these findings suggest that in stage IV melanomas with normal serum LDH, glycolysis and OXPHOS may provide metabolic symbiosis within the same tumor, whereas in stage IV melanomas with high serum LDH glycolysis is the principle source of energy.
Early detection of doxorubicin myocardial injury by ultrasonic tissue characterization in an experimental animal model
Authors: Romano Minna Moreira Dias , Pazin-Filho Antônio , O’Connel João Lucas , Simões Marcus Vinícius , Schmidt André , Campos Érica C , Rossi Marcos , Maciel Benedito Carlos
Published: October 2012

In the clinical setting, the early detection of myocardial injury induced by doxorubicin (DXR) is still considered a challenge. To assess whether ultrasonic tissue characterization (UTC) can identify early DXR-related myocardial lesions and their correlation with collagen myocardial percentages, we studied 60 rats at basal status and prospectively after 2mg/Kg/week DXR endovenous infusion. Echocardiographic examinations were conducted at baseline and at 8,10,12,14 and 16 mg/Kg DXR cumulative dose. The left ventricle ejection fraction (LVEF), shortening fraction (SF), and the UTC indices: corrected coefficient of integrated backscatter (IBS) (tissue IBS intensity/ phantom IBS intensity) (CC-IBS) and the cyclic variation magnitude of this intensity curve (MCV) were measured. The variation of each parameter of study through DXR dose was expressed by the average and standard error at specific DXR dosages and those at baseline. The collagen percent (%) was calculated in six control group animals and 24 DXR group animals. CC-IBS increased (1.29±0.27 x 1.1±0.26-basal; p=0.005) and MCV decreased (9.1± 2.8 x 11.02±2.6-basal; p=0.006) from 8 mg/Kg to 16mg/Kg DXR. LVEF presented only a slight but significant decrease (80.4±6.9% x 85.3±6.9%-basal, p=0.005) from 8 mg/Kg to 16 mg/Kg DXR. CC-IBS was 72.2% sensitive and 83.3% specific to detect collagen deposition of 4.24%(AUC=0.76). LVEF was not accurate to detect initial collagen deposition (AUC=0.54). In conclusion: UTC was able to early identify the DXR myocardial lesion when compared to LVEF, showing good accuracy to detect the initial collagen deposition in this experimental animal model.
Time–frequency based feature selection for discrimination of non-stationary biosignals
Authors: D Martínez-Vargas Juan , I Godino-Llorente Juan , Castellanos‐Dominguez Germán
Published: October 2012

This research proposes a generic methodology for dimensionality reduction upon time–frequency representations applied to the classification of different types of biosignals. The methodology directly deals with the highly redundant and irrelevant data contained in these representations, combining a first stage of irrelevant data removal by variable selection, with a second stage of redundancy reduction using methods based on linear transformations. The study addresses two techniques that provided a similar performance: the first one is based on the selection of a set of the most relevant time–frequency points, whereas the second one selects the most relevant frequency bands. The first methodology needs a lower quantity of components, leading to a lower feature space; but the second improves the capture of the time-varying dynamics of the signal, and therefore provides a more stable performance. In order to evaluate the generalization capabilities of the methodology proposed it has been applied to two types of biosignals with different kinds of non-stationary behaviors: electroencephalographic and phonocardiographic biosignals. Even when these two databases contain samples with different degrees of complexity and a wide variety of characterizing patterns, the results demonstrate a good accuracy for the detection of pathologies, over 98%. The results open the possibility to extrapolate the methodology to the study of other biosignals.
HRP-2 determines HIV-1 integration site selection in LEDGF/p75 depleted cells
Authors: Schrijvers Rik , Vets Sofie , De Rijck Jan , Malani Nirav , Bushman Frederic D , Debyser Zeger , Gijsbers Rik
Published: October 2012

Background

Lens epithelium–derived growth factor (LEDGF/p75) is a cellular co-factor of HIV-1 integrase (IN) that tethers the viral pre-integration complex to the host cell chromatin and determines the genome wide integration site distribution pattern of HIV-1. Recently, we demonstrated that HIV-1 replication was reduced in LEDGF/p75 knockout (KO) cells. LEDGF/p75 KO significantly altered the integration site preference of HIV-1, but the pattern remained distinct from a computationally generated matched random control set (MRC), suggesting the presence of an alternative tethering factor. We previously identified Hepatoma-derived growth factor related protein 2 (HRP-2) as a factor mediating LEDGF/p75-independent HIV-1 replication. However, the role of HRP-2 in HIV-1 integration site selection was not addressed.

Findings

We studied the HIV-1 integration site distribution in the presence and absence of LEDGF/p75 and/or HRP-2, and in LEDGF/p75-depleted cells that overexpress HRP-2. We show that HRP-2 functions as a co-factor of HIV-1 IN in LEDGF/p75-depleted cells. Endogenous HRP-2 only weakly supported HIV-1 replication in LEDGF/p75 depleted cells. However, HRP-2 overexpression rescued HIV-1 replication and restored integration in RefSeq genes to wild-type levels. Additional HRP-2 KD in LEDGF/p75-depleted cells reduces integration frequency in transcription units and shifts the integration distribution towards random.

Conclusions

We demonstrate that HRP-2 overexpression can compensate for the absence of LEDGF/p75 and indicate that the residual bias in integration targeting observed in the absence of LEDGF/p75 can be ascribed to HRP-2. Knockdown of HRP-2 upon LEDGF/p75 depletion results in a more random HIV-1 integration pattern. These data therefore reinforce the understanding that LEDGF/p75 is the dominant HIV-1 IN co-factor.
Comparative evaluation of the QIAsymphony RGQ system with the easyMAG/R-gene combination for the quantitation of cytomegalovirus DNA load in whole blood
Authors: Pillet Sylvie , Bourlet Thomas , Pozzetto Bruno
Published: October 2012

Background

The detection of cytomegalovirus (CMV) DNA in blood is a key feature of the virological surveillance of immunocompromised patients.

Methods

The QIAsymphony RGQ system (QIAGEN S.A.S., France) combines the extraction/distribution steps on QIAsymphony SP/AS instruments with amplification on a Rotor-Gene Q RT-PCR machine. This system was compared to a strategy combining an extraction step on the NUCLISENS easyMAG platform (bioMérieux) with the CMV R-gene kit (Argene) on 100 whole blood specimens collected from immunocompromised patients of the University Hospital of Saint-Etienne, France.

Results

The overall agreement between the two strategies was 86% (kappa coefficient of 0.67); the 14 discrepant results corresponded to low DNA loads. The 62 samples found positive with both tests were correlated (Pearson r coefficient of 0.70, P < 0.01) despite an over quantitation of 0.25 log10 copies/ml with the easyMAG/Argene strategy (P < 0.001). Very close results were also obtained with a commercial panel of 10 samples with CMV loads ranging from 2.36 to 6.41 log10 copies/ml. The inter-run and intra-run variability was consistently lower with the QIAGEN platform.

Conclusions

These results validate the performance of the QIAsymphony RGQ system for the routine quantitation of CMV DNA. This fully-automated platform reduces the hands-on time and improves standardization, traceability and quality control assessment.
Biomechanical effects of steroid injections used to treat pyogenic flexor tenosynovitis
Authors: Turvey Blake R , Weinhold Paul S , Draeger Reid W , Bynum Donald K , Dahners Laurence E
Published: October 2012

Background

A recent study from our laboratory has demonstrated improved range of motion in the toes of broiler chickens afflicted with pyogenic flexor tenosynovitis when treated with local antibiotic and corticosteroid injections, without surgical drainage. However, the use of corticosteroids as an adjunct treatment raised peer concern, as steroids are thought to have deleterious effects on tendon strength. The purpose of this study was to compare the tensile strength of the aforementioned steroid treated tendons, to a group of tendons administered with the current standard treatment: systemic antibiotics, surgical drainage and no corticosteroids.

Methods

Twenty-three tendons’ structural and material properties were investigated (fifteen receiving the standard treatment, eight receiving the steroid treatment). The measurements from each group were interpreted via Student’s unpaired t-test and a post-hoc power analysis.

Results

The steroid treated tendons did demonstrate a trend toward decreased mechanical properties when compared with the standard treatment group, but the results were not statistically significant.

Conclusions

Treatment of septic tenosynovitis with local corticosteroid and local antibiotic injections resulted in better digital motion, without a significant loss of tendon strength, over a twenty-eight day recovery period.
Expression of Fused in sarcoma mutations in mice recapitulates the neuropathology of FUS proteinopathies and provides insight into disease pathogenesis
Authors: Verbeeck Christophe , Deng Qiudong , DeJesus-Hernandez Mariely , Taylor Georgia , Ceballos-Diaz Carolina , Kocerha Jannet , Golde Todd , Das Pritam , Rademakers Rosa , Dickson Dennis W , Kukar Thomas
Published: October 2012

Background

Mutations in the gene encoding the RNA-binding protein fused in sarcoma (FUS) can cause familial and sporadic amyotrophic lateral sclerosis (ALS) and rarely frontotemproal dementia (FTD). FUS accumulates in neuronal cytoplasmic inclusions (NCIs) in ALS patients with FUS mutations. FUS is also a major pathologic marker for a group of less common forms of frontotemporal lobar degeneration (FTLD), which includes atypical FTLD with ubiquitinated inclusions (aFTLD-U), neuronal intermediate filament inclusion disease (NIFID) and basophilic inclusion body disease (BIBD). These diseases are now called FUS proteinopathies, because they share this disease marker. It is unknown how FUS mutations cause disease and the role of FUS in FTD-FUS cases, which do not have FUS mutations. In this paper we report the development of somatic brain transgenic (SBT) mice using recombinant adeno-associated virus (rAAV) to investigate how FUS mutations lead to neurodegeneration.

Results

We compared SBT mice expressing wild-type human FUS (FUSWT), and two ALS-linked mutations: FUSR521Cand FUSΔ14, which lacks the nuclear localization signal. Both FUS mutants accumulated in the cytoplasm relative to FUSWT. The degree of this shift correlated with the severity of the FUS mutation as reflected by disease onset in humans. Mice expressing the most aggressive mutation, FUSΔ14, recapitulated many aspects of FUS proteinopathies, including insoluble FUS, basophilic and eosiniphilic NCIs, and other pathologic markers, including ubiquitin, p62/SQSTM1, α-internexin, and the poly-adenylate(A)-binding protein 1 (PABP-1). However, TDP-43 did not localize to inclusions.

Conclusions

Our data supports the hypothesis that ALS or FTD-linked FUS mutations cause neurodegeneration by increasing cyotplasmic FUS. Accumulation of FUS in the cytoplasm may retain RNA targets and recruit additional RNA-binding proteins, such as PABP-1, into stress-granule like aggregates that coalesce into permanent inclusions that could negatively affect RNA metabolism. Identification of mutations in other genes that cause ALS/FTD, such as C9ORF72, sentaxin, and angiogenin, lends support to the idea that defective RNA metabolism is a critical pathogenic pathway. The SBT FUS mice described here will provide a valuable platform for dissecting the pathogenic mechanism of FUS mutations, define the relationship between FTD and ALS-FUS, and help identify therapeutic targets that are desperately needed for these devastating neurodegenerative disorders.
Approaches to informed consent for hypothesis-testing and hypothesis-generating clinical genomics research
Authors: Facio Flavia M , Sapp Julie C , Linn Amy , Biesecker Leslie G
Published: October 2012

Background

Massively-parallel sequencing (MPS) technologies create challenges for informed consent of research participants given the enormous scale of the data and the wide range of potential results.

Discussion

We propose that the consent process in these studies be based on whether they use MPS to test a hypothesis or to generate hypotheses. To demonstrate the differences in these approaches to informed consent, we describe the consent processes for two MPS studies. The purpose of our hypothesis-testing study is to elucidate the etiology of rare phenotypes using MPS. The purpose of our hypothesis-generating study is to test the feasibility of using MPS to generate clinical hypotheses, and to approach the return of results as an experimental manipulation. Issues to consider in both designs include: volume and nature of the potential results, primary versus secondary results, return of individual results, duty to warn, length of interaction, target population, and privacy and confidentiality.

The categorization of MPS studies as hypothesis-testing versus hypothesis-generating can help to clarify the issue of so-called incidental or secondary results for the consent process, and aid the communication of the research goals to study participants.
GW501516-activated PPARβ/δ promotes liver fibrosis via p38-JNK MAPK-induced hepatic stellate cell proliferation
Authors: Kostadinova Radina , Montagner Alexandra , Gouranton Erwan , Fleury Sébastien , Guillou Hervé , Dombrowicz David , Desreumaux Pierre , Wahli Walter
Published: October 2012

Background

After liver injury, the repair process comprises activation and proliferation of hepatic stellate cells (HSCs), which produce extracellular matrix (ECM) proteins. Peroxisome proliferator-activated receptor beta/delta ( PPARβ/δ) is highly expressed in these cells, but its function in liver repair remains incompletely understood. This study investigated whether activation of PPARβ/δ with the ligand GW501516 influenced the fibrotic response to injury from chronic carbon tetrachloride (CCl4) treatment in mice. Wild type and PPARβ/δ-null mice were treated with CCl4 alone or CCl4 co-administered with GW501516. To unveil mechanisms underlying the PPARβ/δ-dependent effects, we analyzed the proliferative response of human LX-2 HSCs to GW501516 in the presence or absence of PPARβ/δ.

Results

We found that GW501516 treatment enhanced the fibrotic response. Compared to the other experimental groups, CCl4/GW501516-treated wild type mice exhibited increased expression of various profibrotic and pro-inflammatory genes, such as those involved in extracellular matrix deposition and macrophage recruitment. Importantly, compared to healthy liver, hepatic fibrotic tissues from alcoholic patients showed increased expression of several PPAR target genes, including phosphoinositide-dependent kinase-1, transforming growth factor beta-1, and monocyte chemoattractant protein-1. GW501516 stimulated HSC proliferation that caused enhanced fibrotic and inflammatory responses, by increasing the phosphorylation of p38 and c-Jun N-terminal kinases through the phosphoinositide-3 kinase/protein kinase-C alpha/beta mixed lineage kinase-3 pathway.

Conclusions

This study clarified the mechanism underlying GW501516-dependent promotion of hepatic repair by stimulating proliferation of HSCs via the p38 and JNK MAPK pathways.
Dehalogenimonas spp. can Reductively Dehalogenate High Concentrations of 1,2-Dichloroethane, 1,2-Dichloropropane, and 1,1,2-Trichloroethane
Authors: Maness Andrew D , Bowman Kimberly S , Yan Jun , Rainey Fred A , Moe William M
Published: October 2012

The contaminant concentrations over which type strains of the species Dehalogenimonas alkenigignens and Dehalogenimonas lykanthroporepellens were able to reductively dechlorinate 1,2-dichloroethane (1,2-DCA), 1,2-dichloropropane (1,2-DCP), and 1,1,2-trichloroethane (1,1,2-TCA) were evaluated. Although initially isolated from an environment with much lower halogenated solvent concentrations, D. alkenigignens IP3-3T was found to reductively dehalogenate chlorinated alkanes at concentrations comparable to D. lykanthroporepellens BL-DC-9T. Both species dechlorinated 1,2-DCA, 1,2-DCP, and 1,1,2-TCA present at initial concentrations at least as high as 8.7, 4.0, and 3.5 mM, respectively. The ability of Dehalogenimonas spp. to carry out anaerobic reductive dechlorination even in the presence of high concentrations of chlorinated aliphatic alkanes has important implications for remediation of contaminated soil and groundwater.
The use of cognitive ability measures as explanatory variables in regression analysis
Authors: Junker Brian , Schofield Lynne Steuerle , Taylor Lowell J
Published: October 2012

Cognitive ability measures are often taken as explanatory variables in regression analysis, e.g., as a factor affecting a market outcome such as an individual’s wage, or a decision such as an individual’s education acquisition. Cognitive ability is a latent construct; its true value is unobserved. Nonetheless, researchers often assume that a test score, constructed via standard psychometric practice from individuals’ responses to test items, can be safely used in regression analysis. We examine problems that can arise, and suggest that an alternative approach, a “mixed effects structural equations” (MESE) model, may be more appropriate in many circumstances.

JEL Code

J01