bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Type Butterfly-Shaped Transducer Linear Ultrasonic Motor
Authors: Yunlai Shi  , Yubao Li  , Chunsheng Zhao  , Jianhui Zhang
Published: April 2011

This article presents a new type butterfly-shaped transducer linear ultrasonic motor, which utilizes symmetrical modal and anti-symmetric modal of a composite piezoelectric transducer. First, the drive principle of the motor and the formation of the elliptical trajectory of particles on the surface of the driving feet are analyzed. The use of the symmetric modal and anti-symmetric modal of the transducer (stator) realizes the function of driving the slider pressed on the driving feet twice in one cycle. Second, two key problems combined with the design processes of the motor are discussed: frequency consistency adjustment and mounting of the stator to ensure both the high stiffness in the driving direction and elasticity in the direction along which the slider is pressed against the stator. Finally, experimental investigation of the characteristics of the motor is presented. The maximum no-load speed is 870 mm/s, the maximum thrust is 24 N, and the maximum efficiency is 44%.
Conflict, Incommensurability, and Theory Groups
Authors: Roelfs David J.
Published: April 2011

Much is already known about how theory groups—schools of thought centered on the influential works of a small number of scholars—emerge. Yet, little is known about how prolonged periods of conflict between theory groups affects the theory-group life cycle. The author presents a review of critiques and exchanges published by scholars in the organization-environment subfield, and shows that these can be used to identify “emergence,” “conflict,” and “postconflict” periods. Poisson and negative binomial regression analyses of 656 publications show that the frequency of intertheory-group citations decreased following the conflict period (1985-1994). Linear regression models show that, when intertheory-group citations appeared following the conflict period, they were increasingly likely to be of older rather than newer publications. The results suggest that periods of heightened conflict, because of their effect on intertheory-group citations, may impact future theory development.
There's Got to be a Better Way(finding System)
Authors: Watson Tonya L.
Published: April 2011

Aging brings additional challenges to the task of finding one's way around a complex built environment.
Human Factors in Stairway Fall Litigation
Authors: Cohen Joseph , Cohen H. Harvey
Published: April 2011

An empirical study suggests that human factors expert testimony on either side of a case has the potential to influence juror decision making.
Software: SPSS for Windows SPSS Inc. 233 S. Wacker Dr., 11th Floor Chicago, IL 60606 (312) 651-3000 www.spss.com
Authors: Glucroft Brian I.
Published: April 2011

The Eye-CEE System for VDT Users Corporate Vision Consulting 842 Arden Dr. Encinitas, CA 92024 800/838-1202, ext. 5
Influencing Social Problems with Interface Design
Authors: Burns Catherine M. , Proulx Pascale
Published: April 2011

Unusual as it may seem, human factors/ergonomics methods can help in addressing issues such as problem gambling.
Presenting Ergonomics Findings to Management
Authors: Kolich M.
Published: April 2011

Unless the results of ergonomics research can be stated clearly and succinctly, they are not likely to be considered in system improvement.
The Silver Surfer: Making the Internet Usable for Seniors
Authors: Bitterman Noemi , Shalev Ilana
Published: April 2011

Until designers address age-related decrements, Web sites will fail to reach their full potential for older users — and everybody else.
A Look Back: Recollections of My Human Factors Experiences in the 1950s and 1960s
Authors: Shafer John B. , Askren William B.
Published: April 2011

Recollections of My Human Factors Experiences in the 1950s and 1960s
The Gift of Optometers
Authors: Roscoe Stanley N.
Published: April 2011

Exploding myths about how the eyes respond to focal stimuli.
Forensic Ergonomics
Authors: Cohen H. Harvey
Published: April 2011

This article discusses trends in forensic ergonomics from the author’s historical perspective. His premise is that two dominant forces converged in the United States over the past four decades to allow the specialty to emerge, namely, new government legislation and entrepreneurial opportunities for ergonomists in the private sector. He concludes that public policy initiatives, evolving legislation, laws, and the inevitable resulting lawsuits in the coming decades will shape the direction of forensic ergonomics.
Where Human Factors Meets Marketing
Authors: Meyer Joachim , Seagull F. Jacob
Published: April 2011

Promoting the marriage of marketing techniques and human factors research in product development.
A theoretical analysis of dynamic characteristics of finite hydrodynamic journal bearings lubricated with coupled stress fluids
Authors: Guha S K
Published: April 2011

Based on the microcontinuum theory, a theoretical investigation into the rheological effects of coupled stress fluids on the dynamic characteristics of finite hydrodynamic journal bearings is presented. The modified Reynolds equation governing the film pressure is obtained by using the Stokes equation of motion which considers the coupled stress effects resulting from the lubricant blended with various additives. Using the first-order perturbation of the dynamic modified Reynolds equation, the dynamic characteristics in terms of the dynamic response coefficients, stability parameter and whirl ratios are obtained for various eccentricity ratios and coupled stress parameters. According to the results obtained, this theoretical investigation suggests that the influence of coupled stress effects on the dynamic performance of the system is physically apparent and not negligible. Overall, the coupled stress effects improve the dynamic characteristics of the journal bearing system.
Engine friction: The influence of lubricant rheology
Authors: Taylor R. I.
Published: April 2011

The sensitivity of engine friction to lubricant viscometry has been determined for a modern fuelefficient engine, the Mercedes Benz M111 2.0 litre gasoline engine, under both cold starting and fully warmed-up conditions. The study has taken into account realistic lubricant viscometric parameters such as the lubricant viscosity variation with shear rate and temperature. Results are reported for the variation of engine friction with different monograde and multigrade lubricants, including the distribution of friction losses between valve train, piston assembly and bearings with the different lubricant types. The work also enabled estimates to be made of the proportion of hydrodynamic and boundary friction in the engine, since the vast majority of boundary lubrication occurs in the valve train. Knowledge of the ratio of boundary to hydrodynamic lubrication was found to be important since the two key lubricant parameters that can be varied are (a) viscosity and (b) the introduction of a friction modifier additive. The viscosity of the lubricant will affect the hydrodynamically lubricated parts of the engine whereas the presence of a friction modifier will reduce boundary friction in the engine. Brief comparisons are made of the lubricant sensitivity of the Mercedes Benz M111 engine with other important fuel-efficient engines (such as the Ford Sequence VI and Ford Sequence VIA engines).
Transnational Tamil television and diasporic imaginings
Authors: Sankaran Chitra , Pillai Shanthini
Published: April 2011

The dynamics of globalization and digitization are not only shaping a new media order but also making significant impacts on the cultural dimensions of an older societal order in the case of the Tamil Diaspora. The emerging transnational phenomenon of Tamil television challenges constructed boundaries, contests traditionally homogenized spaces such as those of nation and homeland, questions the principle of territoriality and opens up the sphere both from without and within the national space. New media practices and flows are shaping media spaces with a built-in transnational connectivity, creating contemporary cultures pregnant with new meanings and experiences. This article aims to map the developments around transnational Tamil television. It scrutinizes the nature and impact of Tamil media emerging from Singapore and Malaysia on other parts of the diasporic Tamil world, and also alternatively, the nature and effect of Tamil media from India and elsewhere in Singapore and Malaysia. Issues of multiculturalism and the transnational media’s impact and culture will be interrogated to enable the analysis of the global remapping of media spaces and to address key issues related to situated transnational Tamil cultures.
Lost in translation: Centripetal individualism and the classical concept of descending representation
Authors: Fumurescu Alin
Published: April 2011

The article argues that by the 17th century, despite the increased intellectual exchanges of the time, two different kind of individualism were developing across the Channel — one labeled here as ‘centripetal’, the other one as ‘centrifugal’. On the French side, one witnesses a focus on forum internum, as the only site of uniqueness and authenticity. On the British side, the emphasis switched to forum externum and the equality of wills. The article explores the consequences of these different self-apprehensions of the individual in terms of different understandings of political representation. I claim that, despite today’s general consensus, representing ‘the people’ was not naturally assimilated with an ascending theory of representation. ‘The people’, understood as a whole, was apprehended in France as still higher than its representatives — kings, Estates, or Parlements. The idea of individuals willingly delegating their rights and/or authority to a representative remained for more than a century a peculiar British development. The consequences of this ascending understanding of representation are to be seriously reevaluated.
Exercise Training and Immunosenescence
Authors: Pence Brandt D. , Martin Stephen A. , Woods Jeffrey A.
Published: April 2011

During the aging process, a decrease in the ability of the immune system to control infection, known as immunosenescence, takes place. Paradoxically, aging also results in chronic low-level inflammation and exaggerated inflammatory responses. A number of studies have investigated the effects of a variety of exercise training interventions on the immune system both in humans and using animal models of aging. Cross-sectional studies that compared masters athletes to untrained, age-matched controls found that the athletes had significantly better immune function, but these studies suffered because of the difficulty in generalizing results from highly trained athletes to a general population of physically active older adults. Prospective studies in humans have attempted to address this, but these studies have resulted in sometimes equivocal findings, possibly as a result of the differences in exercise training programs used. Finally, animal studies, both observational and mechanistic, have almost universally supported the exercise effect on enhancing immune status in the aged. More research is needed to determine the mechanism by which exercise influences immunity in the aged and to identify exercise training programs for use in this population. It is clear, however, that exercise is likely to be effective at boosting immunity in the older people when undertaken regularly.
Human Papillomavirus and Pap Smear
Authors: Balachandran Indra
Published: April 2011

High-risk human papillomavirus (HPV) infection and viral persistence is a major risk factor in the development of squamous intraepithelial lesions and invasive carcinoma of the cervix. In the United States, deaths due to squamous cell carcinoma of the cervix have fallen by 75% since the 1960s because of Papanicolaou (Pap) smear screening. However, the traditional Pap had a sensitivity of about 70% for detecting clinically significant precancerous lesions and cancer because of sampling and interpretive errors. The introduction of 2 liquid-based Pap smear collection systems in the 1990s, the use of HPV testing as a triage and co-testing with Pap smear, and the introduction of 2 automated screening devices have had a significant impact on improving the detection of such precancerous lesions. This review provides an analysis of the changes in Pap smear collection, improvements in screening, the evolutionary changes of high-risk HPV testing, reporting terminology of Pap smears, and clinical management guidelines. The future impact of 2 prophylactic HPV vaccines on the incidence of cervical carcinoma is also discussed. This article also discusses alternatives such as primary screening for high-risk HPV testing with visual inspection for cervical cancer detection used in resource-poor settings with a high incidence of cervical cancer.
Management of ICU Delirium
Authors: Page Valerie , Katawala Tasneem
Published: April 2011

ICU delirium is increasingly recognized as a major determinant of morbidity and mortality in critical care patients. It develops in around 2 out of every 3 ventilated critically ill patients. To detect ICU delirium, patients need to be actively screened using a validated tool otherwise it is likely to be missed. Good practice requires implementing routine delirium screening of all patients, a series of robust preventative measures targeted at risk factors—in particular sedation practices—treating the cause of delirium and using antipsychotics when indicated. An ABCDE bundle has been designed to improve the management of mechanically ventilated patients and improve outcomes for delirious patients.
How the Grapevine Keeps You in Line
Authors: Beersma Bianca , Van Kleef Gerben A.
Published: April 2011

Gossip is often characterized as bad and immoral. The authors challenge this view and propose that gossip constrains self-serving behavior that harms the group. When people expect their group members to gossip and their decisions are identifiable, they will be concerned about group members' opinions, and this should lead them to contribute more resources to the group. When people believe their group members are unlikely to gossip, identifiability of decisions should have less impact on group opinion concerns and contributions to the group. Participants were led to believe that their fellow group members had a low or high tendency to gossip, and that their contribution to the group was identifiable by the group or not. Results confirmed our hypotheses, demonstrating that gossip is a powerful tool to control self-serving behavior in groups. Indeed, the grapevine keeps group members in line. Although mostly viewed negatively, gossip may be essential for groups' survival.
Role of HLA-G in tumor escape through expansion of myeloid-derived suppressor cells and cytokinic balance in favor of Th2 versus Th1/Th17
Authors: Agaugué Sophie , Carosella Edgardo D. , Rouas-Freiss Nathalie
Published: April 2011

The expression of HLA-G by malignant cells has been proposed as a tumor escape mechanism from immunosurveillance. However, although the inhibitory effect of HLA-G on antitumoral immune effectors has been documented in vitro, it remains to be resolved in vivo. In this context, the development of an animal model is now a priority to establish the proof of concept that an HLA-G+ tumor cell develops and tolerizes the host antitumor immune response in vivo. In the present study, we provide the first in vivo evidence of such a role by a xenotumor model in mice based on the interactions between human HLA-G and the murine paired immunoglobulin–like receptor-B (PIR-B). We demonstrate that human tumor cells expressing HLA-G grow in an immunocompetent host by affecting both innate and adaptive immunity. Expansion of blood myeloid–derived CD11b+Gr1+PIR-B+ suppressor cells, loss of peripheral T cells, and cytokinic balance in favor of Th2 versus Th1/Th17 constitute the main mechanisms by which HLA-G promotes tumor expansion. These data demonstrate for the first time that HLA-G plays a crucial role in in vivo tumor evasion. Finally, blocking HLA-G function by a specific Ab inhibits the in vivo development of the tumor, offering a new innovative therapeutic strategy in cancer.
Clonal origins of relapse in ETV6-RUNX1 acute lymphoblastic leukemia
Authors: van Delft Frederik W. , Horsley Sharon , Colman Sue , Anderson Kristina , Bateman Caroline , Kempski Helena , Zuna Jan , Eckert Cornelia , Saha Vaskar , Kearney Lyndal , Ford Anthony , Greaves Mel
Published: April 2011

B-cell precursor childhood acute lymphoblastic leukemia with ETV6-RUNX1 (TEL-AML1) fusion has an overall good prognosis, but relapses occur, usually after cessation of treatment and occasionally many years later. We have investigated the clonal origins of relapse by comparing the profiles of genomewide copy number alterations at presentation in 21 patients with those in matched relapse (12-119 months). We identified, in total, 159 copy number alterations at presentation and 231 at relapse (excluding Ig/TCR). Deletions of CDKN2A/B or CCNC (6q16.2-3) or both increased from 38% at presentation to 76% in relapse, suggesting that cell-cycle deregulation contributed to emergence of relapse. A novel observation was recurrent gain of chromosome 16 (2 patients at presentation, 4 at relapse) and deletion of plasmocytoma variant translocation 1 in 3 patients. The data indicate that, irrespective of time to relapse, the relapse clone was derived from either a major or minor clone at presentation. Backtracking analysis by FISH identified a minor subclone at diagnosis whose genotype matched that observed in relapse ∼ 10 years later. These data indicate subclonal diversity at diagnosis, providing a variable basis for intraclonal origins of relapse and extended periods (years) of dormancy, possibly by quiescence, for stem cells in ETV6-RUNX1+ acute lymphoblastic leukemia.
A STAT3-decoy oligonucleotide induces cell death in a human colorectal carcinoma cell line by blocking nuclear transfer of STAT3 and STAT3-bound NF-κB
Authors: Souissi Inès , Najjar Imen , Ah-Koon Laurent , Schischmanoff Pierre Olivier , Lesage Denis , Le Coquil Stéphanie , Roger Claudine , Dusanter-Fourt Isabelle , Varin-Blank Nadine , Cao An , Metelev Valeri , Baran-Marszak Fanny , Fagard Remi
Published: April 2011

Background

The transcription factor STAT3 (signal transducer and activator of transcription 3) is frequently activated in tumor cells. Activated STAT3 forms homodimers, or heterodimers with other TFs such as NF-κB, which becomes activated. Cytoplasmic STAT3 dimers are activated by tyrosine phosphorylation; they interact with importins via a nuclear localization signal (NLS) one of which is located within the DNA-binding domain formed by the dimer. In the nucleus, STAT3 regulates target gene expression by binding a consensus sequence within the promoter. STAT3-specific decoy oligonucleotides (STAT3-decoy ODN) that contain this consensus sequence inhibit the transcriptional activity of STAT3, leading to cell death; however, their mechanism of action is unclear.

Results

The mechanism of action of a STAT3-decoy ODN was analyzed in the colon carcinoma cell line SW 480. These cells' dependence on activated STAT3 was verified by showing that cell death is induced by STAT3-specific siRNAs or Stattic. STAT3-decoy ODN was shown to bind activated STAT3 within the cytoplasm, and to prevent its translocation to the nucleus, as well as that of STAT3-associated NF-κB, but it did not prevent the nuclear transfer of STAT3 with mutations in its DNA-binding domain. The complex formed by STAT3 and the STAT3-decoy ODN did not associate with importin, while STAT3 alone was found to co-immunoprecipitate with importin. Leptomycin B and vanadate both trap STAT3 in the nucleus. They were found here to oppose the cytoplasmic trapping of STAT3 by the STAT3-decoy ODN. Control decoys consisting of either a mutated STAT3-decoy ODN or a NF-κB-specific decoy ODN had no effect on STAT3 nuclear translocation. Finally, blockage of STAT3 nuclear transfer correlated with the induction of SW 480 cell death.

Conclusions

The inhibition of STAT3 by a STAT3-decoy ODN, leading to cell death, involves the entrapment of activated STAT3 dimers in the cytoplasm. A mechanism is suggested whereby this entrapment is due to STAT3-decoy ODN's inhibition of active STAT3/importin interaction. These observations point to the high potential of STAT3-decoy ODN as a reagent and to STAT3 nucleo-cytoplasmic shuttling in tumor cells as a potential target for effective anti-cancer compounds.
A systematic analysis of the skeletal muscle miRNA transcriptome of chicken varieties with divergent skeletal muscle growth identifies novel miRNAs and differentially expressed miRNAs
Authors: Li Tingting , Wu Rimao , Zhang Yong , Zhu Dahai
Published: April 2011

Background

Functional studies have demonstrated that microRNAs (miRNAs or miRs) play critical roles in a wide spectrum of biological processes including development and disease pathogenesis. To investigate the functional roles that miRNAs play during chicken skeletal muscle development, the miRNA transcriptomes of skeletal muscles from broiler and layer chickens were profiled using Solexa deep sequencing.

Results

Some miRNAs have multiple isoforms and several miRNAs* are present at higher levels than their corresponding miRNAs. Thirty three novel and 189 known chicken miRNAs were identified using computational approaches. Subsequent miRNA transcriptome comparisons and real-time PCR validation experiments revealed 17 miRNAs that were differentially expressed between broilers and layers, and a number of targets of these miRNAs have been implicated in myogenesis regulation. Using integrative miRNA target-prediction and network-analysis approaches an interaction network of differentially expressed and muscle-related miRNAs and their putative targets was constructed, and miRNAs that could contribute to the divergent muscle growth of broiler and layer chickens by targeting the ACVR2B gene were identified, which can causes dramatic increases in muscle mass.

Conclusions

The present study provides the first transcriptome profiling-based evaluation of miRNA function during skeletal muscle development in chicken. Systematic predictions aided the identification of potential miRNAs and their targets, which could contribute to divergent muscle growth in broiler and layer chickens. Furthermore, these predictions generated information that can be utilized in further research investigating the involvement of interaction networks, containing miRNAs and their targets, in the regulation of muscle development.
Contribution of SecDF to Staphylococcus aureusresistance and expression of virulence factors
Authors: Quiblier Chantal , Zinkernagel Annelies S , Schuepbach Reto A , Berger-Bächi Brigitte , Senn Maria M
Published: April 2011

Background

SecDF is an accessory factor of the conserved Sec protein translocation machinery and belongs to the resistance-nodulation-cell division (RND) family of multidrug exporters. SecDF has been shown in Escherichia coli and Bacillus subtilis to be involved in the export of proteins. RND proteins can mediate resistance against various substances and might be of relevance in antimicrobial therapy. The role of RND proteins in Staphylococcus aureus has not yet been determined.

Results

Markerless deletion mutants were constructed to analyze the impact of the so far uncharacterized RND proteins in S. aureus. While the lack of Sa2056 and Sa2339 caused no phenotype regarding growth and resistance, the secDF mutant resulted in a pleiotropic phenotype. The secDF mutant was cold sensitive, but grew normally in rich medium at 37°C. Resistance to beta-lactams, glycopeptides and the RND substrates acriflavine, ethidium bromide and sodium dodecyl sulfate was reduced. The secDF mutant showed an aberrant cell separation and increased spontaneous and Triton X-100 induced autolysis, although the amounts of penicillin-binding proteins in the membrane were unchanged. The impact of secDF deletion on transcription and expression of specific virulence determinants varied: While coagulase transcription and activity were reduced, the opposite was observed for the autolysin Atl. A reduction of the transcription of the cell wall anchored protein A (spa) was also found. The accumulation of SpA in the membrane and lowered amounts in the cell wall pointed to an impaired translocation.

Conclusions

The combination of different effects of secDF deletion on transcription, regulation and translocation lead to impaired cell division, reduced resistance and altered expression of virulence determinants suggesting SecDF to be of major relevance in S. aureus. Thus SecDF could be a potential target for the control and eradication of S. aureus in the future.
Volume Tracking: A new method for quantitative assessment and visualization of intracardiac blood flow from three-dimensional, time-resolved, three-component magnetic resonance velocity mapping
Authors: Töger Johannes , Carlsson Marcus , Söderlind Gustaf , Arheden Håkan , Heiberg Einar
Published: April 2011

Background

Functional and morphological changes of the heart influence blood flow patterns. Therefore, flow patterns may carry diagnostic and prognostic information. Three-dimensional, time-resolved, three-directional phase contrast cardiovascular magnetic resonance (4D PC-CMR) can image flow patterns with unique detail, and using new flow visualization methods may lead to new insights. The aim of this study is to present and validate a novel visualization method with a quantitative potential for blood flow from 4D PC-CMR, called Volume Tracking, and investigate if Volume Tracking complements particle tracing, the most common visualization method used today.

Methods

Eight healthy volunteers and one patient with a large apical left ventricular aneurysm underwent 4D PC-CMR flow imaging of the whole heart. Volume Tracking and particle tracing visualizations were compared visually side-by-side in a visualization software package. To validate Volume Tracking, the number of particle traces that agreed with the Volume Tracking visualizations was counted and expressed as a percentage of total released particles in mid-diastole and end-diastole respectively. Two independent observers described blood flow patterns in the left ventricle using Volume Tracking visualizations.

Results

Volume Tracking was feasible in all eight healthy volunteers and in the patient. Visually, Volume Tracking and particle tracing are complementary methods, showing different aspects of the flow. When validated against particle tracing, on average 90.5% and 87.8% of the particles agreed with the Volume Tracking surface in mid-diastole and end-diastole respectively. Inflow patterns in the left ventricle varied between the subjects, with excellent agreement between observers. The left ventricular inflow pattern in the patient differed from the healthy subjects.

Conclusion

Volume Tracking is a new visualization method for blood flow measured by 4D PC-CMR. Volume Tracking complements and provides incremental information compared to particle tracing that may lead to a better understanding of blood flow and may improve diagnosis and prognosis of cardiovascular diseases.
Prevalence, predictors and perinatal outcomes of peri-conceptional alcohol exposure - retrospective cohort study in an urban obstetric population in Ireland
Authors: Mullally Aoife , Cleary Brian J , Barry Joe , Fahey Tom P , Murphy Deirdre J
Published: April 2011

Background

Evidence-based advice on alcohol consumption is required for pregnant women and women planning a pregnancy. Our aim was to investigate the prevalence, predictors and perinatal outcomes associated with peri-conceptional alcohol consumption.

Methods

A cohort study of 61,241 women who booked for antenatal care and delivered in a large urban maternity hospital between 2000 and 2007. Self-reported alcohol consumption at the booking visit was categorised as low (0-5 units per week), moderate (6-20 units per week) and high (>20 units per week).

Results

Of the 81% of women who reported alcohol consumption during the peri-conceptional period, 71% reported low intake, 9.9% moderate intake and 0.2% high intake. Factors associated with moderate alcohol consumption included being in employment OR 4.47 (95% CI 4.17 to 4.80), Irish nationality OR 16.5 (95% CI 14.9 to 18.3), private health care OR 5.83 (95% CI 5.38 to 6.31) and smoking OR 1.86 (95% CI 1.73 to 2.01). Factors associated with high consumption included maternal age less than 25 years OR 2.70 (95% CI 1.86 to 3.91) and illicit drug use OR 6.46 (95% CI 3.32 to 12.60). High consumption was associated with very preterm birth (<32 weeks gestation) even after controlling for socio-demographic factors, adjusted OR 3.15 (95% CI 1.26-7.88). Only three cases of Fetal Alcohol Syndrome were recorded (0.05 per 1000 total births), one each in the low, moderate and high consumption groups.

Conclusions

Public Health campaigns need to emphasise the importance of peri-conceptional health and pre-pregnancy planning. Fetal Alcohol Syndrome is likely to be under-reported despite the high prevalence of alcohol consumption in this population.
Developing a method for customized induction of flowering
Authors: Yeoh Chin Chin , Balcerowicz Martin , Laurie Rebecca , Macknight Richard , Putterill Joanna
Published: April 2011

Background

The ability to induce flowering on demand is of significant biotechnological interest. FT protein has been recently identified as an important component of the mobile flowering hormone, florigen, whose function is conserved across the plant kingdom. We therefore focused on manipulation of both endogenous and heterologous FT genes to develop a floral induction system where flowering would be inhibited until it was induced on demand. The concept was tested in the model plant Arabidopsis thaliana (Arabidopsis).

Results

Our starting point was plants with strongly delayed flowering due to silencing of FT with an artificial microRNA directed at FT (amiR-FT) [1]. First, we showed that constitutive expression of a heterologous FT gene (FTa1), from the model legume Medicago truncatula, (Medicago) was able to rescue the amiR-FT late-flowering phenotype. In order to induce flowering in a controlled way, the FTa1 gene was then expressed under the control of an alcohol-inducible promoter in the late flowering amiR-FT plants. Upon exposure to ethanol, FTa1 was rapidly up regulated and this resulted in the synchronous induction of flowering.

Conclusions

We have thus demonstrated a controlled-inducible flowering system using a novel combination of endogenous and heterologous FT genes. The universal florigenic nature of FT suggests that this type of system should be applicable to crops of economic value where flowering control is desirable.
Parasitostatic effect of maslinic acid. I. Growth arrest of Plasmodium falciparum intraerythrocytic stages
Authors: Moneriz Carlos , Marín-García Patricia , García-Granados Andrés , Bautista José M , Diez Amalia , Puyet Antonio
Published: April 2011

Background

Natural products have played an important role as leads for the development of new drugs against malaria. Recent studies have shown that maslinic acid (MA), a natural triterpene obtained from olive pomace, which displays multiple biological and antimicrobial activities, also exerts inhibitory effects on the development of some Apicomplexan, including Eimeria, Toxoplasma and Neospora. To ascertain if MA displays anti-malarial activity, the main objective of this study was to asses the effect of MA on Plasmodium falciparum-infected erythrocytes in vitro.

Methods

Synchronized P. falciparum-infected erythrocyte cultures were incubated under different conditions with MA, and compared to chloroquine and atovaquone treated cultures. The effects on parasite growth were determined by monitoring the parasitaemia and the accumulation of the different infective stages visualized in thin blood smears.

Results

MA inhibits the growth of P. falciparum Dd2 and 3D7 strains in infected erythrocytes in, dose-dependent manner, leading to the accumulation of immature forms at IC50 concentrations, while higher doses produced non-viable parasite cells. MA-treated infected-erythrocyte cultures were compared to those treated with chloroquine or atovaquone, showing significant differences in the pattern of accumulation of parasitic stages. Transient MA treatment at different parasite stages showed that the compound targeted intra-erythrocytic processes from early-ring to schizont stage. These results indicate that MA has a parasitostatic effect, which does not inactivate permanently P. falciparum, as the removal of the compound allowed the infection to continue

Conclusions

MA displays anti-malarial activity at multiple intraerythrocytic stages of the parasite and, depending on the dose and incubation time, behaves as a plasmodial parasitostatic compound. This novel parasitostatic effect appears to be unrelated to previous mechanisms proposed for current anti-malarial drugs, and may be relevant to uncover new prospective plasmodial targets and opens novel possibilities of therapies associated to host immune response.
Icacina senegalensis (Icacinaceae), traditionally used for the treatment of malaria, inhibits in vitro Plasmodium falciparum growth without host cell toxicity
Authors: Sarr Serigne O , Perrotey Sylvie , Fall Ibrahima , Ennahar Saïd , Zhao Minjie , Diop Yérim M , Candolfi Ermanno , Marchioni Eric
Published: April 2011

Background

With the aim of discovering new natural active extracts against malaria parasites, Icacina senegalensis was selected after an ethnopharmacological survey conducted on plants used in traditional malaria treatment in Senegal.

Methods

Different concentrations of the plant extract and fractions were tested on synchronized Plasmodium falciparum cultures at the ring stage using the parasite lactate dehydrogenase assay. Their haemolytic activity and in vitro cytoxicity were evaluated. The chromatographic profiles of active fractions were also established.

Results

The plant extract and fractions revealed anti-plasmodial activity (IC50 < 5 μg/mL) with no toxicity (Selectivity indexes >10). The dichloromethane fraction showed stronger anti-plasmodial activity than the total extract.

Conclusion

Anti-plasmodial activity and toxicity of I. senegalensis are reported for the first time and showed promising results in malaria field research.
Risk assessment of diesel exhaust and lung cancer: combining human and animal studies after adjustment for biases in epidemiological studies
Authors: Pedeli Xanthi , Hoek Gerard , Katsouyanni Klea
Published: April 2011

Background

Risk assessment requires dose-response data for the evaluation of the relationship between exposure to an environmental stressor and the probability of developing an adverse health effect. Information from human studies is usually limited and additional results from animal studies are often needed for the assessment of risks in humans. Combination of risk estimates requires an assessment and correction of the important biases in the two types of studies. In this paper we aim to illustrate a quantitative approach to combining data from human and animal studies after adjusting for bias in human studies. For our purpose we use the example of the association between exposure to diesel exhaust and occurrence of lung cancer.

Methods

Firstly, we identify and adjust for the main sources of systematic error in selected human studies of the association between occupational exposure to diesel exhaust and occurrence of lung cancer. Evidence from selected animal studies is also accounted for by extrapolating to average ambient, occupational exposure concentrations of diesel exhaust. In a second stage, the bias adjusted effect estimates are combined in a common effect measure through meta-analysis.

Results

The random-effects pooled estimate (RR) for exposure to diesel exhaust vs. non-exposure was found 1.37 (95% C.I.: 1.08-1.65) in animal studies and 1.59 (95% C.I.: 1.09-2.10) in human studies, whilst the overall was found equal to 1.49 (95% C.I.: 1.21-1.78) with a greater contribution from human studies. Without bias adjustment in human studies, the pooled effect estimate was 1.59 (95% C.I.: 1.28-1.89).

Conclusions

Adjustment for the main sources of uncertainty produced lower risk estimates showing that ignoring bias leads to risk estimates potentially biased upwards.
Soluble vascular endothelial growth factor receptor-3 suppresses lymphangiogenesis and lymphatic metastasis in bladder cancer
Authors: Yang Hanseul , Kim Chan , Kim Min-Ju , Schwendener Reto A , Alitalo Kari , Heston Warren , Kim Injune , Kim Wun-Jae , Koh Gou Young
Published: April 2011

Background

Most bladder cancer patients experience lymphatic metastasis in the course of disease progression, yet the relationship between lymphangiogenesis and lymphatic metastasis is not well known. The aim of this study is to elucidate underlying mechanisms of how expanded lymphatic vessels and tumor microenvironment interacts each other and to find effective therapeutic options to inhibit lymphatic metastasis.

Results

The orthotopic urinary bladder cancer (OUBC) model was generated by intravesical injection of MBT-2 cell lines. We investigated the angiogenesis, lymphangiogenesis, and CD11b+/CD68+ tumor-associated macrophages (TAM) by using immunofluorescence staining. OUBC displayed a profound lymphangiogenesis and massive infiltration of TAM in primary tumor and lymphatic metastasis in lymph nodes. TAM flocked near lymphatic vessels and express higher levels of VEGF-C/D than CD11b- cells. Because VEGFR-3 was highly expressed in lymphatic vascular endothelial cells, TAM could assist lymphangiogenesis by paracrine manner in bladder tumor. VEGFR-3 expressing adenovirus was administered to block VEGF-C/D signaling pathway and clodronate liposome was used to deplete TAM. The blockade of VEGF-C/D with soluble VEGF receptor-3 markedly inhibited lymphangiogenesis and lymphatic metastasis in OUBC. In addition, the depletion of TAM with clodronate liposome exerted similar effects on OUBC.

Conclusion

VEGF-C/D are the main factors of lymphangiogenesis and lymphatic metastasis in bladder cancer. Moreover, TAM plays an important role in these processes by producing VEGF-C/D. The inhibition of lymphangiogenesis could provide another therapeutic target to inhibit lymphatic metastasis and recurrence in patients with invasive bladder cancer.
Detection of vitellogenin incorporation into zebrafish oocytes by FITC fluorescence
Authors: Matsuda Yohei , Ito Yoshie , Hashimoto Hisashi , Yokoi Hayato , Suzuki Tohru
Published: April 2011

Background

Large volumes of lymph can be collected from the eye-sacs of bubble-eye goldfish. We attempted to induce vitellogenin (Vtg) in the eye-sac lymph of bubble-eye goldfish and develop a method for visualizing Vtg incorporation by zebrafish oocytes using FITC-labeling.

Methods

Estrogen efficiently induced Vtg in the eye-sac lymph of goldfish. After FITC-labeled Vtg was prepared, it was injected into mature female zebrafish.

Results

Incorporation of FITC-labeled Vtg by zebrafish oocytes was detected in in vivo and in vitro experiments. The embryos obtained from zebrafish females injected with FITC-labeled Vtg emitted FITC fluorescence from the yolk sac and developed normally.

Conclusion

This method for achieving Vtg incorporation by zebrafish oocytes could be useful in experiments related to the development and endocrinology of zebrafish oocytes.
A promising routine to fabricate GeSi nanowires via self-assembly on miscut Si (001) substrates
Authors: Zhong Zhenyang , Gong Hua , Ma Yingjie , Fan Yongliang , Jiang Zuimin
Published: April 2011

Very small and compactly arranged GeSi nanowires could self-assembled on vicinal Si (001) substrates with ~8° off toward ⟨110⟩ during Ge deposition. The nanowires were all oriented along the miscut direction. The small ration of height over width of the nanowire indicated that the nanowires were bordered partly with {1 0 5} facets. These self-assembled small nanowires were remarkably influenced by the growth conditions and the miscut angle of substrates in comparison with large dome-like islands obtained after sufficient Ge deposition. These results proposed that the formation of the nanowire was energetically driven under growth kinetic assistance. Three-dimensionally self-assembled GeSi nanowires were first realized via multilayer Ge growth separated with Si spacers. These GeSi nanowires were readily embedded in Si matrix and compatible with the sophisticated Si technology, which suggested a feasible strategy to fabricate nanowires for fundamental studies and a wide variety of applications.

PACS: 81.07.Gf, 81.16.Dn, 68.65.-k, 68.37.Ps
Myelin ingestion alters macrophage antigen-presenting function in vitro and in vivo
Authors: van Zwam Marloes , Samsom Janneke N , Nieuwenhuis Edward E , Melief Marie-José , Wierenga-Wolf Annet F , Dijke I Esmé , Talens Simone , van Meurs Marjan , Voerman Jane S , Boven Leonie A , Laman Jon D
Published: April 2011

During MS, phagocytosing myelin-containing macrophages arise and lie in close proximity to T cells. To date, it has not been addressed whether these myelin-laden macrophages have the capacity to present antigens to T cells and whether this contributes to inflammation in disease. We demonstrate that in vitro-generated human and mouse myelin-laden macrophages expressed MHC class I and II and costimulatory molecules and are thus well equipped for antigen presentation. Human myelin-laden macrophages exhibited normal endocytosis of particulate and soluble antigens. In addition, human myelin-laden macrophages elicited active T cell proliferation of naïve as well as memory T cells. Furthermore, mouse myelin-laden macrophages induced primary antigen-specific CD4+ T cell proliferation in vivo but transiently diminished IFN-γ release. Functionally, MOG peptide-loaded myelin-laden mouse macrophages modestly but significantly reduced the severity of MOG peptide-induced EAE. These data show that myelin uptake results in the induction of a population of macrophages that retains antigen-presenting capacity and limits autoimmune-mediated disease.
Introduction of a Quality Management System and Outcome After Hematopoietic Stem-Cell Transplantation
Authors: Gratwohl Alois , Brand Ronald , Niederwieser Dietger , Baldomero Helen , Chabannon Christian , Cornelissen Jan , de Witte Theo , Ljungman Per , McDonald Fiona , McGrath Eoin , Passweg Jakob , Peters Christina , Rocha Vanderson , Slaper-Cortenbach Ineke , Sureda Anna , Tichelli Andre , Apperley Jane
Published: April 2011

Purpose

A comprehensive quality management system called JACIE (Joint Accreditation Committee International Society for Cellular Therapy and the European Group for Blood and Marrow Transplantation), was introduced to improve quality of care in hematopoietic stem-cell transplantation (HSCT). We therefore tested the hypothesis that the introduction of JACIE improved patient survival.

Patients and Methods

Data on 41,623 allogeneic (39%) and 66,281 autologous (61%) HSCTs for an acquired hematologic disorder performed between 1999 and 2007 by 421 teams in Europe were used to assess the outcomes of patients who received a transplantation at baseline (> 3 years before application or no application), during preparation (3 years before application), during application (time from application to accreditation), and after JACIE accreditation. The analysis was clustered by team and stratified for year of HSCT, donor type, disease, conditioning, and gross national income per capita of the respective country. Patient's risks were adjusted for by their European Group for Blood and Marrow Transplantation score.

Results

Patient outcome was systematically better when the transplantation center was at a more advanced phase of JACIE accreditation, independent of year of transplantation and other risk factors. Improvement was robust as quantified for relapse-free survival after allogeneic HSCT compared with baseline by a hazard ratio (HR) of 0.96 (95% CI, 0.90 to 1.03; P = .22) for preparation, 0.95 (95% CI, 0.88 to 1.03; P = .20) for application, and 0.86 (95% CI, 0.78 to 0.95; P = .01) for the accreditation (test for trend P = .01). Improvement from baseline was similar after autologous HSCT (HR for accreditation, 0.83; 95% CI, 0.74 to 0.93; P < .01).

Conclusion

Even with all the limitations of an observational study, these findings support the hypothesis that introduction of a comprehensive clinical quality management system is associated with improved outcome of patients after HSCT.
Supporting Treatment Decision Making in Advanced Cancer: A Randomized Trial of a Decision Aid for Patients With Advanced Colorectal Cancer Considering Chemotherapy
Authors: Leighl Natasha B. , Shepherd Heather L. , Butow Phyllis N. , Clarke Stephen J. , McJannett Margaret , Beale Philip J. , Wilcken Nicholas R.C. , Moore Malcolm J. , Chen Eric X. , Goldstein David , Horvath Lisa , Knox Jennifer J. , Krzyzanowska Monika , Oza Amit M. , Feld Ronald , Hedley David , Xu Wei , Tattersall Martin H.N.
Published: April 2011

Purpose

Decision making in advanced cancer is increasingly complex. We developed a decision aid (DA) for patients with advanced colorectal cancer who are considering first-line chemotherapy and reviewing treatment options, prognostic information, and toxicities. We examined its impact on patient understanding, treatment decisions, decisional conflict, decision making, consultation satisfaction, anxiety, and quality of life by using a randomized trial design.

Patients and Methods

In all, 207 patients with colorectal cancer who were considering first-line chemotherapy for metastatic disease were randomly assigned to receive a standard medical oncology consultation or a consultation in which the DA (take-home booklet with audio recording, reviewed by an oncologist) was used. Participants completed questionnaires postconsultation, postdecision, and 1 month later.

Results

In this study, 100 patients were randomly assigned to the control arm, and 107 received the DA. Median age of the sample was 62 years, 58% were male, 89% had a performance status of 0 or 1, and 36% had received prior adjuvant chemotherapy. Patients receiving the DA demonstrated a greater increase in understanding of prognosis, options, and benefits, with higher overall understanding (P < .001). Decisional conflict, treatment decisions, and achievement of involvement preferences were similar between the groups. Anxiety was similar across groups and decreased over time. Most patients were confident in a decision during the first consultation; 74% chose chemotherapy, 7% supportive care alone, and 10% observation.

Conclusion

This randomized trial of a decision aid in advanced cancer showed that its use in advanced colorectal cancer improved patient understanding of prognosis, treatment options, risks, and benefits without increasing anxiety. DAs can improve informed consent and can be tested through randomized trials even in the advanced cancer setting.
Current Trends in Autologous Stem-Cell Transplantation for Myeloma in the Era of Novel Therapies
Authors: Moreau Philippe , Avet-Loiseau Hervé , Harousseau Jean-Luc , Attal Michel
Published: April 2011

Since the mid 1990s, high-dose therapy followed by autologous stem-cell transplantation (ASCT) has been considered the standard of care for frontline therapy in younger patients with multiple myeloma (MM). During the past 10 years, thalidomide, bortezomib, and lenalidomide have been widely incorporated to the therapeutic armamentarium for the treatment of this disease. These agents show promise for improving the rate of complete remission both before and after ASCT without increasing toxicity. However, it is not clear whether such therapies are superior if they are used as an alternative to transplantation or whether they may reduce the need for and use of transplantation in patients in whom treatment is indicated. Therefore, the role of ASCT itself is a matter of debate: Should it be used upfront or as salvage treatment at the time of progression in patients initially treated with novel agents? This review presents current trends in ASCT for MM in the era of novel therapies.