bluuebunny/crossref_metadata_2025 huggingface dataset:
Tattoo-Induced Skin “Burn” During Magnetic Resonance Imaging in a Professional Football Player
Authors: Ross James R. , Matava Matthew J.
Published: June 2011

The authors present the case of a professional football player with an immediate and sustained cutaneous reaction (“burn”) at the site of lower extremity tattoos that occurred during magnetic resonance imaging of the pelvis. The burn was attributed to an electromagnetic reaction due to the ferromagnetic metallic compounds found in tattoo pigments, especially iron oxide—a reaction that has the potential to distort the field of image. These compounds can theoretically create an electric current that increases the local skin temperature, enough to cause a cutaneous burn. “At risk” tattoos are those with black pigment or any other pigments containing iron oxide, as well as those with a design that displays loops, large circular objects, or multiple adjacent points. Patients who develop this reaction may be treated prophylactically or symptomatically with a cold compress to assist with completion of the examination. Alternatively, a towel or cloth may be placed between the cutaneous body parts in those patients who experience the typical reaction resulting from an electrical arc between 2 separate cutaneous tattoos. This is likely an underreported issue that merits mention in the sports medicine literature given the frequent occurrence of cosmetic tattoos in athletes requiring magnetic resonance imaging to diagnose a musculoskeletal injury. As in the present patient, no permanent sequelae have been noted in the literature. Therefore, patients who develop this reaction should be reassured that the reaction is only temporary.
Tribological optimization of a toroidal-type continuously variable transmission
Authors: Bell C , Glovnea R
Published: June 2011

Continuously variable transmissions (CVTs) are mechanical devices that allow a continuous variation of the output velocity by adjusting its internal geometrical configuration. Through the use of an epicyclic gear set, a CVT can deliver an infinite number of transmission ratios, allowing the vehicle's engine to operate within a higher efficiency envelope for longer periods of time. This offers several advantages over traditional transmissions such as better fuel efficiency, quieter operation, and a lower mass. Current efforts to reduce the vehicles’ fuel consumption in order to protect the environment and save fuel have seen a recent revival in CVT research, especially in the automotive industry. This article documents a successfully implemented search algorithm for the dimensional optimization of a novel CVT design in order to determine the maximum theoretical efficiency of the device. In addition to showing an economical and simple method of calculating contact losses, this method of optimization also proved to be a powerful tool that can be used to select the dimensions of the transmission to fulfil any desired characteristics.
Tribometer investigation of the frictional response of piston rings with lubricant contaminated with the gasoline engine biofuel ethanol and water
Authors: De Silva P R , Priest M , Lee P M , Coy R C , Taylor R I
Published: June 2011

Ethanol is considered a potential long-term replacement for gasoline but information on the impact of ethanol on engine lubricant performance is scarce. Therefore, it is of prime importance to investigate the effect of ethanol on lubricants and engines that currently operate on gasoline. A bench-top test programme was undertaken on a modified Plint TE77 reciprocating tribometer to simulate the piston ring and cylinder wall interface. The Taguchi statistical experimental design method was used to quantify the effect of ethanol and the associated water contamination on friction with a commercially available fully formulated lubricant. Control factors and potential interactions were selected based on the TE77 capability and typical gasoline engine operating conditions. The statistical results show that while independently ethanol does not significantly contribute to friction reduction, the independent contribution from water is moderate when compared with the combined effect of ethanol and water. The water–temperature and load–speed interactions provide a small contribution to friction reduction while the ethanol–load and temperature–load interactions contribute moderately to the same.
Monoclonal antibodies detect receptor-induced binding sites in Glu-plasminogen
Authors: Han Jaena , Baik Nagyung , Kim Kee-Hwan , Yang Jian-Ming , Han Gye Won , Gong Yun , Jardí Mercè , Castellino Francis J. , Felez Jordi , Parmer Robert J. , Miles Lindsey A.
Published: June 2011

When Glu-plasminogen binds to cells, its activation to plasmin is markedly enhanced compared with the reaction in solution, suggesting that Glu-plasminogen on cell surfaces adopts a conformation distinct from that in solution. However, direct evidence for such conformational changes has not been obtained. Therefore, we developed anti-plasminogen mAbs to test the hypothesis that Glu-plasminogen undergoes conformational changes on its interaction with cells. Six anti-plasminogen mAbs (recognizing 3 distinct epitopes) that preferentially recognized receptor-induced binding sites (RIBS) in Glu-plasminogen were obtained. The mAbs also preferentially recognized Glu-plasminogen bound to the C-terminal peptide of the plasminogen receptor, Plg-RKT, and to fibrin, plasmin-treated fibrinogen, and Matrigel. We used trypsin proteolysis, immunoaffinity chromatography, and tandem mass spectrometry and identified Glu-plasminogen sequences containing epitopes recognized by the anti-plasminogen-RIBS mAbs: a linear epitope within a domain linking kringles 1 and 2; a nonlinear epitope contained within the kringle 5 domain and the latent protease domain; and a nonlinear epitope contained within the N-terminal peptide of Glu-plasminogen and the latent protease domain. Our results identify neoepitopes latent in soluble Glu-plasminogen that become available when Glu-plasminogen binds to cells and demonstrate that binding of Glu-plasminogen to cells induces a conformational change in Glu-plasminogen distinct from that of Lys-Pg.
Angiopoietin-1 promotes endothelial differentiation from embryonic stem cells and induced pluripotent stem cells
Authors: Joo Hyung Joon , Kim Honsoul , Park Sang-Wook , Cho Hyun-Jai , Kim Hyo-Soo , Lim Do-Sun , Chung Hyung-Min , Kim Injune , Han Yong-Mahn , Koh Gou Young
Published: June 2011

Angiopoietin-1 (Ang1) plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor Tie2. However, little is known about the precise role of Ang1 in embryonic stem cell (ESC) differentiation. In the present study, we used COMP-Ang1 (a soluble and potent variant of Ang1) to explore the effect of Ang1 on endothelial and hematopoietic differentiation of mouse ESCs in an OP9 coculture system and found that Ang1 promoted endothelial cell (EC) differentiation from Flk-1+ mesodermal precursors. This effect mainly occurred through Tie2 signaling and was altered in the presence of soluble Tie2-Fc. We accounted for this Ang1-induced expansion of ECs as enhanced proliferation and survival. Ang1 also had an effect on CD41+ cells, transient precursors that can differentiate into both endothelial and hematopoietic lineages. Intriguingly, Ang1 induced the preferential differentiation of CD41+ cells toward ECs instead of hematopoietic cells. This EC expansion promoted by Ang1 was also recapitulated in induced pluripotent stem cells (iPSCs) and human ESCs. We successfully achieved in vivo neovascularization in mice by transplantation of ECs obtained from Ang1-stimulated ESCs. We conclude that Ang1/Tie2 signaling has a pivotal role in ESC-EC differentiation and that this effect can be exploited to expand EC populations.
Enrichment of a microbial community performing anaerobic oxidation of methane in a continuous high-pressure bioreactor
Authors: Zhang Yu , Maignien Loïs , Zhao Xianxian , Wang Fengping , Boon Nico
Published: June 2011

Background

Anaerobic oxidation of methane coupled to sulphate reduction (SR-AOM) prevents more than 90% of the oceanic methane emission to the atmosphere. In a previous study, we demonstrated that the high methane pressure (1, 4.5, and 8 MPa) stimulated in vitro SR-AOM activity. However, the information on the effect of high-pressure on the microbial community structure and architecture was still lacking.

Results

In this study we analysed the long-term enrichment (286 days) of this microbial community, which was mediating SR-AOM in a continuous high-pressure bioreactor. 99.7% of the total biovolume represented cells in the form of small aggregates (diameter less then 15 μm). An increase of the total biovolume was observed (2.5 times). After 286 days, the ANME-2 (anaerobic methanotrophic archaea subgroup 2) and SRB (sulphate reducing bacteria) increased with a factor 12.5 and 8.4, respectively.

Conclusion

This paper reports a net biomass growth of communities involved in SR-AOM, incubated at high-pressure.
A microarray approach to identify genes involved in seed-pericarp cross-talk and development in peach
Authors: Bonghi Claudio , Trainotti Livio , Botton Alessandro , Tadiello Alice , Rasori Angela , Ziliotto Fiorenza , Zaffalon Valerio , Casadoro Giorgio , Ramina Angelo
Published: June 2011

Background

Field observations and a few physiological studies have demonstrated that peach embryogenesis and fruit development are tightly coupled. In fact, attempts to stimulate parthenocarpic fruit development by means of external tools have failed. Moreover, physiological disturbances during early embryo development lead to seed abortion and fruitlet abscission. Later in embryo development, the interactions between seed and fruit development become less strict. As there is limited genetic and molecular information about seed-pericarp cross-talk and development in peach, a massive gene approach based on the use of the μPEACH 1.0 array platform and quantitative real time RT-PCR (qRT-PCR) was used to study this process.

Results

A comparative analysis of the transcription profiles conducted in seed and mesocarp (cv Fantasia) throughout different developmental stages (S1, S2, S3 and S4) evidenced that 455 genes are differentially expressed in seed and fruit. Among differentially expressed genes some were validated as markers in two subsequent years and in three different genotypes. Seed markers were a LTP1 (lipid transfer protein), a PR (pathogenesis-related) protein, a prunin and LEA (Late Embryogenesis Abundant) protein, for S1, S2, S3 and S4, respectively. Mesocarp markers were a RD22-like protein, a serin-carboxypeptidase, a senescence related protein and an Aux/IAA, for S1, S2, S3 and S4, respectively.

The microarray data, analyzed by using the HORMONOMETER platform, allowed the identification of hormone-responsive genes, some of them putatively involved in seed-pericarp crosstalk. Results indicated that auxin, cytokinins, and gibberellins are good candidates, acting either directly (auxin) or indirectly as signals during early development, when the cross-talk is more active and vital for fruit set, whereas abscisic acid and ethylene may be involved later on.

Conclusions

In this research, genes were identified marking different phases of seed and mesocarp development. The selected genes behaved as good seed markers, while for mesocarp their reliability appeared to be dependent upon developmental and ripening traits. Regarding the cross-talk between seed and pericarp, possible candidate signals were identified among hormones.

Further investigations relying upon the availability of whole genome platforms will allow the enrichment of a marker genes repertoire and the elucidation of players other than hormones that are involved in seed-pericarp cross-talk (i.e. hormone peptides and microRNAs).
Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav1.3expression and decreasing spinal microglial activation
Authors: Cheng Kuang-I , Lai Chung-Sheng , Wang Fu-Yuan , Wang Hung-Chen , Chang Lin-Li , Ho Shung-Tai , Tsai Hung-Pei , Kwan Aij-Li
Published: June 2011

Background

Intrathecal lidocaine reverses tactile allodynia after nerve injury, but whether neuropathic pain is attenuated by intrathecal lidocaine pretreatment is uncertain.

Methods

Sixty six adult male Sprague-Dawley rats were divided into three treatment groups: (1) sham (Group S), which underwent removal of the L6 transverse process; (2) ligated (Group L), which underwent left L5 spinal nerve ligation (SNL); and (3) pretreated (Group P), which underwent L5 SNL and was pretreated with intrathecal 2% lidocaine (50 μl). Neuropathic pain was assessed based on behavioral responses to thermal and mechanical stimuli. Expression of sodium channels (Nav1.3 and Nav1.8) in injured dorsal root ganglia and microglial proliferation/activation in the spinal cord were measured on post-operative days 3 (POD3) and 7 (POD7).

Results

Group L presented abnormal behavioral responses indicative of mechanical allodynia and thermal hyperalgesia, exhibited up-regulation of Nav1.3 and down-regulation of Nav1.8, and showed increased microglial activation. Compared with ligation only, pretreatment with intrathecal lidocaine before nerve injury (Group P), as measured on POD3, palliated both mechanical allodynia (p < 0.01) and thermal hyperalgesia (p < 0.001), attenuated Nav1.3 up-regulation (p = 0.003), and mitigated spinal microglial activation (p = 0.026) by inhibiting phosphorylation (activation) of p38 MAP kinase (p = 0.034). p38 activation was also suppressed on POD7 (p = 0.002).

Conclusions

Intrathecal lidocaine prior to SNL blunts the response to noxious stimuli by attenuating Nav1.3 up-regulation and suppressing activation of spinal microglia. Although its effects are limited to 3 days, intrathecal lidocaine pretreatment can alleviate acute SNL-induced neuropathic pain.
Clinical relevance of DNA microarray analyses using archival formalin-fixed paraffin-embedded breast cancer specimens
Authors: Sadi Al Muktafi , Wang Dong-Yu , Youngson Bruce J , Miller Naomi , Boerner Scott , Done Susan J , Leong Wey L
Published: June 2011

Background

The ability of gene profiling to predict treatment response and prognosis in breast cancers has been demonstrated in many studies using DNA microarray analyses on RNA from fresh frozen tumor specimens. In certain clinical and research situations, performing such analyses on archival formalin fixed paraffin-embedded (FFPE) surgical specimens would be advantageous as large libraries of such specimens with long-term follow-up data are widely available. However, FFPE tissue processing can cause fragmentation and chemical modifications of the RNA. A number of recent technical advances have been reported to overcome these issues. Our current study evaluates whether or not the technology is ready for clinical applications.

Methods

A modified RNA extraction method and a recent DNA microarray technique, cDNA-mediated annealing, selection, extension and ligation (DASL, Illumina Inc) were evaluated. The gene profiles generated from FFPE specimens were compared to those obtained from paired fresh fine needle aspiration biopsies (FNAB) of 25 breast cancers of different clinical subtypes (based on ER and Her2/neu status). Selected RNA levels were validated using RT-qPCR, and two public databases were used to demonstrate the prognostic significance of the gene profiles generated from FFPE specimens.

Results

Compared to FNAB, RNA isolated from FFPE samples was relatively more degraded, nonetheless, over 80% of the RNA samples were deemed suitable for subsequent DASL assay. Despite a higher noise level, a set of genes from FFPE specimens correlated very well with the gene profiles obtained from FNAB, and could differentiate breast cancer subtypes. Expression levels of these genes were validated using RT-qPCR. Finally, for the first time we correlated gene expression profiles from FFPE samples to survival using two independent microarray databases. Specifically, over-expression ofANLNandKIF2C, and under-expression ofMAPTstrongly correlated with poor outcomes in breast cancer patients.

Conclusion

We demonstrated that FFPE specimens retained important prognostic information that could be identified using a recent gene profiling technology. Our study supports the use of FFPE specimens for the development and refinement of prognostic gene signatures for breast cancer. Clinical applications of such prognostic gene profiles await future large-scale validation studies.
Randomised cluster trial to support informed parental decision-making for the MMR vaccine
Authors: Jackson Cath , Cheater Francine M , Harrison Wendy , Peacock Rose , Bekker Hilary , West Robert , Leese Brenda
Published: June 2011

Background

In the UK public concern about the safety of the combined measles, mumps and rubella [MMR] vaccine continues to impact on MMR coverage. Whilst the sharp decline in uptake has begun to level out, first and second dose uptake rates remain short of that required for population immunity. Furthermore, international research consistently shows that some parents lack confidence in making a decision about MMR vaccination for their children. Together, this work suggests that effective interventions are required to support parents to make informed decisions about MMR.

This trial assessed the impact of a parent-centred, multi-component intervention (balanced information, group discussion, coaching exercise) on informed parental decision-making for MMR.

Methods

This was a two arm, cluster randomised trial. One hundred and forty two UK parents of children eligible for MMR vaccination were recruited from six primary healthcare centres and six childcare organisations. The intervention arm received an MMR information leaflet and participated in the intervention (parent meeting). The control arm received the leaflet only. The primary outcome was decisional conflict. Secondary outcomes were actual and intended MMR choice, knowledge, attitude, concern and necessity beliefs about MMR and anxiety.

Results

Decisional conflict decreased for both arms to a level where an 'effective' MMR decision could be made one-week (effect estimate = -0.54, p < 0.001) and three-months (effect estimate = -0.60, p < 0.001) post-intervention. There was no significant difference between arms (effect estimate = 0.07, p = 0.215). Heightened decisional conflict was evident for parents making the MMR decision for their first child (effect estimate = -0.25, p = 0.003), who were concerned (effect estimate = 0.07, p < 0.001), had less positive attitudes (effect estimate = -0.20, p < 0.001) yet stronger intentions (effect estimate = 0.09, p = 0.006). Significantly more parents in the intervention arm reported vaccinating their child (93% versus 73%, p = 0.04).

Conclusions

Whilst both the leaflet and the parent meeting reduced parents' decisional conflict, the parent meeting appeared to enable parents to act upon their decision leading to vaccination uptake.
The ward atmosphere important for the psychosocial work environment of nursing staff in psychiatric in-patient care
Authors: Tuvesson Hanna , Wann-Hansson Christine , Eklund Mona
Published: June 2011

Background

The nursing staff working in psychiatric care have a demanding work situation, which may be reflected in how they view their psychosocial work environment and the ward atmosphere. The aims of the present study were to investigate in what way different aspects of the ward atmosphere were related to the psychosocial work environment, as perceived by nursing staff working in psychiatric in-patient care, and possible differences between nurses and nurse assistants.

Methods

93 nursing staff working at 12 general psychiatric in-patient wards in Sweden completed two questionnaires, the Ward Atmosphere Scale and the QPSNordic 34+. Data analyses included descriptive statistics, the Mann-WhitneyU-test, Spearman rank correlations and forward stepwise conditional logistic regression analyses.

Results

The data revealed that there were no differences between nurses and nurse assistants concerning perceptions of the psychosocial work environment and the ward atmosphere. The ward atmosphere subscales Personal Problem Orientation and Program Clarity were associated with a psychosocial work environment characterized by Empowering Leadership. Program Clarity was related to the staff's perceived Role Clarity, and Practical Orientation and Order and Organization were positively related to staff perceptions of the Organizational Climate.

Conclusions

The results from the present study indicate that several ward atmosphere subscales were related to the nursing staff's perceptions of the psychosocial work environment in terms of Empowering Leadership, Role Clarity and Organizational Climate. Improvements in the ward atmosphere could be another way to accomplish improvements in the working conditions of the staff, and such improvements would affect nurses and nurse assistants in similar ways.
Concordant and opposite roles of DNA-PK and the "facilitator of chromatin transcription" (FACT) in DNA repair, apoptosis and necrosis after cisplatin
Authors: Sand-Dejmek Janna , Adelmant Guillaume , Sobhian Bijan , Calkins Anne S , Marto Jarrod , Iglehart Dirk J , Lazaro Jean-Bernard
Published: June 2011

Background

Platinum-containing chemotherapy produces specific DNA damage and is used to treat several human solid tumors. Tumors initially sensitive to platinum-based drugs frequently become resistant. Inhibition of DNA repair is a potential strategy to enhance cisplatin effectiveness. After cisplatin treatment, a balance between repair and apoptosis determines whether cancer cells proliferate or die. DNA-dependent protein kinase (DNA-PK) binds to DNA double strand breaks (DSBs) through its Ku subunits and initiates non-homologous end joining. Inhibition of DNA-PK sensitizes cancer cells to cisplatin killing. The goal of this study is to elucidate the mechanism underlying the effects of DNA-PK on cisplatin sensitivity.

Results

Silencing the expression of the catalytic subunit of DNA-PK (DNA-PKcs) increased sensitivity to cisplatin and decreased the appearance of γH2AX after cisplatin treatment. We purified DNA-PK by its Ku86 subunit and identified interactors by tandem mass spectrometry before and after cisplatin treatment. The structure specific recognition protein 1 (SSRP1), Spt16 and γH2AX appeared in the Ku86 complex 5 hours after cisplatin treatment. SSRP1 and Spt16 form the facilitator of chromatin transcription (FACT). The cisplatin-induced association of FACT with Ku86 and γH2AX was abrogated by DNase treatment. In living cells, SSRP1 and Ku86 were recruited at sites of DSBs induced by laser beams. Silencing SSRP1 expression increased sensitivity to cisplatin and decreased γH2AX appearance. However, while silencing SSRP1 in cisplatin-treated cells increased both apoptosis and necrosis, DNA-PKcs silencing, in contrast, favored necrosis over apoptosis.

Conclusions

DNA-PK and FACT both play roles in DNA repair. Therefore both are putative targets for therapeutic inhibition. Since DNA-PK regulates apoptosis, silencing DNA-PKcs redirects cells treated with cisplatin toward necrosis. Silencing FACT however, allows both apoptosis and necrosis. Targeting DNA repair in cancer patients may have different therapeutic effects depending upon the roles played by factors targeted.
Analysis of time-dependent adaptations in whole-body energy balance in obesity induced by high-fat diet in rats
Authors: So Mandy , Gaidhu Mandeep P , Maghdoori Babak , Ceddia Rolando B
Published: June 2011

Background

High-fat (HF) diet has been extensively used as a model to study metabolic disorders of human obesity in rodents. However, the adaptive whole-body metabolic responses that drive the development of obesity with chronically feeding a HF diet are not fully understood. Therefore, this study investigated the physiological mechanisms by which whole-body energy balance and substrate partitioning are adjusted in the course of HF diet-induced obesity.

Methods

Male Wistar rats were fed ad libitum either a standard or a HF diet for 8 weeks. Food intake (FI) and body weight were monitored daily, while oxygen consumption, respiratory exchange ratio, physical activity, and energy expenditure (EE) were assessed weekly. At week 8, fat mass and lean body mass (LBM), fatty acid oxidation and uncoupling protein-1 (UCP-1) content in brown adipose tissue (BAT), as well as acetyl-CoA carboxylase (ACC) content in liver and epidydimal fat were measured.

Results

Within 1 week of ad libitum HF diet, rats were able to spontaneously reduce FI to precisely match energy intake of control rats, indicating that alterations in dietary energy density were rapidly detected and FI was self-regulated accordingly. Oxygen consumption was higher in HF than controls throughout the study as whole-body fat oxidation also progressively increased. In HF rats, EE initially increased, but then reduced as dark cycle ambulatory activity reached values ~38% lower than controls. No differences in LBM were detected; however, epidydimal, inguinal, and retroperitoneal fat pads were 1.85-, 1.89-, and 2.54-fold larger in HF-fed than control rats, respectively. Plasma leptin was higher in HF rats than controls throughout the study, indicating the induction of leptin resistance by HF diet. At week 8, UCP-1 content and palmitate oxidation in BAT were 3.1- and 1.5-fold higher in HF rats than controls, respectively, while ACC content in liver and epididymal fat was markedly reduced.

Conclusion

The thermogenic response induced by the HF diet was offset by increased energy efficiency and time-dependent reduction in physical activity, favoring fat accumulation. These adaptations were mainly driven by the nutrient composition of the diet, since control and HF animals spontaneously elicited isoenergetic intake.
Identification of two internal signal peptide sequences: critical for classical swine fever virus non-structural protein 2 to trans-localize to the endoplasmic reticulum
Authors: Guo Kang-kang , Tang Qing-hai , Zhang Yan-ming , Kang Kai , He Lei
Published: June 2011

Background

The membrane topology and molecular mechanisms for endoplasmic reticulum (ER) localization of classical swine fever virus (CSFV) non-structural 2 (NS2) protien is unclear. We attempted to elucidate the subcellular localization, and the molecular mechanisms responsible for the localization of this protein in our study. The NS2 gene was amplified by reverse transcription polymerase chain reaction, with the transmembrane region and hydrophilicity of the NS2 protein was predicted by bioinformatics analysis. Twelve cDNAs of the NS2 gene were amplified by the PCR deletion method and cloned into a eukaryotic expression vector, which was transfected into a swine umbilical vein endothelial cell line (SUVEC). Subcellular localization of the NS2 protein was characterized by confocal microscopy, and western blots were carried out to analyze protein expression.

Results

Our results showed that the -NH2terminal of the CSFV NS2 protein was highly hydrophobic and the protein localized in the ER. At least four transmembrane regions and two internal signal peptide sequences (amino acids103-138 and 220-262) were identified and thought to be critical for its trans-localization to the ER.

Conclusions

This is the first study to identify the internal signal peptide sequences of the CSFV NS2 protein and its subcellular localization, providing the foundation for further exploration of this protein's function of this protein and its role in CSFV pathogenesis.
NOTCH-1 and NOTCH-4 are novel gene targets of PEA3 in breast cancer: novel therapeutic implications
Authors: Clementz Anthony G , Rogowski Allison , Pandya Kinnari , Miele Lucio , Osipo Clodia
Published: June 2011

Introduction

Women with triple-negative breast cancer have the worst prognosis, frequently present with metastatic tumors and have few targeted therapy options. Notch-1 and Notch-4 are potent breast oncogenes that are overexpressed in triple-negative and other subtypes of breast cancer. PEA3, an ETS transcription factor, is also overexpressed in triple-negative and other breast cancer subtypes. We investigated whether PEA3 could be the critical transcriptional activator of Notch receptors in MDA-MB-231 and other breast cancer cells.

Methods

Real-time PCR and Western blot analysis were performed to detect Notch-1, Notch-2, Notch-3 and Notch-4 receptor expression in breast cancer cells when PEA3 was knocked down by siRNA. Chromatin immunoprecipitation was performed to identify promoter regions for Notch genes that recruited PEA3. TAM-67 and c-Jun siRNA were used to identify that c-Jun was necessary for PEA3 enrichment on the Notch-4 promoter. A Notch-4 luciferase reporter was used to confirm that endogenous PEA3 or AP-1 activated the Notch-4 promoter region. Cell cycle analysis, trypan blue exclusion, annexin V flow cytometry, colony formation assay and an in vivo xenograft study were performed to determine the biological significance of targeting PEA3 via siRNA, Notch signaling via a γ-secretase inhibitor, or both.

Results

Herein we provide new evidence for transcriptional regulation of Notch by PEA3 in breast cancer. PEA3 activates Notch-1 transcription in MCF-7, MDA-MB-231 and SKBr3 breast cancer cells. PEA3 activates Notch-4 transcription in MDA-MB-231 cells where PEA3 levels are endogenously high. In SKBr3 and BT474 breast cancer cells where PEA3 levels are low, overexpression of PEA3 increases Notch-4 transcripts. Chromatin immunoprecipitation confirmed the enrichment of PEA3 on Notch-1 and Notch-4 promoters in MDA-MB-231 cells. PEA3 recruitment to Notch-1 was AP-1-independent, whereas PEA3 recruitment to Notch-4 was c-JUN-dependent. Importantly, the combined inhibition of Notch signaling via a γ-secretase inhibitor (MRK-003 GSI) and knockdown of PEA3 arrested growth in the G1 phase, decreased both anchorage-dependent and anchorage-independent growth and significantly increased apoptotic cells in vitro. Moreover, either PEA3 knockdown or MRK-003 GSI treatment significantly reduced tumor growth of MDA-MB-231 xenografts in vivo.

Conclusions

Taken together, the results from this study demonstrate for the first time that Notch-1 and Notch-4 are novel transcriptional targets of PEA3 in breast cancer cells. Targeting of PEA3 and/or Notch pathways might provide a new therapeutic strategy for triple-negative and possibly other breast cancer subtypes.
Requirement for N-cadherin–catenin complex in heart development
Authors: Piven Oksana O , Kostetskii Igor E , Macewicz Larysa L , Kolomiets Yurii M , Radice Glenn L , Lukash Lubov L
Published: June 2011

Cell adhesion, mediated by N-cadherin, is critical for embryogenesis since N-cadherin-null embryos die during mid-gestation with multiple developmental defects. To investigate the role of N-cadherin in heart muscle development, N-cadherin was specifically deleted from myocardial cells in mice. The structural integrity of the myocardial cell wall was compromised in the N-cadherin mutant embryos, leading to a malformed heart and a delay in embryonic development. In contrast, cardiac-specific deletion of αE-catenin, found in adherens junctions, or β-catenin, did not cause any morphological defects in the embryonic heart, presumably due to compensation by αT-catenin that is normally found in intercalated disks and γ-catenin (plakoglobin), respectively. Embryos lacking β-catenin in the heart also exhibited a cardiac defect, but only later in development resulting in partial lethality. These genetic studies underscore the importance of the N-cadherin/catenin complex in cardiogenesis.
Factors associated with a clinician's offer of screening HIV-positive patients for sexually transmitted infections, including syphilis
Authors: Heller R , Fernando I , Macdougall M
Published: June 2011

This retrospective study assessed whether Quality Improvement Scotland national standards for the sexual health care offered to HIV-positive individuals are being met by the Edinburgh genitourinary (GU) medicine clinic; specifically whether HIV-positive patients are offered: (a) sexually transmitted infection (STI) screening annually and (b) syphilis testing six-monthly. The study also reviewed what factors were associated with a clinician's offer of STI screening and syphilis testing. Of the 509 patients seen within the study period, case notes documented that 64% were offered STI screens, and 69% were offered syphilis testing, results consistent with audits of services elsewhere. Sexual orientation ( P < 0.0005), relationship status ( P = 0.007) and receipt of antiretrovirals ( P = 0.001) were independent predictors of clinician offer of STI screening, while gender ( P < 0.0005) and receipt of antiretrovirals ( P = 0.063) were independent predictors of offer of syphilis testing. Our results suggest that one explanation for clinicians failing to offer STI screens and syphilis serology testing is their (implicit) risk assessment that STI testing is not required in individual patients.
Different trends for different sexually transmissible infections despite increased testing of men who have sex with men
Authors: Ryder N , Bourne C , Donovan B
Published: June 2011

Australian and New South Wales Sexually Transmissible Infections Strategies recommend sexual health clinics actively target particular populations, including men who have sex with men (MSM), who have increasing rates of sexually transmitted infections (STIs). We describe trends in MSM attendances, STI testing and diagnostic yield from 1996 to 2007 at a Sydney public sexual clinic. Aggregate data were extracted from the clinic database. There was a 76% increase in the number of individual MSM attending, more than three-fold increase in the number of STI tests performed and the proportion of MSM tested. The increase in testing was greatest for rectal infections. The positive yield increased for rectal chlamydia and infectious syphilis; remained stable for pharyngeal gonorrhoea; and decreased for urethral gonorrhoea, rectal gonorrhoea and urethral chlamydia. Our results demonstrate successful service reorientation in response to a local STI epidemic. Differing trends suggest evolving transmission dynamics for different STIs in the context of increased testing of asymptomatic MSM.
Osteomyelitis as the only manifestation of late latent syphilis: case report and literature review
Authors: Liu Z-Y , Zhang Y , Qiu K-F , Du S-X
Published: June 2011

Bone infection, particularly of the skull and the long bones of the legs and arms, despite being a common characteristic of tertiary stage syphilis and congenital syphilis in the past, is seldom encountered clinically due to effective antibiotic therapy. We report a case of a 62-year-old man who presented with one-month acute pain in the left leg. Treponema pallidum particle agglutination test was positive, and radiography showed a pathological fracture of the left tibiofibula. Surgical debridement and biopsy of the bone marrow were performed and a pathological diagnosis of syphilis osteomyelitis was entertained. The patient's symptoms resolved completely after a six-week course of penicillin. We identified 17 previously published cases of bone lesions of syphilis, eight of which had syphilitic osteomyelitis, seven were syphilitic osteitis and two had syphilitic periostitis. We suggest that bone lesions such as osteomyelitis caused by syphilis can be the only manifestation of late latent syphilis.
Testing the children of HIV-positive mothers
Authors: Briggs A , Bond K , Rogstad K E
Published: June 2011

We aimed to establish current practice regarding the testing of children of HIV-positive women in two centres in the South Yorkshire HIV Network, UK. Notes were reviewed from 59 women who attended clinic over a three-month period from 01 September 2009 to 30 November 2009. In our sample, only 29 of 52 (56%) children living in the UK who required testing had been HIV tested. Testing rates were high in preschool children (15/15) and fell with age to 2/11 (18%) in the 16–20 years age group. Uptake of testing for children of HIV-positive parents could potentially be improved if testing was incorporated into routine clinic practice as part of the package of care offered to a newly diagnosed individual.
Intimate partner violence and partner notification of sexually transmitted infections among adolescent and young adult family planning clinic patients
Authors: Decker M R , Miller E , Mccauley H L , Tancredi D J , Levenson R R , Waldman J , Schoenwald P , Silverman J G
Published: June 2011

Patient-initiated partner notification of sexually transmitted infection (STI), i.e. patients informing their sexual partners of a diagnosis, is a cornerstone of STI prevention. Growing evidence suggests that women exposed to intimate partner violence (IPV) may fear such notification, or face negative consequences in response to STI disclosure. The current study assessed associations of IPV with fear of partner notification, and experiences of partner notification, among adolescent and young adult female family planning clinic patients. Women aged 16–29 years attending five family planning clinics in Northern California, USA ( n = 1282) participated in a cross-sectional survey. A history of physical or sexual IPV was associated with fear of partner notification. Moreover, participants exposed to IPV were more likely to have partners say that it was not from them or otherwise accuse them of cheating in response to partner notification. Such partners were less likely to seek indicated STI treatment or testing. Current findings suggest that partner notification for STI may be compromised by IPV. Clinical practices and policies to support effective partner notification should include IPV assessment, and provide mechanisms to address related fears concerning partner notification.
Is male intent to be vaccinated against HPV a function of the promotion message?
Authors: Diclemente R J , Crosby R A , Salazar L F , Nash R , Younge S
Published: June 2011

We aimed to determine whether the type of outcome expectation, stemming from HPV vaccination, would have any effect on young men's HPV vaccine intent. We recruited young men (18–24 years of age) from two university campuses ( n = 150). After answering a series of questions they were randomly assigned to one of three information conditions (all delivered by computer): (1) how women may benefit from men's HPV vaccination, (2) preventing genital warts and (3) preventing head and neck cancers. Intent to be vaccinated against HPV in the next 12 months was assessed before and after receiving the informational session corresponding to the assigned condition. A repeated-measures t-test indicated that a significant increase in young men's intent to be vaccinated after they received the assigned information ( t = 9.48, [147], P = 0.0001). However, the increase in intent to be vaccinated did not vary by group assignment as there were no significant differences in mean intent scores between the three groups ( F = 0.59, [2/144], ( P = 0.56). Information that promotes the outcome expectations of protecting women from cervical cancer, preventing genital warts for men and preventing head and neck cancers for men may be equally effective in promoting increased intent for HPV vaccine acceptance among young university men.
Research Note—Trust Is in the Eye of the Beholder: A Vignette Study of Postevent Behavioral Controls' Effects on Individual Trust in Virtual Teams
Authors: Dennis Alan R. , Robert Lionel P. , Curtis Aaron M. , Kowalczyk Stacy T. , Hasty Bryan K.
Published: June 2011

Research in face-to-face teams shows conflicting results about the impact of behavioral controls on trust; some research shows that controls increase the salience of good behavior, which increases trust while other research shows that controls increase the salience of poor behavior that decreases trust. The only study in virtual teams, which examined poorly functioning teams, found that controls increased the salience of poor behavior, which decreased trust. We argue that in virtual teams behavioral controls amplify the salience of all behaviors (positive and negative) and that an individual's selective perception bias influences how these behaviors are interpreted. Thus the link from behavioral controls to trust is more complex than first thought. We conducted a 2 × 2 experiment, varying the use of behavioral controls (controls, no controls) and individual team member behaviors (reneging behaviors designed to reduce trust beliefs and fulfilling behaviors designed to increase trust beliefs). We found that behavioral controls did amplify the salience of all behaviors; however, contrary to what we expected, this actually weakened the impact of reneging and fulfilling behaviors on trust. We believe that completing a formal evaluation increased empathy and the awareness of context in which the behaviors occurred and thus mitigated extreme perceptions. We also found that behavioral controls increased the selective perception bias which induced participants to see the behaviors their disposition to trust expected rather than the behaviors that actually occurred.
The Windy Clustered Prize-Collecting Arc-Routing Problem
Authors: Corberán Ángel , Fernández Elena , Franquesa Carles , Sanchis José María
Published: June 2011

This paper introduces the windy clustered prize-collecting arc-routing problem. It is an arc-routing problem where each demand edge is associated with a profit that is collected once if the edge is serviced, independent of the number of times the edge is traversed. It is further required that if a demand edge is serviced, then all the demand edges of its component are also serviced. A mathematical programming formulation is given and some polyhedral results including several facet-defining and valid inequalities are presented. The separation problem for the different families of inequalities is studied. Numerical results from computational experiments are analyzed.
Identification of Robust Terminal-Area Routes in Convective Weather
Authors: Pfeil Diana Michalek , Balakrishnan Hamsa
Published: June 2011

Convective weather is responsible for large delays and widespread disruptions in the U.S. National Airspace System, especially during summer. Traffic flow management algorithms require reliable forecasts of route blockage to schedule and route traffic. This paper demonstrates how raw convective weather forecasts, which provide deterministic predictions of the vertically integrated liquid (the precipitation content in a column of airspace) can be translated into probabilistic forecasts of whether or not a terminal area route will be blocked. Given a flight route through the terminal area, we apply techniques from machine learning to determine the likelihood that the route will be open in actual weather. The likelihood is then used to optimize terminal-area operations by dynamically moving arrival and departure routes to maximize the expected capacity of the terminal area. Experiments using real weather scenarios on stormy days show that our algorithms recommend that a terminal-area route be modified 30% of the time, opening up 13% more available routes that were forecast to be blocked during these scenarios. The error rate is low, with only 5% of cases corresponding to a modified route being blocked in reality, whereas the original route is in fact open. In addition, for routes predicted to be open with probability 0.95 or greater by our method, 96% of these routes (on average over time horizon) are indeed open in the weather that materializes.
Natura e fine dei Caratteri di Teofrasto. Storia di un enigma
Authors: Ranocchia Graziano
Published: June 2011

The question of the nature and the scope of Theophrastus’ Characters is one of the most intricated and most desperate puzzles of classical studies. Today many scholars are either sceptical about the possibility of giving a univocal answer to this vexatissima quaestio or prefer not to take position about it. Among the most various interpretations four principal theses arise. According to them, the Characters represent respectively: 1. a complement to a treatise of moral philosophy; 2. a literary work written in an artistic prose with a humorous intention; 3. a rhetorical exercise for training in schools of rhetoric; 4. the appendix to a treatise of poetical theory. Through a historical survey of the relevant scholarship, I will show that the first two positions cannot reasonably be held any more. The last two ones, instead, conserve most of their scientific value and should be used in the next future as a new hermeneutical basis for a possible solution or semplification of the ‘Theophrastean question’.
Folklorica
Authors: Lelli Emanuele
Published: June 2011

A comparison with south-Italian folklore can be an interesting key to interpret some aspects of ancient culture.

For instance, Theocr. id. 10, 11 χαλεπὸν χορίω κύνα γεῦσαι could be explained as “it’s a risk for a dog to taste a doggy placenta”, on the basis of Geopon. 19, 2, 17; also numerous evidences of the superstitious practices of dog ‘magic binding’ support this interpretation. In the famous scene of Aeschylus’ Choeph. 894–924 Clytaimestra shows her breast in front of Orestes: I suggest here a different set from the suppliant’s one. In fact, in south-Italian folklore, to show the breast in front of a son is the traditional set of a mother’s malediction. In Varro rust. 1, 37, 2 the text of all manuscripts decrescente
luna is correct: cutting the hair is to be avoided on waning moon, as well as it is widely believed in ancient and modern folklore.
Regucalcin is broadly expressed in male reproductive tissues and is a new androgen-target gene in mammalian testis
Authors: Laurentino S S , Correia S , Cavaco J E , Oliveira P F , Rato L , Sousa M , Barros A , Socorro S
Published: June 2011

Regucalcin (RGN) is a calcium (Ca2+)-binding protein which regulates intracellular Ca2+homeostasis by modulating the activity of enzymes regulating Ca2+concentration and enhancing Ca2+-pumping activity. Several studies have described the pivotal role of proper Ca2+homeostasis regulation to spermatogenesis and male fertility. Recently,RGNwas identified as a sex steroid-regulated gene in prostate and breast; however, a possible role of RGN in spermatogenesis has not been examined. In this study, the expression and localization of RGN in rat and human testis, and other rat reproductive tissues was analyzed. Moreover, we studied whether RGN protein was present in seminiferous tubule fluid (STF). Finally, we examined the effect of 5α-dihydrotestosterone (DHT) on the expression ofRgnmRNA in rat seminiferous tubules (SeT) culturedex vivo. The results presented in this study show that RGN is expressed in Leydig and Sertoli cells, as well as in all types of germ cells of both rat and human testis. RGN is also expressed in rat prostate, epididymis, and seminal vesicles. Moreover, RGN protein is present in rat STF. The results also demonstrate thatRgnexpression is age dependent in rat testis, and is upregulated by the non-aromatizable androgen DHT in rat SeT culturedex vivo. Taken together, these findings indicate thatRgnis a novel androgen-target gene in rat testis and that it may have a role in male reproductive function, particularly in the control of spermatogenesis.