bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving weld strength of magnesium to aluminium dissimilar joints via tin interlayer during ultrasonic spot welding
Authors: Patel V K , Bhole S D , Chen D L
Published: March 2012

Welding of magnesium to aluminium alloys is enormously challenging due to the formation of brittle Al12Mg17 intermetallic compounds (IMCs). This study was aimed at improving the strength of dissimilar joints of AZ31B-H24 magnesium alloy to 5754-O aluminium alloy by using a tin interlayer inserted in between the faying surfaces during ultrasonic spot welding. The addition of tin interlayer was observed to successfully eliminate the brittle Al12Mg17 IMCs, which were replaced by a layer of composite-like tin and Mg2Sn structure. Failure during the tensile lap shear tests occurred through the interior of the blended interlayer as revealed by X-ray diffraction and SEM observations. As a result, the addition of a tin interlayer resulted in a significant improvement in both joint strength and failure energy of magnesium to aluminium dissimilar joints and also led to an energy saving because the optimal welding energy required to achieve the highest strength decreased from ∼1250 to ∼1000 J.
Formation of nanocrystalline FeAl2O4 matrix coating by plasma spraying
Authors: Yang Y , Yan D R , Dong Y C , Chen X G , Wang L , Zhang J X , He J N
Published: March 2012

Al–Fe2O3 composite powders were deposited onto steel substrate by plasma spraying. The state (temperature and velocity) of the Al–Fe2O3 composite powders in plasma flame and the formation mechanism of the nanostructured coating were investigated and analysed. The maximum temperature and velocity of the composite particles in plasma flame were 3274·5°C and 179 m s−1 respectively. FeAl2O4, Fe and Al2O3 multiphase composite coatings were formed, which presented a microstructure with a number of spherical Fe and Al2O3 nanosized grains embedded within the equiaxed and columnar FeAl2O4 nanograin matrix. The formation process of the nanocrystalline composite coating prepared by plasma spraying can be described as follows. When smaller size droplets spread on the substrate, they were quickly chilled to form nanosized equiaxed grains. Nanosized equiaxed and columnar grains were formed in the larger size spreading droplets due to the high chilling, large undercooling and non-equilibrium directional solidification of the ceramic melt.
The role of thrombomodulin lectin-like domain in inflammation
Authors: Li Yi-Heng , Kuo Cheng-Hsiang , Shi Guey-Yueh , Wu Hua-Lin
Published: March 2012

Thrombomodulin (TM) is a cell surface glycoprotein which is widely expressed in a variety of cell types. It is a cofactor for thrombin binding that mediates protein C activation and inhibits thrombin activity. In addition to its anticoagulant activity, recent evidence has revealed that TM, especially its lectin-like domain, has potent anti-inflammatory function through a variety of molecular mechanisms. The lectin-like domain of TM plays an important role in suppressing inflammation independent of the TM anticoagulant activity. This article makes an extensive review of the role of TM in inflammation. The molecular targets of TM lectin-like domain have also been elucidated. Recombinant TM protein, especially the TM lectin-like domain may play a promising role in the management of sepsis, glomerulonephritis and arthritis. These data demonstrated the potential therapeutic role of TM in the treatment of inflammatory diseases.
Characterization of proximal pulmonary arterial cells from chronic thromboembolic pulmonary hypertension patients
Authors: Quarck Rozenn , Wynants Marijke , Ronisz Alicja , Sepulveda Maria Rosario , Wuytack Frank , Van Raemdonck Dirk , Meyns Bart , Delcroix Marion
Published: March 2012

Background

Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with proximal pulmonary artery obstruction and vascular remodeling. We hypothesized that pulmonary arterial smooth muscle (PASMC) and endothelial cells (PAEC) may actively contribute to remodeling of the proximal pulmonary vascular wall in CTEPH. Our present objective was to characterize PASMC and PAEC from large arteries of CTEPH patients and investigate their potential involvement in vascular remodeling.

Methods

Primary cultures of proximal PAEC and PASMC from patients with CTEPH, with non-thromboembolic pulmonary hypertension (PH) and lung donors have been established. PAEC and PASMC have been characterized by immunofluorescence using specific markers. Expression of smooth muscle specific markers within the pulmonary vascular wall has been studied by immunofluorescence and Western blotting. Mitogenic activity and migratory capacity of PASMC and PAEC have been investigated in vitro.

Results

PAEC express CD31 on their surface, von Willebrand factor in Weibel-Palade bodies and take up acetylated LDL. PASMC express various differentiation markers including α-smooth muscle actin (α-SMA), desmin and smooth muscle myosin heavy chain (SMMHC). In vascular tissue from CTEPH and non-thromboembolic PH patients, expression of α-SMA and desmin is down-regulated compared to lung donors; desmin expression is also down-regulated in vascular tissue from CTEPH compared to non-thromboembolic PH patients. A low proportion of α-SMA positive cells express desmin and SMMHC in the neointima of proximal pulmonary arteries from CTEPH patients. Serum-induced mitogenic activity of PAEC and PASMC, as well as migratory capacity of PASMC, were increased in CTEPH only.

Conclusions

Modified proliferative and/or migratory responses of PASMC and PAEC in vitro, associated to a proliferative phenotype of PASMC suggest that PASMC and PAEC could contribute to proximal vascular remodeling in CTEPH.
Skeletal muscle regeneration in Xenopus tadpoles and zebrafish larvae
Authors: Rodrigues Alexandre Miguel Cavaco , Christen Bea , Martí Mercé , Izpisúa Belmonte Juan Carlos
Published: March 2012

Background

Mammals are not able to restore lost appendages, while many amphibians are. One important question about epimorphic regeneration is related to the origin of the new tissues and whether they come from mature cells via dedifferentiation and/or from stem cells. Several studies in urodele amphibians (salamanders) indicate that, after limb or tail amputation, the multinucleated muscle fibres do dedifferentiate by fragmentation and proliferation, thereby contributing to the regenerate. In Xenopus laevis tadpoles, however, it was shown that muscle fibres do not contribute directly to the tail regenerate. We set out to study whether dedifferentiation was present during muscle regeneration of the tadpole limb and zebrafish larval tail, mainly by cell tracing and histological observations.

Results

Cell tracing and histological observations indicate that zebrafish tail muscle do not dedifferentiate during regeneration. Technical limitations did not allow us to trace tadpole limb cells, nevertheless we observed no signs of dedifferentiation histologically. However, ultrastructural and gene expression analysis of regenerating muscle in tadpole tail revealed an unexpected dedifferentiation phenotype. Further histological studies showed that dedifferentiating tail fibres did not enter the cell cycle and in vivo cell tracing revealed no evidences of muscle fibre fragmentation. In addition, our results indicate that this incomplete dedifferentiation was initiated by the retraction of muscle fibres.

Conclusions

Our results show that complete skeletal muscle dedifferentiation is less common than expected in lower vertebrates. In addition, the discovery of incomplete dedifferentiation in muscle fibres of the tadpole tail stresses the importance of coupling histological studies with in vivo cell tracing experiments to better understand the regenerative mechanisms.
Expression variation in connected recombinant populations of Arabidopsis thaliana highlights distinct transcriptome architectures
Authors: Cubillos Francisco A , Yansouni Jennifer , Khalili Hamid , Balzergue Sandrine , Elftieh Samira , Martin-Magniette Marie-Laure , Serrand Yann , Lepiniec Loïc , Baud Sébastien , Dubreucq Bertrand , Renou Jean-Pierre , Camilleri Christine , Loudet Olivier
Published: March 2012

Background

Expression traits can vary quantitatively between individuals and have a complex inheritance. Identification of the genetics underlying transcript variation can help in the understanding of phenotypic variation due to genetic factors regulating transcript abundance and shed light into divergence patterns. So far, only a limited number of studies have addressed this subject in Arabidopsis, with contrasting results due to dissimilar statistical power. Here, we present the transcriptome architecture in leaf tissue of two RIL sets obtained from a connected-cross design involving 3 commonly used accessions. We also present the transcriptome architecture observed in developing seeds of a third independent cross.

Results

The utilisation of the novel R/eqtl package (which goal is to automatize and extend functions from the R/qtl package) allowed us to map 4,290 and 6,534 eQTLs in the Cvi-0 × Col-0 and Bur-0 × Col-0 recombinant populations respectively. In agreement with previous studies, we observed a larger phenotypic variance explained by eQTLs in linkage with the controlled gene (potentially cis-acting), compared to distant loci (acting necessarily indirectly or in trans). Distant eQTLs hotspots were essentially not conserved between crosses, but instead, cross-specific. Accounting for confounding factors using a probabilistic approach (VBQTL) increased the mapping resolution and the number of significant associations. Moreover, using local eQTLs obtained from this approach, we detected evidence for a directional allelic effect in genes with related function, where significantly more eQTLs than expected by chance were up-regulated from one of the accessions. Primary experimental data, analysis parameters, eQTL results and visualisation of LOD score curves presented here are stored and accessible through the QTLstore service database http://qtlstore.versailles.inra.fr/.

Conclusions

Our results demonstrate the extensive diversity and moderately conserved eQTL landscape between crosses and validate the utilisation of expression traits to explore for candidates behind phenotypic variation among accessions. Furthermore, this stresses the need for a wider spectrum of diversity to fully understand expression trait variation within a species.
Assessment of liver fibrosis and associated risk factors in HIV-infected individuals using transient elastography and serum biomarkers
Authors: Vermehren Johannes , Vermehren Annika , Mueller Axel , Carlebach Amina , Lutz Thomas , Gute Peter , Knecht Gaby , Sarrazin Christoph , Friedrich-Rust Mireen , Forestier Nicole , Poynard Thierry , Zeuzem Stefan , Herrmann Eva , Hofmann Wolf Peter
Published: March 2012

Background

Liver fibrosis in human immunodeficiency virus (HIV)-infected individuals is mostly attributable to co-infection with hepatitis B or C. The impact of other risk factors, including prolonged exposure to combined antiretroviral therapy (cART) is poorly understood. Our aim was to determine the prevalence of liver fibrosis and associated risk factors in HIV-infected individuals based on non-invasive fibrosis assessment using transient elastography (TE) and serum biomarkers (Fibrotest [FT]).

Methods

In 202 consecutive HIV-infected individuals (159 men; mean age 47 ± 9 years; 35 with hepatitis-C-virus [HCV] co-infection), TE and FT were performed. Repeat TE examinations were conducted 1 and 2 years after study inclusion.

Results

Significant liver fibrosis was present in 16% and 29% of patients, respectively, when assessed by TE (≥ 7.1 kPa) and FT (> 0.48). A combination of TE and FT predicted significant fibrosis in 8% of all patients (31% in HIV/HCV co-infected and 3% in HIV mono-infected individuals). Chronic ALT, AST and γ-GT elevation was present in 29%, 20% and 51% of all cART-exposed patients and in 19%, 8% and 45.5% of HIV mono-infected individuals. Overall, factors independently associated with significant fibrosis as assessed by TE (OR, 95% CI) were co-infection with HCV (7.29, 1.95-27.34), chronic AST (6.58, 1.30-33.25) and γ-GT (5.17, 1.56-17.08) elevation and time on dideoxynucleoside therapy (1.01, 1.00-1.02). In 68 HIV mono-infected individuals who had repeat TE examinations, TE values did not differ significantly during a median follow-up time of 24 months (median intra-patient changes at last TE examination relative to baseline: -0.2 kPa, p = 0.20).

Conclusions

Chronic elevation of liver enzymes was observed in up to 45.5% of HIV mono-infected patients on cART. However, only a small subset had significant fibrosis as predicted by TE and FT. There was no evidence for fibrosis progression during follow-up TE examinations.
Effects and predictors of shoulder muscle massage for patients with posterior shoulder tightness
Authors: Yang Jing-lan , Chen Shiau-yee , Hsieh Ching-Lin , Lin Jiu-jenq
Published: March 2012

Background

Clinical approaches like mobilization, stretching, and/or massage may decrease shoulder tightness and improve symptoms in subjects with stiff shoulders. We investigated the effect and predictors of effectiveness of massage in the treatment of patients with posterior shoulder tightness.

Methods

A randomized controlled trial was conducted in a hospital-based outpatient practice (orthopedic and rehabilitation). Forty-three women and 17 men (mean age = 54 years, range 43-73 years) with posterior shoulder tightness participated and were randomized into massage and control groups (n = 30 per group). A physical therapist provided the massage on the posterior deltoid, infraspinatus, and teres minor of the involved shoulder for 18 minutes [about 6 minutes for each muscle] two times a week for 4 weeks. For the control group, one therapist applied light hand touch on the muscles 10 minutes two times a week for 4 weeks. Glenohumeral internal rotation ROM, functional status, and muscle tightness were the main outcomes. Additionally, the potential factors on the effectiveness of massage were analyzed by multivariate logistic regression. For this analysis, patients with functional score improvement at least 20% after massage were considered responsive, and the others were considered nonresponsive.

Results

Fifty-two patients completed the study (29 for the massage and 23 for the control). The overall mean internal rotation ROM increased significantly in the massage group compared to the control (54.9° v.s. 34.9°;P≤ 0.001). There were 21 patients in the responsive group and 8 in the nonresponsive group. Among the factors, duration of symptoms, functional score, and posterior deltoid tightness were significant predictors of effectiveness of massage.

Conclusions

Massage was an effective treatment for patients with posterior shoulder tightness, but was less effective in patients with longer duration of symptoms, higher functional limitation, and less posterior deltoid tightness.

Trial registration

This clinical trial is registered at Trial Registration "Trial registration: Clinicaltrials.govNCT01022827".
A high normal TSH level is associated with an atherogenic lipid profile in euthyroid non-smokers with newly diagnosed asymptomatic coronary heart disease
Authors: Wanjia Xing , Chenggang Wang , Aihong Wang , Xiaomei Yang , Jiajun Zhao , Chunxiao Yu , Jin Xu , Yinglong Hou , Ling Gao
Published: March 2012

Background

Serum lipid profiles may be influenced by thyroid function, but the detailed mechanism remains unclear. Increasing evidence suggests that thyrotropin (TSH) may exert extra-thyroidal effects. The goal of this study was to evaluate the relationship between serum TSH levels and the lipid profiles in euthyroid non-smokers with newly diagnosed asymptomatic coronary heart disease (CHD).

Methods

This was a retrospective study of 406 euthyroid non-smokers (187 males and 219 females) with newly diagnosed asymptomatic CHD from 2004 to 2010 in Jinan, China. Lipid parameters and the levels of TSH, FT3, and FT4 were determined. Multiple linear regression analysis and Logistic regression analysis were used to assess the influence of TSH on the lipid profiles and the risks of dyslipidemia.

Results

The TSH level, even within the normal range, was positively and linearly correlated with total cholesterol (TC), non-high density lipoprotein cholesterol (non-HDL-C) and triglycerides (TG) (Beta = 0.173, 0.181 and 0.103, respectively, P < 0.01 in all). With 1 mIU/L rise of TSH, the levels of TC, TG and non-HDL-C will increase by 1.010, 1.064, and 1.062 mmol/L, respectively. The odds ratio of hypercholesterolemia and hypertriglyceridemia with respect to the serum TSH level was 1.640 (95% CI 1.199-2.243, P = 0.002) and 1.349 (95% CI 1.054-1.726, P = 0.017), respectively.

Conclusions

TSH levels were correlated in a positive linear manner with the TC, non-HDL-C and TG levels in euthyroid non-smokers with newly diagnosed asymptomatic CHD. TSH in the upper limits of the reference range might exert adverse effects on lipid profiles and thus representing as a risk factor for hypercholesterolemia and hypertriglyceridemia in the context of CHD.
Percutaneous treatment of patients with heart diseases: selection, guidance and follow-up. A review
Authors: Contaldi Carla , Losi Maria-Angela , Rapacciuolo Antonio , Prastaro Maria , Lombardi Raffaella , Parisi Valentina , Parrella Lucia S , Di Nardo Carlo , Giamundo Alessandra , Puglia Roberto , Esposito Giovanni , Piscione Federico , Betocchi Sandro
Published: March 2012

Aortic stenosis and mitral regurgitation, patent foramen ovale, interatrial septal defect, atrial fibrillation and perivalvular leak, are now amenable to percutaneous treatment. These percutaneous procedures require the use of Transthoracic (TTE), Transesophageal (TEE) and/or Intracardiac echocardiography (ICE). This paper provides an overview of the different percutaneous interventions, trying to provide a systematic and comprehensive approach for selection, guidance and follow-up of patients undergoing these procedures, illustrating the key role of 2D echocardiography.
The Chinese version of the cardiac depression scale: Mokken scaling
Authors: Watson Roger , Wang Wenru , Hare David L , Ski Chantal F , Thompson David R
Published: March 2012

Background

Myocardial infarction is a major cause of death and morbidity in many countries, including China. The aim of this study was to analyse a Mandarin Chinese translation of the Cardiac Depression Scale for a hierarchy of items according to the criteria of Mokken scaling.

Findings

Data from 438 Chinese participants who completed the Chinese translation of the Cardiac Depression Scale were analysed using the Mokken scaling procedure and the 'R' statistical programme using the diagnostics available in these programmes. Correlations between Mandarin Chinese items and Chinese translations of the Hospital Anxiety and Depression Scale and the Beck Depression Inventory were also analysed. Fifteen items from the Mandarin Chinese Cardiac Depression Scale were retained in a weak but reliable Mokken scale; invariant item ordering was evident but of low accuracy and the Mokken scaled items of the Chinese Cardiac Depression Scale correlated with the Hospital Anxiety and Depression Scale and the Beck Depression Inventory.

Conclusions

Items from the Mandarin Chinese Cardiac Depression Scale form a Mokken scale and this offers further insight into how the items of the Cardiac Depression Scale relate to the measurement of depression in people with a myocardial infarction.
A multilayered approach of Si/SiO to promote carrier transport in electroluminescence of Si nanocrystals
Authors: Li Ding , Chen Yong-Bin , Ren Yong , Zhu Jiang , Zhao You-Yuan , Lu Ming
Published: March 2012

The electroluminescence (EL) and photoluminescence of Si nanocrystals (Si-nc) from multilayered samples of Si/SiO are investigated. Si-nc are formed within Si and SiO layers after furnace annealing. It is found that the presence of Si interlayers creates extra carrier paths for EL emission. A comparative study is further performed on a multilayered Si/SiO sample and a single-layered one with Si and SiO homogeneously mixed. Both samples have the same ratio of Si to O and the same contents of Si and O. The multilayered sample is found to have higher EL intensity, less turn-on voltage, lower resistance, and higher current efficiency than the single-layered one. The results indicate that Si interlayers in Si/SiO may act as carrier channels, which promote carrier transport and enhance the EL emission of Si-nc.
Design and implementation of a distributed fall detection system based on wireless sensor networks
Authors: Luo Xiaomu , Liu Tong , Liu Jun , Guo Xuemei , Wang Guoli
Published: March 2012

Pervasive healthcare is one of the most important applications of the Internet of Things (IoT). As part of the IoT, the wireless sensor networks (WSNs) are responsible for sensing the abnormal behavior of the elderly or patients. In this article, we design and implement a fall detection system called SensFall. With the resource restricted sensor nodes, it is vital to find an efficient feature to describe the scene. Based on the optical flow analysis, it can be observed that the thermal energy variation of each sub-region of the monitored region is a salient spatio-temporal feature that characterizes the fall. The main contribution of this study is to develop a feature-specific sensing system to capture this feature so as to detect the occurrence of a fall. In our system, the three-dimensional (3D) object space is segmented into some distinct discrete sampling cells, and pyroelectric infrared (PIR) sensors are employed to detect the variance of the thermal flux within these cells. The hierarchical classifier (two-layer HMMs) is proposed to model the time-varying PIR signal and classify different human activities. We use self-developed PIR sensor nodes mounted on the ceiling and construct a WSN based on ZigBee (802.15.4) protocol. We conduct experiments in a real office environment. The volunteers simulate several kinds of activities including falling, sitting down, standing up from a chair, walking, and jogging. Encouraging experimental results confirm the efficacy of our system.
Isolation and identification of a distinct strain of Culex Flavivirus from mosquitoes collected in Mainland China
Authors: Huanyu Wang , Haiyan Wang , Shihong Fu , Guifang Liu , Hong Liu , Xiaoyan Gao , Lizhi Song , Rayner Simon , Aiqiang Xu , Guodong Liang
Published: March 2012

Background

Culexflavivirus (CxFV) is an insect specific virus that has been isolated fromCulexpipiens, Culexquinquefasciatus, Culextritaeniorhynchusand otherCulexmosquitoes. It is a novel flavivirus isolated in Asia, North America, Central America and Africa. Phylogenetic analysis indicates that, based on the envelope gene (E gene) sequence, the worldwide CxFV strains can be divided into two genotypes.

Result

A virus (SDDM06-11) was isolated fromCulexpipienscollected in Shandong Province, China in 2006. The strain caused cytopathic effect (CPE) inAedesalbopictus(C6/36) cells by 3 days post-infection and immunofluorescence assay (IFA) showed a reaction with Japanese encephalitis virus (JEV) polyclonal antibodies. Phylogenetic analysis of the E gene sequence showed CxFV formed two genotypes with the SDDM06-11 strain assigned to genotype 1. Analysis of the E gene nucleotide homology showed the virus possessed characteristic amino acids at specific sites. The nucleotide homology of the open reading frame (ORF) was 94.8%-95.1% between SDDM06-11 and isolates from Japan, Iowa and Texas, and 90.2%-90.5% between SDDM06-11 and isolates from Uganda and Mexico.

Conclusion

In this paper we report the first isolation and identification of an isolate of CxFV in mainland China. Phylogenetic analysis indicates the isolate belongs to genotype 1. Our findings provide insight into the occurrence of CxFV inCulexmosquito populations and its distribution on a global scale.
Hypoxia-inducible factor-2a is associated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma
Authors: Xiang Lei , Liu Zhi-Heng , Huan Qin , Su Peng , Du Guang-Jun , Wang Yan , Gao Peng , Zhou Geng-Yin
Published: March 2012

Background

Breast cancer is the most common cancer and the leading cause of cancer mortality in women worldwide. Hypoxia is an important factor involved in the progression of solid tumors and has been associated with various indicators of tumor metabolism, angiogenesis and metastasis. But little is known about the contribution of Hypoxia-Inducible Factor-2a (HIF-2a) to the drug resistance and the clinicopathological characteristics in breast cancer.

Methods

Immunohistochemistry was employed on the tissue microarray paraffin sections of surgically removed samples from 196 invasive breast cancer patients with clinicopathological data. The correlations between the expression of HIF-2a and ABCG2 as well as other patients' clinicopathological data were investigated.

Results

The results showed that HIF-2a was expressed in different intensities and distributions in the tumor cells of the breast invasive ductal carcinoma. A positive staining for HIF-2a was defined as a brown staining observed mainly in the nucleus. A statistically significant correlation was demonstrated between HIF-2a expression and ABCG2 expression (p = 0.001), histology-grade (p = 0.029), and Ki67 (p = 0. 043) respectively.

Conclusion

HIF-2a was correlated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma. HIF-2a could regulate ABCG2 in breast cancer cells, and could be a novel potential bio-marker to predict chemotherapy effectiveness. The hypoxia/HIF-2a/ABCG2 pathway could be a new mechanism of breast cancer multidrug-resistance.

Virtual slides

http://www.diagnosticpathology.diagnomx.eu/vs/2965948166714795
NVP-BEZ235 and NVP-BGT226, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors, enhance tumor and endothelial cell radiosensitivity
Authors: Fokas Emmanouil , Yoshimura Michio , Prevo Remko , Higgins Geoff , Hackl Wolfgang , Maira Sauveur-Michel , Bernhard Eric J , McKenna WGillies , Muschel Ruth J
Published: March 2012

Background

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in tumor cells and promotes tumor cell survival after radiation-induced DNA damage. Because the pathway may not be completely inhibited after blockade of PI3K itself, due to feedback through mammalian target of rapamycin (mTOR), more effective inhibition might be expected by targeting both PI3K and mTOR inhibition.

Materials and methods

We investigated the effect of two dual PI3K/mTOR (both mTORC1 and mTORC2) inhibitors, NVP-BEZ235 and NVP-BGT226, on SQ20B laryngeal and FaDu hypopharyngeal cancer cells characterised by EGFR overexpression, on T24 bladder tumor cell lines with H-Ras mutation and on endothelial cells. Analysis of target protein phosphorylation, clonogenic survival, number of residual γH2AX foci, cell cycle and apoptosis after radiation was performed in both tumor and endothelial cells. In vitro angiogenesis assays were conducted as well.

Results

Both compounds effectively inhibited phosphorylation of Akt, mTOR and S6 target proteins and reduced clonogenic survival in irradiated tumor cells. Persistence of DNA damage, as evidenced by increased number of γH2AX foci, was detected after irradiation in the presence of PI3K/mTOR inhibition, together with enhanced G2 cell cycle delay. Treatment with one of the inhibitors, NVP-BEZ235, also resulted in decreased clonogenicity after irradiation of tumor cells under hypoxic conditions. In addition, NVP-BEZ235 blocked VEGF- and IR-induced Akt phosphorylation and increased radiation killing in human umbilical venous endothelial cells (HUVEC) and human dermal microvascular dermal cells (HDMVC). NVP-BEZ235 inhibited VEGF-induced cell migration and capillary tube formation in vitro and enhanced the antivascular effect of irradiation. Treatment with NVP-BEZ235 moderately increased apoptosis in SQ20B and HUVEC cells but not in FaDu cells, and increased necrosis in both tumor and endothelial all cells tumor.

Conclusions

The results of this study demonstrate that PI3K/mTOR inhibitors can enhance radiation-induced killing in tumor and endothelial cells and may be of benefit when combined with radiotherapy.
The prognostic significance of p63 and Ki-67 expression in myoepithelial carcinoma
Authors: Jiang You-Hua , Cheng Bo , Ge Ming-Hua , Zhang Gu
Published: March 2012

Background

Myoepithelial carcinoma is a rare tumour. The clinical and biological behaviours of these tumours are variable. Although many factors have been evaluated as potential prognostic indicators, including clinical stage, site and size of the tumour, high proliferative activity, extensive invasion into the surrounding tissue, perineural permeation, the abnormal presence of nuclear DNA content, and marked cellular pleomorphism, there are no definite histological features that clearly correlate with their behaviour. Thus, conclusions regarding prognostic factors and ideal treatment may emerge as the number of investigated myoepithelial carcinoma cases accumulate.

Methods

Using immunohistochemistry, expression levels of p63 and Ki-67 were determined in 16 myoepithelial carcinoma samples and correlated with clinicopathological characteristics and patient prognosis.

Results

p63 expression was detected in six of the myoepithelial carcinoma tissues (37.5%) and Ki-67 was detected in five (31.3%). In addition, p63 and Ki-67 expression levels were associated with myoepithelial carcinoma recurrence and metastasis. All six patients with p63-positive expression died due to disease or cardiovascular disease (mean survival time = 50.5 months), and p63 expression was statistically significant with respect to survival (P= 0.01). Four patients with Ki-67-positive expression died due to disease or cardiovascular disease (mean survival time = 44.0 months); however, there was no statistically significant difference between Ki-67 expression and survival (P= 0.24).

Conclusions

Recurrence and metastasis in myoepithelial carcinomas are more frequent in p63-positive and Ki-67-positive EMCs, and poor prognosis is associated with overexpression of p63.
Heterologous expression of Oenococcus oeni malolactic enzyme in Lactobacillus plantarum for improved malolactic fermentation
Authors: Schümann Christina , Michlmayr Herbert , Eder Reinhard , del Hierro Andrés M , Kulbe Klaus D , Mathiesen Geir , Nguyen Thu-Ha
Published: March 2012

Lactobacillus plantarumis involved in a multitude of food related industrial fermentation processes including the malolactic fermentation (MLF) of wine. This work is the first report on a recombinantL. plantarumstrain successfully conducting MLF. The malolactic enzyme (MLE) fromOenococcus oeniwas cloned into the lactobacillal expression vector pSIP409 which is based on the sakacin P operon ofLactobacillus sakeiand expressed in the host strainL. plantarumWCFS1. Both recombinant and wild-typeL. plantarumstrains were tested for MLF using a buffered malic acid solution in absence of glucose. Under the conditions with L-malic acid as the only energy source and in presence of Mn2+and NAD+, the recombinantL. plantarumand the wild-type strain converted 85% (2.5 g/l) and 51% (1.5 g/l), respectively, of L-malic acid in 3.5 days. Furthermore, the recombinantL. plantarumcells converted in a modified wine 15% (0.4 g/l) of initial L-malic acid concentration in 2 days. In conclusion, recombinantL. plantarumcells expressing MLE accelerate the malolactic fermentation.
Occurrence of breast cancer subtypes in adolescent and young adult women
Authors: Keegan Theresa HM , DeRouen Mindy C , Press David J , Kurian Allison W , Clarke Christina A
Published: March 2012

Introduction

Breast cancers are increasingly recognized as heterogeneous based on expression of receptors for estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2). Triple-negative tumors (ER-/PR-/HER2-) have been reported to be more common among younger women, but occurrence of the spectrum of breast cancer subtypes in adolescent and young adult (AYA) women aged between 15 and 39 years is otherwise poorly understood.

Methods

Data regarding all 5,605 AYA breast cancers diagnosed in California during the period 2005 to 2009, including ER and PR status (referred to jointly as hormone receptor (HR) status) and HER2 status, was obtained from the population-based California Cancer Registry. Incidence rates were calculated by subtype (triple-negative; HR+/HER2-; HR+/HER2+; HR-/HER2+), and logistic regression was used to evaluate differences in subtype characteristics by age group.

Results

AYAs had higher proportions of HR+/HER2+, triple-negative and HR-/HER2+ breast cancer subtypes and higher proportions of patients of non-White race/ethnicity than did older women. AYAs also were more likely to be diagnosed with stage III/IV disease and high-grade tumors than were older women. Rates of HR+/HER2- and triple-negative subtypes in AYAs varied substantially by race/ethnicity.

Conclusions

The distribution of breast cancer subtypes among AYAs varies from that observed in older women, and varies further by race/ethnicity. Observed subtype distributions may explain the poorer breast cancer survival previously observed among AYAs.
Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma
Authors: Younes Anas , Gopal Ajay K. , Smith Scott E. , Ansell Stephen M. , Rosenblatt Joseph D. , Savage Kerry J. , Ramchandren Radhakrishnan , Bartlett Nancy L. , Cheson Bruce D. , de Vos Sven , Forero-Torres Andres , Moskowitz Craig H. , Connors Joseph M. , Engert Andreas , Larsen Emily K. , Kennedy Dana A. , Sievers Eric L. , Chen Robert
Published: March 2012

Purpose

Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. In phase I studies, brentuximab vedotin demonstrated significant activity with a favorable safety profile in patients with relapsed or refractory CD30-positive lymphomas.

Patients and Methods

In this multinational, open-label, phase II study, the efficacy and safety of brentuximab vedotin were evaluated in patients with relapsed or refractory Hodgkin's lymphoma (HL) after autologous stem-cell transplantation (auto-SCT). Patients had histologically documented CD30-positive HL by central pathology review. A total of 102 patients were treated with brentuximab vedotin 1.8 mg/kg by intravenous infusion every 3 weeks. In the absence of disease progression or prohibitive toxicity, patients received a maximum of 16 cycles. The primary end point was the overall objective response rate (ORR) determined by an independent radiology review facility.

Results

The ORR was 75% with complete remission (CR) in 34% of patients. The median progression-free survival time for all patients was 5.6 months, and the median duration of response for those in CR was 20.5 months. After a median observation time of more than 1.5 years, 31 patients were alive and free of documented progressive disease. The most common treatment-related adverse events were peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea.

Conclusion

The ADC brentuximab vedotin was associated with manageable toxicity and induced objective responses in 75% of patients with relapsed or refractory HL after auto-SCT. Durable CRs approaching 2 years were observed, supporting study in earlier lines of therapy.
Safety, Pharmacokinetic, and Pharmacodynamic Phase I Dose-Escalation Trial of PF-00562271, an Inhibitor of Focal Adhesion Kinase, in Advanced Solid Tumors
Authors: Infante Jeffrey R. , Camidge D. Ross , Mileshkin Linda R. , Chen Eric X. , Hicks Rodney J. , Rischin Danny , Fingert Howard , Pierce Kristen J. , Xu Huiping , Roberts W. Gregory , Shreeve S. Martin , Burris Howard A. , Siu Lillian L.
Published: March 2012

Purpose

PF-00562271 is a novel inhibitor of focal adhesion kinase (FAK). The objectives of this study were to identify the recommended phase II dose (RP2D) and assess safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of PF-00562271.

Patients and Methods

Part 1 was a dose escalation without and with food. Part 2 enrolled specific tumor types in an expansion at the RP2D and also assessed the effect of PF-00562271 on single-dose midazolam PK in a subgroup of patients.

Results

Ninety-nine patients (median age, 60 years; 98% with Eastern Cooperative Oncology Group performance status of 0 or 1) were treated in 12 fasting and three fed cohorts. The 125-mg twice-per-day fed dose was deemed the maximum-tolerated dose (MTD) and RP2D. Grade 3 dose-limiting toxicities included headache, nausea/vomiting, dehydration, and edema. Nausea was the most frequently observed toxicity (60% of patients, all grades 1 or 2 at RP2D). PF-00562271 exposure increased with increasing dose; serum concentration–time profiles showed characteristic nonlinear disposition. Steady-state exposures were reached within 1 week. On coadministration, geometric mean values of midazolam maximal observed serum concentration and area under the serum concentration–time curve increased by 60% and more than two-fold, respectively. Of 14 patients evaluable by [18F]fluorodeoxyglucose positron emission tomography in the expansion cohorts, seven metabolic responses were observed. With conventional imaging, 31 patients had stable disease at first restaging scans, and 15 of these remained stable for six or more cycles.

Conclusion

The MTD and RP2D of PF-00562271 is 125 mg twice per day with food. PF-00562271 displayed time- and dose-dependent nonlinear PK and is likely a potent CYP 3A inhibitor. This first-in-class study supports further investigation of FAK as a promising therapeutic target.
Prevalence, risk and aggravating factors of chronic venous disease: an epidemiological survey of the general population of Greece
Authors: Dimakakos E , Syrigos K , Scliros E , Karaitianos I
Published: March 2012

Introduction

Chronic venous disease (CVD) is a common disease all over the world, mainly in Western Europe and the USA.

Aim

To evaluate the prevalence of CVD in the Greek general population and the characteristics of CVD.

Materials and methods

The study sample included 1500 individuals, 15–64 years of age, who were citizens of Athens, Thessaloniki, or one of five Greek cities with more than 10,000 in the population. The sample was selected by a stratified, multistage, random sampling procedure based on the Greek Census 2001. Questionnaires were completed for each individual by personal interview.

Results

From 1500 individuals, 224 (14.9%) had symptoms and/or signs of CVD, 9.6% were men and 20.1% were women. The highest percentage of presenting CVD symptoms was among 45–54-year-olds (23.4%) and 55–64-year-olds (27%). The symptoms that were mostly mentioned among sufferers were 58% achy legs, 37.4% swollen legs and 25.3% heavy legs, whereas the frequent signs were broken capillaries – telangiectasia (19.2%) and varicose veins (14.8%). About 62.9% with CVD had an obese body mass index (BMI > 25). The prevalence of CVD in patients with prolonged standing hours at work (4+ hours) was 20.8%. The symptoms of CVD were worse during the summer period only in 26.8% of the patients whereas in 50.8% during all the year. Regarding quality of life, more than 40% of the patients had either health or cosmetic problems. Sufferers mentioned that they took first advice from physicians (28%), or from friends and relatives (27%) or from pharmacists (26%).

Conclusion

This is a real whole-population study of Greece – a Mediterranean country that provides important and remarkable data on the epidemiology of CVD and highlights that we need improvement of relations within the triangle constituted by physicians, patients and disease.
LocARNA-P: Accurate boundary prediction and improved detection of structural RNAs
Authors: Will Sebastian , Joshi Tejal , Hofacker Ivo L. , Stadler Peter F. , Backofen Rolf
Published: March 2012

Current genomic screens for noncoding RNAs (ncRNAs) predict a large number of genomic regions containing potential structural ncRNAs. The analysis of these data requires highly accurate prediction of ncRNA boundaries and discrimination of promising candidate ncRNAs from weak predictions. Existing methods struggle with these goals because they rely on sequence-based multiple sequence alignments, which regularly misalign RNA structure and therefore do not support identification of structural similarities. To overcome this limitation, we compute columnwise and global reliabilities of alignments based on sequence and structure similarity; we refer to these structure-based alignment reliabilities as STARs. The columnwise STARs of alignments, or STAR profiles, provide a versatile tool for the manual and automatic analysis of ncRNAs. In particular, we improve the boundary prediction of the widely used ncRNA gene finder RNAz by a factor of 3 from a median deviation of 47 to 13 nt. Post-processing RNAz predictions, LocARNA-P's STAR score allows much stronger discrimination between true- and false-positive predictions than RNAz's own evaluation. The improved accuracy, in this scenario increased from AUC 0.71 to AUC 0.87, significantly reduces the cost of successive analysis steps. The ready-to-use software tool LocARNA-P produces structure-based multiple RNA alignments with associated columnwise STARs and predicts ncRNA boundaries. We provide additional results, a web server for LocARNA/LocARNA-P, and the software package, including documentation and a pipeline for refining screens for structural ncRNA, at http://www.bioinf.uni-freiburg.de/Supplements/LocARNA-P/.
Primary Care Physicians’ Perceptions of Barriers To Preventive Reproductive Health Care In Rural Communities
Authors: Chuang Cynthia H. , Hwang Sandra W. , McCall‐Hosenfeld Jennifer S. , Rosenwasser Lara , Hillemeier Marianne M. , Weisman Carol S.
Published: March 2012

CONTEXT: Women residing in rural areas are less likely than urban women to receive preventive reproductive health care, but reasons for this disparity remain largely unexplored.

METHODS: In 2010, semistructured interviews were conducted with 19 rural primary care physicians in central Pennsylvania regarding their experiences in two domains of preventive reproductive health—contraceptive care and preconception care. Major themes were identified using a modified grounded theory approach.

RESULTS: Physicians perceived that they had a greater role in providing contraceptive care than did nonrural physicians and that contraceptives were widely accessible to patients in their communities; however, the scope of contraceptive services they provided varied widely. Participants were aware of the importance of optimal health prior to pregnancy, but most did not routinely initiate preconception counseling. Physicians perceived rural community norms of unintended pregnancies, large families, and indifference toward career and educational goals for young women as the biggest barriers to both contraceptive and preconception care, as these attitudes resulted in a lack of patient interest in family planning. Lack of time and resources were identified as additional barriers to providing preconception care.

CONCLUSIONS: Rural women’s low use of contraceptive and preconception care services may reflect that preventive reproductive health care is not a priority in rural communities, rather than that it is inaccessible. Efforts to motivate rural women to engage in reproductive life planning, including more proactive counseling by providers, merit examination as ways to improve use of services.
Activin B is produced early in antral follicular development and suppresses thecal androgen production
Authors: Young J M , Henderson S , Souza C , Ludlow H , Groome N , McNeilly A S
Published: March 2012

Little is known about the role of activin B during folliculogenesis. This study investigated the expression levels of activin/inhibin subunits (βA, βB, and α), steroid enzyme, and gonadotrophin receptors in theca (TC) and granulosa cells (GC) by QPCR and activin A and B and inhibin A protein levels in follicular fluid (FF) of developing sheep follicles during estrus and anestrus. The effect of activin B on androgen production from primary TC culturesin vitrowas also assessed. During folliculogenesis, in anestrus and estrus, FF activin B concentrations and thecal and GC activin βB mRNA levels decreased as follicle diameter increased from 1–3 to >6 mm regardless of estrogenic status. Estrogenic preovulatory follicles had reduced concentrations of FF activins B and A, and TC and GCs expressed higher levels of activin βA mRNA at 3–4 mm, and TCs more inhibin α mRNA at >4 mm stages of development compared with nonestrogenic follicles. Activin B decreased androstenedione production from primary TCsin vitro, an effect blocked by inhibin A. Thus, sheep follicles 1–3 mm in diameter contained high FF levels of activin B, which decreased as the follicle size increased, and, like activin A, suppressed thecal androgen productionin vitro, an effect blocked by inhibin. Furthermore, the theca of large estrogenic follicles expressed high levels of inhibin α and activin βA mRNA suggesting local thecal derived inhibin A production. This would inhibit the negative effects of thecal activins B and A ensuring maximum androgen production for enhanced estradiol production by the preovulatory follicle(s).
Sperm transport and retention at the fertilization site is orchestrated by a chemical guidance and oviduct movement
Authors: Guidobaldi H A , Teves M E , Uñates D R , Giojalas L C
Published: March 2012

In mammals, only a few spermatozoa arrive at the fertilization site. During the last step in the journey to the egg, apart from their self-propulsion, spermatozoa may be assisted by oviduct movement and/or a guidance mechanism. The proportion of rabbit spermatozoa that arrive at the fertilization site was determined under in vivo conditions, in which either the ovulation products (secreting chemoattractants) and/or the oviduct movement (causing the displacement of the oviductal fluid) was inhibited. When only one of these components was inhibited, sperm transport to the fertilization site was partially reduced. However, when both the ovulation products and the oviduct movement were inhibited, almost no spermatozoa arrived at the fertilization site. The results suggest that spermatozoa are transported to and retained at the fertilization site by the combined action of a chemical guidance and the oviduct movement. A working model is proposed to explain how these two mechanisms may operate to transport spermatozoa to the fertilization site, probably as an evolutionary adaptation to maximize the chance of fertilizing an egg.