bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of electrical parameters, its interaction and tool geometry in electric discharge machining of titanium grade 5 alloy with graphite tool
Authors: Sivam Saravanan P , Michaelraj Antony L , S Satish Kumar , R Varahamoorthy , D Dinakaran
Published: November 2012

In this study, the effect of electrical parameters such as current, pulse-on time, pulse-off time, their interaction, tool geometry, and cross-sectional area over the important machining responses such as metal removal rate, tool wear rate, surface roughness, and entry–exit deviation were studied while machining titanium grade 5 alloy with graphite tool electrode at negative polarity in sink electric discharge machining process. The experiment was designed with Taguchi’s L27 orthogonal array with interaction between factors. The analysis of variance was used to check the significance of parameters effect. The data obtained were analyzed with signal-to-noise ratio analysis. Residual analysis was performed to check the fitness, and a regression model had been created and validated to relate the experiment factors with the responses. The model was found to be good after experimental validation. The ranking of influence of the factors over the responses was also presented.
The effect of geometrical and flow parameters on mixed convection of developing flow in vertical and inclined microchannels
Authors: Baheri Sima , Falaki Seyedeh Zobeydeh , Gharraei Reza
Published: November 2012

In this study, mixed convection in vertical and inclined parallel plate microchannels, has been investigated. The flow is steady, laminar, and incompressible and the walls are at constant temperature. A FORTRAN program has been written to solve the governing equations with wall velocity slip and temperature jump boundary conditions, and the results have been presented for Reynolds numbers of 25, 50, and 100, Knudsen numbers of 0, 0.005, 0.02, and 0.09, Richardson numbers of 0, 1, and 1.77, and microchannel inclination angles of 10°, 30°, 50°, and 90°. Results showed that wall velocity slip, friction coefficient, centerline velocity, and heat transfer rate decreases with increasing the Knudsen number. Increasing the Richardson number, for a given Reynolds number, decreases the microchannel centerline velocity because of the increasing of wall adjacent velocity, which is due to the promotion effect of natural convection. Also, the friction coefficient and Nusselt number increases with channel inclination angle.
Message framing, it does a body good: Effects of message framing and motivational orientation on young women’s calcium consumption
Authors: Gerend Mary A , Shepherd Melissa A
Published: November 2012

We investigated the effects of gain-framed versus loss-framed messages and motivational orientation on calcium consumption. After completing a motivational orientation scale (behavioral inhibition system/behavioral activation system), undergraduate women ( N = 141) were randomly assigned to read a gain-framed or loss-framed pamphlet promoting calcium consumption. Calcium consumption was assessed 1 month later. For calcium supplement behavior, a gain-framed advantage was observed for behavioral activation system–oriented individuals, whereas a loss-framed advantage was observed for behavioral inhibition system–oriented individuals. For dietary calcium intake, a gain-framed advantage was observed among behavioral activation system–oriented individuals; however, no framing effect emerged for behavioral inhibition system–oriented individuals. The success of framed messages depends on the message recipient’s motivational orientation.
An HLA-based tactical environment application framework
Authors: Çelik Turgay , Gökdoğan Göktuğ F , Öztürk Karahan , Sarikaya Bircan
Published: November 2012

Using Tactical Environment Simulations as part of simulation systems or real systems; increases the reality and quality of the applications, reduces development time, increases interoperability and reusability of systems. Tactical Environment Simulations are utilized by integrating them into applications which can have a wide variety of requirements; so, they are generally customized to meet specific requirements of the applications. Apart from most of the Commercial-Off-The-Shelf (COTS) tools that are used directly, Tactical Environment Simulations are often provided as Application Frameworks which contain readily available simulation models, middleware, extension points and a tool set to ease customization and integration. In this paper, the requirements and a design overview for an easily extensible, customizable and integrable, High Level Architecture (HLA)-based Tactical Environment Application Framework are provided. After defining the requirements and giving an overview of design, an Application Framework that realizes the defined system is also explained.
Integrated phase II/III clinical trials in oncology: A case study
Authors: Wang Meihua , Dignam James J , Zhang Qiang E , DeGroot John F , Mehta Minesh P , Hunsberger Sally
Published: November 2012

Background

Integrated phase II/III trial designs implement the phase II and phase III aspects of oncology studies into a single trial. Despite a body of literature discussing the merits of integrated phase II/III clinical trial designs within the past two decades, implementation of this design has been limited in oncology studies.

Purpose

We provide a brief discussion of the potential advantages and disadvantages of integrated phase II/III clinical trial designs in oncology and provide an example of the operating characteristics of a Radiation Therapy Oncology Group (RTOG) trial.

Methods

We review the differences among proposed integrated phase II/III designs. Then, we illustrate the use of the design in a brain tumor trial to be conducted by the RTOG and examine the impact of association between endpoints on design performance in terms of type I error, power, study duration, and expected sample size.

Results

Although integrated phase II/III designs should not be used in all situations, under appropriate conditions, significant gains can be achieved when using integrated phase II/III designs, including smaller sample size, time and resources savings, and shorter study duration.

Limitations

Data submission without delay and sufficient evaluation of intermediate endpoints are assumed.

Conclusions

Although there are potential benefits in using phase II/III designs, there also may be disadvantages. We recommend running design simulations incorporating theoretical and practical issues before implementing an integrated phase II/III design.
EKLF-driven PIT1 expression is critical for mouse erythroid maturation in vivo and in vitro
Authors: Forand Anne , Beck Laurent , Leroy Christine , Rousseau Alice , Boitez Valérie , Cohen Isabelle , Courtois Geneviève , Hermine Olivier , Friedlander Gérard
Published: November 2012

The PIT1/SLC20A1 protein, a well-described sodium/phosphate cotransporter and retrovirus receptor, has been identified recently as a modular of proliferation and apoptosis in vitro. The targeted deletion of the PIT1 gene in mice revealed a lethal phenotype due to severe anemia attributed to defects in liver development. However, the presence of immature erythroid cells associated with impaired maturation of the globin switch led us to investigate the role of PIT1 in hematopoietic development. In the present study, specific deletion of PIT1 in the hematopoietic system and fetal liver transplantation experiments demonstrated that anemia was associated with an erythroid cell– autonomous defect. Moreover, anemia was not due to RBC destruction but rather to maturation defects. Because Erythroid Krüppel-like Factor (EKLF)–knockout mice showed similar maturation defects, we investigated the functional link between PIT1 and EKLF. We demonstrated that EKLF increases PIT1 expression during RBC maturation by binding to its promoter in vivo and that shRNA-driven depletion of either PIT1 or EKLF impairs erythroid maturation of G1E cells in vitro, whereas reexpression of PIT1 in EKLF-depleted G1E cells partially restores erythroid maturation. This is the first demonstration of a physiologic involvement of PIT1 in erythroid maturation in vivo.
Analysis of the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) cistrome reveals novel co-regulatory role of ATF4
Authors: Khozoie Combiz , Borland Michael G , Zhu Bokai , Baek Songjoon , John Sam , Hager Gordon L , Shah Yatrik M , Gonzalez Frank J , Peters Jeffrey M
Published: November 2012

Background

The present study coupled expression profiling with chromatin immunoprecipitation sequencing (ChIP-seq) to examine peroxisome proliferator-activated receptor-β/δ (PPARβ/δ)-dependent regulation of gene expression in mouse keratinocytes, a cell type that expresses PPARβ/δ in high concentration.

Results

Microarray analysis elucidated eight different types of regulation that modulated PPARβ/δ-dependent gene expression of 612 genes ranging from repression or activation without an exogenous ligand, repression or activation with an exogenous ligand, or a combination of these effects. Bioinformatic analysis of ChIP-seq data demonstrated promoter occupancy of PPARβ/δ for some of these genes, and also identified the presence of other transcription factor binding sites in close proximity to PPARβ/δ bound to chromatin. For some types of regulation, ATF4 is required for ligand-dependent induction of PPARβ/δ target genes.

Conclusions

PPARβ/δ regulates constitutive expression of genes in keratinocytes, thus suggesting the presence of one or more endogenous ligands. The diversity in the types of gene regulation carried out by PPARβ/δ is consistent with dynamic binding and interactions with chromatin and indicates the presence of complex regulatory networks in cells expressing high levels of this nuclear receptor such as keratinocytes. Results from these studies are the first to demonstrate that differences in DNA binding of other transcription factors can directly influence the transcriptional activity of PPARβ/δ.
Thin-film fixed-bed reactor for solar photocatalytic inactivation of Aeromonas hydrophila: influence of water quality
Authors: Khan Sadia J , Reed Robert H , Rasul Mohammad G
Published: November 2012

Background

Controlling fish disease is one of the major concerns in contemporary aquaculture. The use of antibiotics or chemical disinfection cannot provide a healthy aquaculture system without residual effects. Water quality is also important in determining the success or failure of fish production. Several solar photocatalytic reactors have been used to treat drinking water or waste water without leaving chemical residues. This study has investigated the impact of several key aspects of water quality on the inactivation of the pathogenic bacterium Aeromonas hydrophila using a pilot-scale thin-film fixed-bed reactor (TFFBR) system.

Results

The level of inactivation of Aeromonas hydrophila ATCC 35654 was determined using a TFFBR with a photocatalytic area of 0.47 m2 under the influence of various water quality variables (pH, conductivity, turbidity and colour) under high solar irradiance conditions (980–1100 W m-2), at a flow rate of 4.8 L h-1 through the reactor. Bacterial enumeration were obtained through conventional plate count using trypticase soy agar media, cultured in conventional aerobic conditions to detect healthy cells and under ROS-neutralised conditions to detect both healthy and sub-lethally injured (oxygen-sensitive) cells. The results showed that turbidity has a major influence on solar photocatalytic inactivation of A. hydrophila. Humic acids appear to decrease TiO2 effectiveness under full sunlight and reduce microbial inactivation. pH in the range 7–9 and salinity both have no major effect on the extent of photoinactivation or sub-lethal injury.

Conclusions

This study demonstrates the effectiveness of the TFFBR in the inactivation of Aeromonas hydrophila under the influence of several water quality variables at high solar irradiance, providing an opportunity for the application of solar photocatalysis in aquaculture systems, as long as turbidity remains low.
Clinical identification of bacteria in human chronic wound infections: culturing vs. 16S ribosomal DNA sequencing
Authors: Rhoads Daniel D , Cox Stephen B , Rees Eric J , Sun Yan , Wolcott Randall D
Published: November 2012

Background

Chronic wounds affect millions of people and cost billions of dollars in the United States each year. These wounds harbor polymicrobial biofilm communities, which can be difficult to elucidate using culturing methods. Clinical molecular microbiological methods are increasingly being employed to investigate the microbiota of chronic infections, including wounds, as part of standard patient care. However, molecular testing is more sensitive than culturing, which results in markedly different results being reported to clinicians. This study compares the results of aerobic culturing and molecular testing (culture-free 16S ribosomal DNA sequencing), and it examines the relative abundance score that is generated by the molecular test and the usefulness of the relative abundance score in predicting the likelihood that the same organism would be detected by culture.

Methods

Parallel samples from 51 chronic wounds were studied using aerobic culturing and 16S DNA sequencing for the identification of bacteria.

Results

One hundred forty-five (145) unique genera were identified using molecular methods, and 68 of these genera were aerotolerant. Fourteen (14) unique genera were identified using aerobic culture methods. One-third (31/92) of the cultures were determined to be < 1% of the relative abundance of the wound microbiota using molecular testing. At the genus level, molecular testing identified 85% (78/92) of the bacteria that were identified by culture. Conversely, culturing detected 15.7% (78/497) of the aerotolerant bacteria and detected 54.9% of the collective aerotolerant relative abundance of the samples. Aerotolerant bacterial genera (and individual species including Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis) with higher relative abundance scores were more likely to be detected by culture as demonstrated with regression modeling.

Conclusion

Discordance between molecular and culture testing is often observed. However, culture-free 16S ribosomal DNA sequencing and its relative abundance score can provide clinicians with insight into which bacteria are most abundant in a sample and which are most likely to be detected by culture.
White matter connectivity in children with autism spectrum disorders: a tract-based spatial statistics study
Authors: Billeci Lucia , Calderoni Sara , Tosetti Michela , Catani Marco , Muratori Filippo
Published: November 2012

Background

Autism spectrum disorders (ASD) are associated with widespread alterations in white matter (WM) integrity. However, while a growing body of studies is shedding light on microstructural WM alterations in high-functioning adolescents and adults with ASD, literature is still lacking in information about whole brain structural connectivity in children and low-functioning patients with ASD. This research aims to investigate WM connectivity in ASD children with and without mental retardation compared to typically developing controls (TD).

Methods

Diffusion tensor imaging (DTI) was performed in 22 young children with ASD (mean age: 5.54 years) and 10 controls (mean age: 5.25 years). Data were analysed both using the tract-based spatial statistics (TBSS) and the tractography. Correlations were investigated between the WM microstructure in the identified altered regions and the productive language level.

Results

The TBSS analysis revealed widespread increase of fractional anisotropy (FA) in major WM pathways. The tractographic approach showed an increased fiber length and FA in the cingulum and in the corpus callosum and an increased mean diffusivity in the indirect segments of the right arcuate and the left cingulum. Mean diffusivity was also correlated with expressive language functioning in the left indirect segments of the arcuate fasciculus.

Conclusions

Our study confirmed the presence of several structural connectivity abnormalities in young ASD children. In particular, the TBSS profile of increased FA that characterized the ASD patients extends to children a finding previously detected in ASD toddlers only. The WM integrity abnormalities detected may be relevant to the pathophysiology of ASD, since the structures involved participate in some core atypical characteristics of the disorder.
Salinomycin induces cell death and differentiation in head and neck squamous cell carcinoma stem cells despite activation of epithelial-mesenchymal transition and Akt
Authors: Kuo Selena Z , Blair Katherine J , Rahimy Elham , Kiang Alan , Abhold Eric , Fan Jian-Bing , Wang-Rodriguez Jessica , Altuna Xabier , Ongkeko Weg M
Published: November 2012

Background

Cancer stem cells (CSC) are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Recent studies have reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells 100-fold more effectively than paclitaxel. In our study we sought to determine the effects of salinomycin on head and neck squamous cell carcinoma (HNSCC) stem cells.

Methods

MTS and TUNEL assays were used to study cell proliferation and apoptosis as a function of salinomycin exposure in JLO-1, a putative HNSCC stem cell culture. MTS and trypan blue dye exclusion assays were performed to investigate potential drug interactions between salinomycin and cisplatin or paclitaxel. Stem cell-like phenotype was measured by mRNA expression of stem cell markers, sphere-forming capacity, and matrigel invasion assays. Immunoblotting was also used to determine expression of epithelial-mesenchymal transition (EMT) markers and Akt phosphorylation. Arrays by Illumina, Inc. were used to profile microRNA expression as a function of salinomycin dose.

Results

In putative HNSCC stem cells, salinomycin was found to significantly inhibit cell viability, induce a 71.5% increase in levels of apoptosis, elevate the Bax/Bcl-2 ratio, and work synergistically with cisplatin and paclitaxel in inducing cell death. It was observed that salinomycin significantly inhibited sphere forming-capability and repressed the expression of CD44 and BMI-1 by 3.2-fold and 6.2-fold, respectively. Furthermore, salinomycin reduced invasion of HNSCC stem cells by 2.1 fold. Contrary to expectations, salinomycin induced the expression of EMT markers Snail, vimentin, and Zeb-1, decreased expression of E-cadherin, and also induced phosphorylation of Akt and its downstream targets GSK3-β and mTOR.

Conclusions

These results demonstrate that in HNSCC cancer stem cells, salinomycin can cause cell death and decrease stem cell properties despite activation of both EMT and Akt.
A comparative study on the hepatoprotective action of bear bile and coptidis rhizoma aqueous extract on experimental liver fibrosis in rats
Authors: Wang Ning , Feng Yibin , Cheung Fan , Chow Oi-Yee , Wang Xuanbin , Su Weiwei , Tong Yao
Published: November 2012

Aim of the study

Bear bile and Coptidis Rhizoma have been used in Chinese medicine with a long tradition in treating heat-diseases. Both bear bile and Coptidis Rhizoma are used to treat liver diseases in clinical practice of Chinese Medicine. Since bears are currently endangered, it raises the question whether the use of bear bile is ethical. To look for substitute for bear bile, the aim of this study is to compare the anti-fibrotic effects of Coptidis Rhizoma and its major component berberine with the actions of bear bile and its major compound tauroursodeoxycholic acid on experimental liver fibrosis in rats.

Method

Quality assessment was conducted with high performance liquid chromatography. The experimental liver fibrosis in rats was induced by carbon tetrachloride, alcohol, and bile duct ligation respectively. The biochemical criteria in the blood and tissue samples were measured to evaluate the anti-fibrotic properties and underlying mechanisms of the drugs.

Results

Coptidis Rhizoma Aqueous Extract (CRAE), berberine, and bear bile exerted anti-fibrotic properties on various liver fibrosis models in rats. CRAE and berberine significantly reduced the peroxidative stress in liver through increasing the superoxide dismutase enzyme activity. CRAE and berberine were able to excrete bilirubin products from the liver and protect hepatocytes from cholestatic damage. The effect of CRAE and berberine are comparable to that of bear bile.

Conclusion

Instead of using bear bile, CRAE and berberine can be potential substitutes in treating liver fibrosis.
Nerve growth factor: from the early discoveries to the potential clinical use
Authors: Aloe Luigi , Rocco Maria Luisa , Bianchi Patrizia , Manni Luigi
Published: November 2012

The physiological role of the neurotrophin nerve growth factor (NGF) has been characterized, since its discovery in the 1950s, first in the sensory and autonomic nervous system, then in central nervous, endocrine and immune systems. NGF plays its trophic role both during development and in adulthood, ensuring the maintenance of phenotypic and functional characteristic of several populations of neurons as well as immune cells. From a translational standpoint, the action of NGF on cholinergic neurons of the basal forebrain and on sensory neurons in dorsal root ganglia first gained researcher’s attention, in view of possible clinical use in Alzheimer’s disease patients and in peripheral neuropathies respectively. The translational and clinical research on NGF have, since then, enlarged the spectrum of diseases that could benefit from NGF treatment, at the same time highlighting possible limitations in the use of the neurotrophin as a drug. In this review we give a comprehensive account for almost all of the clinical trials attempted until now by using NGF. A perspective on future development for translational research on NGF is also discussed, in view of recent proposals for innovative delivery strategies and/or for additional pathologies to be treated, such as ocular and skin diseases, gliomas, traumatic brain injuries, vascular and immune diseases.
Preparation of hollow TiO2 nanoparticles through TiO2 deposition on polystyrene latex particles and characterizations of their structure and photocatalytic activity
Authors: Wang Jingang , Yu Jiemei , Zhu Xiaoli , Kong Xiang Zheng
Published: November 2012

In a mixed solvent of water and ethanol, polystyrene/titanium dioxide (PSt/TiO2) composite particles of core-shell structure were prepared by hydrolysis of tetrabutyl titanate in the presence of cationic PSt particles or anionic PSt particles surface-treated using γ-aminopropyl triethoxysilane. Hollow TiO2 particles were obtained through calcination of the PSt/TiO2 core-shell particles to burn off the PSt core or through dissolution of the core by tetrahydrofuran (THF). An alternative process constituted of preheating the PSt/TiO2 particles at 200°C to allow partial crystallization followed by calcination or PSt dissolution by THF. The outcome TiO2 particles thus prepared were examined by TEM, and hollow TiO2 particles were observed. The crystalline phase structure and phase transformation were characterized, which revealed that preheating before the removal of the PSt core was useful to achieve the desired hollow TiO2 particles, and the calcination process was beneficial to the formation of anatase and rutile structures. The tests of TiO2 particles as catalyst in the photodegradation of Rhodamine B demonstrated that a much higher catalytic activity was observed with the TiO2 hollow particles prepared through calcination combined with preheating.
Effectiveness of photochemical and sonochemical processes in degradation of Basic Violet 16 (BV16) dye from aqueous solutions
Authors: Rahmani Zahra , Kermani Majid , Gholami Mitra , Jafari Ahmad Jonidi , Mahmoodi Niyaz Mohammad
Published: November 2012

In this study, degradation of Basic Violet 16 (BV16) by ultraviolet radiation (UV), ultrasonic irradiation (US), UV/H2O2and US/H2O2processes was investigated in a laboratory-scale batch photoreactor equipped with a 55W immersed-type low-pressure mercury vapor lamp and a sonoreactor with high frequency (130kHz) plate type transducer at 100W of acoustic power. The effects of initial dye concentration, concentration of H2O2and solution pH and presence of Na2SO4was studied on the sonochemical and photochemical destruction of BV16 in aqueous phase. The results indicated that in the UV/H2O2and US/H2O2systems, a sufficient amount of H2O2was necessary, but a very high H2O2concentration would inhibit the reaction rate. The optimum H2O2concentration was achieved in the range of 17 mmol/L at dye concentration of 30 mg/L. A degradation of 99% was obtained with UV/H2O2within 8 minutes while decolorization efficiency by using UV (23%), US (<6%) and US/H2O2(<15%) processes were negligible for this kind of dye. Pseudo-first order kinetics with respect to dyestuffs concentrations was found to fit all the experimental data.
1,8-Cineole, a TRPM8 Agonist, is a Novel Natural Antagonist of Human TRPA1
Authors: Takaishi Masayuki , Fujita Fumitaka , Uchida Kunitoshi , Yamamoto Satoshi , Sawada (Shimizu) Maki , Hatai (Uotsu) Chihiro , Shimizu Mayumi , Tominaga Makoto
Published: November 2012

Background:

Essential oils are often used in alternative medicine as analgesic and anti-inflammatory remedies. However, the specific compounds that confer the effects of essential oils and the molecular mechanisms are largely unknown. TRPM8 is a thermosensitive receptor that detects cool temperatures and menthol whereas TRPA1 is a sensor of noxious cold. Ideally, an effective analgesic compound would activate TRPM8 and inhibit TRPA1.

Results:

We screened essential oils and fragrance chemicals showing a high ratio of human TRPM8-activating ability versus human TRPA1-activating ability using a Ca2+-imaging method, and identified 1,8-cineole in eucalyptus oil as particularly effective. Patch-clamp experiments confirmed that 1,8-cineole evoked inward currents in HEK293T cells expressing human TRPM8, but not human TRPA1. In addition, 1,8-cineole inhibited human TRPA1 currents activated by allyl isothiocyanate, menthol, fulfenamic acid or octanol in a dose-dependent manner. Furthermore, in vivo sensory irritation tests showed that 1,8-cineole conferred an analgesic effect on sensory irritation produced by TRPA1 agonists octanol and menthol. Surprisingly, 1,4-cineole, which is structurally similar and also present in eucalyptus oil, activated both human TRPM8 and human TRPA1.

Conclusions:

1,8-cineole is a rare natural antagonist of human TRPA1 that has analgesic and anti-inflammatory effects possibly due to its inhibition of TRPA1.
Engaging people who use drugs in policy and program development: A review of the literature
Authors: Ti Lianping , Tzemis Despina , Buxton Jane A
Published: November 2012

Health policies and programs are increasingly being driven by people from the community to more effectively address their needs. While a large body of evidence supports peer engagement in the context of policy and program development for various populations, little is known about this form of engagement among people who use drugs (PWUD). Therefore, a narrative literature review was undertaken to provide an overview of this topic. Searches of PubMed and Academic Search Premier databases covering 1995–2010 were conducted to identify articles assessing peer engagement in policy and program development. In total, 19 articles were included for review. Our findings indicate that PWUD face many challenges that restrict their ability to engage with public health professionals and policy makers, including the high levels of stigma and discrimination that persist among this population. Although the literature shows that many international organizations are recommending the involvement of PWUD in policy and program development, our findings revealed a lack of published data on the implementation of these efforts. Gaps in the current evidence highlight the need for additional research to explore and document the engagement of PWUD in the areas of policy and program development. Further, efforts to minimize stigmatizing barriers associated with illicit drug use are urgently needed to improve the engagement of PWUD in decision making processes.
Spontaneous perforation of jejunal gastrintestinal stromal tumour (gist). Case report and review of literature
Authors: Roy Somsubhra Datta , Khan Dawood , De Krishna K , De Utpal
Published: November 2012

GIST is the commonest mesenchymal tumour of the gastrointestinal tract. Jejunal GIST is rare and spontaneous perforation of asymptomatic jejunal GIST is unique. A review of the English literature reveals only fifteen cases of perforated GIST till date. Pre-operative diagnosis is difficult. Diagnosis is confirmed on histopathology and immuno-histochemistry. Complete removal with postoperative imatinib therapy entails optimal treatment. Perforated GIST is associated with high recurrence.
Antioxidant and anti-inflammatory activities of selected medicinal plants and fungi containing phenolic and flavonoid compounds
Authors: Diaz Patricia , Jeong Sang Chul , Lee Samiuela , Khoo Cheang , Koyyalamudi Sundar Rao
Published: November 2012

Background

This study aims to determine the relationship between the antioxidant and anti-inflammatory activities of the thirteen herbs and two fungi extracts, and their total phenolic and flavonoid contents.

Methods

Antioxidant activities were evaluated by four assays: an antioxidant activity assay usingSaccharomyces cerevisiae, a DPPH ((2, 2-diphenyl-1-picrylhydrazyl) assay to assess free radical scavenging, an assay assessing ferrous ions or iron (II) chelating ability, and a ferric reducing antioxidant power (FRAP) assay. Total phenolic and flavonoid contents were determined using the Folin-Ciocalteu and aluminium chloride methods, respectively. Anti-inflammatory activities were determined by measuring the inhibition of nitric oxide and TNF-α production in lipopolysaccharide- and interferon-γ-activated J774A.1 macrophages. Their cytotoxicities against macrophages were determined by MTT assay.

Results

A positive linear correlation between antioxidant activities and the total phenolic and flavonoid content of the plant extracts was found. The plant extracts with high phenolic and flavonoid content also exhibited significant anti-inflammatory activity with good cell viability.

Conclusion

The selected herbs could be a rich source of antioxidants and free radical scavenging compounds. The levels of phenolic and flavonoid compounds were correlated with the antioxidant and anti-inflammatory activities of the extracts from the herbs.
UPLC-QTOF-MS with chemical profiling approach for rapidly evaluating chemical consistency between traditional and dispensing granule decoctions of Tao-Hong-Si-Wu decoction
Authors: Shang Erxin , Zhu Zhenhua , Liu Li , Tang Yuping , Duan Jin-ao
Published: November 2012

Background

In the present study, chemical consistency between traditional and dispensing granule decoctions of Tao-Hong-Si-Wu decoction was rapidly evaluated by UPLC-QTOF-MS coupled with the MarkerLynx software. Two different kinds of decoctions, namely traditional decoction: water extract of mixed six constituent herbs of Tao-Hong-Si-Wu decoction, and dispensing granules decoction: mixed water extract of each individual herbs of Tao-Hong-Si-Wu decoction, were prepared.

Results

Chemical difference was found between traditional and dispensing granule decoctions, and albiflorin, paeoniflorin, gallic acid, amygdalin, and hydroxysafflor yellow A were identified as the significantly changed components during decocting Tao-Hong-Si-Wu decoction. All the peaks of mass spectrum from Tao-Hong-Si-Wu decoction and each herb were extracted and integration by using QuanLynx™. And the optimized data was used for linear regression analysis. The contribution of each herb in Tao-Hong-Si-Wu decoction, and the optimal compatibility proportion of dispensing granule decoction were derived from the linear regression equation.

Conclusions

The optimal dosage proportionality of Tao-Hong-Si-Wu dispensing granule decoction was obtained as 2.5:0.2:1:0.5:0.6:0.1 (DG : CX : BS : SD : TR : HH), which guided better clinic application of Tao-Hong-Si-Wu decoction as dispensing granule decoctions usage, and it also provided some experimental data to reveal the compatibility rule of the relative TCM formulae.
Associations of the TNF-alpha -308 G/A, IL6 -174 G/C and AdipoQ 45 T/G polymorphisms with inflammatory and metabolic responses to lifestyle intervention in Brazilians at high cardiometabolic risk
Authors: Curti Maira LR , Pires Milena M , Barros Camila R , Siqueira-Catania Antonela , Rogero Marcelo Macedo , Ferreira Sandra RG
Published: November 2012

Background

Cytokines secreted by the adipose tissue influence inflammation and insulin sensitivity, and lead to metabolic disturbances. How certain single-nucleotide polymorphisms (SNPs) interfere on lifestyle interventions is unclear. We assessed associations of selected SNPs with changes induced by a lifestyle intervention.

Methods

This 9-month intervention on diet and physical activity included 180 Brazilians at high cardiometabolic risk, genotyped for the TNF-α -308 G/A, IL-6 -174 G/C and AdipoQ 45 T/G SNPs. Changes in metabolic and inflammatory variables were analyzed according to these SNPs. Individuals with at least one variant allele were grouped and compared with those with the reference genotype.

Results

In the entire sample (66.7% women; mean age 56.5 ± 11.6 years), intervention resulted in lower energy intake, higher physical activity, and improvement in anthropometry, plasma glucose, HOMA-IR, lipid profile and inflammatory markers, except for IL-6 concentrations. After intervention, only variant allele carriers of the TNF-α -308 G/A decreased plasma glucose, after adjusting for age and gender (OR 2.96, p = 0.025). Regarding the IL6 -174 G/C SNP, carriers of the variant allele had a better response of lipid profile and adiponectin concentration, but only the reference genotype group decreased plasma glucose. In contrast to individuals with the reference genotype, carriers of variant allele of AdipoQ 45 T/G SNP did not change plasma glucose, apolipoprotein B, HDL-c and adiponectin concentrations in response to intervention.

Conclusion

The TNFα -308 G/A SNP may predispose a better response of glucose metabolism to lifestyle intervention. The IL-6 -174 G/C SNP may confer a beneficial effect on lipid but not on glucose metabolism. Our findings reinforce unfavorable effects of the AdipoQ 45 T/G SNP in lipid profile and glucose metabolism after intervention in Brazilians at cardiometabolic risk. Further studies are needed to direct lifestyle intervention to subsets of individuals at cardiometabolic risk.
Raised circulating tenascin-C in rheumatoid arthritis
Authors: Page Theresa H , Charles Peter J , Piccinini Anna M , Nicolaidou Vicky , Taylor Peter C , Midwood Kim S
Published: November 2012

Introduction

The aim of this study was to examine whether circulating levels of the pro-inflammatory glycoprotein tenascin-C (TNC) are elevated in musculoskeletal disorders including rheumatoid arthritis (RA) and to assess in RA whether levels are related to clinical disease status and/or patient response to treatment.

Methods

TNC in serum or plasma was quantified by ELISA. Samples from 4 cohorts of RA patients were examined and compared to normal human subjects and to patients with other inflammatory diseases.

Results

Circulating TNC levels were significantly raised in patients with RA, as well as patients with systemic lupus erythematosus, idiopathic inflammatory myositis, psoriatic arthritis and ankylosing spondylitis, whilst patients with Sjogren's syndrome displayed levels similar to healthy controls. The highest levels of TNC were observed in RA patients with late stage disease. In early disease TNC levels correlated positively with ultrasound determined erosion scores. Treatment of early RA patients with infliximab plus methotrexate (MTX) resulted in a transient decrease in circulating TNC over the first year of therapy. In contrast, TNC levels increased over time in RA patients receiving MTX alone. In patients treated with infliximab plus MTX, baseline TNC levels significantly correlated with tender joint counts (TJC) at 18 and 54 weeks after initiation of infliximab therapy.

Conclusions

Raised circulating TNC levels are detected in specific inflammatory diseases. Levels are especially high in RA where they may act as a biomarker of bone erosion and a predictor of the effect of infliximab on RA patient joint pain.
Markers of intestinal inflammation in patients with ankylosing spondylitis: a pilot study
Authors: Matzkies Franziska G , Targan Stephan R , Berel Dror , Landers Carol J , Reveille John D , McGovern Dermot PB , Weisman Michael H
Published: November 2012

Introduction

Inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) are similar chronic inflammatory diseases whose definitive etiology is unknown. Following recent clinical and genetic evidence supporting an intertwined pathogenic relationship, we conducted a pilot study to measure fecal calprotectin (fCAL) and IBD-related serologies in AS patients.

Methods

Consecutive AS patients were recruited from a long-term prospectively collected longitudinal AS cohort at Cedars-Sinai Medical Center. Controls were recruited from Cedars-Sinai Medical Center employees or spouses of patients with AS. Sera were tested by ELISA for IBD-associated serologies (antineutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibody IgG and IgA, anti-I2, anti-OmpC, and anti-CBir1). The Bath Ankylosing Spondylitis Disease Activity Index, the Bath Ankylosing Spondylitis Functional Index, and the Bath Ankylosing Spondylitis Radiology Index were completed for AS patients.

Results

A total of 81 subjects (39 AS patients and 42 controls) were included for analysis. The average age of AS patients was 47 years and the average disease duration was 22 years. AS patients were predominantly male; 76% were HLA-B27-positive. Median fCAL levels were 42 μg/g and 17 μg/g in the AS group and controls, respectively (P < 0.001). When using the manufacturer's recommended cutoff value for positivity of 50 μg/g, stool samples of 41% of AS patients and 10% of controls were positive for fCAL (P = 0.0016). With the exception of ANCA, there were no significant differences in antibody levels between patients and controls. Median ANCA was 6.9 ELISA units in AS patients and 4.3 ELISA units in the controls. Among AS patients stratified by fCAL level, there were statistically significant differences between patients and controls for multiple IBD-associated antibodies.

Conclusion

Calprotectin levels were elevated in 41% of patients with AS with a cutoff value for positivity of 50 μg/g. fCAL-positive AS patients displayed higher medians of most IBD-specific antibodies when compared with healthy controls or fCAL-negative AS patients. Further studies are needed to determine whether fCAL can be used to identify and characterize a subgroup of AS patients whose disease might be driven by subclinical bowel inflammation.
Modelling the overdiagnosis of breast cancer due to mammography screening in womenaged 40 to 49 in the United Kingdom
Authors: Gunsoy Necdet B , Garcia-Closas Montserrat , Moss Sue M
Published: November 2012

Introduction

Overdiagnosis of breast cancer due to mammography screening, defined as thediagnosis of screen-detected cancers that would not have presented clinically in awomen's lifetime in the absence of screening, has emerged as a highly contentiousissue, as harm caused may question the benefit of mammographic screening. Moststudies included women over 50 years old and little information is available foryounger women.

Methods

We estimated the overdiagnosis of breast cancer due to screening in women aged 40to 49 years using data from a randomised trial of annual mammographic screeningstarting at age 40 conducted in the UK. A six-state Markov model was constructedto estimate the sensitivity of mammography for invasive and insitu breast cancer and the screen-detectable mean sojourn time fornon-progressive in situ, progressive in situ, and invasivebreast cancer. Then, a 10-state simulation model of cancer progression, screening,and death, was developed to estimate overdiagnosis attributable to screening.

Results

The sensitivity of mammography for invasive and in situ breast cancerswas 90% (95% CI, 72 to 99) and 82% (43 to 99), respectively. The screen-detectablemean sojourn time of preclinical non-progressive and progressive in situ cancers was 1.3 (0.4 to 3.4) and 0.11 (0.05 to 0.19) years, respectively, and0.8 years (0.6 to 1.2) for preclinical invasive breast cancer. The proportion ofscreen-detected in situ cancers that were non-progressive was 55% (25 to77) for the first and 40% (22 to 60) for subsequent screens. In our main analysis,overdiagnosis was estimated as 0.7% of screen-detected cancers. A sensitivityanalysis, covering a wide range of alternative scenarios, yielded a range of 0.5%to 2.9%.

Conclusion

Although a high proportion of screen-detected in situ cancers werenon-progressive, a majority of these would have presented clinically in theabsence of screening. The extent of overdiagnosis due to screening in women aged40 to 49 was small. Results also suggest annual screening is most suitable forwomen aged 40 to 49 in the United Kingdom due to short cancer sojourn times.
MIRAGE: a functional genomics-based approach for metabolic network model reconstruction and its application to cyanobacteria networks
Authors: Vitkin Edward , Shlomi Tomer
Published: November 2012

Genome-scale metabolic network reconstructions are considered a key step in quantifying the genotype-phenotype relationship. We present a novel gap-filling approach, MetabolIc Reconstruction via functionAl GEnomics (MIRAGE), which identifies missing network reactions by integrating metabolic flux analysis and functional genomics data. MIRAGE's performance is demonstrated on the reconstruction of metabolic network models of E. coli and Synechocystis sp. and validated via existing networks for these species. Then, it is applied to reconstruct genome-scale metabolic network models for 36 sequenced cyanobacteria amenable for constraint-based modeling analysis and specifically for metabolic engineering. The reconstructed network models are supplied via standard SBML files.
Coordinate regulation of N-glycosylation gene DPAGT1, canonical Wnt signaling and E-cadherin adhesion
Authors: Sengupta Pritam K. , Bouchie Meghan P. , Nita-Lazar Mihai , Yang Hsiao-Ying , Kukuruzinska Maria A.
Published: November 2012

The metabolic pathway of protein N-glycosylation influences intercellular adhesion by affecting the composition and cytoskeletal association of E-cadherin protein complexes, or adherens junctions (AJs). In sparse cells, E-cadherin is modified extensively with complex N-glycans and forms nascent AJs, while in dense cultures, hypoglycosylated E-cadherin drives the assembly of mature AJs with increased levels of γ- and α-catenins. N-glycosylation of E-cadherin is controlled by the DPAGT1 gene, a key regulator of the N-glycosylation pathway. DPAGT1 is a target of the canonical Wnt signaling pathway, with both β- and γ-catenins binding to Tcf at its promoter. We now report that DPAGT1 senses cell density through canonical Wnt signaling. In dense cells, depletion of β-catenin from the DPAGT1 promoter correlated with downregulation of its cellular abundance, while loss of nuclear γ-catenin reflected its greater recruitment to AJs. DPAGT1 itself affected canonical Wnt signaling, with forced changes in its expression resulting in corresponding changes in transcriptionally active β-catenin and canonical Wnt activity. Remarkably, a 2.4-fold increase in the DPAGT1 mRNA level resulted in increased N-glycosylation and reduced membrane localization of E-cadherin, coincident with dramatic changes in cell morphology. Lastly, we present evidence that N-glycosylation status of E-cadherin controls its antagonism of canonical Wnt signaling. Transfection of hypoglycosylated E-cadherin mutant, V13, but not fully N-glycosylated E-cadherin, into sparse cells inhibited canonical Wnt activity by depleting nuclear β- and γ-catenins. Collectively, our studies show that cells coordinate DPAGT1 expression and protein N-glycosylation with canonical Wnt signaling and E-cadherin adhesion via positive and negative feedback mechanisms.
Regulation of telomere length and homeostasis by telomerase enzyme processivity
Authors: D'Souza Yasmin , Lauzon Catherine , Chu Tsz Wai , Autexier Chantal
Published: November 2012

Telomerase is a ribonucleoprotein consisting of a catalytic subunit, the telomerase reverse transcriptase (TERT), and an integrally associated RNA that contains a template for the synthesis of short repetitive G-rich DNA sequences at the ends of telomeres. Telomerase can repetitively reverse transcribe its short RNA template, acting processively to add multiple telomeric repeats onto the same DNA substrate. The contribution of enzyme processivity to telomere length regulation in human cells is not well characterized. In cancer cells, under homeostatic telomere length-maintenance conditions, telomerase acts processively, whereas under nonequilibrium conditions, telomerase acts distributively on the shortest telomeres. To investigate the role of increased telomerase processivity on telomere length regulation in human cells with limited lifespan that are dependent on human TERT for lifespan extension and immortalization, we mutated the leucine at position 866 in the reverse transcriptase C motif of human TERT to a tyrosine (L866Y), which is the amino acid found at the equivalent position in HIV-1 reverse transcriptase. We report that, similar to the previously reported gain-of-function Tetrahymena telomerase mutant (L813Y), the human telomerase variant displays increased processivity. Human TERT-L866Y, like wild-type human TERT, can immortalize and extend the lifespan of limited-lifespan cells. Moreover, cells expressing human TERT-L866Y display heterogenous telomere lengths, telomere elongation, multiple telomeric signals indicative of fragile sites and replicative stress, and an increase in short telomeres, which is accompanied by telomere trimming events. Our results suggest that telomere length and homeostasis in human cells may be regulated by telomerase enzyme processivity.
The Meanings of the Term ḥrj-ib in Divine Epithets
Authors: Eaton Katherine
Published: November 2012

The epithet “ḥrj-ib temple X”, when inscribed in scenes or texts within “temple X” designates deities with divine images which received cult in that temple. Those images might be permanently resident in that temple, or just visiting for a festival. Thus, the deity’s association with that temple was indicated, without providing any definitive indication concerning the permanency or duration of that association. Deities could also visit temple X without residing in it, or receive cult remotely with no three-dimensional physical presence in temple X. These deities were sometimes localized externally with the epithet “ḥrj-ib temple Y” in scenes and texts in temple X.
The Peculiar Naophorous Statuette of a Heliopolitan Priest
Authors: Klotz David
Published: November 2012

First publication of a naophorous statuette from the Museum August Kestner, Hannover. This object belongs to the Heliopolitan priest Psamtek, apparently the son of the well-known vizier Psamtek-Seneb, and thus likely dates to the Thirtieth Dynasty. The statue owner’s titles provide further evidence for lesser known cults of Heliopolis, and the autobiographical inscription is unique for its concentration of unconventional enigmatic orthographies.