bluuebunny/crossref_metadata_2025 huggingface dataset:
Micro- and macro-creep damage formation for P92 under multiaxial stress related to circular notched specimen
Authors: Shigeyama H. , Sugiura R. , Matsuzaki T. , Yokobori A. T.
Published: October 2013

In this study, to clarify the behaviour of micro- and macro-creep damage progression for P92 under multiaxial stress field, interrupted creep tests, analysis of multiaxial stress and detailed the cross-sectional observations were conducted on a circular notched round bar specimen which produces the multiaxial stress field due to the plastic constraint. As a result, creep voids were initiated at the early stage and they were formed up to the final fracture. These phenomena were found to be detected using direct current potential drop (DCPD) method. These results concern the development of the measurement of creep crack initiation. The distribution of high void area fraction was in good agreement with that of high hydrostatic stress and high multiaxial stress. This result indicates that multiaxial stress affects the void formation. Furthermore, the micro-creep damage of each interrupted specimen was evaluated by using the electron backscatter diffraction (EBSD) method which can analyse crystallographic misorientation caused by creep strain. The results of EBSD analyses indicated that the value of grain reference orientation deviation (GROD) closely concerns the void initiation.
Diffusion brazing of cast INCONEL 718 superalloy utilising standard heat treatment cycle
Authors: Pouranvari M. , Ekrami A. , Kokabi A. H.
Published: October 2013

The time required to ensure completion of the isothermal solidification process is the key in obtaining an intermetallic free and robust joint after diffusion brazing. In view of economic considerations, it is interesting to perform bonding process trials using standard heat treatment cycles. This paper addresses the effect of applying the standard heat treatment cycle including homogenisation, solution and double aging treatments on the microstructural and mechanical response of diffusion brazed IN718. A commercial Ni–7Cr–4·5Si–3·2B–3Fe (wt-) brazing alloy was used as the interlayer. Results showed that bonds made with the standard homogenisation treatment, at 1100°C, exhibited a eutectic free joint centreline. After applying the standard solution and double aging treatment, a bond with a joint efficiency of 82 relative to base metal was obtained in terms of shear strength. Room temperature tensile properties and stress rupture properties of the diffusion brazed joint were better than the minimum requirement of the AMS5383 acceptance standard.
Influence of single and double aging treatment on microstructures and mechanical properties of cold rolled Ti–30Nb–5Ta–6Zr alloy
Authors: Wang Y. , Dai S. , Chen F. , Yu X. , Zhang Y.
Published: October 2013

A new β type Ti–30Nb–5Ta–6Zr alloy with low Young's modulus, high tensile strength, good plasticity and biocompatibility was designed according to d-electron alloy design method. The influence of single and double aging time on microstructures and mechanical properties of the cold rolled and then soluted alloy was investigated. It was found that the cold rolled Ti–30Nb–5Ta–6Zr alloy is composed of single β phase after solution treatment at 750°C. With increasing single aging time that varied from 2 to 8 h at 450 and 500°C, the size and quantity of acicular α phase increased gradually, as well as the strength and elastic modulus. As compared with single aging process, the acicular α phase became coarsen with increasing double aging time that varied from 0·5 to 2 h, while the quantity of α phase decreased. The strength and elastic modulus of the alloy decreased, and the ductility was improved after double aging treatment. Ti–30Nb–5Ta–6Zr alloy obtained excellent integrated mechanical properties through first aging at low temperature for long time and then second aging at high temperature for short time.
Influence of copper on hardness of amorphous As–Se–I thin films
Authors: Štrbac D. D. , Lukić-Petrović S. R. , Petrović D. M. , Videnović I. R. , Dramićanin M.
Published: October 2013

The paper reports on hardness of thin amorphous films of the Cux(As38·5Se54I7·5)100–x type for x = 10, 15, 20 and 25 at- evaluated by microindentation measurements and instrumented nanoindentation testing. Values of determined microhardness are in the interval of 748–1137 MPa, while nanohardness are in the interval of 930–1591 MPa and can be regarded as moderate in the category of chalcogenide glasses. Isotropic mechanical properties on thin films surface are determined. Influence of copper on mechanical properties of As–Se–I films is discussed in terms of possible structural units in glass matrix.
Numerical analysis of layered surface mechanical attrition treated 304SS with nanograin layer based on cohesive model
Authors: Wang X. , Fang B. , Zhao W. , Zhang Y.
Published: October 2013

Based on the techniques of surface mechanical attrition treatment, laminated and nanostructured materials with high strength and high ductility can be produced. In order to capture the deformation behaviour and associated damage initiation/evolution process in the layered surface mechanical attrition treated 304SS (stainless steel), a cohesive model is employed into finite element method to investigate the effects of the constituent materials on the overall strength and ductility of layered surface mechanical attrition treated 304SS in the present paper. It is found that the normal cohesive strength, tangential cohesive strength and fracture energy of both the nanograin layer and the surface mechanical attrition treated 304SS layer have a significant influence on the failure strain of layered corolled surface mechanical attrition treated 304SS. Simulation results also indicate that the layered bonded surface mechanical attrition treated 304SS may be superior to the layered corolled surface mechanical attrition treated 304SS when the adhesive is suitably chosen.
Comparing bond formation mechanism between similar and dissimilar aluminium alloy friction welds
Authors: Ashfaq M. , Rao K. J.
Published: October 2013

Friction welding of high strength aluminium alloys was considered in the current study. The mechanism of bond formation in dissimilar alloy welding was compared to similar alloy welding. The differences in flow properties between two different alloys of aluminium lead to uneven deformation behaviour while welding. Since flow behaviour directly affects bond formation and strength, it is important to understand its behaviour. Rods of aluminium alloys AA 2024 and AA 6061 were welded to themselves and to each other denoting similar and dissimilar weld systems. Burn-off length, which is one of the important parameters in friction welding was varied in steps to see how it affects the bond formation. The flash geometry of the welds was observed to interpret the flow differences. Reasons for variations in bond formation were discussed with the help of fracture surfaces.
Correlation between fractal dimension and strength of brittle bulk metallic glasses
Authors: Yang W. , Zhao Y. , Dou L. , Dun C. , Zhang J. , Li M. , Zhao G. , Xue L. , Bian H. , Liu H.
Published: October 2013

In this paper, the strength of brittle bulk metallic glasses (BMGs) was investigated, and a corresponding theoretical model was proposed by modification of Griffith theory using fractal geometry. It was shown that the fracture energy and strength of brittle BMGs not only are related to the plastic zone size, the length scales of atomic order range and the surface energy but also has significant relationship with the fractal dimension in fracture surface. The strength of typical BMGs was also calculated by our improved model, which is in excellent agreement with the experimental data. This study provides a compelling approach for investigating and understanding the high strength of BMGs.
Analysis of single spray beads prepared using low-pressure cold spraying
Authors: Koivuluoto Heli , Vuoristo Petri
Published: October 2013

Cold spraying is a coating deposition method for the production of high-quality metallic coatings. Copper, for instance, is widely used as a coating material due to its suitability for cold spray process. Cold-sprayed copper coatings are known to have interesting technical properties such as high electrical and thermal conductivity. Low-pressure cold spraying (LPCS) is a cold spray technique of preparing relatively dense and pure copper coatings. The deposition behaviour of low-pressure cold-sprayed spherical and dendritic copper particles impacting the substrate was evaluated in this study. The effect of powder type was clearly detected in the observations of single spray beads. Higher deposition efficiency and denser coatings were prepared by using the spherical copper powder.
G protein–dependent basal and evoked endothelial cell vWF secretion
Authors: Rusu Luiza , Andreeva Alexandra , Visintine David J. , Kim Kyungho , Vogel Stephen M. , Stojanovic-Terpo Aleksandra , Chernaya Olga , Liu Guoquan , Bakhshi Farnaz R. , Haberichter Sandra L. , Iwanari Hiroko , Kusano-Arai Osamu , Suzuki Nobuchika , Hamakubo Takao , Kozasa Tohru , Cho Jaehyung , Du Xiaoping , Minshall Richard D.
Published: October 2013

Key Points

Gα12 interaction with α-SNAP regulates basal EC vWF secretion. PAR-1 activation-dependent signaling via Gα12/RhoA and Gαq/11 enhances vWF secretion.
Ceramides: a potential therapeutic target in pulmonary emphysema
Authors: Tibboel Jeroen , Reiss Irwin , de Jongste Johan C , Post Martin
Published: October 2013

Background

The aim of this manuscript was to characterize airway ceramide profiles in a rodent model of elastase-induced emphysema and to examine the effect of pharmacological intervention directed towards ceramide metabolism.

Methods

Adult mice were anesthetized and treated with an intratracheal instillation of elastase. Lung function was measured, broncho-alveolar lavage fluid collected and histological and morphometrical analysis of lung tissue performed within 3 weeks after elastase injection, with and without sphingomyelinase inhibitors or serine palmitoyltransferase inhibitor. Ceramides in broncho-alveolar lavage (BAL) fluid were quantified by tandem mass spectrometry.

Results

BAL fluid showed a transient increase in total protein and IgM, and activated macrophages and neutrophils. Ceramides were transiently upregulated at day 2 after elastase treatment. Histology showed persistent patchy alveolar destruction at day 2 after elastase installation. Acid and neutral sphingomyelinase inhibitors had no effect on BAL ceramide levels, lung function or histology. Addition of a serine palmitoyltransferase inhibitor ameliorated lung function changes and reduced ceramides in BAL.

Conclusions

Ceramides were increased during the acute inflammatory phase of elastase-induced lung injury. Since addition of a serine palmitoyltransferase inhibitor diminished the rise in ceramides and ameliorated lung function, ceramides likely contributed to the early phase of alveolar destruction and are a potential therapeutic target in the elastase model of lung emphysema.
Y Chromosome analysis of prehistoric human populations in the West Liao River Valley, Northeast China
Authors: Cui Yinqiu , Li Hongjie , Ning Chao , Zhang Ye , Chen Lu , Zhao Xin , Hagelberg Erika , Zhou Hui
Published: October 2013

Background

The West Liao River valley in Northeast China is an ecologically diverse region, populated in prehistory by human populations with a wide range of cultures and modes of subsistence. To help understand the human evolutionary history of this region, we performed Y chromosome analyses on ancient human remains from archaeological sites ranging in age from 6500 to 2700 BP.

Results

47 of the 70 individuals provided reproducible results. They were assigned into five different Y sub-haplogroups using diagnostic single nucleotide polymorphisms, namely N1 (xN1a, N1c), N1c, C/C3e, O3a (O3a3) and O3a3c. We also used 17 Y short tandem repeat loci in the non-recombining portion of the Y chromosome. There appears to be significant genetic differences between populations of the West Liao River valley and adjacent cultural complexes in the prehistoric period, and these prehistoric populations were shown to carry similar haplotypes as present-day Northeast Asians, but at markedly different frequencies.

Conclusion

Our results suggest that the prehistoric cultural transitions were associated with immigration from the Yellow River valley and the northern steppe into the West Liao River valley. They reveal the temporal continuity of Y chromosome lineages in populations of the West Liao River valley over 5000 years, with a concurrent increase in lineage diversity caused by an influx of immigrants from other populations.
Selective photoinactivation of Candida albicans in the non-vertebrate host infection model Galleria mellonella
Authors: Chibebe Junior José , Sabino Caetano P , Tan Xiaojiang , Junqueira Juliana C , Wang Yan , Fuchs Beth B , Jorge Antonio OC , Tegos George P , Hamblin Michael R , Mylonakis Eleftherios
Published: October 2013

Background

Candida spp. are recognized as a primary agent of severe fungal infection in immunocompromised patients, and are the fourth most common cause of bloodstream infections. Our study explores treatment with photodynamic therapy (PDT) as an innovative antimicrobial technology that employs a nontoxic dye, termed a photosensitizer (PS), followed by irradiation with harmless visible light. After photoactivation, the PS produces either singlet oxygen or other reactive oxygen species (ROS) that primarily react with the pathogen cell wall, promoting permeabilization of the membrane and cell death. The emergence of antifungal-resistant Candida strains has motivated the study of antimicrobial PDT (aPDT) as an alternative treatment of these infections. We employed the invertebrate wax moth Galleria mellonella as an in vivo model to study the effects of aPDT against C. albicans infection. The effects of aPDT combined with conventional antifungal drugs were also evaluated in G. mellonella.

Results

We verified that methylene blue-mediated aPDT prolonged the survival of C. albicans infected G. mellonella larvae. The fungal burden of G. mellonella hemolymph was reduced after aPDT in infected larvae. A fluconazole-resistant C. albicans strain was used to test the combination of aPDT and fluconazole. Administration of fluconazole either before or after exposing the larvae to aPDT significantly prolonged the survival of the larvae compared to either treatment alone.

Conclusions

G. mellonella is a useful in vivo model to evaluate aPDT as a treatment regimen for Candida infections. The data suggests that combined aPDT and antifungal therapy could be an alternative approach to antifungal-resistant Candida strains.
Bactericidal activity of PA-824 against Mycobacterium tuberculosis under anaerobic conditions and computational analysis of its novel analogues against mutant Ddn receptor
Authors: Somasundaram Sulochana , Anand Ramaian Santhaseela , Venkatesan Perumal , Paramasivan Chinnambedu N
Published: October 2013

Background

The resurgence of multi-drug resistant tuberculosis (MDR-TB) and HIV associated tuberculosis (TB) are of serious global concern. To contain this situation, new anti-tuberculosis drugs and reduced treatment regimens are imperative. Recently, a nitroimidazole, PA-824, has been shown to be active against both replicating and non-replicating bacteria. It is activated by the enzyme Deazaflavin-dependent nitroreductase (Ddn) present inMycobacterium tuberculosiswhich catalyzes the reduction of PA-824, resulting in the release of lethal reactive nitrogen species (RNS) within the bacteria. In this context, PA-824 was analyzed for its activity against latent tuberculosis under anaerobic conditions and compared with rifampicin (RIF) and pyrazinamide (PZA). Recent mutagenesis studies have identified A76E mutation which affects the above mentioned catalysis and leads to PA-824 resistance. Hence, novel analogues which could cope up with their binding to mutant Ddn receptor were also identified through this study.

Results

PA-824 at an optimum concentration of 12.5 μg/ml showed enhanced bactericidal activity, resulting in 0 CFU/ml growth when compared to RIF and PZA at normal pH and anaerobic condition. Further docking studies revealed that a combinatorial structure of PA-824 conjugated with moxifloxacin (ligand 8) has the highest binding affinity with the wild type and mutant Ddn receptor.

Conclusions

PA-824 has been demonstrated to have better activity under anaerobic condition at 12.5 μg/ml, indicating an optimized dose that is required for overcoming the detoxifying mechanisms ofM.tuberculosisand inducing its death. Further, the development of resistance through A76E mutation could be overcome through thein silicoevolved ligand 8.
Glutaminyl cyclase-mediated toxicity of pyroglutamate-beta amyloid induces striatal neurodegeneration
Authors: Becker Andreas , Kohlmann Stephanie , Alexandru Anca , Jagla Wolfgang , Canneva Fabio , Bäuscher Christoph , Cynis Holger , Sedlmeier Reinhard , Graubner Sigrid , Schilling Stephan , Demuth Hans-Ulrich , von Hörsten Stephan
Published: October 2013

Background

Posttranslational modifications of beta amyloid (Aβ) have been shown to affect its biophysical and neurophysiological properties. One of these modifications is N-terminal pyroglutamate (pE) formation. Enzymatic glutaminyl cyclase (QC) activity catalyzes cyclization of truncated Aβ(3-x), generating pE3-Aβ. Compared to unmodified Aβ, pE3-Aβ is more hydrophobic and neurotoxic. In addition, it accelerates aggregation of other Aβ species. To directly investigate pE3-Aβ formation and toxicity in vivo, transgenic (tg) ETNA (E at the truncated N-terminus of Aβ) mice expressing truncated human Aβ(3–42) were generated and comprehensively characterized. To further investigate the role of QC in pE3-Aβ formation in vivo, ETNA mice were intercrossed with tg mice overexpressing human QC (hQC) to generate double tg ETNA-hQC mice.

Results

Expression of truncated Aβ(3–42) was detected mainly in the lateral striatum of ETNA mice, leading to progressive accumulation of pE3-Aβ. This ultimately resulted in astrocytosis, loss of DARPP-32 immunoreactivity, and neuronal loss at the sites of pE3-Aβ formation. Neuropathology in ETNA mice was associated with behavioral alterations. In particular, hyperactivity and impaired acoustic sensorimotor gating were detected. Double tg ETNA-hQC mice showed similar Aβ levels and expression sites, while pE3-Aβ were significantly increased, entailing increased astrocytosis and neuronal loss.

Conclusions

ETNA and ETNA-hQC mice represent novel mouse models for QC-mediated toxicity of truncated and pE-modified Aβ. Due to their significant striatal neurodegeneration these mice can also be used for analysis of striatal regulation of basal locomotor activity and sensorimotor gating, and possibly for DARPP-32-dependent neurophysiology and neuropathology. The spatio-temporal correlation of pE3-Aβ and neuropathology strongly argues for an important role of this Aβ species in neurodegenerative processes in these models.
Brain activity and medical diagnosis: an EEG study
Authors: Ribas Laila Massad , Rocha Fábio Theoto , Ortega Neli Regina Siqueira , da Rocha Armando Freitas , Massad Eduardo
Published: October 2013

Background

Despite new brain imaging techniques that have improved the study of the underlying processes of human decision-making, to the best of our knowledge, there have been very few studies that have attempted to investigate brain activity during medical diagnostic processing. We investigated brain electroencephalography (EEG) activity associated with diagnostic decision-making in the realm of veterinary medicine using X-rays as a fundamental auxiliary test. EEG signals were analysed using Principal Components (PCA) and Logistic Regression Analysis

Results

The principal component analysis revealed three patterns that accounted for 85% of the total variance in the EEG activity recorded while veterinary doctors read a clinical history, examined an X-ray image pertinent to a medical case, and selected among alternative diagnostic hypotheses. Two of these patterns are proposed to be associated with visual processing and the executive control of the task. The other two patterns are proposed to be related to the reasoning process that occurs during diagnostic decision-making.

Conclusions

PCA analysis was successful in disclosing the different patterns of brain activity associated with hypothesis triggering and handling (pattern P1); identification uncertainty and prevalence assessment (pattern P3), and hypothesis plausibility calculation (pattern P2); Logistic regression analysis was successful in disclosing the brain activity associated with clinical reasoning success, and together with regression analysis showed that clinical practice reorganizes the neural circuits supporting clinical reasoning.
Influenza: a scientometric and density-equalizing analysis
Authors: Fricke Ralph , Uibel Stefanie , Klingelhoefer Doris , Groneberg David A
Published: October 2013

Background

Novel influenza in 2009 caused by H1N1, as well as the seasonal influenza, still are a challenge for the public health sectors worldwide. An increasing number of publications referring to this infectious disease make it difficult to distinguish relevant research output. The current study used scientometric indices for a detailed investigation on influenza related research activity and the method of density equalizing mapping to make the differences of the overall research worldwide obvious. The aim of the study was to compare scientific effort over the time as well as geographical distribution including the cooperation on national and international level.

Methods

Therefore, publication data was retrieved from Web of Science (WoS) of Thomson Scientific. Subsequently the data was analysed in order to show geographical distributions and the development of the research output over the time.

The query retrieved 51,418 publications that are listed in WoS for the time interval from 1900 to 2009. There is a continuous increase in research output and general citation activity especially since 1990.

Results

The identified all in all 51,418 publications were published by researchers from 151 different countries. Scientists from the USA participate in more than 37 percent of all publications, followed by researchers from the UK and Germany with more than five percent. In addition, the USA is in the focus of international cooperation.

In terms of number of publications on influenza, the Journal of Virology ranks first, followed by Vaccine and Virology. The highest impact factor (IF 2009) in this selection can be established for The Lancet (30.75). Robert Webster seems to be the most prolific author contributing the most publications in the field of influenza.

Conclusions

This study reveals an increasing and wide research interest in influenza. Nevertheless, citation based-declaration of scientific quality should be considered critically due to distortion by self-citation and co-authorship.
Preoperative neutrophil/lymphocyte ratio predicts overall survival but does not predict recurrence or cancer-specific survival after curative resection of node-positive colorectal cancer
Authors: Jankova Lucy , Dent Owen F , Chan Charles , Chapuis Pierre , Clarke Stephen J
Published: October 2013

Background

The preoperative ratio of neutrophils to lymphocytes (NLR) has been proposed as a marker of poor outcome in patients having a resection for colorectal cancer (CRC). This study investigated the association between NLR and overall survival, cancer-specific survival and recurrent cancer in patients who had a potentially curative resection for node-positive CRC.

Methods

Data on 322 patients were drawn from a prospectively recorded registry operated on between 1999 and 2007. Analyses of survival involved the Kaplan-Meier method, Cox regression and competing risks Cox regression.

Results

Increasing NLR as a continuous variable was independently though weakly associated with diminishing overall survival after adjustment for other prognostic variables (HR 1.06, 95% CI 1.01-1.11, p = 0.013). Receiver operating characteristic analysis to dichotomize NLR as a predictor of overall survival yielded relatively poor sensitivity (55%), specificity (66%) and positive predictive value (56%, CI 47%-64%). Competing risks regression also showed that NLR was not independently associated with recurrence at any site (HR 1.04, CI 0.97-1.11, p = 0.241) or CRC-specific mortality (HR 1.02, CI 0.92-1.12, p = 0.782) but was associated with non-CRC mortality (HR 1.09, CI 1.03-1.15, p = 0.004).

Conclusion

In patients with stage C tumor the weak link between NLR and overall mortality was not specific to CRC but apparently arose because patients with an elevated inflammatory status preoperatively were likely to progress to earlier death but not necessarily because of their cancer.
Constitutive expression of selected genes from the pentose phosphate and aromatic pathways increases the shikimic acid yield in high-glucose batch cultures of an Escherichia coli strain lacking PTS and pykF
Authors: Rodriguez Alberto , Martínez Juan A , Báez-Viveros José L , Flores Noemí , Hernández-Chávez Georgina , Ramírez Octavio T , Gosset Guillermo , Bolivar Francisco
Published: October 2013

Background

During the last two decades many efforts have been directed towards obtaining efficient microbial processes for the production of shikimic acid (SA); however, feeding high amounts of substrate to increase the titer of this compound has invariably rendered low conversion yields, leaving room for improvement of the producing strains. In this work we report an alternative platform to overproduce SA in a laboratory-evolved Escherichia coli strain, based on plasmid-driven constitutive expression of six genes selected from the pentose phosphate and aromatic amino acid pathways, artificially arranged as an operon. Production strains also carried inactivated genes coding for phosphotransferase system components (ptsHIcrr), shikimate kinases I and II (aroK and aroL), pyruvate kinase I (pykF) and the lactose operon repressor (lacI).

Results

The strong and constitutive expression of the constructed operon permitted SA production from the beginning of the cultures, as evidenced in 1 L batch-mode fermentors starting with high concentrations of glucose and yeast extract. Inactivation of the pykF gene improved SA production under the evaluated conditions by increasing the titer, yield and productivity of this metabolite compared to the isogenic pykF
+ strain. The best producing strain accumulated up to 43 g/L of SA in 30 h and relatively low concentrations of acetate and aromatic byproducts were detected, with SA accounting for 80% of the produced aromatic compounds. These results were consistent with high expression levels of the glycolytic pathway and synthetic operon genes from the beginning of fermentations, as revealed by transcriptomic analysis. Despite the consumption of 100 g/L of glucose, the yields on glucose of SA and of total aromatic compounds were about 50% and 60% of the theoretical maximum, respectively. The obtained yields and specific production and consumption rates proved to be constant with three different substrate concentrations.

Conclusions

The developed production system allowed continuous SA accumulation until glucose exhaustion and eliminated the requirement for culture inducers. The obtained SA titers and yields represent the highest reported values for a high-substrate batch process, postulating the strategy described in this report as an interesting alternative to the traditionally employed fed-batch processes for SA production.
Clear cell tumor of the lung: a case report and literature review
Authors: Wang Guang-xian , Zhang Dong , Diao Xin-wei , Wen Li
Published: October 2013

Clear cell tumor of the lung is a rare and benign pulmonary tumor; only sporadic cases have been reported. Here, we report the case of a 38-year-old man with recurrent cough, blood-streaked sputum and left chest pain. A chest computed tomography scan showed a round, homogeneous pulmonary mass in the left lower lobe, which exhibited intense heterogeneous enhancement in the arterial phase and homogeneous in the delay phase after injecting a contrast agent. The patient underwent a fine-needle aspiration biopsy and was diagnosed as having a benign clear cell tumor of the lung. The clinical presentation and radiographic investigation of this tumor are summarized in this paper to recognize this rare disease. Interestingly, we found some differences with previously reported cases.
A retrospective study: the prognostic value of anemia, smoking and drinking in esophageal squamous cell carcinoma with primary radiotherapy
Authors: Zhang Fang , Han Hui , Wang Chuansheng , Wang Jianbo , Zhang Guangyu , Cao Fangli , Cheng Yufeng
Published: October 2013

Background

Few studies have investigated the relationship between anemia, smoking, drinking and survival in esophageal squamous cell carcinoma (ESCC) with primary radiotherapy. This study had the aim of evaluating the prognostic value of anemia, smoking and drinking in patients receiving primary radiotherapy for ESCC.

Methods

A total of 79 patients who underwent radiotherapy during initial treatment for ESCC were included in this study. The 2-year overall survival (OS) and disease-free survival (DFS) were analyzed between the anemic and non-anemic groups, non-smokers and smokers, and non-drinkers and drinkers using the Kaplan-Meier method and the Cox proportional hazards model.

Results

There were 79 patients (10 male) of median age 63 (range 38 to 84) years. The 2-year OS and DFS were 36% and 25%, respectively, in the non-anemic group, and 17% and 13%, respectively, in the anemic group (P = 0.019 for OS; P = 0.029 for DFS) using the Kaplan-Meier method. Survival analysis using the Kaplan-Meier method showed that the 2-year OS and DFS had no statistical difference between smoking, drinking and survival. In a univariate analysis, anemia was identified as a significant prognostic factor for 2-year OS (hazard ratio (HR) = 1.897; P = 0.024) and 2-year DFS (HR = 1.776; P = 0.036), independent of tumor, lymph node, metastasis (TNM) stage. In a multivariate analysis, anemia was identified as a highly significant prognostic factor for 2-year OS (HR = 2.125; P = 0.011) and 2-year DFS (HR = 1.898; P = 0.025), independent of TNM stage and initial treatment. We found no statistical difference in the 2-year OS and DFS associated with smoking (P > 0.2) and drinking (P > 0.6) using univariate and multivariate analysis.

Conclusions

Smoking and drinking were not prognostic for 2-year OS or DFS. Anemia before radiotherapy was associated with poor prognosis and an increased risk of relapse, which may serve as a new prognostic characteristic in ESCC treated with primary radiotherapy. Hemoglobin is a routine examination and anemia is therefore simple and quick to determine.
Sulindac activates NF-κB signaling in colon cancer cells
Authors: Mladenova Dessislava , Pangon Laurent , Currey Nicola , Ng Irvin , Musgrove Elizabeth A , Grey Shane T , Kohonen-Corish Maija RJ
Published: October 2013

Background

The non-steroidal anti-inflammatory drug (NSAID) sulindac has shown efficacy in preventing colorectal cancer. This potent anti-tumorigenic effect is mediated through multiple cellular pathways but is also accompanied by gastrointestinal side effects, such as colon inflammation. We have recently shown that sulindac can cause up-regulation of pro-inflammatory factors in the mouse colon mucosa. The aim of this study was to determine the signaling pathways that mediate the transcriptional activation of pro-inflammatory cytokines in colon cancer epithelial cells treated with sulindac sulfide.

Results

We found that sulindac sulfide increased NF-κB signaling in HCT-15, HCT116, SW480 and SW620 cells, although the level of induction varied between cell lines. The drug caused a decrease in IκBα levels and an increase of p65(RelA) binding to the NF-κB DNA response element. It induced expression of IL-8, ICAM1 and A20, which was inhibited by the NF-κB inhibitor PDTC. Sulindac sulfide also induced activation of the AP-1 transcription factor, which co-operated with NF-κB in up-regulating IL-8. Up-regulation of NF-κB genes was most prominent in conditions where only a subset of cells was undergoing apoptosis. In TNFα stimulated conditions the drug treatment inhibited phosphorylation on IκBα (Ser 32) which is consistent with previous studies and indicates that sulindac sulfide can inhibit TNFα-induced NF-κB activation. Sulindac-induced upregulation of NF-κB target genes occurred early in the proximal colon of mice given a diet containing sulindac for one week.

Conclusions

This study shows for the first time that sulindac sulfide can induce pro-inflammatory NF-κB and AP-1 signaling as well as apoptosis in the same experimental conditions. Therefore, these results provide insights into the effect of sulindac on pro-inflammatory signaling pathways, as well as contribute to a better understanding of the mechanism of sulindac-induced gastrointestinal side effects.
Role of viral and host factors in interferon based therapy of hepatitis C virus infection
Authors: Imran Muhammad , Manzoor Sobia , Ashraf Javed , Khalid Madiha , Tariq Muqddas , Khaliq Hafiza Madeha , Azam Sikandar
Published: October 2013

The current standard of care (SOC) for hepatitis C virus (HCV) infection is the combination of pegylated interferon (PEG-IFN), Ribavirin and protease inhibitor for HCV genotype 1. Nevertheless, this treatment is successful only in 70-80% of the patients. In addition, the treatment is not economical and is of immense physical burden for the subject. It has been established now, that virus-host interactions play a significant role in determining treatment outcomes. Therefore identifying biological markers that may predict the treatment response and hence treatment outcome would be useful. Both IFN and Ribavirin mainly act by modulating the immune system of the patient. Therefore, the treatment response is influenced by genetic variations of the human as well as the HCV genome. The goal of this review article is to summarize the impact of recent scientific advances in this area regarding the understanding of human and HCV genetic variations and their effect on treatment outcomes. Google scholar and PubMed have been used for literature research. Among the host factors, the most prominent associations are polymorphisms within the region of the interleukin 28B (IL28B) gene, but variations in other cytokine genes have also been linked with the treatment outcome. Among the viral factors, HCV genotypes are noteworthy. Moreover, for sustained virological responses (SVR), variations in core, p7, non-structural 2 (NS2), NS3 and NS5A genes are also important. However, all considered single nucleotide polymorphisms (SNPs) of IL28B and viral genotypes are the most important predictors for interferon based therapy of HCV infection.
Intravenous transplantation of mesenchymal stem cells preconditioned with early phase stroke serum: current evidence and study protocol for a randomized trial
Authors: Kim Suk Jae , Moon Gyeong Joon , Chang Won Hyuk , Kim Yun-Hee , Bang Oh Young ,   For the STARTING-2 (STem cell Application Researches and Trials In NeuroloGy-2) collaborators
Published: October 2013

Background

Recovery after a major stroke is usually limited, but cell therapy for patients with fixed neurologic deficits is emerging. Several recent clinical trials have investigated mesenchymal stem cell (MSC) therapy for patients with ischemic stroke. We previously reported the results of a controlled trial on the application of autologous MSCs in patients with ischemic stroke with a long-term follow-up of up to 5 years (the 'STem cell Application Researches and Trials In NeuroloGy’ (STARTING) study). The results from this pilot trial are challenging, but also raise important issues. In addition, there have been recent efforts to improve the safety and efficacy of MSC therapy for stroke.

Methods and design

The clinical and preclinical background and the STARTING-2 study protocol are provided. The trial is a prospective, randomized, open-label, blinded-endpoint (PROBE) clinical trial. Both acute and chronic stroke patients will be selected based on clinical and radiological features and followed for 3 months after MSC treatment. The subjects will be randomized into one of two groups: (A) a MSC group (n = 40) or (B) a control group (n = 20). Autologous MSCs will be intravenously administered afterex vivoculture expansion with autologous ischemic serum obtained as early as possible, to enhance the therapeutic efficacy (ischemic preconditioning). Objective outcome measurements will be performed using multimodal MRI and detailed functional assessments by blinded observers.

Discussion

This trial is the first to evaluate the efficacy of MSCs in patients with ischemic stroke. The results may provide better evidence for the effectiveness of MSC therapy in patients with ischemic stroke.

Trial registration

This trial was registered with ClinicalTrials.gov, numberNCT01716481.
Superplot3d: an open source GUI tool for 3d trajectory visualisation and elementary processing
Authors: Whitehorn Luke J , Hawkes Frances M , Dublon Ian AN
Published: October 2013

When acquiring simple three-dimensional (3d) trajectory data it is common to accumulate large coordinate data sets. In order to examine integrity and consistency of object tracking, it is often necessary to rapidly visualise these data. Ordinarily, to achieve this the user must either execute 3d plotting functions in a numerical computing environment or manually inspect data in two dimensions, plotting each individual axis.

Superplot3d is an open source MATLAB script which takes tab delineated Cartesian data points in the form x, y, z and time and generates an instant visualization of the object’s trajectory in free-rotational three dimensions. Whole trajectories may be instantly presented, allowing for rapid inspection. Executable from the MATLAB command line (or deployable as a compiled standalone application) superplot3d also provides simple GUI controls to obtain rudimentary trajectory information, allow specific visualization of trajectory sections and perform elementary processing.

Superplot3d thus provides a framework for non-programmers and programmers alike, to recreate recently acquired 3d object trajectories in rotatable 3d space. It is intended, via the use of a preference driven menu to be flexible and work with output from multiple tracking software systems. Source code and accompanying GUIDE .fig files are provided for deployment and further development.
Emergency department waiting room: many requests, many insured and many primary care physician referrals
Authors: Kamali Michael F , Jain Minal , Jain Anunaya R , Schneider Sandra M
Published: October 2013

Background

Increase in waiting time often results in patients leaving the emergency department (ED) without being seen, ultimately decreasing patient satisfaction. We surveyed low-acuity patients in the ED waiting room to understand their preferences and expectations.

Methods

An IRB approved, 42-item survey was administered to 400 adult patients waiting in the ED waiting room for >15 min from April to August 2010. Demographics, visit reasons, triage and waiting room facility preferences were collected.

Results

The mean age of patients was 38.9 years (SD = 14.8), and 52.5% were females. About 53.8% of patients were employed, 79.4% had access to a primary care physician (PCP), and 17% did not have any medical insurance. The most common complaint was pain. A total of 44.4% respondents reported that they believed their problems were urgent and required immediate attention, prompting them to come to the ED, while 14.6% reported that they could not get a timely PCP appointment, and 42.9% were actually referred by their PCP to come to the ED. About 57.7% of patients considered leaving the ED if the waiting times were too long. The mean acceptable waiting time before leaving ED was 221 min (SD = 194; median 180 min, IQR 120–270). A total of 39.1% survey respondents reported being most comfortable being triaged by a physician. Respondents were least comfortable being triaged by residents. On analyzing waiting room expectations for the survey respondents, we found that 70% of the subjects wanted a better estimate of waiting time and 43.5% wanted better information on reasons for the long wait.

Conclusion

Contrary to popular belief, at our ED a large proportion of low-acuity patients has a PCP and is medically insured. Providing patients with appropriate reasons for the wait, an accurate estimate of waiting time and creating separate areas to examine minor illness/injuries would increase patient satisfaction within our population subset.
The relationship between consumption of tyrosine and phenylalanine as precursors of catecholamine at breakfast and the circadian typology and mental health in Japanese infants aged 2 to 5 years
Authors: Akimitsu Osami , Wada Kai , Noji Teruki , Taniwaki Nozomi , Krejci Milada , Nakade Miyo , Takeuchi Hitomi , Harada Tetsuo
Published: October 2013

Background

This study aims to examine the relationship between tyrosine and phenylalanine intake at breakfast as precursors of dopamine, and scores on the Torsvall-Åkerstedt Diurnal Type Scale and of mental health in Japanese infants aged 2 to 5 years.

Results

An integrated questionnaire was administered to parents of 1,367 infants attending one of ten nursery schools governed by Kochi City or a kindergarten affiliated with the Faculty of Education at Kochi University (775 answers for analysis: 56.7%) in May and June 2008. Questionnaires included the Torsvall-Åkerstedt Diurnal Type Scale and questions on sleep habits (onset, offset, quality, quantity, and so on), meal habits (content and regularity of timing), and mental health (depressive states). Amount of tyrosine and phenylalanine intake was calculated based on a breakfast content questionnaire and data on the components of amino acids in foods. Infants who ingested more than 800 mg of tyrosine or phenylalanine at breakfast per meal were more morning-type than those who ingested less than 800 mg (ANOVA: P= 0.005). However, this relationship disappeared in the ANCOVA analysis (with the covariance of tryptophan intake, P= 0.894). Infants who ingested more than 800 mg of the two amino acids at breakfast showed significantly higher mental health scores (lower frequency of depressive states) than those who ingested less than 800 mg (ANOVA: P = 0.004). This relationship remained significant when ANCOVA analysis was performed with the covariance of tryptophan (ANCOVA: P= 0.017).

Conclusions

These results suggest that tyrosine and phenylalanine ingested at breakfast are not related with circadian phase, but are relate with mental health in infants.
Identification of biomarkers for hepatocellular carcinoma using network-based bioinformatics methods
Authors: Zhang Lingyan , Guo Ying , Li Bibo , Qu Juan , Zang Chunbao , Li Fang , Wang Ying , Pang Hua , Li Shaolin , Liu Qingjun
Published: October 2013

Background

Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide. Despite several efforts to elucidate molecular mechanisms involved in this cancer, they are still not fully understood.

Methods

To acquire further insights into the molecular mechanisms of HCC, and to identify biomarkers for early diagnosis of HCC, we downloaded the gene expression profile on HCC with non-cancerous liver controls from the Gene Expression Omnibus (GEO) and analyzed these data using a combined bioinformatics approach.

Results

The dysregulated pathways and protein-protein interaction (PPI) network, including hub nodes that distinguished HCCs from non-cancerous liver controls, were identified. In total, 29 phenotype-related differentially expressed genes were included in the PPI network. Hierarchical clustering showed that the gene expression profile of these 29 genes was able to differentiate HCC samples from non-cancerous liver samples. Among these genes, CDC2 (Cell division control protein 2 homolo g), MMP 2 (matrix metalloproteinase-2) and DCN (Decorin were the hub nodes in the PPI network.

Conclusions

This study provides a portfolio of targets useful for future investigation. However, experimental studies should be conducted to verify our findings.
Identification of harmful cyanobacteria in the Sacramento-San Joaquin Delta and Clear Lake, California by DNA barcoding
Authors: Kurobe Tomofumi , Baxa Dolores V , Mioni Cécile E , Kudela Raphael M , Smythe Thomas R , Waller Scott , Chapman Andrew D , Teh Swee J
Published: October 2013

Accurate identification of cyanobacteria using traditional morphological taxonomy is challenging due to the magnitude of phenotypic plasticity among natural algal assemblages. In this study, molecular approach was utilized to facilitate the accurate identification of cyanobacteria in the Sacramento-San Joaquin Delta and in Clear Lake in Northern California where recurring blooms have been observed over the past decades. Algal samples were collected from both water bodies in 2011 and the samples containing diverse cyanobacteria as identified by morphological taxonomy were chosen for the molecular analysis. The 16S ribosomal RNA genes (16S rDNA) and the adjacent internal transcribed spacer (ITS) regions were amplified by PCR from the mixed algal samples using cyanobacteria generic primers. The obtained sequences were analyzed by similarity search (BLASTN) and phylogenetic analysis (16S rDNA) to differentiate species sharing significantly similar sequences. A total of 185 plasmid clones were obtained of which 77 were successfully identified to the species level: Aphanizomenon flos-aquae, Dolichospermum lemmermannii (taxonomic synonym: Anabaena lemmermannii), Limnoraphis robusta (taxonomic synonym: Lyngbya hieronymusii f. robusta) and Microcystis aeruginosa. To date, Dolichospermum and Limnoraphis found in Clear Lake have only been identified to the genus lavel by microscopy. During the course of this study, morphological identification and DNA barcoding confirmed A. flos-aquae as the predominant cyanobacterium in the Sacramento-San Joaquin Delta indicating a shift from M. aeruginosa that have dominated the blooms in the past decade. Lastly, the species-specific identification of Limnoraphis robusta in Clear Lake is another significant finding as this cyanobacterium has, thus far, only been reported in Lake Atitlan blooms in Guatemala.