bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of annealing on microstructure and mechanical properties of Al 6061 alloy processed by cryorolling
Authors: Rao P Nageswara , Singh D , Jayaganthan R
Published: January 2013

An ultrafine grained (UFG) structure developed in precipitation hardenable Al alloys through cryorolling by suppression of dynamic recovery followed by low temperature aging has received great research interest because of its high strength and very good ductility. In the present work, Al 6061 alloy was solution treated and deformed by cryorolling up to an effective true strain of 2·6 and then subjected to annealing at the temperature range from 150 to 350°C to study the effect of annealing on the microstructure and mechanical properties. The evolution of microstructure and precipitates was investigated by employing X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques. Vickers hardness and tensile testings were performed at room temperature to evaluate the effect of annealing on the mechanical properties. It was observed that the strength and ductility increased upon annealing at 150°C, and further annealing at high temperatures (200–350°C) results in reduction in hardness and strength but increase in ductility. A significant improvement in strength observed at low temperature annealing (150°C) is due to the precipitation of metastable phase β″. It overcompensates the reduction in hardness that occurred due to the softening caused by the recovery effect. It was found that the cryorolled Al 6061 alloy with UFG structure is thermally stable up to temperatures 250°C with slight grain coarsening. At this temperature, the TEM studies revealed that second phase Mg2Si particles are effectively pinning the grain boundaries due to the Zener drag effect. Owing to the presence of heterogeneities in the material, a duplex structure was observed upon annealing at temperatures 150 and 200°C. Abnormal grain growth was observed after annealing at high temperatures (300°C).
Effects of different solution heat treatments on the hot ductility of superalloys
Authors: Andersson J , Sjöberg G P , Viskari L , Chaturvedi M
Published: January 2013

The susceptibility to heat affected zone cracking of Waspaloy has been investigated in terms of its hot ductility, measured as the reduction of area (RA). Gleeble testing with on-heating as well as on-cooling test cycles was carried out to illuminate the influence of different 4 h solution heat treatments between 996 and 1080°C. A ductility maximum of between 80 and 90%RA was found at 1050–1100°C for all conditions in the on-heating tests. Although the different heat treatment conditions showed similar macrohardness, the particle size and distribution of the γ′ and M23C6 phases differed, which significantly affected the on-heating ductility in the lower temperature test region. The ductile to brittle transition was initiated at 1100°C in the on-heating testing with indications of grain boundary liquation at the higher test temperatures. Ductility recovery, as measured in the on-cooling tests from 1240°C, was very limited with <30%RA for all conditions and test temperatures except for the 1080°C/4 h treatment, which exhibited 60%RA at 980°C.
Influence of microstructural evolution on mechanical behaviour of AZ31 alloy sheet processed by flat extrusion container
Authors: Yang Q S , Jiang B , Huang X Y , Zhou G Y , Dai J H , Pan F S
Published: January 2013

Influence of microstructural evolution on the mechanical behaviour of AZ31 alloy sheet processed by flat extrusion container is analysed upon annealing treatments. The basal texture is significantly increased as a result of the formation of new grains with a largely altered c axis orientation relative to the initial basal orientation owing to static recrystallisation. The results reveal that the ductility of the alloys without annealing treatments is the highest, but the strength is the lowest, which confirms the strong anisotropy of stress–strain behaviour with respect to the initial textures. Significant differences in the stress–strain curves are observed for the as received and annealed specimens.
Structure and properties of low modulus titanium alloy Ti–26Nb–7Mo–12Zr
Authors: Golosova O A , Ivanov M B , Kolobov Y R , Vershinina T N
Published: January 2013

The calculation of the choice of a new low modulus titanium β alloy was described. The investigations of the structure and properties (mechanical, tribological and corrosive) of low modulus titanium β alloy Ti–26Nb–7Mo–12Zr after mechanical–thermal processing were carried out. An analysis of the results of experimental research showed that the formation of homogeneous fine grained structure by sheet rolling with subsequent annealing before quenching leads to decreased elastic modulus, increased plasticity and wear resistance. Therefore, new titanium β alloy designed in the present study, Ti–26Nb–7Mo–12Zr, is expected to have good properties as biomaterial.
Effect of strain rate on acoustic emission during tensile deformation of α-brass
Authors: Pattnaik A B , Jha B B , Sahoo R
Published: January 2013

In the present investigation, acoustic emission (AE) technique has been used to study the effect of variation in strain rate on AE signals during tensile deformation of α-brass. Tensile tests have been carried out at four different strain rates, i.e. 3·33×10−4, 6·66×10−4, 1·33×10−3 and 2×10−3 s−1 with simultaneous monitoring of AE parameters. Results indicated that the intensity of AE signals increased with increase in strain rate, which had been attributed to the combined effect of dislocation motion and twinning. Optical microscopy results of deformed samples showed an increase in twin density, i.e. the number of twins per unit area with that of strain rate, which had a profound effect on AE cumulative counts. The fracture surface analysis of deformed sample by field emission scanning electron microscopy showed a transition from ductile to brittle behaviour with increase in the value of strain rate.
Synthesis and characterisation of Cu–W nanocomposite strips
Authors: Vajpai S K , Dube R K , Kanwat A , Kumawat S
Published: January 2013

The present work deals with the preparation of near full density Cu–5 wt-%W, Cu–20 wt-%Wand Cu–40 wt-%W nanocomposite strips from elemental copper and tungsten powders. The proposed route consists of preparing Cu–W nanocomposite powders via high energy ball milling of mixture of elemental powders followed by die compaction of the milled powder, sintering of the powder preforms at 1273 K and hot rolling of the unsheathed sintered preforms at 1273 K under protective atmosphere. The microstructural characteristics of the ball milled Cu–W composite powder as well as finished hot rolled strips of Cu–W composites have been investigated, and the mechanism underlying such microstructural evolution has been discussed. Ball milled composite powder particles as well as hot rolled finished Cu–W composite strips consisted of uniform distribution of submicrometre sized and nanosized tungsten particles embedded in the copper matrix. The microhardness of the finished Cu–W composite strips increased with increasing W content, whereas electrical conductivity decreased with increasing tungsten content in the finished Cu–W nanocomposite strips.
Investigation on microstructural properties of transient liquid phase (TLP) bonded IN-738LC superalloy with AMS 4776 filler metal
Authors: Jalilvand V , Omidvar H , Rahimipour M R , Shakeri H R
Published: January 2013

In the present study, microstructural evolutions at the joint region of transient liquid phase bonded IN-738LC superalloy were examined. The experiments were carried out at 1100°C with different holding times using Ni–B–Si–Cr–Fe filler alloy, AMS 4776, with B and Si as the melting point depressant elements. It was found that insufficient isothermal solidification of liquated insert caused the formation of continuous centreline eutectic phases. The width of the eutectic decreased with the increase in holding time. Complete isothermal solidification, which precluded the formation of the centreline eutectic, occurred within 45 min of holding time. In addition to the centreline eutectic products, precipitation of boron rich particles was observed at the diffusion affected zone. Homogenisation of isothermally solidified joints at 1120°C for 300 min resulted in the elimination of intermetallic phases formed at the diffusion affected zone and formation of significant γ′ precipitates in the joint region.
Novel flow stress model of AA 4343 aluminium alloy under high temperature deformation
Authors: Guo J H , Zhao S D , Yan G H , Wang Z B
Published: January 2013

The flow stress of AA 4343 aluminium alloy under high temperature deformation is modelled by a novel constitutive equation. In order to describe the deformation characterisation, a novel function combining the Voce type hardening model with the linear softening term was proposed to describe the flow stress in a wide range of strain. The effects of strain rate and temperature on the Voce model parameters were analysed empirically, and multiple linear functions were proposed. The effects of strain rate and temperature on the peak flow stress were represented by the Zener–Hollomon parameter, including the Arrhenius term. Experimental stress–strain data from isothermal hot compression tests, in a wide range of temperatures ranging from 300 to 450°C and strain rates ranging from 0·01 to 1 s−1, were employed to find material parameters. The constitutive equations were verified by comparing the experimental and predicted results, and good agreement was achieved.
On the lattice rotations accompanying slip
Authors: Wroński M , Wierzbanowski K , Leffers T
Published: January 2013

The texture (crystallographic texture) of a polycrystalline material is the statistical representation of the preferred orientation of the crystal lattices in the various grains. The great majority of the materials that we encounter do have a texture, some degree of preferred orientation of the crystal lattices, and this texture may have a strong effect on the properties of the materials. The texture is introduced by lattice rotations in the individual grains during processing. The present critical assessment deals with the lattice rotations during rolling of face centred cubic (fcc) metals and alloys. Sixteen years ago, a modification of the traditional procedure for the calculation of these lattice rotations was suggested, a modification that would permit a realistic modelling of the development of the brass type texture, one of the two types of texture developed during rolling of fcc materials. However, this modification was not given serious consideration by the texture community. Recently, two new independent investigations have supported the modification. We argue that this new situation should lead to a general acceptance of the modification, and we discuss the scientific and technological aspects of the modification. We also discuss possible modifications beyond that of the original suggestion.
Application of improved analytical model for non-isothermal phase transformation
Authors: Jiang Y H , Liu F , Song S J , Sun B
Published: January 2013

For the transformations with different overall effective activation energies occurring at different transformation temperatures, the effect of initial transformation temperature T0 has been quantitatively studied. Consequently, a guideline for selecting a proper model (analytical model or improved analytical model) to describe the transformation kinetics was given. For transformations with low overall effective activation energy occurring at high temperature, the terms involving T0 cannot be neglected, and the application of the improved analytical model is indispensable. The second crystallisation stage of amorphous Ti50Cu42Ni8 alloy as measured by differential scanning calorimetry was described by the improved analytical model. On this basis, the prevailing mechanisms of the transformation can be described as follows: mixed nucleation (combination of site saturation and continuous nucleation), interface controlled growth and impingement mode due to random nuclei dispersion. Reasonable kinetic parameters of the transformation were determined, especially the nucleation and growth activation energies (i.e. QN = 233 kJ mol−1 and QG = 288 kJ mol−1).
Thermomechanical–microstructural modelling of nodular cast iron solidification
Authors: Celentano D J , Dardati P M , Carazo F D , Godoy L A
Published: January 2013

This paper presents a thermomechanical–microstructural formulation for the analysis of the solidification process of nodular cast irons of eutectic composition. This formulation is defined in a finite strain thermoplasticity framework considering multinodular microstructure based liquid–solid phase change effects. The performance of this model is evaluated in the analysis of a solidification test for which some laboratory measurements are available. Computed temperature and displacement evolutions together with final values of austenite and graphite volumetric fractions and density of graphite nodules are all found to reasonably agree with the corresponding experimental measurements. This analysis illustrates the possibility of tackling different coupled and complex phenomena occurring in casting problems.
Calculation of stationary creep rate of tempered martensite
Authors: Vodopivec F , Žužek B , Jenko M , Skobir-Balantič D A , Godec M
Published: January 2013

The effect of grain space orientation and particle–matrix stress transfer on dislocation movement forces with difference of acting stress components in slip plane in climb direction is discussed. A modified equation for calculation of creep rate of creep resistant steel including M23C6 particles size and spacing is proposed. Small differences of experimental and calculated creep rates are obtained by stress exponent n = 3·65.
Effect of ball milling time on microstructure and electrochemical properties of CeMg12+100%Ni hydrogen storage alloy
Authors: Hu F , Zhang Y H , Zhang Y , Chai Y , Dong Z P
Published: January 2013

In order to improve hydrogen storage performances of CeMg12 type alloys, ball milling technology was used for preparing nanocrystalline/amorphous CeMg12+100%Ni composite hydrogen storage alloys. The microstructures and morphologies of alloy samples were characterised by X-ray diffraction, scanning electron microscopy and high resolution transmission electron microscopy. The electrochemical hydrogen storage characteristics of as milled alloys were tested by an automatic galvanostatic system. The electrochemical impedance spectra were plotted by an electrochemical workstation (PARSTAT2273). The hydrogen diffusion coefficients D in the alloys were calculated by virtue of potential step method. The results show that the amount of nanocrystalline/amorphous Mg2Ni phase and Ni phase within alloy samples increase with prolonging milling time. Prolonging of ball milled duration markedly improves the electrochemical discharge properties and cyclic stability of alloy samples. The amorphisation degree of the milling alloys increases with rising milling duration. Furthermore, the high rate dischargeability, electrochemical impedance spectra and potential step measurement all indicate that electrochemical kinetics of alloy electrodes first increases and then decreases with increasing ball milling.
Effect of nano/ultrafine grain with orientation obtained by reversion transformation on tensile behaviour of austenitic stainless steel
Authors: Lv J L , Luo H Y
Published: January 2013

The nano/ultrafine grains with different orientations were obtained by reversion transformation for austenitic stainless steel, and their tensile properties were investigated at room temperature. Comparing with the transverse direction sample, the much slower transformation induced plasticity was responsible for excellent elongation of rolled direction sample and the much higher strength originated from the presence of a considerable number of nanotwin bundles and the finer dislocations inside twins. The lower strength and plasticity in transverse direction sample could be attributed to the forming of shear bands and lack of deformation nanotwins.
Enhanced sintering properties of yttria face coat by addition of B2O3, YF3, Al2O3 and ZrO2
Authors: Cheng X , Yuan C , Green N R , Withey P A
Published: January 2013

Yttria is widely used as a key material in the manufacture of the mould face coat for the investment casting of Ti or titanium aluminide alloys, as it has the required thermal and chemical inertness. Because of the high melting temperature of yttria, moulds manufactured using an yttria face coat need high sintering temperatures to achieve a good surface finish, which increases the production cost of the mould. In this research, small amounts of sintering aids, B2O3, YF3, Al2O3 and ZrO2, were added into a simple yttria face coat and sintered at temperatures from 1000 to 1400°C to investigate the influence on the sintering properties of yttria. These experiments found that the sintering additive B2O3 showed the best performance in enhancing yttria face coat sintering over the test temperatures. Sintering aids such as YF3 only slightly altered the sintering properties of yttria at temperatures around 1000–1200°C, and powders such as YAZ were seen to be more suitable for sintering at temperatures around 1300–1400°C. It may be possible to use these sintering aids for the production of investment casting moulds.
Embrittlement of ADI by contact with liquids: Influence of alloy content and preventive methods
Authors: Boeri R E , Martínez R A
Published: January 2013

In view of its excellent mechanical properties and low cost when compared to high strength steels, austempered ductile iron (ADI) is being applied to replace mechanical components in different applications. However, ADI is known to suffer noticeable embrittlement when its surface is in contact with liquids during quasi-static tensile testing. Although the embrittlement phenomena has been characterised in detail, the acting mechanism is not well understood at the present time. Water has shown to cause the greatest degree of embrittlement, while other liquids, such as alcohol and other organic reagents, cause milder though noticeable effects, too. An apparently obvious protection of ADI against the embrittlement caused by liquid environments would be through ADI surface isolation from the environment. The present article examines the efficiency of several paints and coatings by means of tensile tests carried out under dry and wet conditions. From a good number of protective coatings applied on the tensile samples, only one was able to protect the sample under stress from water contact, thus preventing the embrittlement phenomena. The protection method is effective when the layer integrity is not affected by the deformation undergone by the substrate. Another aspect dealt with in the present paper is the assessment of the influence of the chemical composition on the susceptibility of ADI to embrittlement. The results show that the presence of alloy elements in the melt does not influence the degree of embrittlement in the samples.
Phase reversion induced nanograined austenitic stainless steels: Microstructure, reversion and deformation mechanisms
Authors: Misra R. D. K. , Shah J. S. , Mali S. , Venkata Surya P. K. C. , Somani M. C. , Karjalainen L. P.
Published: January 2013

We describe here the attributes of a promising ‘phase reversion’ approach that results in nanograined/ultrafine grained (NG/UFG) structure in austenitic stainless steels with high strength–high ductility combination. The approach involves severe cold deformation (about 45–75) of metastable austenite to martensite, which, on annealing for short durations, reverts to austenite via diffusional or shear mechanism, depending on the chemical composition of steel. There was, however, a need to optimise the severity of cold deformation and temperature–time annealing sequence to obtain NG/UFG structure. The fundamental criteria to obtain NG/UFG structure via ‘phase reversion’ approach were to obtain dislocation cell type martensite. In high strength NG/UFG steel, mechanical twinning contributed to the excellent ductility, while in low strength coarse grained (CG) steel, ductility was also good, but due to nucleation of strain induced martensite at shear bands. The difference in deformation mechanism between NG/UFG and CG steels was attributed to increase in the stability of austenite with decrease in austenite grain size.
Microstructure in hot cracking mechanism of welded aluminium alloys
Authors: Chang C C
Published: January 2013

Microstructure in the hot cracking mechanism was investigated via the Spot-Varestraint test to assess the sensitivity of hot cracking for three aluminium alloys, i.e. A2024-T351, A2219-T87 and A7050-T6, after gas tungsten arc welding. A stereomicroscope, an optical microscope and a scanning electron microscope were adapted to observe the microstructure of hot cracking mechanisms in the weld metal fusion zone (WMFZ), the weld metal heat affected zone (WMHAZ) and the partially melted zone (PMZ). The results indicate that the hot cracking structures differ: solidification cracking in the WMFZ and liquefaction cracking in the WMHAZ. An energy dispersive spectrometer was used to analyse the PMZ of WMHAZ to confirm the segregation of elemental Cu in the liquefaction cracking mechanism at grain boundaries.
Microstructure evolution and mechanical properties of ultrafine grained IF steel via multipass differential speed rolling
Authors: Ko Y G , Lee J S , Loorentz
Published: January 2013

The microstructural evolution and mechanical properties of ultrafine grained interstitial free steel fabricated by multipass differential speed rolling (DSR) technique were investigated. A series of DSR operations were performed up to four passes under a roll speed ratio of 1∶4 for lower and upper rolls. Microstructural observations using a transmission electron microscope showed that the deformed microstructure comprised the severely deformed ferrite grains with a mean size of ∼0·7 μm having a relatively high dislocation density. In addition, the nearly equiaxed grains were effectively formed due to the sample rotation of 180° around the transverse axis between each passage where the macroscopic shearing was reversed. Electron backscattered diffraction analysis revealed an increase in the fraction of the high angle grain boundaries in the severely deformed samples with increasing number of DSR operations. The mechanical properties were also examined utilising microhardness and tensile tests, and these were discussed in relation to the shearing and microstructural characteristics.
Integrin alpha4 blockade sensitizes drug resistant pre-B acute lymphoblastic leukemia to chemotherapy
Authors: Hsieh Yao-Te , Gang Eun Ji , Geng Huimin , Park Eugene , Huantes Sandra , Chudziak Doreen , Dauber Katrin , Schaefer Paul , Scharman Carlton , Shimada Hiroyuki , Shojaee Seyedmehdi , Klemm Lars , Parameswaran Reshmi , Loh Mignon , Kang Eun-Suk , Koo Hong Hoe , Hofmann Wolf-Karsten , Andrade Jacob , Crooks Gay M. , Willman Cheryl L. , Müschen Markus , Papayannopoulou Thalia , Heisterkamp Nora , Bönig Halvard , Kim Yong-Mi
Published: January 2013

Key Points

We evaluated interference with integrin alpha4–mediated stromal adhesion as a new acute lymphoblastic leukemia treatment. Integrin alpha4 blockade using natalizumab in combination with chemotherapy sensitizes pre-B acute lymphoblastic leukemia to chemotherapy.
Both Kdr and Flt1 play a vital role in hypoxia-induced Src-PLD1-PKCγ-cPLA2 activation and retinal neovascularization
Authors: Singh Nikhlesh K. , Hansen Dale E. , Kundumani-Sridharan Venkatesh , Rao Gadiparthi N.
Published: January 2013

Key Points

Both VEGFA and VEGFB and their receptors, Kdr and Flt1, are involved in retinal neovascularization.
Clonal architecture of chronic myelomonocytic leukemias
Authors: Itzykson Raphaël , Kosmider Olivier , Renneville Aline , Morabito Margot , Preudhomme Claude , Berthon Céline , Adès Lionel , Fenaux Pierre , Platzbecker Uwe , Gagey Olivier , Rameau Philippe , Meurice Guillaume , Oréar Cédric , Delhommeau François , Bernard Olivier A. , Fontenay Michaela , Vainchenker William , Droin Nathalie , Solary Eric
Published: January 2013

Key Points

Early clonal dominance may distinguish chronic myelomonocytic leukemia from other chronic myeloid neoplasms with similar gene mutations. Early dominance of TET2-mutated cells in the hematopoietic tissue promotes myeloid differentiation skewing toward the granulomonocytic line.
Genome-wide identification of alternate bearing-associated microRNAs (miRNAs) in olive (Olea europaeaL.)
Authors: Yanik Huriye , Turktas Mine , Dundar Ekrem , Hernandez Pilar , Dorado Gabriel , Unver Turgay
Published: January 2013

Background

Alternate bearing is a widespread phenomenon among crop plants, defined as the tendency of certain fruit trees to produce a high-yield crop one year ("on-year"), followed by a low-yield or even no crop the following year ("off-year"). Several factors may affect the balance between such developmental phase-transition processes. Among them are the microRNA (miRNA), being gene-expression regulators that have been found to be involved as key determinants in several physiological processes.

Results

Six olive (Olea europaea L. cv. Ayvalik variety) small RNA libraries were constructed from fruits (ripe and unripe) and leaves (”on year” and ”off year” leaves in July and in November, respectively) and sequenced by high-throughput Illumina sequencing. The RNA was retrotranscribed and sequenced using the high-throughput Illumina platform. Bioinformatics analyses of 93,526,915 reads identified 135 conserved miRNA, belonging to 22 miRNA families in the olive. In addition, 38 putative novel miRNAs were discovered in the datasets. Expression of olive tree miRNAs varied greatly among the six libraries, indicating the contribution of diverse miRNA in balancing between reproductive and vegetative phases. Predicted targets of miRNA were categorized into 108 process ontology groups with significance abundance. Among those, potential alternate bearing-associated processes were found, such as development, hormone-mediated signaling and organ morphogenesis. The KEGG analyses revealed that the miRNA-targeted genes are involved in seven main pathways, belonging to carbohydrate metabolism and hormone signal-transduction pathways.

Conclusion

A comprehensive study on olive miRNA related to alternate bearing was performed. Regulation of miRNA under different developmental phases and tissues indicated that control of nutrition and hormone, together with flowering processes had a noteworthy impact on the olive tree alternate bearing. Our results also provide significant data on the miRNA-fruit development interaction and advance perspectives in the miRNA profile of the olive tree.
A study of two Chinese patients with tetrasomy and pentasomy 15q11q13 including Prader-Willi/Angelman syndrome critical region present with developmental delays and mental impairment
Authors: Yang Jing , Yang Yongchen , Huang Yi , Hu Yan , Chen Xi , Sun Hengjuan , Lv Zhibao , Cheng Qian , Bao Liming
Published: January 2013

Background

The proximal chromosome 15q is prone to unequal crossover, leading to rearrangements. Although 15q11q13 duplications are common in patients with developmental delays and mental impairment, 15q aneusomies resulting in greater or equal to 4 copies of 15q11q13 are rare and no pentasomy 15q11q13 has been reported in the literature. Thus far, all reported high copy number 15q11q13 cases are from the West populations and no such study in Chinese patients have been documented. Dosage-response pattern of high copy number 15q11q13 on clinical presentations is still a subject for further study.

Case Presentation

In this study, we characterized two Han Chinese patients with high copy number 15q11q13. Using chromosome banding, high resolution SNP-based cytogenomic array, Fluorescence in situ hybridization, and PCR-based microsatellite analysis, we identified two patients with tetrasomy 15q11q13 and pentasomy 15q11q13. Both 15q11q13 aneusomies resulted from a maternally inherited supernumerary marker chromosome 15, and each was composed of two different sized 15q11q13 segments covering the Prader-Willi/Angelman critical region: one being about 10 Mb with breakpoints at BP1 and BP5 regions on 15q11 and 15q13, respectively, and another about 8 Mb in size with breakpoints at BP1 and BP4 regions on 15q. Both patients presented with similar clinical features that included neurodevelopmental delays, mental impairment, speech and autistic behavior, and mild dysmorphism. The patient with pentasomy 15q11q13 was more severely affected than the patient with tetrasomy 15q11q13. Low birth weight was noted in patient with pentasomy 15q1q13.

Conclusions

To the best of our knowledge, this is the first case of pentasomy 15q11q13 and the first study of high copy number 15q11q13 in Han Chinese patients. Our findings demonstrate that patients with tetrasomy and pentasomy of chromosome 15q11q13 share similar spectrum of phenotypes reported in other high copy number 15q11q13 patients in the West, and positive correlation between 15q11q13 copy number and degree of severity of clinical phenotypes. Low birth weight observed in the pentasomy 15q11q13 patient was not reported in other patients with high copy number 15q11q13. Additional studies would be necessary to further characterize high copy number 15q11q13 aneusomies.
A pri-miR-218variant and risk of cervical carcinoma in Chinese women
Authors: Shi Ting-Yan , Chen Xiao-Jun , Zhu Mei-Ling , Wang Meng-Yun , He Jing , Yu Ke-Da , Shao Zhi-Ming , Sun Meng-Hong , Zhou Xiao-Yan , Cheng Xi , Wu Xiaohua , Wei Qingyi
Published: January 2013

Background

MicroRNA (miRNA)-related single nucleotide polymorphisms (SNPs) may compromise miRNA binding affinity and modify mRNA expression levels of the target genes, thus leading to cancer susceptibility. However, few studies have investigated roles of miRNA-related SNPs in the etiology of cervical carcinoma.

Methods

In this case–control study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between two miR-218-related SNPs involved in the LAMB3-miR-218 pathway and the risk of cervical carcinoma in Eastern Chinese women.

Results

We found that the pri-miR-218 rs11134527 variant GG genotype was significantly associated with a decreased risk of cervical carcinoma compared with AA/AG genotypes (adjusted OR=0.77, 95% CI=0.63-0.95, P=0.015). However, this association was not observed for the miR-218 binding site SNP (rs2566) on LAMB3. Using the multifactor dimensionality reduction analysis, we observed some evidence of interactions of these two SNPs with other risk factors, especially age at primiparity and menopausal status, in the risk of cervical carcinoma.

Conclusions

The pri-miR-218 rs11134527 SNP was significantly associated with the risk of cervical carcinoma in Eastern Chinese women. Larger, independent studies are warranted to validate our findings.
Similar decline in mortality rate of older persons with and without type 2 diabetes between 1993 and 2004 the Icelandic population-based Reykjavik and AGES-Reykjavik cohort studies
Authors: Olafsdottir Elin , Aspelund Thor , Sigurdsson Gunnar , Benediktsson Rafn , Thorsson Bolli , Harris Tamara B , Launer Lenore J , Eiriksdottir Gudny , Gudnason Vilmundur
Published: January 2013

Background

A decline in mortality rates due to cardiovascular diseases and all-cause mortality has led to increased life expectancy in the Western world in recent decades. At the same time, the prevalence of type 2 diabetes, a disease associated with a twofold excess risk of cardiovascular disease and mortality, has been increasing. The objective of this study was to estimate the secular trend of cardiovascular and all-cause mortality rates in two population-based cohorts of older persons, with and without type 2 diabetes, examined 11 years apart.

Methods

1506 participants (42% men) from the population-based Reykjavik Study, examined during 1991–1996 (median 1993), mean age 75.0 years, and 4814 participants (43% men) from the AGES-Reykjavik Study, examined during 2002–2006 (median 2004), mean age 77.2 years, age range in both cohorts 70–87 years. The main outcome measures were age-specific mortality rates due to cardiovascular disease and all causes, over two consecutive 5.7- and 5.3-year follow-up periods.

Results

A 32% decline in cardiovascular mortality rate and a 19% decline in all-cause mortality rate were observed between 1993 and 2004. The decline was greater in those with type 2 diabetes, as illustrated by the decline in the adjusted hazard ratio of cardiovascular mortality in individuals with diabetes compared to those without diabetes, from 1.88 (95% CI 1.24-2.85) in 1993 to 1.46 (95% CI 1.11-1.91) in 2004. We also observed a concurrent decrease in major cardiovascular risk factors in both those with and without diabetes. A higher proportion of persons with diabetes received glucose-lowering, hypertensive and lipid-lowering medication in 2004.

Conclusions

A decline in cardiovascular and all-cause mortality rates was observed in older persons during the period 1993–2004, in both those with and without type 2 diabetes. This decline may be partly explained by improvements in cardiovascular risk factors and medical treatment over the period studied. However, type 2 diabetes still persists as an independent risk factor for cardiovascular mortality.
Glycemic variability is associated with subclinical atherosclerosis in Chinese type 2 diabetic patients
Authors: Mo Yifei , Zhou Jian , Li Mei , Wang Yuwei , Bao Yuqian , Ma Xiaojing , Li Ding , Lu Wei , Hu Cheng , Li Minghua , Jia Weiping
Published: January 2013

Background

The contribution of glycemic variability to macrovascular complications remains unclear. We therefore investigated the association between glycemic variability and cervical and/or intracranial atherosclerosis in Chinese type 2 diabetic patients.

Methods

We conducted a cross-sectional study in 216 type 2 diabetic patients with a hemoglobin A1c of 8.3 ± 1.7% and a median diabetes duration of 9.0 years. The standard deviation of blood glucose values (SDBG) and the mean amplitude of glycemic excursion (MAGE) were calculated from continuous glucose monitoring system data for assessing glycemic variability while 24h mean blood glucose (MBG) was calculated for measuring overall blood glucose level. Magnetic resonance angiography (MRA) was used to detect cervical and/or intracranial plaque, and ultrasonography was used to quantify carotid intima-media thickness (IMT) as an index of subclinical atherosclerosis.

Results

One hundred and fifty-three patients (70.8%) presented with cervical and/or intracranial lesions on MRA among 216 patients in the study. Elder age, increased systolic blood pressure, increased MBG and elevated low density lipoprotein cholesterol were independent contributors to plaque formation. In patients without stenosis (n = 63), SDBG (r = 0.412, P = 0.001) and MAGE (r = 0.365, P = 0.005) were both correlated with carotid IMT and these relationships remained significant in multiple linear regression analysis (multiple R

2
 = 0.314 for the model including SDBG and multiple R

2
 = 0.268 for the model including MAGE). However, SDBG and MAGE were not significantly different among patients with different stenosis degrees.

Conclusions

Glycemic variability is associated with subclinical atherosclerosis in Chinese type 2 diabetic patients.
MEK inhibition induced downregulation of MRP1 and MRP3 expression in experimental hepatocellular carcinoma
Authors: Lin Shibo , Hoffmann Katrin , Xiao Zhi , Jin Nan , Galli Uwe , Mohr Elvira , Büchler Markus W , Schemmer Peter
Published: January 2013

Background

Hepatocellular carcinoma (HCC) exhibits strong intrinsic and acquired drug resistance which is the main obstacle to chemotherapy. Overexpression of ATP binding cassette (ABC) proteins correlates with activation of mitogen activated protein kinase (MAPK) pathway in HCC. Here, we systematically investigated the inhibition of MAPK pathway and its role in regulating HCC cell growth as well as ABC proteins MRP1 and MRP3 expression.

Methods

The Raf1 kinase inhibitor (GW5074) and different MEK inhibitors (U0126 and AZD6244) were used to treat HCC cells to identify their effects on HCC cell growth and ABC proteins expression in vitro. Cell viability tests were performed after the treatment of MAPK pathway inhibitors and in combination with gemcitabine or doxorubicin. Western blot was applied to assess the changes of MAPK pathway and protein expression of MRP1 and MRP3. Flow cytometry was used to measure intracellular doxorubicin accumulation after the treatment of MEK inhibitors.

Results

Both Raf1 inhibitor (GW5074) and MEK inhibitors (U0126 and AZD6244) suppressed HCC cell growth in a dose dependent manner. Pre-treatment of MEK inhibitor U0126 or AZD6244 sensitized HCC cells to gemcitabine or doxorubicin based chemotherapy. Raf1 inhibitor GW5074 had no effect on MRP1 and MRP3 protein expression. Treatment of gemcitabine or doxorubicin activated phosphorylated ERK and induced the upregulation of MRP1 and MRP3. MEK inhibitors U0126 and AZD6244 deactivated phosphorylated ERK, decreased endogenous MRP1 expression, reversed gemcitabine or doxorubicin induced MRP1 and MRP3 upregulation, and increased the intracellular doxorubicin accumulation.

Conclusion

This study provides evidence that MEK inhibitors sensitize HCC cells to chemotherapy by increasing intracellular chemodrug accumulation. MEK inhibirors U0126 and AZD6244 reduced MRP1 as well as MRP3 expression, and may contribute partially to the sensitization. The combination of MEK inhibitor and conventional chemotherapy may offer new therapeutic option for the treatment of resistant HCC.
Waist circumference vs body mass index in association with cardiorespiratory fitness in healthy men and women: a cross sectional analysis of 403 subjects
Authors: Dagan Shiri Sherf , Segev Shlomo , Novikov Ilya , Dankner Rachel
Published: January 2013

Objective

Body mass index (BMI) is more commonly used than waist circumference as a measure of adiposity in clinical and research settings. The purpose of this study was to compare the associations of BMI and waist circumference with cardiorespiratory fitness.

Methods

In a cross-sectional study of 403 healthy men and women aged 50 ± 8.8 years, BMI and waist circumference were measured. Cardiorespiratory fitness was assessed from estimated maximal O2 uptake (VO2max), as calculated from a maximal fitness test.

Results

Mean BMI (kg/m2) was 27.8 ± 3.7 and 25.5 ± 4.6; and mean waist circumference (cm) 94.1 ± 9.7 and 84.3 ± 10.4 for men and women, respectively. Both men and women reported an average of 2.5 hours of weekly sports related physical activity, and 18% were current smokers. Correlation coefficients between both BMI and waist circumference, and VO2max were statistically significant in men (r = −0.280 and r = −0.377, respectively, p > 0.05 for both) and in women (r = −0.514 and r = −0.491, respectively, p > 0.05 for both). In women, the contribution of BMI to the level of VO2max in a regression model was greater, while in men waist circumference contributed more to the final model. In these models, age, hours of training per week, and weekly caloric expenditure in sport activity, significantly associated with VO2max, while smoking did not.

Conclusion

The differences observed between the sexes in the associations of BMI and waist circumference with VO2max support the clinical use of both obesity measures for assessment of cardiorespiratory fitness.
Bioenergetics of murine lungs infected with respiratory syncytial virus
Authors: Alsuwaidi Ahmed R , Benedict Sheela , Kochiyil Jose , Mustafa Farah , Hartwig Stacey M , Almarzooqi Saeeda , Albawardi Alia , Rizvi Tahir A , Varga Steven M , Souid Abdul-Kader
Published: January 2013

Background

Cellular bioenergetics (cellular respiration and accompanying ATP synthesis) is a highly sensitive biomarker of tissue injury and may be altered following infection. The status of cellular mitochondrial O2 consumption of the lung in pulmonary RSV infection is unknown.

Methods

In this study, lung fragments from RSV-infected BALB/c mice were evaluated for cellular O2 consumption, ATP content and caspase activity. The disease was induced by intranasal inoculation with the RSV strain A2 and lung specimens were analyzed on days 2–15 after inoculation. A phosphorescence O2 analyzer that measured dissolved O2 concentration as a function of time was used to monitor respiration. The caspase-3 substrate analogue N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin (Ac-DEVD-AMC) was used to monitor intracellular caspases.

Results

O2 concentration declined linearly with time when measured in a sealed vial containing lung fragment and glucose as a respiratory substrate, revealing its zero-order kinetics. O2 consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Cellular respiration increased by 1.6-fold (p<0.010) and ATP content increased by 3-fold in the first week of RSV infection. Both parameters returned to levels found in uninfected lungs in the second week of RSV infection. Intracellular caspase activity in infected lungs was similar to uninfected lungs throughout the course of disease.

Conclusions

Lung tissue bioenergetics is transiently enhanced in RSV infection. This energy burst, triggered by the virus or virus-induced inflammation, is an early biomarker of the disease and may be targeted for therapy.
Response to Dr. Roger’s letter: further studies are necessary in order to conclude a causal association between the consumption of monosodium L-glutamate (MSG) and the prevalence of metabolic syndrome in the rural Thai population
Authors: Insawang Tonkla , Selmi Carlo , Cha’on Ubon , Gershwin M Eric , Yongvanit Puangrat , Prasongwattana Vitoon
Published: January 2013

See related article: http://www.nutritionandmetabolism.com/content/10/1/14
Improving knowledge and changing behavior towards guideline based decisions in diabetes care: a controlled intervention study of a team-based learning approach for continuous professional development of physicians
Authors: Kühne-Eversmann Lisa , Fischer Martin R
Published: January 2013

Background

Continuing Professional Development (CPD) courses should ideally improve a physician’s knowledge and change their professional behavior in daily practice towards a best clinical practice reference model and guideline adherence. Interactive methods such as team-based learning and case-based learning, as compared to lectures, can impart sustainable knowledge and lead to high satisfaction among participants. We designed an interactive case-based CPD-seminar on diabetes care using a team-based learning approach to evaluate whether it leads to an improvement of short-term knowledge and changing of behavior towards guideline based decisions and how this learning approach is perceived by participants.

Methods

Questionnaires and an electronic voting system were used to evaluate motivation, acceptance and knowledge of voluntary participants. Furthermore, we analyzed data on index diagnostic tests and referrals of patients with diabetes of participating physicians over a period of six months before and after the course in comparison with a matched control group in a quasi-experimental design.

Results

Participants (n=103) rated the interactivity and team-based discussions as the main reasons for enhanced learning. They also expected that the course would change their professional behavior. Participants scored a mean of 43.9% right answers before and 62.6% after the course (p<0.001). The referral to diabetes specialists increased by 30.8% (p<0.001). Referral for fundoscopy also increased (8.5%, n.s.) while it dropped in the control group. Furthermore, the participating physicians tested their patients more often for microalbuminuria (7.1%, n.s.).

Conclusions

Our team-based learning CPD-approach was highly accepted and resulted in an increase of short-term knowledge. It significantly increased the referral to diabetes specialists in daily practice whereas all other key professional behavior indicators did change but not significantly.
TFPIα and TFPIβ are expressed at the surface of breast cancer cells and inhibit TF-FVIIa activity
Authors: Stavik Benedicte , Tinholt Mari , Sletten Marit , Skretting Grethe , Sandset Per Morten , Iversen Nina
Published: January 2013

Background

Tissue factor (TF) pathway inhibitor-1 (TFPI) is expressed in several malignant tissues- and cell lines and we recently reported that it possesses anti-tumor effects in breast cancer cells, indicating a biological role of TFPI in cancer. The two main splice variants of TFPI; TFPIα and TFPIβ, are both able to inhibit TF-factor VIIa (FVIIa) activity in normal cells, but only TFPIα circulates in plasma. The functional importance of TFPIβ is therefore largely unknown, especially in cancer cells. We aimed to characterize the expression and function of TFPIα, TFPIβ, and TF in a panel of tumor derived breast cancer cell lines in comparison to normal endothelial cells.

Methods

TFPIα, TFPIβ, and TF mRNA and protein measurements were conducted using qRT-PCR and ELISA, respectively. Cell-associated TFPI was detected after phosphatidylinositol-phospholipase C (PI-PLC) and heparin treatment by flow cytometry, immunofluorescence, and Western blotting. The potential anticoagulant activity of cell surface TFPI was determined in a factor Xa activity assay.

Results

The expression of both isoforms of TFPI varied considerably among the breast cancer cell lines tested, from no expression in Sum149 cells to levels above or in the same range as normal endothelial cells in Sum102 and MDA-MB-231 cells. PI-PLC treatment released both TFPIα and TFPIβ from the breast cancer cell membrane and increased TF activity on the cell surface, showing TF-FVIIa inhibitory activity of the glycosylphosphatidylinositol- (GPI-) anchored TFPI. Heparin treatment released TFPIα without decreasing the cell surface levels, thus indicating the presence of intracellular storage pools of TFPIα in the breast cancer cells.

Conclusion

GPI-attached TFPI located at the surface of breast cancer cells inhibited TF activity and could possibly reduce TF signaling and breast cancer cell growth locally, indicating a therapeutic potential of the TFPIβ isoform.