Dynamic recrystallization (DRX) is an important grain refinement mechanism to fabricate steels with high strength and high ductility (toughness). The conventional DRX mechanism has reached the limitation of refining grains to several microns even though employing high-strain deformation. Here we show a DRX phenomenon occurring in the dynamically transformed (DT) ferrite, by which the required strain for the operation of DRX and the formation of ultrafine grains is significantly reduced. The DRX of DT ferrite shows an unconventional temperature dependence, which suggests an optimal condition for grain refinement. We further show that new strategies for ultra grain refinement can be evoked by combining DT and DRX mechanisms, based on which fully ultrafine microstructures having a mean grain size down to 0.35 microns can be obtained without high-strain deformation and exhibit superior mechanical properties. This study will open the door to achieving optimal grain refinement to nanoscale in a variety of steels requiring no high-strain deformation in practical industrial application. Grain refinement can also result in a decrease of the ductile-to-brittle transition temperature , which extends the application of steels to some extreme (cryogenic) conditions14Steels are basic and by far the most important materials in human civilization. Improving mechanical properties of steels, e.g., to achieve excellent balance of strength and ductility (or toughness), has always been generating great excitement in metallurgy community1234567891012The control of grain refinement through thermomechanically controlled process (TMCP) where dynamic recrystallization (DRX) occurs has been extensively developed in the past decades1617181920212223242526272824252227281618Industrially speaking, it is generally accepted that DRX of ferrite is still difficult to happen. Fully DRX ferrite structures have hardly been achieved except for the UFG interstitial free (IF) steel produced by very high strain in torsion at laboratory scale3020213223293435Another promising grain refinement mechanism for ferrite is dynamic transformation (DT)3738394041424344413738424330−2 s−1 at different temperatures. Low-angle boundaries (LABs) with misorientation of 2–15° and high-angle boundaries (HABs) with misorientation above 15° are drawn in red and blue lines, respectively. At 560 °C, the ferrite microstructure consists of coarse elongated grains and fine equiaxed grains. The coarse elongated grains containing LABs represent unrecrystallized microstructure during the deformation. The fine equiaxed grains surrounded by HABs are confirmed to be formed through DRX mechanism. At 520 °C, the volume fraction of DRX grains decreases, and the DRX grains become finer than those at 560 °C. With decreasing the temperature to 480 °C, less DRX grains are formed and the grain size of DRX ferrite keeps decreasing. The distribution of ferrite grain size (in diameter) obtained by EBSD analysis is shown in An investigation on conventional DRX behavior, especially its temperature dependence, was conducted employing a 10Ni-0.1C steel with statically transformed ferrite (fully ferrite phase with a mean grain size of 6.7 μm). Z:The general view of the temperature dependence of conventional DRX behavior is illustrated in 23Q, R, and T refer to the strain rate, the activation energy, the gas constant, and the absolute temperature, respectively. Under the constant strain and strain rate, high temperature (low Z) enhances the initiation of DRX and the grain growth, resulting in higher fraction of DRX grains with larger grain size. Low temperature (high Z) deformation can generate more dislocations and deformation microstructures in ferrite, which could act as nucleation sites for DRX of ferrite. While due to the sluggish atom diffusion rate, low temperature leads to finer DRX ferrite with smaller volume fraction.where Conventional DRX of ferrite occurs during the deformation of single ferrite phase with a certain initial grain size. Here we confirm a DRX phenomenon that can occur during the deformation of ferrite which is dynamically transformed from austenite. That is, firstly ferrite is transformed from austenite during hot deformation, then further deformed and lead to the occurrence of DRX in the continuous deformation.−2 s−1. At a strain of 0.11, very fine and nearly equiaxed ferrite grains are formed along a PAGB. With increasing the strain to 0.29, the ferrite grains grow into prior austenite grain and exhibit an irregular morphology. In addition to the coarsening of ferrite, LABs are observed within the coarse ferrite grains, indicating that a deformed structure is introduced. The fraction of LABs increases with increasing the strain to 0.60. Equiaxed ultrafine ferrite (UFF) grains surrounded by HABs start to form along the grain boundaries of coarse ferrite (as marked by blue arrows). The fraction of the equiaxed UFF increases with increasing the strain to 1.39, at which the ferrite microstructure is composed of equiaxed UFF grains and elongated coarse grains containing subgrains. The misorientation caused by deformation within each grain could be evaluated by GAM value, which can show average misorientation angle among all pairs of adjacent points in each grain. A higher GAM value (dark red color) indicates higher misorientation. The equiaxed UFF grains show lower GAM values (light red color) than the elongated coarse grains (dark red color), implying that they may be undergoing some restoration process. As shown in the TEM image and corresponding misorientation map of the specimen processed at a strain of 1.39 (The DRX of DT ferrite (termed as DTRX hereafter) can be interpreted by  of 1.39 , equiaxe of 1.39 . Higher  of 1.39 . Finally of 1.39  surround3 and e4) in the continuous deformation, which implies a new grain refinement process happening during deformation. Here it could be concluded that the DRX of ferrite occurs at a certain strain after the onset of DT. It is the formation of DRX grains that leads to the further grain refinement of ferrite.The mechanism of DTRX is interpreted by 48εmac on the bulk specimens is homogenously distributed in each ferrite grain (εαd(Vi)), i.e., εαd(Vi) ≈ εmac. While in the case of the DRX of DT ferrite (30εαd(Vi) > εγd(Vj)). The soft ferrite grains could absorb plastic deformation to a greater extent than the macroscopic plastic strainεαd(Vi) ≥ kεmac, k > 1), which increases the driving force for the initiation of DRX. The other reason is attributed to the grain size effect on DRX (2). Therefore, it is believed that the decrease in ferrite grain size can not only decrease the critical strain for the operation of the DRX of ferrite, but also accelerate the kinetics of DRX30There are mainly two reasons for the occurrence of DRX of DT ferrite (DTRX). One is due to the strain concentration effect . In the  ferrite , austenit on DRX . Finer gt on DRX  and b2. −2 s−1 at different temperatures. At 560 °C, the ferrite mostly shows coarse and elongated morphologies. The volume fraction of DT ferrite is 52% at this temperature, and only a few of DRX grains  can be observed, as marked by blue arrows. At 520 °C, the fraction of DRX grains increases compared to that at 560 °C. With decreasing the temperature to 440 °C, the fraction of DRX grains (as marked by blue arrows) decreases. Most of the grains are elongated and contain a large amount of LABs, exhibiting a more deformed structure. The distributions of the ferrite grain size are shown in The temperature dependence of DTRX behavior is further investigated in order to compare with the conventional DRX under the same deformation condition. 1 , the driving force and nucleation density for ferrite transformation are low, but the diffusivity of atoms is high. Therefore, the grain growth of DT ferrite is rather dominant, resulting in a large grain size , both the driving force and the nucleation density for ferrite transformation increase, which lead to faster transformation kinetics. The fast transformation kinetics results in finer ferrite grain size due to the sufficient impingement effect between ferrite grains. Furthermore, the strain concentration on ferrite becomes higher at fast transformation kinetics. The high strain concentration and fine ferrite grain size greatly increase the driving force for DRX , the fraction of DRX grains becomes smaller  counting only HABs along compression direction can be expressed as30It has been well known that finer initial grains can enhance DRX and lead to finer DRX grains30ε and d0 are applied strain and initial grain size, respectively. It is indicated that if the initial grain size (d0) could be decreased, then the required strain (ε) to achieve DRX grains with a certain grain size would be reduced. For conventional DRX of ferrite, the initial grain size is constant. The grain refinement effect of conventional DRX is limited because it is technically difficult to enhance DRX through refining the initial grains. While for the DTRX mechanism, transformed ferrite firstly experiences nucleation and growth to some extent, which means the ferrite grain size is variable prior to DRX. Our study has proved two important points: (1) DT can greatly affect the subsequent DRX behavior; (2) There exists an optimal deformation temperature at which the kinetics of DRX of DT ferrite is the fastest. These two points imply a new grain refinement strategy by controlling two mechanisms, i.e. DT and DRX, in one TMCP route. That is, at the optimal temperature, DRX should be enhanced by accelerating DT kinetics and consequently leads to finer grains with improved mechanical properties.where d2), a small pre-deformation is applied for accelerating DT and subsequent DRX at the high temperature (Td1). Even though the total strain is the same in the route-1 and route-2, the final microstructures are significantly different. 343656583) and para-equilibrium temperature (Ap3) of the steel, calculated by Thermo-Calc software, are 686 °C and 583 °C, respectively. The as-received hot-rolled plate 15 mm thick was cold-rolled to a thickness of 11.2 mm with a reduction of 25%, and then homogenized at 1100 °C for 172,800 s in vacuum. Two procedures were designed for the sample preparation. In the first case (specimens for new DTRX study), the homogenized plate was water-quenched after the homogenization at 1100 °C to have a martensite structure. In the other case , the homogenized plate was firstly water-quenched to obtain martensite, then austenitized again at 750 °C for 900 s or at 900 °C for 1,800 s, and slowly furnace-cooled to obtain a fully ferrite microstructure with a mean grain size of 6.7 μm and 17 μm, respectively. Cylindrical specimens with a height of 12 mm and a diameter of 8 mm were machined from the two kinds of plate and installed in a thermomechanical processing simulator  for conducting thermomechanically controlled processes (TMCP).The material used in this study is a 10Ni-0.1C steel, of which the chemical composition and temperature-time-transformation (TTT) diagram are shown in −1, held for 60 s to homogenize the temperature, and then uniaxially compressed to a strain of 0.92 at a strain rate of 10−2 s−1 followed by water-quenching.TMCP including compression deformations were conducted at high temperatures achieved by induction heating in a vacuum chamber. For the hot deformation of single ferrite structure , the specimens with a mean grain size of 6.7 μm were heated from room temperature to the deformation temperatures from 480 °C to 560 °C at a rate of 10 °C s−1, held for 60 s to homogenize the temperature of the cylindrical specimens, and then uniaxially compressed to various strains ranging from 0.05 to 1.39 (5% to 75% reduction in height) at a strain rate of 10−2 s−1 followed by water-quenching.For the hot deformation of austenite , the specimens were austenitized at 1000 °C for 300 s or at 700 °C for 900 s to obtain different austenite grain sizes of around 125 μm or 10 μm, respectively. The austenitized specimens were cooled to the deformation temperatures ranging from 560 °C to 440 °C at a rate of 30 °C s−1, held for 60 s to homogenize the temperature, and then uniaxially compressed by 60% reduction  at a strain rate of 10−2 s−1 followed by water quenching. The TMCP route-2 is composed of two-step deformation at different temperatures. The austenitized specimens were firstly cooled to 410–300 °C (above the Ms temperature (250 °C)) at a rate of 30 °C s−1, deformed by 10% reduction (or 30% reduction for the case of 0.35 μm) at a strain rate of 100 s−1, reheated up to 520 °C at a rate of 55 °C s−1 and then deformed by 50% reduction (45% reduction for 0.35 μm) at a strain rate of 10−2 s−1 (10−1 s−1 for 0.35 μm) followed by water quenching.For the study of new strategies for grain refinement, two kinds of TMCP routes were designed. The TMCP route-1 is for comparison, the TMCP route-2 is newly designed for obtaining ultrafine ferrite with grain sizes of 0.55 μm, 0.46 μm  to 0.35 4 and 90% CH3COOH at 20 °C. For the TEM observations, thin-foil specimens were prepared by twin-jet electropolishing using the same solution as that for EBSD.Microstructures at the center of the cylindrical specimens on the sections parallel to the compression axis were characterized by a field-emission type scanning electr on microscope  equipped with an electron back-scattering diffraction (EBSD) system operated at an accelerating voltage of 15 kV and a transmission electron microscope  at 200 kV. For the EBSD measurement, the specimens were mechanically polished using 4000 grit SiC paper and then electrically polished in a solution of 10% HClO−4 s−1 at room temperature. The present study confirmed the reliability of the small-size tensile specimens by comparing the engineering stress-strain curves of the small-size and large-size  tensile specimens cut from the same 10Ni-0.1C steel with full ferrite phase (grain size of 6.7 μm), as shown in the Sheet-type specimens for tensile test were machined from the compressed samples. The tensile direction was perpendicular to the compression direction. Small-size tensile specimens with gage length, width and thickness of 2 mm, 1 mm and 0.5 mm, respectively, were cut from the compressed specimens, so that the gage parts corresponded to the center of the specimens. A CCD camera taking 10 images per second was used to precisely measure the displacement during the tensile test. Tensile test was conducted at an initial strain rate of 8.3 × 10How to cite this article: Zhao, L. et al. Combination of dynamic transformation and dynamic recrystallization for realizing ultrafine-grained steels with superior mechanical properties. Sci. Rep.6, 39127; doi: 10.1038/srep39127 (2016).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Isoamylases hydrolyse (1–6)-alpha-D-glucosidic linkages in starch and are involved in both starch granule formation and starch degradation. In plants, three isoamylase isoforms with distinct functions in starch synthesis (ISA1 and ISA2) and degradation (ISA3) have been described. Here, we created transgenic potato plants with simultaneously decreased expression of all three isoamylases using a chimeric RNAi construct targeting all three isoforms. Constitutive expression of the hairpin RNA using the 35S CaMV promoter resulted in efficient silencing of all three isoforms in leaves, growing tubers, and sprouting tubers. Neither plant growth nor tuber yield was effected in isoamylase-deficient potato lines. Interestingly, starch metabolism was found to be impaired in a tissue-specific manner. While leaf starch content was unaffected, tuber starch was significantly reduced. The reduction in tuber starch content in the transgenic plants was accompanied by a decrease in starch granules size, an increased sucrose content and decreased hexose levels. Despite the effects on granule size, only little changes in chain length composition of soluble and insoluble glucose polymers were detected. The transgenic tubers displayed an early sprouting phenotype that was accompanied by an increased level of sucrose in parenchyma cells below the outgrowing bud. Since high sucrose levels promote sprouting, we propose that the increased number of small starch granules may cause an accelerated turnover of glucan chains and hence a more rapid synthesis of sucrose. This observation links alterations in starch structure/degradation with developmental processes like meristem activation and sprout outgrowth in potato tubers. Solanum tuberosum) is a staple food and belongs to the economically most important crops. Tubers formed can store up to 20% of their fresh weight as starch. Starch constitutes a major proportion of the human diet and has also many industrial applications. It is a glucose polymer consisting of two fractions; amylose and amylopectin. Amylose is an essentially linear alpha-1,4-linked polymer, while amylopectin is composed of alpha-1,4-linked chains that are branched via alpha-1,6-bonds resulting in a racemose or tree-like structure P-labelled probes and a with 18S rRNA probe as loading control. B) Tuber starch content in transgenic lines. Two replicates were taken from 5 tubers per line after harvest. Values are the mean +/- SE. Asterisks indicate statistically significant differences at 5% level (* p < 0.05).A) Analysis of transgenic lines by northern blotting. Total RNA was extracted from 13 pre-selecetd transgenic lines. Twenty μg of total RNA was separated in a formaldehyde-containing agarose gel and blotted onto nitrocellulose membrane. The membrane was consecutively probed with (TIF)Click here for additional data file.S2 FigSlices were taken from 5 tubers per line and the fresh weight was determined. Subsequently, slices were dried in an oven at ca. 60°C for 2 days and weighed. Values are the mean +/- SE. Asterisks indicate statistically significant differences at 5% level (* p < 0.05).(TIF)Click here for additional data file.


Journal of Applied Clinical Medical Physics three months ago, I have been serving as the de facto editor‐in‐chief since 1 July 2007. The four and a half months from July to November served as my apprenticeship, as I was learning my new trade under the supervision of Mike Mills. Mike has been a most able and patient mentor during the time it took for me to learn the intricate mechanisms that we use to operate the journal web site, enabling the move from submitted manuscript through review and revision, and through editing, layout, and proofreading eventually to the final result—an e‐published edition of JACMP. All who are involved in the journal—editors, reviewers, authors, and readers—owe Mike a tremendous debt of gratitude for bringing JACMP to its current situation. When Mike took over as editor‐in‐chief, the journal was in a serious financial condition, and it was not known whether it would survive. Fortunately, Mike took a series of steps that provided JACMP with both a viable business model and a viable editorial model, and he left me a journal that is fiscally and editorially healthy, and a pleasure to work on. Thank you, Mike.Although I assumed the mantle of editor‐in‐chief of the JACMP, several people have asked me about the impact factor of the journal, and so I would like to use this editorial opportunity to address that subject.Since the announcement that I would take over as editor‐in‐chief of In combination with number of publications and number of first authorships (among other considerations), the impact factor is often used as a metric to evaluate the productivity of academic faculty members. The impact factor embraces the concept that the journals considered the most prestigious and the most difficult from which to gain a manuscript acceptance have higher impact factors. Publication in a journal with a high impact factor presumably counts more toward academic stature than does publication in a journal with a lower impact factor.A is the number of times a paper published in a particular journal in the period 2005–2006 is cited in all journals during 2007, and B is the number of papers published in that journal during 2005–2006, then the impact factor of that journal in 2007 is A divided by B. The mathematics are profoundly simple.The impact factor of a journal is defined to be the number of times papers published in that journal are cited for a two‐year period after their publication, divided by the number of papers published in that journal during the two‐year period. For example, if The numbers used in evaluating the impact factor are obtained from an organization called Thompson Scientific, formerly Thompson Institute for Scientific Information. Thompson Scientific is a private organization that, among other activities, monitors activity in the scientific journals. One of its products is evaluation of the impact factor for a very large number of journals.Journal of Applied Clinical Medical Physics?Now, how does impact factor relate to the JACMP was listed in Thompson Scientific only about two years ago, and so it might be another year or two before an impact factor is published for the journal.Note that the 2007 impact factor is actually released in 2008 and that it relies on publications in a journal from 2005 and 2006. en.wikipedia.org/wiki/Impact_factor) provides a discussion of the pros and cons of its use. The bottom line is that the impact factor may not necessarily be relevant to manuscripts published in JACMP.However, the impact factor is not without its detractors. As is the case with many statistics, this particular statistic can be misused, abused, and manipulated. The Wikipedia entry for impact factor (Journal of Applied Clinical Medical Physics, then, is the number of times the information in that paper is used by a practitioner of medical physics to improve the quality of medical physics practice.Why would I say this? Essentially, the impact factor is a measure of citations of a paper. A published paper is cited when another author uses information from that paper in another publication. Consequently, the number of citations of a paper is a measure of the utility of that paper in the propagation of knowledge. But the information presented in our journal is directed more toward improving the clinical practice of medical physics than toward propagating knowledge. Consequently, much of the information provided never finds its way into further publications. The real measure of impact of a paper in the JACMP.A better way to assess the impact of clinical journals needs to be identified. Once that better way is found, we will have an effective and relevant metric for evaluating the impact of papers in George StarkschallEditor‐in‐Chief15 February 2008


The application of transcranial direct current stimulation (tDCS) has moved from the laboratory to the wider community. This form of non-invasive brain stimulation has been shown in a number of controlled animal and human experiments, over nearly five decades, to modulate brain physiology, cognitive functions, and behavior. While its effects are variable across and within individuals, it is not unreasonable to state that tDCS harbors the potential to enhance executive and physical human performance. In a society increasingly driven to succeed with less effort, performance enhancement with an intervention that has an excellent safety record, is well tolerated, relatively inexpensive and readily available, is particularly appealing. Here, we offer a perspective on tDCS for the enhancement of physical performance in sport. The ethical and legal implications of the transition of tDCS from academic experimental work to general-public use, are discussed elsewhere  tDCS  on trained cyclists , the Football Players Health Study at Harvard University, and Harvard Catalyst|The Harvard Clinical and Translational Science Center .The content is solely the responsibility of the authors and does not necessarily represent the official views ofHarvard Catalyst,Harvard University and its affiliated academic health care centers, the National Institutes of Health, or the Sidney R. Baer Jr. Foundation.AP serves on the scientific advisory boards for Nexstim, Neuronix, Starlab Neuroscience, Neuroelectrics, Axilum Robotics, Magstim Inc., and Neosync; and is listed as an inventor on several issued and pending patents on the real-time integration of transcranial magnetic stimulation with electroencephalography and magnetic resonance imaging. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


With the globalization of the world economy, international innovation collaboration has taken place all over the world. This study selects three emerging technologies  among 20 countries as the research objects, using three patent-based indicators and network relationship analysis to reflect international collaboration patterns. Then we integrate empirical analyses to show effecting factors of international collaboration degrees by using panel data. The results indicate that while 3D printing technology is associated with a “balanced collaboration” mode, big data technology is more accurately described by a radial pattern, centered on the United States, and carbon nanotubes and graphene technology exhibits “small-world” characteristics in this respect. It also shows that the factors GDP per capita (GPC), R&D expenditure (RDE) and the export of global trade value (ETV) negatively affect the level of international collaboration. It could be useful for China and other developing countries to make international scientific and technological collaboration strategies and policies in the future. With the globalization of the world economy and the internationalization of innovation resources, international collaboration has taken place all over the world . Both prThe latest technological achievements could be reflected by patents, which include meaningful information of international innovation collaboration , 7. ManyBecause emerging technologies are an important way for different countries to engage in technological competitiveness , major cTo study the collaboration patterns of emerging technologies, international co-inventions (patent-based) data are used to do indicator analysis and network relationship analysis. In addition, determinants of international collaboration level via empirical analysis are explored. To be specific, this paper aims to discuss the following two questions:What is the international collaboration pattern characteristic of emerging technologies?What are the effecting factors of emerging technologies’ international collaboration levels?Despite the proliferation of studies on various dimensions of international collaboration, there is still a dearth of empirical analysis on international collaboration of emerging technologies . The exiThe rest of this paper is organized as follows: Section 2 introduces the data and methods. Section 3 analyzes international collaboration patterns. Section 4 discusses effecting factors of international collaboration levels by using empirical analysis. Section 5 concludes with the findings and suggestions for making technology strategies and policies.Three representative emerging technologies are selected for this study: 3D printing, big data, and carbon nanotubes and graphene technology. 3D printing technology takes the digital model as a template to create solid objects through addition processes . RecentlSixteen member countries of the Organization for Economic Co-operation and Development (OECD)—the Unite States, Germany, Japan, South Korea, the United Kingdom, Canada, Israel, the Netherlands, Switzerland, France, Australia, Italy, Sweden, Belgium, Spain and Denmark and four non-OECD member countries—China, India, Russia and Brazil are investigated, as all of them owned selected emerging technology patents and nearly all countries participate in international collaboration.https://worldwide.espacenet.com/advancedSearch?locale=en_EP). In this database, the patent applications are submitted to about 90 Patent Offices worldwide. Therefore, patents related to emerging technologies in the PATSTAT database are representative, comprehensive, and international [Our data source is the European Patent Office (EPO) Worldwide Patent Statistical Database (PATSTAT), November 2015 version  domestic inventions. The computation formula is as follows:i is the total number of patents controlled by the residents of country i and invented by foreign residents and PAi is the total number of patents owned by the residents of country i.SHAI is the share for a given country of patents with a foreign inventor and a domestic applicant in the country’s total domestic applications. It reflects the extent to which domestic firms control (own) foreign inventions. The computation formula is as follows:Drawing maps is a relatively common method of displaying network relationships ; the mapRegression analysis is a statistical process for estimating the relationships among variables and helps one understand how the typical value of the dependent variable changes when any one of the independent variables is varied, while the other independent variables are held fixed . We inteIn this section, we focus on international collaboration characteristic of three emerging technologies among 20 countries.From the perspective of collaboration indicators:Indicator SHII: Except for South Korea and Japan, there is a certain degree of international collaboration among other countries in 3D printing technology. For big data technology, there is a polarization trend, namely, the collaboration proportion is extremely high or low. There is no cooperation among South Korea, Russia, and Denmark, but the patents in Italy and Brazil are all products of international collaboration. In the field of carbon nanotubes and graphene, the frequency of collaboration is higher than in the other two fields.Indicators SHIA and SHAI: The level of SHAI in developed countries is higher than the level of SHIA, which indicates that developed countries mainly depend on independent innovation in emerging technology fields. However, developing countries have the opposite situation, which confirms that developing countries weakly control the ownership of co-patents and are in the position of being workers for developed countries.From the perspective of countries, as reported in Developing countries  have strong SHII and SHIA and weak SHAI, which shows that the control ability of patent ownership in developing countries is rather weak; the inventors in these countries are in a migrant worker position and a large proportion of patent ownership is controlled by developed countries. The reason is as follows: It is very common that researchers from a developing country have fewer intelligent local colleagues in emerging technology fields and need to look abroad for collaboration . FurtherNetwork relationship can reflect the international collaboration patterns of emerging technologies on the other side . In FigsIn the field of 3D printing , combiniIn the carbon nanotubes and graphene technology field, the network relationship shows characteristics of a “small world”, which refers to having higher clustering coefficients and shorter average path length  Fig 3)..Fig 3). All in all, the capacity of collaboration depends not only on the capability and quality of the national research base but also on the existing volume of activity. If there is little activity, thus leading to a limited output, then the opportunity for collaboration is naturally constrained. China is a good example: it holds a large number of patents, so its international collaboration level is higher than that of other developing countries. So the developing countries should improve both the volume of activity and the quality of their national research. Furthermore, it is advisable that China, India, Russia and Brazil increase their betweenness centrality and improve their control ability. Only in this way can they boost their collaboration ability and control ability.By studying the collaboration patterns of 20 countries, we found that the international collaboration patterns of different countries are rather different from each other in the three emerging technologies of 3D printing, big data, and carbon nanotubes and grapheme technology. In this section we discuss the effecting factors of international collaboration levels among 20 countries. There is a wide range of rationales for why countries and their scientific communities enter into cross-country science, technology and innovation (STI) cooperation . A few sGenerally speaking, there is an inverse relationship between the scale of the scientific community in a given country and the amount of international collaboration for innovation associated with that country . And resHypothesis 1. Country size negatively affects the country’s level of international collaboration in emerging technologies.Researchers or scientists from countries with high technical expertise do not necessarily have appropriate incentives to collaborate with foreign scientists or researchers because their own knowledge reserves are already large enough . So, theHypothesis 2. The stage of a country’s R&D level negatively affects this country’s level of international collaboration in emerging technologies.The larger the R&D full-time equivalent (FTE) of one country, the more inventors participate in research activities . CountriHypothesis 3. A country’s FTE negatively affects the level of international collaboration in emerging technologies.The geographical concentration discussed in a previous study  indicateHypothesis 4. Geographical proximity negatively affects the level of international collaboration in emerging technologies.An important strategy for acquiring advanced technology by developing countries is to encourage FDI from developed countries . InternaHypothesis 5. Out-flows of FDI positively affect the level of international collaboration in emerging technologies.When an existing industry of one country improves in terms of quality metrics , technology-oriented international collaboration may concomitantly happen .Hypothesis 6. International trade positively affects the level of international collaboration in emerging technologies.The indicators of SHII (there is a SHII indicator for each country for each year) of 20 countries as the measurement of international collaboration level in three emerging technologies are used. Since the early data are not complete, the choosing period is from 2008 to 2015.Gross Domestic Product (GDP) per capita (GPC). GDP represents a country’s advanced degree, namely, country size. The variable we want to focus on and compare over time and across countries is GDP per capita rather than GDP itself, since we are unable to define the GDP of each emerging technology field. We get the data from the Organization for Economic Co-operation and Development (OECD) statistic database .R&D Expenditure (RDE). R&D expenditure per capita is selected to represent a country’s R&D level; we get this data from the Main Science and Technology Indicator (MSTI) of the OECD database (http://stats.oecd.org/viewhtml.aspx?datasetcode=MSTI_PUB&lang=en.), as it provides more than 100 countries’ science and technology input and output index data since 1981.Full-time equivalent (FTE). We get R&D FTE data from the MSTI database.Geographic proximity (GEO). We calculate the average space distance between one country  and other countries  inspired by the work of Knack [We use the latitude and longitude of one country to calculate the distance between two countries:AB is the distance between country A and country B,DR indicates the radius of the earth,Aw and Bw are the latitude of country A and country B,Aj and Bj are the longitude of country A and country B.We seek the latitude and longitude of each country  and put them into the formula above, then the calculation process is realized by C Language programming.We calculate the average distance between each country and the others.of Knack . The algFlows of foreign direct investment (FDI). We consider outflows of FDI indicator to explain this variable since the outflows could better reflect the international collaboration capability of a country. We get the data from the OECD statistic database.The export of global trade value (ETV). The international trade situation is proxied by the export of global trade value. We get the data from the OECD statistic database.The control variables are as follows:Degree centrality (DEG).Betweenness centrality (BET).Closeness centrality (CLO).The three centrality indicators of each country from the years 2008–2015 in one emerging technology field can be calculated by Ucinet software .For the sake of getting linear effects, all the independent variables and control variables are taken in logarithmic form. p = 0.0012).In general, since the panel data include both cross-sectional data and time-series data, parameter estimation may be simultaneously affected by the inter-group effect (which here refers to differences between countries) and the inner effect group (in this case the same differences between countries in different years). Because eliminating differences between country panel data may cause a heteroscedasticity problem in the regression model, we used White’s heteroscedasticity  correctiTo methodically investigate the effecting factors of the international collaboration levels among 20 countries, eight models were estimated in each emerging technology field. We refer to the existing models  and our The baseline model only considers the influence of control variables, and nearly all the control variables passed the significance test in the three emerging technology fields. We can draw the conclusion that degree centrality and betweenness centrality are positively correlated with SHII, and closeness centrality is negatively related to SHII by the estimating coefficients. Compared with the baseline model, model 2–7  and network relationship analysis, then finds effecting factors of international collaboration levels by constructing regression modes. The conclusions are as follows.First, international innovation collaboration patterns across 20 countries exist striking heterogeneities: developed countries, like the US and Germany, tend to have more international cooperation with other countries. However, Japan and South Korea have little cooperation with other countries. These differences are related to national technology development strategies. Take Japan, for example, it is known that Japan has implemented a technology statehood policy since the mid-1980s. Moreover, they have the self-contained technology system . So in oSecond, the collaboration patterns of three emerging technologies exhibit as follows: the balanced collaboration mode (3D printing), the radial mode (big data) and the “small-world” mode (carbon nanotubes and graphene). Different patterns are primarily related to the characteristics of the technology itself. Specifically, the United States masters the main core technology of big data, so other countries need to cooperate with them to cooperatively invent patents. Therefore, the international collaboration pattern of big data technology forms a radial mode, centered on the United States.Last but not the least, the effecting factors of international collaboration levels among different emerging technologies are similar. From the results of empirical analysis, the main factors, GPC, RDE, and ETV negatively associated with international collaboration levels, indicating that the existing international cooperation mode is not conducive for developing countries to cooperate on emerging technology patent inventions. Developing countries need to make efforts on strategic transformation, namely, from imitation to innovation and implement R&D investment strategies to adapt to the new economic and social situation. Then they should strengthen the rational allocation of resources and management of R&D to accelerate the transformation of economic development. Doing so will have theoretical and practical significance for enhancing the international competitiveness of developing countries.S1 FileTable A. The centrality indicators of 3D printing technology. Table B. The centrality indicators of big data technology. Table C. The centrality indicators of carbon nanotubes and graphene technology. Table D. Robust analysis results of 3D printing technology. Table E. Robust analysis results of big data technology. Table F. Robust analysis results of carbon nanotubes and graphene technology. Table G. Raw data of three emerging technologies. Text H. The retrieved strategy for three emerging technologies.(DOCX)Click here for additional data file.


Post-ischemic reperfusion injury (PIRI) triggers an intense inflammatory response which is essential for repair but is also implicated in pathogenesis of post-ischemic remodeling in several organs in human. Stem cell therapy has recently emerged as a promising method for treatment of PIRI in human. However, satisfactory results have not been reported due to severe loss of injected stem cells in PIRI including critical limb ischemia (CLI). For investigating the advanced glycation end-product-albumin  from activated macrophages is critical in both muscle cell and stem cell death, we evaluated the recovery of PIRI-CLI by injection of human bone marrow derived mesenchymal stem cells (hBD-MSCs) with or without soluble receptor for AGEs (sRAGE). Our results showed that activated M1 macrophages synthesize and secrete AGE-albumin, which induced the skeletal muscle cell death and injected hBD-MSCs in PIRI-CLI through RAGE increase. Combined injection of sRAGE and hBD-MSCs resulted in enhanced survival of hBD-MSCs and angiogenesis in PIRI-CLI mice. Taken together, AGE-albumin from activated macrophages is critical for both skeletal muscle cell and hBD-MSCs death in PIRI-CLI. Therefore, the inhibition of AGE-albumin from activated macrophages could be a successful therapeutic strategy for treatment of PIRI including CLI with or without stem cell therapy. Although PIRI occurs in the presence of vascular access, the severity of cell death, organ dysfunction, post-ischemic remodeling and infarct size are similar or worse when compared to the ischemic organs without reperfusion in the cardiovascular, neurologic, and musculoskeletal systems6. Critical limb ischemia (CLI) is one of the most debilitating sequela of peripheral arterial disease. PIRI has been implicated as one of the underlying pathophysiology of CLI where the skeletal muscle cells in the infarct area are induced to undergo apoptosis and suffer the similar consequence of acute myocardial infarction (AMI) and cerebrovascular accident (CVA)8.Post-ischemic reperfusion injury (PIRI) is associated with the pathogenesis of post-ischemic remodeling in many human and animal organs9. For an example, acute infarction rapidly triggers innate pathways to trigger an inflammatory reaction by secretion of molecules such as high motility group protein 1 (HMGB1) or monocyte chemo-attractant protein 1 (MCP-1)12. Apoptosis of the majority of host cells follows and the infarct matures with high amounts of fibrosis including collagen fibers13. The inflammatory consequences of PIRI include a cascade of diverse cell types and reactions, resulting in newly recruited cells. As the most abundant non-host cell population in the inflammatory site of PIRI, M1/M2 macrophages infiltrate and contribute to the pro-inflammatory milieu in the infarcted area19. This recruitment of two different populations of monocytes or macrophages in the infarct area has been the subject of many debates on the roles of these cell types. The exact contribution of either cell types remains unclear.Several studies targeted the inflammatory process, however, anti-inflammatory treatment for clinical PIRI did not protect against the host cell death such as cardiomyocytes, skeletal myocytes, or neurons due to the multifactorial complexity of inflammation, involving multiple molecule and cell types22. However, there are no reports to show that AGE-albumin is critical in PIRI and the inhibition can protect the host cell death. Recently, stem cell therapy has emerged as a promising method for management of PIRI clinically. However, satisfactory results have not been reported by stem cells in the treatment of PIRI associated with many debilitating human diseases such as AMI, CVA, or CLI due to significant and rapid loss of stem cells in the area of injury26.Recently, we have been reported that AGE-albumin (advanced glycation end product), the most abundant AGE product, is synthesized and secreted from activated macrophages and reported as a key inducer of host cell death in various degenerative diseases by increased expression of receptor-AGEs (RAGE)In this study, we hypothesized that AGE-albumin secreted from activated macrophages induces cell death of both the native skeletal muscle cells and the newly introduced stem cells by a RAGE-dependent pathway. Therefore, inhibition of AGE-albumin can protect against the death of skeletal muscle cells and stem cells after PIRI and enhance the recovery of infarcted organs.28. First, we checked the macrophage activation and skeletal muscle cell death in the PIRI-critical limb ischemia (CLI) animal model. Total population of activated macrophages showed a dramatic increase from control (Con) day 1 (1d) to day 3 (3d) and a rapid decrease on day 7 (7d) after PIRI-CLI  and receptor-AGEs (RAGE)CLI Fig. . For anaCLI Fig. . HoweverCLI Fig. . alpha-aCLI Fig. . These rNext, we investigated whether AGE-albumin from activated macrophages is critical in skeletal muscle cell death leading to PIRI-CLI. To determine the expression level of AGE-albumin, triple-labeled fluorescent staining was performed in M1 or M2 macrophages after differentiation from Raw 264.7 cells Fig. . This laFor analysis of the distribution of AGE-albumin from activated macrophages in animal models, we performed triple immunohistochemical staining in skeletal muscles after PIRI-CLI in mice Fig. . AGE-alb29. Therefore, we assessed the question of whether AGE-albumin from activated macrophages can induce RAGE expression in skeletal muscle and leads to skeletal muscle cell death. Immunohistochemical data showed that the amount of RAGE in skeletal muscle cells was increased after exposure to AGE-albumin (AA) only but decreased significantly after combined treatment of AGE-albumin and soluble RAGE (AA/sRAGE)  is known to be expressed in skeletal muscles after PIRI, and its increased level is highly correlated with skeletal muscle cell deathGE) Fig. . A similGE) Fig. . TUNEL aGE) Fig. .Figure 321, we checked the changes of the MAPK and RAGE levels in the PIRI-CLI animal model. Immunohistochemical and immunoblot analyses showed that the levels of RAGE and pp38 were significantly increased after PIRI-CLI compared with control, but decreased significantly after treatment with sRAGE in PIRI-CLI  was used to visualize the population of living hBD-MSCs. IVIS results showed that the fluorescence intensity ratio was 0.58 and 0.65 on day 3 and day 9, respectively. This decreased rapidly to 0.28 on day 20 in the PIRI-CLI animal model compared to control/hBD-MSCs injected mice. However, the survival rate of hBD-MSCs was dramatically increased to 0.87 and 0.81 on days 9 and 20, respectively, after sRAGE treatment in PIRI-CLI  in PIRI-CLI mice. The results showed that the level of CD44 positive cells decreased rapidly by 1.48-fold compared to control/hBD-MSCs (Con/MS) injected mice. However, co-treatment with sRAGE in PIRI-CLI animals prevented the decrease significantly by 1.02-fold reduction of hBD-MSCs survival Fig. .in vitro after treatment of AGE-albumin with or without sRAGE. The intensities of RAGE and TUNEL increased significantly but decreased dramatically after subsequent co-treatment with sRAGE  staining showed that the number of the damaged muscle cells, demonstrated by nuclear atypia, was decreased by 1.88-fold after hBD-MSC treatment, which was further dramatically decreased by 3.46-fold by co-treatment of hBD-MSC with sRAGE compared to the PIRI-CLI animals Fig. . Masson’Together, our data showed that AGE-albumin from activated M1 macrophages induces skeletal muscle cell death and the inhibition of AGE-albumin promoted hBD-MSC survival and protected the severity of PIRI-CLI.30. However, it is poorly understood whether activated macrophages promote skeletal muscle cell damage or not. We recently reported that AGE-albumin can be synthesized in activated mononuclear phagocytic cells in several areas of the body including brain and lung32. We also demonstrated that the synthesis and extracellular secretion of AGE-albumin from microglial cells were elevated upon activation and is critical for host cell death33.Many investigators have reported the recruitment of activated macrophage cells in various post-ischemic reperfusion injury areas35. In addition, triple fluorescent labeling and immunoblot analyses showed that the AGE-albumin synthesis in M1 macrophage cells36 and its extracellular secretion were significantly elevated compared to M2 macrophages in PIRI-CLI animals. Based on these findings, we could conclude that the synthesis of AGE-albumin in M1 macrophage cells and its extracellular secretion are closely related to increased skeletal muscle death in PIRI-CLI. This result is consistent with those of several reports on the more deleterious role of M1 macrophages in the inflammatory site than M2 macrophages36.Similarly, we first hypothesized that activated macrophages can induce skeletal muscle cell death based on an increase in AGE-albumin and RAGE in PIRI-CLI. First we checked the macrophage activation and skeletal muscle cell death in the PIRI-CLI animal model. Our result of alpha actinin and TUNEL assay showed that human skeletal muscle cell death increased gradually in the PIRI-CLI model. The numbers of M1 macrophages increased more than those of M2 macrophages on day 3 after PIRI-CLI. Then, the numbers of both macrophage cell types showed a rapid decrease until day 7 after PIRI-CLI. According to these results the total number of macrophages increased initially, the M1 macrophages were more dominant than M2 sub-population, and the end-result was skeletal muscle cell death. These findings are similar to several other observations of macrophage recruitment, activation and host cell death in PIRI such as acute myocardial infarction and stroke39. Therefore, we also assessed the question of whether AGE-albumin from activated macrophages increases the expression of RAGE, leading to skeletal muscle cell death. Our data demonstrated that the amounts of RAGE in human skeletal muscle cells were increased upon exposure to AGE-albumin but showed a rapid decrease after treatment with sRAGE, an AGE inhibitor. The PIRI-CLI animal result showed that the RAGE increase induced skeletal muscle cell death while sRAGE inhibited such death. This AGE-RAGE dependent cell death has been well established by many reports including AMI, stroke, and other degenerative diseases. Remodeling after PIRI undergoes the same RAGE dependent muscle cell death43. In terms of the mechanism of cell death after RAGE increase, immunoblot analysis showed that the level of pp38 was significantly increased in both cell and animal models exposed to AGE-albumin compared to control. But the level of pp38 was decreased after exposure of human skeletal muscle cells to AGE-albumin and sRAGE. These data demonstrate that AGE-albumin directly promotes apoptosis of neuronal cells through activation of the RAGE-p38 pathway. This is also similar to microglial activation in degenerative diseases in brain and explains further how mononuclear phagocytic cells are activated21.A receptor protein for AGEs (RAGE) is known to be expressed in the muscles after PIRI and its increased level is highly correlated with muscle cell death45. Our result showed that the origin of AGE-albumin is activated macrophages and its inhibition can protect against tissue damage as well as hBD-MSC survival in PIRI-CLI.Second, we hypothesized that stem cell survival is also limited due to AGE-albumin from activated macrophages and hardly improve the recovery of PIRI. We used an in vivo imaging system (IVIS) to determine the survival rate of hBD-MSC in the PIRI-CLI mouse model. The population of viable hBD-MSCs decreased rapidly in the PIRI-CLI animal model but increased dramatically after AGE-albumin inhibition. The result was confirmed by immunohistochemistry using human MSC specific marker (CD44) in both hBD-MSCs and skeletal muscles of PIRI-CLI mice. Immunohistochemical data also showed that RAGE labeling was increased in the hBD-MSCs in animal models of PIRI-CLI. The labeling intensity showed a dramatic decrease after co-treatment of hBD-MSCs with sRAGE. These results strongly indicate that the main cause of death of injected hBD-MSCs and skeletal muscle cells is due to increase in RAGE and AGE-albumin from activated M1 macrophages in PIRI. There are many reports supporting this finding that the inhibition of AGE-albumin or RAGE can protect against tissue damagein vivo inhibition dramatically enhanced the survival of skeletal muscles and angiogenic capacity in PIRI-CLI animals.To determine the angiogenic capacity of hBD-MSCs and their improved survival by AGE-albumin inhibition, we first measured the size of blood vessels in PIRI-CLI animals. The size increased after BD-MSC injection in leg muscles and was further enhanced dramatically after co-treatment with sRAGE for AGE-albumin inhibition in the leg muscles of PIRI-CLI animals. This was confirmed by immunofluorescent confocal microscopy of vWF- and α-SMA-staining in leg muscles of PIRI-CLI mice. The result of the microscopy was consistent, which demonstrated increased immunostain of both markers and subsequent dramatic increase after treatment with hBD-MSC and sRAGE in leg muscles of PIRI-CLI animals. AGE-albumin is critical in determining the survival of hBD-MSC. Its Finally, we checked the recovery of skeletal muscles by the AGE-albumin inhibition of hBD-MSCs in the PIRI-CLI model. The number of muscle fibers increased after hBD-MSC treatment but it further enhanced dramatically after co-treatment with sRAGE. Masson’s trichrome staining also showed a decrease in interstitial tissue after hBD-MSC treatment compared to control but dramatically decreased further after co-treatment with sRAGE. TUNEL staining also showed that the number of apoptotic muscle cells was decreased after hBD-MSC treatment but similarly demonstrated a dramatic decrease after treatment with sRAGE in leg muscles of PIRI-CLI animals.In summary, our data show for the first time that AGE-albumin is synthesized mainly in activated M1 macrophage cells and secreted into areas of PIRI-CLI mice to induce the death of both skeletal muscle cells and newly injected hBD-MSCs. The inhibition of AGE-albumin promoted the survival of both skeletal muscle cells and hBD-MSCs in PIRI-CLI and enhanced angiogenic activity to protect against skeletal muscle injury in PIRI. As well as local effects, sRAGE-MSC reduced systemic reaction such as kidney or liver malfunction Fig. .Our results, therefore, provide a new mechanistic insight by which activated macrophage cells play an important role in promoting muscle cell death in PIRI-CLI by synthesizing and secreting potentially toxic AGE-albumin. Co-treatment of hBD-MSCs with AGE-albumin inhibition could be an excellent therapeutic strategy for many human diseases of PIRI.Seven weeks of male Balb/c mice were purchased from Orient Bio  and these mice were maintained on a light/dark cycle (12 hrs/12 hrs) with adequate access to food and water for at least one week prior to their usage. All animal experiments were approved by the Institute Animal Care and Use Committee  of Lee Gil Ya Cancer and Diabetes Institute of Gachon University.6 human bone marrow-derived mesenchymal stem cells (hBD-MSCs), and 3) hBD-MSCs with 0.8 μg/8 μl soluble RAGE recombinant protein treatment . These agents were injected directly into the PIRI-CLI muscles.The mice were anesthetized with a mixture of 2% xylazine hydrochloride  and tiletamine/zolazepam  through intra-peritoneal injection. After induction of anesthesia, surgical procedures were performed by following protocol. Briefly, longitudinal incision of left thigh skin was made. Proximal and distal ends of the femoral artery was ligated. Complete femoral artery occlusion was achieved and continued for 1 hr. The ligation was removed and blood reperfusion was allowed into the ischemic muscle. After recovery of blood supply to the damaged muscles, the following 3 treatment arms were established: 1) 8 μl normal saline, 2) 1 × 10One million hBD-MSCs were stained with Vivo track 680 fluorescence reagent  according to the manufacturer’s instructions. Briefly, hBD-MSCs were incubated with Vivo track 680 reagent for 15 mins at room temperature in the dark. After washing with 0.1 M phosphate buffered saline , the labeled hBD-MSCs with or without sRAGE were injected directly into the damaged muscle. Grafted hBD-MSCs were checked by fluorescence intensities from 1 to 20 days after injection. The fluorescence intensity was detected by In Vivo Imaging System  and the expression level was quantified.μg/hBD-MSCs were passaged 5–6 times and cultured in Dulbecco’s modified Eagle’s medium  containing a low glucose concentration supplemented with 10% fetal bovine serum  and 1% gentamycin. Then, hBD-MSCs were incubated with basal medium  with serum  and with 800 TM-2 growth medium including bovine brain extract with heparin, human epithelial growth factor, hydrocortisone and GA-1000  in a 1% gelatin  coated culture dish. Murine macrophage cells (Raw 264.7) and rattus norvegicus skeletal muscle cells (L6) were also used in this study. These cells were purchased from Korean Cell Line Bank and cultured in DMEM with a high glucose concentration supplemented with 10% FBS and 100 U/2 humidified incubator at 37 °C.Human umbilical vein endothelial cells  were cultivated with EGM2, 5% CO2, and 94% N2 for 24 hrs. Finally, the treated cells and supernatant were collected.To mimic ischemia reperfusion condition of animal, L6 cells were treated with serum free DMEM medium and were incubated with in a hypoxia chamber filled with a gas mixture consisting 1% Oμm) were performed on a cryostat . Ten percent normal goat serum was used for blocking of non-specific binding at 4 °C overnight. The tissue sections were incubated with the primary antibodies , washed with PBS, fixed with methanol for 15 mins on ice, and washed again with PBS. After fixation, these cells were incubated with primary antibodies at 4 °C overnight. The cells were rinsed with PBS, followed by incubation with secondary antibodies at room temperature for 1 hr in the dark. The antibodies used for this study are listed in Table μg/μg protein/lane) were separated by 8–12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and then transferred to polyvinylidene fluoride (PVDF). PVDF membrane was incubated with appropriate diluted primary antibodies at 4 °C overnight. The membrane was washed with tris buffered saline with 1% tween 20 (TTBS) three times and incubated with secondary antibodies for 1 hr at room temperature. The primary and secondary antibodies are listed in Table To validate relationship between AGE-albumin and mitogen-activated protein kinases (MAPK) in skeletal muscle, L6 cells were firstly exposed to 400 ng/RNA was isolated from each group by using Trizol reagent , and cDNA was synthesized by using a PrimeScript 1st strand cDNA Synthesis Kit (TAKARA) according to the manufacturer’s protocol. qRT-PCR was performed by using CFX384 Touch™ Real-Time PCR detection system  and, reaction efficiency and threshold cycle number were determined by using CFX Manager™ Software. All reacted primers are shown in Table 28, 5,000 cells of L6 per well were seeded in 96 well culture plate  and conditioned medium from M1 or M2 macrophages was directly treated to L6 cell for 48 hrs in a 5% CO2 humidified incubator at 37 °C. WST was mixed with serum free DMEM with high glucose  was purchased from Daeil Lab Service . To analyze skeletal muscle cell viability using AGE-albuminμg/μg/2SO4) and the optical density was read at 450 nm using an ELISA plate reader .For measurement of secreted and synthesized AGE-albumin from the activated macrophages and PIRI-CLI injured skeletal muscles, a 96 well-plate was coated with 1 4 cells/well) were seeded on solidified matrigel and were treated with BM, CM, AA/CM, or AA/CM/sRAGE, respectively. After 20 hrs of incubation, the images were captured by fluorescent confocal microscopy (Carl Zeiss 710).HUVECs were stained with acetylated low-density lipoprotein (Invitrogen) as endothelial cell specific marker and conjugated with DiI fluorescent dye according to the manufacturer’s protocol. To remove FBS effects, HUVECs were incubated with medium containing 1% FBS without growth factors for 24 hrs. Tube formation capacity was estimated in matrigel tube formation assay. Growth factor-reduced matrigel  was spread onto a 24-well plate (Invitrogen) and incubated for 40 mins at 37 °C. HUVECs (5.0 × 105 cells/well) were seeded on a 24-well transwell plate and treated with BM, CM, AA/CM, or AA/CM/sRAGE for 48 hrs. Un-migrated HUVECs were discarded and hematoxylin stained migrated HUVECs were counted on light microscopy .To confirm chemotactic motility of hBD-MSCs, transwell migration of HUVECs was implemented. HUVECs  for 1 min and then, washed with running tap water for 3 mins. The tissues were immerged within Eosin Y solution (Sigma-Aldrich) for 20 secs and were finished with serial ethanol step and zylene.To determine fibrosis area in the PIRI-CLI injured muscles, we performed Masson’s Trichrome staining (Sigma-Aldrich) and all components was used in commercial kit. Briefly, put skeletal muscle slides in the bouin’s solution for 15 mins at 56 °C for fixation and the slides were stained with Iron hematoxylin for 5 mins to nucleus. Biebrich Scarlet was used to stain acidophilic components and Phosphomolybdic-phosphotungstic acid was used for differentiating tissues. Finally, collagen of fibrosis area was stained by Aniline blue.All stained slides were immersed in gradient alcohol and 100% of xylene and the slides were sealed with cover glass by using DPX medium (Sigma-Aldrich) and these were analyzed on light microscope.Given the small samples, non-parametric analysis was used in this study. SPSS version 22  statistical program was used and Mann-Whitney U test was used to compare groups. P values < 0.05 (*), <0.01 (†), <0.001 (#) were deemed significant. All results are expressed as the mean ± standard deviations (s.d.).Supplementary figures and tables


To present a method, alternative to penetrating keratoplasty, for the restoration of impaired corneal clarity with anterior stromal scarring following long-standing corneal graft failure.A 48-year old female who had previously underwent Descemet stripping automated endothelial keratoplasty (DSAEK) for the treatment of pseudophakic bullous keratopathy, presented with long-standing corneal oedema and anterior corneal scarring. A significant improvement in corrected distance visual acuity was demonstrated, as corneal clarity was restored following graft exchange and phototherapeutic keratectomy (PTK).The combination of corneal graft exchange and phototherapeutic keratectomy may represent an effective therapeutic option for long-standing corneal oedema with concomitant anterior corneal scarring after failure of a DSAEK graft. Descemet stripping automated endothelial keratoplasty (DSAEK) has become the modality of choice for the treatment of corneal oedema arising from corneal endothelial diseases including Fuchs endothelial dystrophy and pseudophakic bullous keratopathy .In cases of DSAEK graft failure or rejection, corneal graft exchange could be attempted. Nevertheless, when corneal oedema is left to ensue, the subsequent chronic corneal decompensation may result in anterior corneal fibrosis. The aforementioned complication limits the final visual outcome of a new DSAEK procedure and, thus, may alter the surgeon’s plan in favour of penetrating keratoplasty (PK).A 48-year old female sought medical consultation due to decreased vision of the left eye. Her past medical history included no necessity for spectacle correction at a younger age and phacoemulsification surgery of the left eye 4 years ago. Following cataract surgery, no improvement of her visual acuity was noticed due to pseudophakic bullous keratopathy. Therefore, the patient underwent DSAEK procedure in the left eye six months post cataract extraction. Restoration of good visual acuity following DSAEK that lasted for the next year was noticed; upon the aforementioned period the patient reported gradual deterioration of vision. Gradual visual impairment was attributed to graft failure.The ophthalmic examination of the left eye revealed uncorrected distance visual acuity HM (hand movement) that could not be improved with spectacles. Slit-lamp biomicroscopy of the left eye showed corneal oedema accompanied by anterior corneal fibrosis.We proceeded with a second Descemet stripping endothelial keratoplasty  in order to replace the non-functional graft with a healthy one. The procedure resulted in complete resolution of corneal oedema within the first postoperative month Fig . NeverthIn the first postoperative month, anterior corneal fibrosis resolved Fig  and the Corneal decompensation arising from a non-functional graft or from endothelial diseases such as Fuchs endothelial dystrophy  and pseuIn our case, failure of DSAEK graft led to chronic corneal oedema with a central opacity that involved the anterior stroma. We decided against PK in an attempt to achieve not only satisfying post-keratoplasty visual acuity, as well as to obviate the increased morbidity of a full-thickness corneal graft. A two-step procedure that included DSAEK graft exchange and phototherapeutic keratectomy with adjunctive MMC was performed. To date, 6 months following PTK, no recurrence of the anterior corneal fibrosis has been observed.Manual debridement of the fibrosis would be an alternative in case of a superficial scar. However, in the case of scar extension into the anterior stroma, manual peeling may give rise to deep corneal defects that may, in turn, lead to uneven healing and an unpredictable visual outcome . In addiIn conclusion, DSAEK graft failure prompts consideration for timely restoration of subsequent corneal oedema, as chronic corneal decompensation can result in anterior corneal fibrosis. In the adverse event of graft failure with anterior corneal scarring, combined graft exchange and PTK should be considered in an effort to spare the patient from the increased morbidity of a PK graft and to achieve a greater visual outcome.


Tuning the stiffness balance is crucial to full-band common-mode rejection for a superconducting gravity gradiometer (SGG). A reliable method to do so has been proposed and experimentally tested. In the tuning scheme, the frequency response functions of the displacement of individual test mass upon common-mode accelerations were measured and thus determined a characteristic frequency for each test mass. A reduced difference in characteristic frequencies between the two test masses was utilized as the criterion for an effective tuning. Since the measurement of the characteristic frequencies does not depend on the scale factors of displacement detection, stiffness tuning can be done independently. We have tested this new method on a single-component SGG and obtained a reduction of two orders of magnitude in stiffness mismatch. Sry today .However, lower fundamental noise does not mean better resolution for airborne measurements. In the notorious aviation environment, the vibration level of the platform is higher than that in the laboratory by 4–6 orders of magnitude . The plaTo reject the common-mode noise, the rotating accelerometer gravity gradiometer ingeniously introduces regular common-mode modulation acceleration by rotating the installation disc . With thHowever, the question of how to precisely tune the stiffness remains unsolved. The difficulty mainly comes from the lack of a reliable criterion to evaluate the tuning effect. In , Moody aIn this paper, a new scheme is proposed to tune the stiffness. In this scheme, the characteristic frequencies of the SGG oscillators are adopted as the criterion. Since these frequencies do not depend on the scale factors of displacement-detecting, the criterion works even if the scale factors are badly matched. Furthermore, once the characteristic frequencies have been measured, one can immediately know how far away the working state deviated from the ideally matched state. Through simple calculations, one can easily estimate how much the currents should be adjusted in the next step. The tuning scheme was successfully applied to a single-component SGG, where the stiffness balance was improved by about two orders of magnitude.zz single-component SGG as an example, a superconducting vertical spring oscillator is constructed by levitating a test mass in the superconducting Meissner state using a current-carrying superconducting coil. A pair of oscillators are installed along the vertical direction at a certain distance. For the convenience of optimizing the performance, the levitating superconducting coils of two oscillators are incorporated into the same superconducting circuit. Governed by the flux conservation law of superconducting loops, the motions of two oscillators are coupled by the superconducting circuit. These two coupled oscillators can be modeled as a two-degree-of-freedom vibration system. The vibration can be decomposed into two normal modes: the common mode and the differential mode. The differential-mode displacement is detected as a gravity gradient signal. By coupling the two oscillators together through the superconducting circuit, the differential-mode stiffness can be designed to be much smaller than that of the common mode; consequently, the instrument sensitivity and the ability to reject common-mode noise can be improved.The working principles of the SGG have been described in detail in a number of references ,11,12,13m1 and m2 are the masses; x1 and x2 are the displacements of the test masses; a1 and a2 are the input accelerations that act on the test masses; c1 and c2 are the damping coefficient of the spring oscillators. K10, K20, K12 and K21 are the stiffness coefficients, which are determined by the parameters of the superconducting circuit and the injected supercurrents. Their expressions are given in K12 and K21 are always identical because of the exchange symmetry of the superconducting circuit with respect to the test masses. By definingThe dynamic equations of the oscillators are written asIt can be clearly seen that, if the parameters of the oscillators are not matched, the platform acceleration will enter into the expression of the differential displacement. To achieve an excellent full-band common-mode balance, the correlated parameters should be elaborately adjusted to minimize the dependence of differential displacement on the platform acceleration. It is easy to derive two conditions from Equation (4) for an ideal balance, which areK10 = K20 and c1 = c2. In the SGGs, stiffness coefficients are determined by parameters of the levitating coils, the supercurrents in the coils and the parameters of the superconducting circuit . This sets an upper limit for the mismatch of the damping coefficients. Even at the upper limit, the mismatch of Equations (5a) and (5b) tell us that the balance tuning actually includes stiffness tuning and damping coefficient tuning. Since the mass of the test masses can be easily matched to 1 ppm, we can neglect the minute difference in mass tentatively, and the balance conditions are simplified as K10, K20, or the difference between them, but the displacements of two test masses can be easily monitored. Keeping this in mind, one would naturally think of whether an analysis of the motion of the test masses would provide a useful guide to the tuning. Indeed, Equation (3) implies a positive answer to the question.As mentioned previously, the stiffness coefficients can be tuned by injecting an adjusting current into the superconducting circuit that is associated with the levitating coils. The tuning principle is illustrated in When acceleration is applied to the instrument, the amplitude–frequency response functions of the displacement of two test masses, which are denoted by These functions are plotted in One can find a number of interesting things in Consequently, a scheme to tune the stiffness parameters emerges. In the scheme, the displacement responses of the two test masses to common-mode acceleration are measured simultaneously as functions of frequency. The characteristic frequencies The underlying theoretic basis for the tuning scheme will be more intuitive if the damping effect is neglected. In this case, Equations (6a) and (6b) becomei = 1 and 2). The Assuming the test masses are reasonably identical, the displacement response now vanishes at the frequency of −4 N/(m/s), and the tuning accuracy could reach 10−4 with this scheme.For a real SGG, damping, albeit slight, inevitably exists. The damping effect on the tuning accuracy should be evaluated. Noticing that the depth of the valley around zz single-component SGG, which is under development in our group. The stiffness tuning scheme was tested on a TThe superconducting circuit for levitating is shown in 2 in amplitude. The sinusoidal motion of the test mass could be immediately monitored as shown in The SGG sensor was installed in a vacuum chamber with a residual helium pressure of about 10 Pa. After the system was cooled to 4.2 K, a persistent current of 6.8 A was injected into the levitating coils. The current of the sensing coils was set to 10 mA. The displacement of the test masses was transferred to the Superconducting Quantum Interference Device (SQUID)’s output by the sensing circuit. To obtain a common-mode agitating acceleration, a sinusoidal current with a constant amplitude of 20 mA was applied to the second winding of the mutual inductance by a current source meter. The produced modulation acceleration was roughly estimated to be 0.01 m/sobtained b.−3. Furthermore, the adjusting current was set to 0.25 A deliberately to see the over-tuning results. In this case, the appearance sequence with increasing frequency of the valley and the peak on the curves changed for each test mass, and the absolute value of the difference between the two characteristic frequencies increased. The measured displacement response functions under different adjusting currents are shown in −3.In the experiment, the first turn of the measurement of the response functions yielded Based on a systematic theoretical analysis, a new tuning scheme was experimentally tested for the stiffness balance of an SGG. In this scheme, characteristic frequencies are adopted as the tuning criterion. The criterion did not depend on the mismatch of the scale factors for displacement detection, so stiffness tuning could be conducted independently. This was of great advantage in terms of tuning the full-band common-mode balance. However, the criterion would only work if the damping coefficient was relatively small and the mass of the oscillators had already been balanced at a relatively high accuracy. Otherwise, the tuning accuracy was limited by the effects induced by these two factors rather than the measurement resolution of the characteristic frequencies.


This historical issue kicks off celebrations after 30 years of continuous publication ofthe Revista Brasileira de Cirurgia Cardiovascular, known today as the Brazilian Journalof Cardiovascular Surgery (BJCVS).These 30 years represent the history of our Society.The journal was founded by idealists led by Dr. Adib Jatene, and they represent thepioneers of cardiac surgery in Brazil and South America.Professor Adib was the Editor-in-Chief for the first 10 years, from 1986 to 1996.Our current President followed in his footsteps, showing his permanent dedication to theBrazilian Society of Cardiovascular Surgery (BSCVS).Prof. Fabio Jatene was the Editor-in-Chief during 6 years, from 1996 to 2002.In 2002, I put myself at disposal and I have been the Editor-in-chief since then.Due to our growth and complexity, our Associated Editors currently play a bigger role, inwhich they are responsible for the entire process of dealing with the articles they areattributed. The Editor-in-Chief still has the final word.Space limitations do not allow me to name every single person that has worked, withoutpay or advantage, for the greater good of the BJCVS.www.bjcvs.org, inthe "Editorial Board" session to see the names of those who throughout our history havegone to great lengths to create and maintain the BJCVS and that is why they deserve tobe praised by all.I ask all the coleagues to access at the journal's webpage at In addition, at the end of every issue, all our reviewers are listed, to whom I paytribute for sacrificing their leisure time not only to review the manuscripts, butespecially to guide the authors who show potential, helping them conform to scientificmethods, to the guidelines of the journal and standard language, thereby acting asprofessors.This kind of attitude has gradually improved the level of our publications, though westill have to improve our work.th anniversary was a difficultdecision, but a necessary one in order to meet the needs of a new internationalreality.Changing the name of the journal on its 30Nowadays, English is the lingua franca of scientific communication.We could not be tied down by nostalgia, remaining unread and not understood by theinternational community.You are witness to the care we took to make this transition.First, as required by SciELO, PubMed etc., the abstract was published in Portuguese andEnglish.Then, for a long time, we became a bilingual publication, which was very interesting, butalso a demanding job since for every issue we actually published two "journals", one inPortuguese and the other in English.The titles of the articles continued in Portuguese for some time, until we decided topublish them in English to call the attention of readers who did not understand ourlanguage.We also modified our submission system, which became fully in English to make it easierfor researchers from other countries.Such measures had some effect as we have received articles from Portugal, Colombia,United States, Canada, Germany, Iraq, Iran, Mexico , and many from China and Turkey, but not enough to increase our citations andImpact Factor, which is now our main goal.We are in almost all international databases, allowing easy access to our articles, whichis essential to attract readers, especially because our journal is completely free, bothfor authors and readers.The change in our designation to English required several démarches, both inBrazil and abroad.Finally, it became a reality, primarily because we had had the designation in English asa subtitle for a long time!Another question arose: whether to completely change our identity and remove the word"Brazilian", following in the footsteps of many other publications that do not identifytheir country of origin.Many people helped us with this task, Professor Abel Packer, Director of SciELO, beingone of them, who insisted we should not lose our national identity.I believe it was a wise decision. Brazil is much greater than the crises it faces. It isessential to show what we are capable of in order to stand amidst other nations.Among the advantages of producing our issues in only one language, there was an importantbyproduct: we went from quarterly to bimonthly publication, that is, six issues peryear.I would like to call your attention to an important fact: every economic sacrifice hasbeen made, but the new changes will have been in vain unless we publish work of provenscientific value.Dear colleagues, I ask you to ponder these terms. We have a modern tool in accordancewith global standards; however, we will not fall within the scope of leadingpublications if our articles are mediocre.Our constant obsession with having a better impact factor and, as a result, a Qualisranking compatible with our specialty, will suffer another drawback: due to the changeof name, the BJCVS citation will be only in English and thereby counted by Thomson andScopus from now on. These are problems to be faced in order to improve for thefuture.In this issue, there are 13 articles, six originals, three reviews, oneclinical-surgical correlation, one brief communication, one experimental work, and aletter to the editor.versus Surgical Aortic Valve Replacement to ImproveQuality of Life in Patients >70 Years of Age with Severe Aortic Stenosis (page1), from Turkey; and Aberrant Origin of Vertebral Artery and its ClinicalImplications (page 52) and Myocardial Bridging (page 60), from China.Among these articles, we have four international studies - Transposition of GreatArteries with Intramural Coronary Artery: Experience with a Modified SurgicalTechnique (page 15), from India; Comparison of Transcatheter Aortic ValveImplantation In this BJCVS issue, the following articles are available to test the ContinuingMedical Education (CME): "Results of Open and Endovascular Abdominal Aortic AneurysmRepair According to the E-PASS Score" (page 22); "Congenital Heart Disease andImpacts on Child Development" (page 31); and "Double Aortic Arch Associated withPulmonary Atresia with Ventricular Septal Defect" (page 63)thanniversary, written with warmth by the following colleagues:It is with great joy that we also publish reviews celebrating our 30th Anniversary ofthe Brazilian Journal of Cardiovascular Surgery" (page 75); Rubens Tofano de Barros,"BJCVS: A Success Story" (page 77); Milton de Miranda Santoro, "The Myth of Atlas"(page 78); and Luiz César Guarita-Souza, "The Thirty Years of the BrazilianJournal of Cardiovascular Surgery" (page 79).Marcela da Cunha Sales, "The Evolution of Cardiac Surgery in Brazil and the BJCVS"(page 74); Vinicius José da Silva Nina, "The 30In the next issues, we wish to have many more descriptions of the history of theBrazilian cardiovascular surgery, including the BJCVS.Among all the changes we have been through, there is one more: the resignation ofRicardo Brandau Quitete, who throughout the last 13 years helped us shape theprofile of the journal. That is how life is, things change and we have to changealong. All BSCVS partners and I can only thank Brandau for his dedication and workand wish him success in the new challenges to come.rd Brazilian Congress of Cardiovascular Surgerywill take place at Centro de Eventos do Ceará in Fortaleza, CE.From April 7 to 9, the 43th anniversary of the BJCVS.Besides the scientific program, containing innovations that make it an all-aroundevent, on par with similar international events, this year the Congress will markthe celebration of the 30This year's theme is "Innovation, New Horizons in Cardiovascular Surgery".th Symposium of Nursing in Cardiovascular Surgery,the 6th Symposium of Physiotherapy in Cardiovascular Surgery, the5th Academic Congress in Cardiovascular Surgery, the 34thBrazilian Congress of Cardiopulmonary Bypass, the Female Surgeons Meeting, and theResidents Meeting will take place.At the same time, the 6With the purpose of discussing the most recent advances in surgical techniques andthe incorporation of new technology, we will have important internationalguests.The presence of several international guests consolidates the growth and fundamentalintegration of BSCVS with international Societies and values the essential exchangeof knowledge. In addition, participants will enjoy moments with colleagues andfamily as well as leisure time visiting the beautiful capital of Ceará.I congratulate the Board of the BSCVS and the Organizing Committee, coordinated byDr. Glauco Lobo, on the effort made so that the scientific program was interestingfor all the Congress participants.th, from 10am to 12pm in Auditorium 7, there will be a meetingof the Editorial Board of the BJCVS with Associate Editors and Editorial Boardmembers, also open to all members. We will address very strongly the issues that Imentioned above and it will be of great importance to have all suggestions andcriticisms in this transitional phase, so that we can improve the journal and makeit in accordance with the requirements of all Databases and aspiration of ourreaders around the globe.On April 8Warm regards,Editor-in-Chief - BJCVSDomingo M. Braile


Arquivos Brasileiros deCardiologia in January 2010, the journal was more than 60 years old and hadalready attained complete maturity from the huge work developed by the great masters ofthe Brazilian cardiology who had preceded us as Editors. Present in the most relevantinternational citation indexing services, the Arquivos Brasileiros deCardiologia is the major outreach channel of the Brazilian scientificresearch in cardiovascular diseases, representing the major asset of the BrazilianSociety of Cardiology. Several suggestions were implanted aimed at consolidating oureditorial structure and reaching the position as the major scientific forum incardiology in Latin America.1When we took over as Editor-in-Chief of Arquivos Brasileiros deCardiologia was characterized mainly by actions to improve its editorialprocess and to incorporate new edition technologies and new digital media. To face thegreat demand of the manuscripts submitted to publishing, which nowadays add up to 500articles per year, the Arquivos Brasileiros de Cardiologia improvedtheir electronic submission system and the review and editing processes, ensuring fasterresponses to the authors and better editorial quality publishing of the articlesselected. Currently, the mean time of assessment and correction of the articles isaround four months, while that time for Portuguese and English language publications isaround four to five months. In addition, we provide the authors with the previouspublishing of their articles in PubMed within less than eight months from their initialsubmission, guaranteeing the researchers the fast insertion of their work in theinternational literature. In parallel, we strived to incorporate the major editorialpractices of the most prestigious international journals, such as the policiesrecommended by the International Committee of Medical Journal Editors (ICMJE) and theAssociation of the Editors of the European Society of Cardiology-affiliated journals, inaddition to the inclusion of processes of language review, statistical review andantiplagiarism. Available in the electronic pdf format since 2011, the ArquivosBrasileiros de Cardiologia have counted since July 2012 with formatscompatible with most tablets and smartphones, facilitating integral access to thejournal in the major electronic media access systems.In the past eight years, the trajectory of the Arquivos Brasileiros de Cardiologia receivedmore than 4700 scientific article submissions, being responsible for publishing 1813articles between 2010 and 2017, of which, 1014 (56%) were contributions and 101 (6%)were review articles , the major Latin-Americanplatform for indexing and scientific journals, evidenced the need for a new journal withan English name and totally written in English, which is currently required forattaining indexing in the major international access systems. However, the scientificpublications from countries with specific cultural characteristics, such asPortuguese-speaking countries, should be guided by policies that consider not only theneed for wide content dissemination at international level but also the appropriatedissemination among their professional community members.8 We identified that our leaders and associates wanted tomaintain the name of our major journal in Portuguese, going along with the preservationof its 70 years of history and the perspective to continue to have its contentdisseminated to all Brazilian cardiologists.Contacting several Editors of international journals and the leaders of SciELO(Arquivos Brasileiros deCardiologia (CONDARQ) defined the feasibility of a new journal with anEnglish name and written in English, as well as the maintenance of the currentcharacteristics of our major journal. This, following the guidance of the SciELOleaders, would open the perspective of rapid indexing of the new journal, which wouldremain affiliated to the Arquivos Brasileiros de Cardiologia, althoughhaving its own name, and there would be no competition between the associated journals,despite the similar content of the publications. This is ensured by the jointadministration of both journals by the Brazilian Society of Cardiology, by the commonpolicies of submission and peer review, and by the different levels of indexing andimpact factors of the journals. In addition, the joint management of the journalsreduces the financial costs of their maintenance, increases agility and sharing of theeditorial and peer-review processes, magnifies their visibility due to the concomitantdissemination of their contents, in addition to encouraging the scientific debaterelated to the studies published.In the beginning of 2016, the Board of the InternationalJournal of Cardiovascular Sciences, then published by the Rio de JaneiroState Society of Cardiology, into the Brazilian Society of Cardiology. As predicted inthe SciELO guidance, the incorporation of the new journal into the Brazilian Society ofCardiology facilitated its final indexing in that international platform, which happenedless than one year from the beginning of the process mentioned, opening the perspectiveof its rapid indexing by the PubMed, PubMed Central and Scopus systems.9Based on those arguments, the CONDARQ decided to incorporate the International Journal of Cardiovascular Sciences to the groupresponsible for the Arquivos Brasileiros de Cardiologia were defined,and both journals were integrated, with the construction of common access pages andsubmission systems. The priority of the Arquivos Brasileiros deCardiologia regarding the manuscript submission system was defined, as werethe mechanisms to direct at the International Journal of CardiovascularSciences those relevant manuscripts whose publishing was rejected by themajor journal. This mechanism accounted for the referral of more than 150 articles tothe new journal in the past 15 months, contributing to its regular publishing and toindexing a significant number of Brazilian articles, which otherwise would not have theperspective of rapid dissemination in indexed international journals, many of themoriginating from postgraduation programs. Finally, the future Editors-in-Chief of bothjournals were concomitantly approved through an exam-based selection process for the2018-2021 period, and aspects regarding the interaction between the journals wereconsidered during the process. The definitive implantation of that project, followingthe instructions of the major international indexing systems, awaits final approval bythe Brazilian Society of Cardiology, leaving that important perspective still open.During 2016, the bases for transferring the editorial process of theArquivos Brasileiros de Cardiologia inthe past eight years, we claim that we hand a structured journal over to the BrazilianSociety of Cardiology, in accordance with the editorial recommendations followed by themajor international scientific journals, with adequate agility and infrastructure tokeep its position as the major outreach channel of the Brazilian cardiology andcardiovascular science. However, we could neither effectively internationalize it, norcomplete the restructuring process of the Brazilian Society of Cardiology publishingpolicies, which is undoubtedly fundamental for the scientific growth of cardiology andfor the formation of new researchers through new postgraduation programs.Based on the trajectory of the Arquivos Brasileiros deCardiologia during the 2010-2017 period, we leave an even greater challengeto the next Editor. The future expectations of that journal include the continuinggrowth of its internationalizing process, increasing the participation of the AssociatedEditors, reviewers and foreign authors. However, this should happen without puttingaside the mission of the Brazilian Society of Cardiology scientific publishing, whichcontinues to represent the major outreach channel of the Brazilian cardiology andcardiovascular sciences.By concluding the challenging mission of conducting the


The Brazilian Journal of Cardiovascular Surgery (BJCVS) has been going through arestructuring phase and has also conquered a large number of legacies in the last twomonths. We had the opportunity to notice the interest of the Associate Editors, JuniorEditor, Reviewers, Authors and Contributors, thus, helping our journal to have a futureof progressive steps, increasing the frequency and regularity of our publications.The BJCVS currently has 13 volunteer Associate Editors who are striving to fit therequirements of the new submission system in addition to capturing articles in therespective areas: Advances in Cardiovascular Surgery, Diseases of the Aorta, BasicResearch, Cardiovascular Surgery, Cardiovascular Rehabilitation, Continuous MedicalEducation (CME), Congenital Diseases, Coronary Surgery, Transcatheter Aortic ValveImplantation (TAVI) and Valvar Surgery.The submission system has already received 50 manuscripts for evaluation. Thebarriers are being broken, and with each obstacle the BJCVS team develops acommendable advisory work so that all doubts are quickly cleared up.We are involved in a rigorous process for meeting deadlines. Reviewers who do notmeet deadlines are replaced, resulting in the automatic generation of negativepunctuation on ScholarOne evaluation system. Likewise, Associate Editors are alsoevaluated according to the fulfillment of deadlines and quality of opinions.We are very excited about this systematics, because Authors who do not submit themanuscript correction within the determined period, have the manuscriptsinvalidated, and must submit it as a new manuscript, losing its position inpublication queue.Spelling and Grammar have strongly been questioned by the Reviewers and AssociateEditors, a reason of great concern for us; because English language is often sounsatisfactory, and in some cases it prevents content analysis.I request the Authors to collaborate with the BJCVS by sending us the manuscriptsreviewed by professionals who are able to translate them accurately, thus, theywon't be returned, there will be no delays or higher costs to be paid by theauthors. Our reviewers do not correct articles, they only check if the Englishlanguage is good enough to be published., published in Clinics, which brings together the 10 mostcommon mistakes made by Brazilians when writing English manuscripts.We would like to ask you to read the editorial written by Dr. MarielMarlowhttps://bjcvs.wordpress.com and the BJCVS Facebook page https://www.facebook.com/bjcvs.Under the guidance of the BJCVS team, the Junior Editor Dr. Gabriel Liguori took overthe social media two months ago and created a team composed of Residents inCardiovascular Surgery and Medical Academics, who update the Blog After posting the material, the number of likes in 2 months  was incrWe had more than a 15-fold increase in the number of visitors and more than a14-fold increase in the number of blog views in the first month .Top Posts by Blog Viewing:Forming a Cardiac Surgeon - The New American Alternatives - 1,103viewsHow a Cardiac Surgeon Won a Nobel Prize in Medicine: The Invention ofCatheterization - 550 viewsThe woman as a cardiovascular surgeon: Is the cup half empty or halffull? - 516 viewsAccess to BJCVS pages in September and October 2016  and 5:These accesses correspond only to those related to our site. We have a similarnumber of readers accessing our journal through Scielo or other Databases.In this issue, there are two international editorials and 10 articles, eight of themare national and two international in the original article, review article andhow-to article categories.In-Vitro Evaluation of TwoTypes of Neonatal Oxygenators in Handling Gaseous Microemboli and MaintainingOptimal Hemodynamic Stability During Cardiopulmonary Bypass" (page 343);"Intraoperative Analysis of Flow Dynamics in Arteriovenous Composite Y Grafts" (page351); "Comparison of Early Outcomes with Three Approaches for Combined CoronaryRevascularization and Carotid Endarterectomy" (page 365) and "Reference Values forthe Six-Minute Walk Test in Healthy Children and Adolescents: a Systematic Review"(page 381).The following articles that have been chosen to be part of Continuing MedicalEducation (CME) are also available, now under the responsibility of an AssociateEditor specific to this important area: "I emphasize that the CME is a valuable tool for learning and updating the knowledge,besides being important for the test to obtain the Specialist Title of theSBCCV.As always, I deeply thank all the Directors of the SBCCV, Associate Editors, PeerReviewers, all the dedicated staff that help me a lot, and, finally, but not lessimportant, I also thank the Authors who give prestige to our Journal sending themanuscripts to be considered for publication.Sincerely,Domingo M. Braile1Editor-in-Chief - BJCVS