In this paper, we consider the state estimation problem for flexible joint manipulators that involve nonlinear characteristics in their stiffness. The two key ideas of our design are that (a) an accelerometer is used in order that the estimation error dynamics do not depend on nonlinearities at the link part of the manipulators and (b) the model of the nonlinear stiffness is indeed a Lipschitz function. Based on the measured acceleration, we propose a nonlinear observer under the Lipschitz condition of the nonlinear stiffness. In addition, in order to effectively compensate for the estimation error, the gain of the proposed observer is chosen from the ARE  which depend on the Lipschitz constant. Comparative experimental results verify the effectiveness of the proposed method. Flexible joint manipulators are widely used in industrial applications that require high productivity ,2. FurthRecently, observers based on the acceleration information have been proposed to obtain more accurate states ,13,14,15In this paper, we propose an acceleration based nonlinear observer that takes into consideration the nonlinear stiffness of the robot manipulator. We transform the robot model with nonlinear stiffness into a Lipschitz nonlinear system , and theThe paper adheres to the following organizational structure: In τ is the torque applied to the motor. The link inertia D have constant values. The nonlinear stiffness function While the eventual goal of this paper is to estimate the states of the multiaxis flexible joint manipulator, we consider the observation problem for a two-inertia system since it appropriately describes the dynamic characteristics of a single manipulator with a flexible joint . The twoOur goal is to design an observer that guarantees the estimation performance of all the states of the Equation . In partNow, some assumptions are made, on which the proposed observer will be designed in the next section.Assumption 1.The motor position ◊Assumption 2.The system parameters ◊Define Equation  is dividquations  and 2)  θd:=θm-θNote that the matrix Lemma 1. The function ◊L is a suitable observer gain (which will be designed in the following).Now, we propose a nonlinear observer for the System  as folloDefine the estimation error by L. When the nonlinear term L is designed such that the matrix i.e., all its eigenvalues have negative real parts). However, since the Equation ,,7), we oThen, by  . The design parameters for the proposed Observer (In this section, an experiment on a real industrial robot was carried out in order to verify the effectiveness of the observer proposed in this paper. As shown in Now, as shown in In this paper, we have presented a state observer for flexible joint manipulators using the acceleration information of the link side. The observer has been designed on the basis of the Lipschitz nonlinear system, and the stability and performance have been analyzed. In particular, unlike conventional approaches, the study has dealt with the nonlinear stiffness in order to estimate real systems more closely. Therefore, the proposed observer has improved performance compared to that of the conventional observer considering the linear stiffness. Finally, the proposed observer is applied to the real industrial robot, and its effectiveness is confirmed via experiments.


Zea mays L.) as it accounts for 65–75% of the dry kernel weight and positively correlates with seed yield. A number of starch synthesis-related genes have been identified in maize in recent years. However, many loci underlying variation in starch content among maize inbred lines still remain to be identified. The current study is a genome-wide association study that used a set of 263 maize inbred lines. In this panel, the average kernel starch content was 66.99%, ranging from 60.60 to 71.58% over the three study years. These inbred lines were genotyped with the SNP50 BeadChip maize array, which is comprised of 56,110 evenly spaced, random SNPs. Population structure was controlled by a mixed linear model (MLM) as implemented in the software package TASSEL. After the statistical analyses, four SNPs were identified as significantly associated with starch content (P ≤ 0.0001), among which one each are located on chromosomes 1 and 5 and two are on chromosome 2. Furthermore, 77 candidate genes associated with starch synthesis were found within the 100-kb intervals containing these four QTLs, and four highly associated genes were within 20-kb intervals of the associated SNPs. Among the four genes, Glucose-1-phosphate adenylyltransferase  is known as an important regulator of kernel starch content. The identified SNPs, QTLs, and candidate genes may not only be readily used for germplasm improvement by marker-assisted selection in breeding, but can also elucidate the genetic basis of starch content. Further studies on these identified candidate genes may help determine the molecular mechanisms regulating kernel starch content in maize and other important cereal crops.Kernel starch content is an important trait in maize ( Zea mays L.) is one of the most widely grown crops in the world, serving as the staple food for more than 900 million people. Maize seeds  provide a rich source of carbohydrates, mostly in the form of starch, which accounts for 65–75% of kernel dry weight. Therefore, the seed yield of maize is largely determined by the efficient biosynthesis and storage of starch (Maize (f starch . Accordif starch .Sh1 gene (Shrunken2 (Sh2) and Brittle2 (Bt2) genes, respectively , can induce significant increases of the starch content in maize endosperm  and converted to uridine diphosphate (UDP)-glucose and fructose by sucrose synthase encoded by the Sh1 gene , and theSh1 gene . AGPase,ectively . Overexpndosperm . In contndosperm . Additio content .Kernel starch content is a typical quantitative trait controlled by a large number of quantitative trait loci (QTL). Despite recent progress in understanding starch biosynthesis and accumulation at molecular levels, QTLs underlying phenotypic variation in starch content across maize lines are still to be defined . AdditioAccurate quantification of the target trait is a prerequisite for molecular mapping and a biased population structure can lead to false positive associations . In this study, a population comprised of a global core collection of 263 maize inbred lines was used to represent a wide range of diversity, among them, 71 inbred lines are from tropical and subtropical zones, while the remainder are from temperate regions. In order to ensure the normal flowering and pollination of the tropical germplasm, we choose to conduct this study in the tropical regions of Sanya. All the inbred lines were planted in a field in Ledong  in Nov. 2011, 2012, and 2013. The average annual rainfall total was 1,181 mm. The average annual temperature is 23°C. The average annual sunshine total is 1039.6 h. The accumulated temperature (in excess of 10°C) is 9,300.7°C. In the field plot, 24 seeds of each maize inbred line were planted in a randomized complete block design with three replicates (across growing seasons). In one block, eight seeds of each maize inbred line were planted in a row, leaving a 20-cm gap between each line. During the growing seasons, plants were irrigated and given extra doses of pollen by hand. The mature seeds of each inbred line were harvested in bulk and used for starch content analysis.H2B (%) = σ2G/(σ2G + σ2GE/n + σ2e/nb) ∗100, where σ2G is the genetic variance, σ2GE is the genotype × environment interaction variance, σ2e is the error variance, n is the number of environments, and b is the number of replications in each experiment. A frequency map was made using Origin 8.0 . Using an R package, the best linear unbiased prediction (BLUP) values were estimated from the average value of each inbred line across the 3 years. The BLUP values were used as the input data for the association mapping analysis.For three consecutive years, the maize kernels of 263 lines were harvested and analyzed each year to minimize variation across different years. The subsampled kernels from the bulk harvest were used for starch content measurement with a near-infrared analyzer  according to the method described by A modified CTAB procedure was followed for DNA extraction in this study , and theThe panel consisting of 263 inbred lines was genotyped with the Illumina MaizeSNP50 chip  according to the method described by 1. A 100-kb window was selected in order to fall within the estimated 100-kb window of linkage disequilibrium (LD) decay that occurs in our association panel. The genes within this window size were identified in MaizeGDB according to the positions of the closest flanking significant SNPs (P < 0.0001) or supporting intervals  were measured using the NIRS method. In this panel, the average kernel starch content was 66.99% with a range from 60.60% to 71.58% (Table 1). Additionally, the starch content showed a high heritability of 88.30%. The majority of inbred lines produced kernels that were of 65–70% starch content exhibited a normal distribution . Starch content varied significantly among different germplasms . These results suggested that the selected population was suitable for the association analysis of kernel starch content.The starch contents of the 263 maize lines . LD was reached within 30–45 kb on Chr 1, 50–60 kb on Chr 4 and 5, and 80–150 kb on the remaining Chr. The mean length of LD decay across all Chr was 80–100 kb (r2 = 0.1). At a cut-off of r2 = 0.2, the mean length of LD decay decreased rapidly to 5 kb.All 52,370 SNPs (MAF > 0.05) were used as input data to calculate the genome-wide LD in the present panel. A rapid decline in LD was observed with increasing physical distance on all chromosomes (Chr), but the decay rate varied among Chr  showed that the MLM model with six PC axes effectively accounted for the population substructure of starch content. A total of four SNPs (Supplementary Table S2) significantly associated (P < 0.0001) with starch content were detected on Chr 1, 2, and 5 , among which SNP SYN1878 was the most significant (P = 2.9 × 10-5). These results are consistent with the quantitative nature of starch content, which is known to be controlled by a large number of genes with small effects.In the present study, population structure was controlled for by using the PC matrix, with six PC axes explaining about 6.9% of the variance. Quantile–quantile plots . The genes within this 200-kb window size were identified through MaizeGDB according to the positions of the closest flanking SNPs or supporting intervals3. Based on the gene annotation of the B73 maize genome, some genes that are likely involved in starch synthesis were subjected to gene ontology (GO) analysis. The Blast2Go program was used to predict the functions of these genes (Table 2), and at least two of these genes or their orthologs were known functional genes involved in the starch synthesis pathway: .The overall LD decay across the genome of this panel was 100 kb; as such, a 200-kb region flanking the left and right side of each SNP was defined as a QTL, which were then used to identify genes from the maize genome browser publically available at r2 = 0.961) between the values measured by NIRS and those obtained by traditional chemical methods. In our study, the NIRS method also yielded reliable results as demonstrated by the small deviations (<5% in most cases) among the biological replicates (Supplementary Table S1).Traditional starch content measurement protocols employ kernel powdering and starch hydrolysis to measure starch content according to the percentage of hydrolyzed soluble sugar glucose in the dry kernel . This meIn previous studies, kernel starch content was often studied together with protein or oil content  and mostThe complex genetic architecture of starch content has been demonstrated through long-term selection experiments using inbred lines . The conThe maize SNP50 BeadChip maize array used in this study contains a total of 56,110 SNPs. Given the 2,300-Mb genome size of maize, there is approximately 50 kb of total sequence for each SNP marker used in this study. Therefore, a significantly associated SNP may represent an approximately 100-kb region covering the 50 kb upstream and downstream along each chromosome. Thanks to the publically available maize genome browser, we were able to browse and retrieve the coding gene information from the associated QTLs .Sh2, Bt2, opaque-2 (O2), and Sh1 (Glucose-1-phosphate adenylyltransferase (APS1) gene (gene ID GRMZM2G163437) was identified as a closely linked gene; this protein presumably catalyzes the alpha-D-glucose-1-phosphate to ADP-glucose (ADPG) pathway and plays an important role in starch synthesis  becomes available. Furthermore, SNPs within candidate genes can also be used to further test the contributions of these genes to traits like kernel starch content.This study was conceived by JT and NL. GWAS and GO analyses were conducted by YX and ZG. Collections of maize were performed by WL. NL wrote the manuscript. All authors read and approved the final manuscript.The 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.


In this issue of journal, we have an observational study on left main PCI, a hot debate in interventional cardiology field . They re


Brachypodium distachyon and compared the findings with those reported for common wheat  and Aegilops peregrina.Thorough understanding of seed starch biosynthesis and accumulation mechanisms is of great importance for agriculture and crop improvement strategies. We conducted the first comprehensive study of the dynamic development of starch granules and the regulation of starch biosynthesis in Brachypodium Bd21, and the shape variation and development of starch granules were similar in the B-granules of CS and Bd21. Phylogenetic analysis showed that most of the Bd21 starch synthesis-related genes were more similar to those in wheat than in rice. Early expression of key genes in Bd21 starch biosynthesis mediate starch synthesis in the pericarp; intermediate-stage expression increases the number and size of starch granules. In contrast, these enzymes in CS and Ae. peregrina were mostly expressed at intermediate stages, driving production of new B-granules and increasing the granule size, respectively. Immunogold labeling showed that granule-bound starch synthase  was mainly present in starch granules: at lower levels in the B-granules of Bd21 than in CS. Furthermore, GBSSI was phosphorylated at threonine 183 and tyrosine 185 in the starch synthase catalytic domain in CS and Ae. peregrina, but neither site was phosphorylated in Bd21, suggesting GBSSI phosphorylation could improve amylose biosynthesis.Only B-granules were identified in Triticum and Aegilops; these sites were not phosphorylated in Bd21. GBSSI phosphorylation may reflect its importance in amylose synthesis.Bd21 contains only B-granules, and the expression of key genes in the three studied genera is consistent with the dynamic development of starch granules. GBSSI is present in greater amounts in the B-granules of CS than in Bd21; two phosphorylation sites (Thr183 and Tyr185) were found in The online version of this article (doi:10.1186/s12870-014-0198-2) contains supplementary material, which is available to authorized users. Starch is the major storage carbohydrate in the seeds of cereal crops. Starch comprises approximately 90% and 65–75% of the dry weight of rice and wheat, respectively . Starch Triticum aestivum L.) contains three types of starch granules: A, B, and C. A-granules, from 10 to 50 μm in diameter, constitute up to 70% of the volume and 10% of the total number of starch granules [Triticeae endosperm are separated in time and space. A-granules are formed approximately 4–14 days post-anthesis (DPA) when the endosperm is still actively dividing [Triticeae starch [The endosperm of mature wheat  linkages that form the branched structure of amylopectin. SBEI plays an important but not exclusive role in the synthesis of B1-, B2-, and B3-chains. The SBEII-a and SBEII-b genes also perform a distinct function in the formation of A-chains [Amylose synthesis is controlled by granule-bound starch synthase (GBSSI) . Amylopelopectin ,21. The lopectin . Analysilopectin –25. Althe number . Starch-A-chains –29. Two A-chains . PullulaBrachypodium distachyon L. was completed in 2010; analysis suggests Brachypodium is much more closely related to wheat and barley than to rice, sorghum, or maize [Brachypodium, but the properties and development of starch granules remains poorly studied. We performed a comprehensive survey of the dynamic development of starch granules and regulation of starch synthesis in Brachypodium through comparative analysis with Triticum and Aegilops. We also studied the phosphorylation status of GBSSI, which controls amylase synthesis. Our results provide new insights into the molecular mechanisms of starch granule development and starch biosynthesis.The genome sequence of or maize ,31. In-dAe. peregrina are shown in Additional file Ae. peregrina; at subsequent developmental stages, grain length increased slightly, while grain width and weight gradually increased until maturity , and The dynamic accumulation patterns of starch granules in the grain endosperm and pericarp during grain development were examined by light microcopy and SEM. In this study, plenty of starch appeared in the pericarp at the beginning of the seed formation. As shown in Additional file Ae. peregrina; these were classified as A-granules . Twenty-four nonredundant enzymes related to starch synthesis were identified. Their distribution on the five Brachypodium chromosomes and their domain structures are shown in Additional files AGPII-b, SBEI, SBEIII, SSII-a, SSI, GBSSI, and AGPL IV) were located on chromosome 1 from 0 to 74.8 Mb, four genes  on chromosome 2 from 0 to 59.3 Mb, six genes  on chromosome 3 from 0 to 59.8 Mb, three genes  on chromosome 4 from 0 to 48.6 Mb, and four genes  on chromosome 5 from 0 to 28.1 Mb  and Ae. peregrina were analyzed by qRT-PCR  in Bd21 and exhibited higher early expression (4–8 DPA) and weaker expression at later stages (10–30 DPA). In contrast, GBSSI exhibited an up-down expression trend (Type II) and was mainly expressed at the intermediate stages of growth in wheat and Ae. peregrina  and starch branching enzyme  mainly exhibited a Type III expression pattern, whereas starch branching enzymes ISAI, ISAII, ISAIII, and PUL displayed a Type I expression pattern (Table SSII-a and SSIII-a showed a down-up-down expression trend (Type III) in Bd21, and was strongly expressed at 4 DPA and 18–25 DPA, and then moderately expressed during grain filling (8–16 DPA), but minimally expressed at 30 DPA  in Bd21: expression was very strong at 4 DPA, decreased rapidly at 10 DPA, stabilized at the later stages, and then increased at 30 DPA  in all three genera  and revealed the phosphorylated and unphosphorylated sites of CS and Bd21. The figure shows that in the 3D model, structurally relevant amino acids forming the starch synthase catalytic domain are well conserved. There are 12 α-helices and 11 β-strands in the starch synthase catalytic domains of CS and Bd21, and the phosphorylated amino acid was always located between the third and fourth helix.In this study, we detected two phosphorylated peptides: one at threonine 183 and one at tyrosine 185 in GBSSI of CS and e Figure B confirme Figure C and 7D Triticum aestivum L.), the endosperm contains three types of starch granules: A-granules 10–50 μm in diameter and B-granules (including C-granules) less than 10 μm in diameter [et al. [Ae. peregrina appeared early and reached a diameter up to 10 μm at 10 DPA; all starch granules in Ae. peregrina were A-granules, as reported previously [Ae. peregrina and Bd21 contained only A-granules or B-granules.In mature wheat  responsible for A- or B-granule initiation remains to be done.granules . In wheagranules , and thegranules . In barlgranules . A recenAegilops . Those aAegilops . Howeverp codons –41. Morevolution . We alsoears ago ,44. FinaBrachypodium attracted our attention. Other studies have shown that in the outer layers of cereal grains, starch accumulates transiently at the beginning of grain development, where it contributes to carbon storage during the earlier phases [et al. [Ae. peregrina, even though there were four genes, including SSIII-a, SBEI, SBEII-b, PUL, whose expression was nearly undetectable [The high expression level of starch synthesis-related genes at very early stages in r phases . Nakamur [et al.  reported [et al. . In our tectable . On the SSI, SSII-a, SSIII-a, SBEI, SBEII-a, and SBEII-b) also appeared at 16 to 18 DPA, and may be responsible for the synthesis of B-granules and increase of the endosperm. In this study, genes controlling synthesis of B-chains were expressed earlier than the genes related to A-chains. As shown in Figures SSII-a (controls synthesis of B1-chains), SSIII-a (controls synthesis of B2-chains) and SBEI (controls synthesis of B1/B2-chains or others) were expressed earlier than SS-I and SBEIIa and SBEIIb (control synthesis of A-chains). A-chains are linked to B-chains; therefore, B-chains should be synthesized early to provide support for A-chains. Although in CS, strong expression mostly appeared ~12 DPA, which was responsible for the synthesis of B-granules, it is unexpected that SBEI was expressed later than SBEII-a and SBEII-b. The same phenomenon was also observed in Ae. peregrina: SBEI was expressed later than SBEII-a and SBEII-b were. Since the sequence of SBEs in Brachypodium, wheat, rice and maize showed a high similarity and were classified into the same cluster, respectively  of α-(1–6)-linkages in amylopectin and pullulan during formation of new chains  [Brachypodium, and the expression of starch synthesis-related genes was lower in the endosperm of Brachypodium compared to wheat and Ae. peregrina.Nevertheless, these genes showed a relatively different expression pattern in the endosperm of these 3 genera. The amount of starch in the developing Bd21 seeds increased steadily between 8 and 20 DAF; in particular, the amount of starch showed an obvious increase at 16 and 18 DPA. At the same time, most of the genes exhibited high expression at approximately 16–18 DPA  . On the et al. [Ae. peregrina, including threonine 183 and tyrosine 185, and both of which are located within the starch synthase catalytic domain. Although no phosphorylated peptides were found at these positions in Bd21, sequence alignment suggests the Thr183 in CS and Ae. peregrina is replaced by Val in Bd21; this substitution may be responsible for the lack of phosphorylation sites in Bd21. Few studies have described how phosphorylation sites influence amylase activity. Some have indicated that the starch synthase catalytic domain is responsible for glucan-substrate recognition and affinity; meanwhile, Tetlow et al. [Protein phosphorylation, as the most common posttranslational modification in vivo, regulates and controls biological processes such as transcription and translation, cellular and communication, proliferation and differentiation . Other set al.  showed tw et al.  showed tw et al. ,57. Finaw et al. . Thus, wAe. peregrina is mostly responsible for production of new B-granules and for the increase in the size of starch granules, respectively. The expression of the genes controlling synthesis of B1- or B2-chains occurs earlier compared to A-chains. GBSSI exists in B-granules of CS, in greater amounts compared to Bd21. There are two phosphorylation sites (Thr183 and Tyr185) in Triticum and Aegilops, whereas Thr183 was replaced by Val in Bd21. Phosphorylation of GBSSI may play a central role in amylose synthesis.We demonstrated the presence of only B-granules in Bd21, and they appear at ~8 DPA with a diameter of 4–6 μm. The expression of key genes in the studied genera is consistent with the dynamic development of starch granules. The expression of key genes in starch biosynthesis of Bd21 mainly occurs at early and intermediate stages, for the synthesis of starch in the pericarp and for the increase of the number or size of starch granules, respectively. In contrast, the high expression of biosynthetic genes at intermediate stages in CS and B. distachyon inbred line Bd21, the common wheat variety  Chinese Spring (CS), and Aegilops peregrina, accession # AP200201  were used in this study. Ae. peregrina was kindly provided by the Department of Plant Breeding, Technical University of Munich, Germany. The grains were first stratified at 4°C for 7 d on moist paper to promote synchronous germination, then transferred to soil and grown in a growth chamber at 21/18°C (day/night) and 65% relative humidity under a short-day (8/16 h light/dark) photoperiod with light intensity of 120 μmol m−2∙s−1 for 4 weeks. The plants were then switched to long-day conditions with a 16/8 h light/dark photoperiod and the same light intensity. The plants were irrigated twice a week with a mineral nutrient solution. To harvest grains at defined developmental stages, individual flowers were tagged using colored tape at various stages post-anthesis. Grains were harvested at 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 25, and 30 days post-anthesis (DPA).A diploid et al. [2 were used to stain the proteins and the starchy endosperm. In this study, three grains, nine sections, and ~600 starch granules were used to quantify starch granule sizes at each stage.A modification of Guillon et al.  was usedStarch granules from different species and various grain developmental stages were dusted on the surface of a carbon-adhesive tab and sputter-coated with gold-palladium particles using Dentum Vacuum Desk II. SEM examination of starch granules was performed using a Hitachi Model S-4700 scanning electron microscope at 10.0 kV.et al. [et al. [g for 5 min. The precipitate containing the starch granules was then washed 3 times with 1 mL of washing buffer  for 30 min at 20°C. At the beginning of each washing step, the granules were disrupted using sonication by means of an ultrasonic processor  at the power of 20 W with a 20-s pulse before continuous mixing. The granules were washed three times (10 min each time), and then washed three times (5 min each time) with cold water, once with cold acetone, and finally were air-dried. Each washing step was followed by centrifugation at 3500 × g for 5 min. All washing and centrifugation steps were carried out at room temperature to avoid precipitation of SDS. The purity of the starch fraction was monitored using SEM.Starch granules were separated and purified according to Branlard et al.  and Banc [et al.  with somB. distachyon genome sequences [B. distachyon amino acid sequences of the genes related to starch synthesis with those from wheat and rice [The locations of the motifs in starch synthesis-related genes were confirmed using the database containing complete equences . Using tand rice  using deand rice .Ae. peregrina were harvested at 12 developmental stages of the grain . Total RNA of individual samples from different grain-developmental stages were extracted with TRIzol Reagent according to the manufacturer’s instructions (Invitrogen), and the purification of mRNA was performed, as described by Li et al. [Developing grains from the central part of the spikes in Bd21, CS, and i et al. . With olet al. [Transcriptional expression patterns of these genes were detected using qRT-PCR according to Paolacci et al.  with minThe seeds were manually crushed and soaked overnight in 1 mL of washing buffer  at 4°C. After centrifugation at 16000 rpm for 1 min, 1 mL of washing buffer was added to the pellets, and the mixture was vibrated. After centrifugation (16000 rcf for 1 min) and air drying, 1 mL of the extraction solution  was added, and then the pellets were boiled at 100°C for 4 min. After centrifugation at 16000 rpm for 1 min, the supernatant was stored at 4°C.Triticum (16682) via the MASCOT software with GPS Explorer software version 2.0 (Applied Biosystems). The peptide tolerance was set as 100 ppm and fragment mass tolerance was 0.4 Da. One missed cleavage was allowed, and carbamidomethyl (Cys) and oxidation (Met) were specified as variable modifications. MASCOT scores greater than 65 (p < 0.05) were accepted [Protein bands were manually excised from the gels, and after trypsin digestion, these were analyzed on a 4800 Plus MALDI TOF/TOF Analyzer . All MS spectra were used for search in the NCBI database Viridiplantae (900091) and riticum 1682 via tet al. [The monoclonal antibody against GBSSI (peptide SEWDPAKDKFLA) was developed by Abmart . The extracted proteins described above were separated by SDS-PAGE. After silver staining, the expected protein bands were collected and digested by trypsin, and then identified by MALDI-TOF/TOF-MS as described above. The identified GBSSI was further confirmed by western blotting according to Li et al. .3) and fixed with 4% glutaraldehyde in 0.1 M PBS (pH 7.4) for 12 h. Then, the samples were directly dehydrated in a series ethanol solutions, and permeated and polymerized in medium-grade LR White resin. Ultrathin (70 nm) sections were prepared on an ultramicrotome (Leica EM UC6) with a diamond knife and placed on Formvar-coated grids. Subsequently, the grids were rinsed for 2 × 5 min in PBG (0.1 M PBS with 35 mM glycine), and transferred to PBT  2 × 5 min, then incubated overnight with an anti-GBSSI antibody diluted 1:1000. The sections were rinsed 6 × 5 min in PBT the next day, and the grids were incubated with a secondary antibody: a goat anti-mouse IgG antibody conjugated to colloid gold  diluted 1:20 in the blocking solution  for 15 min. The sections were washed 2 × 2 min in PBT and 2 × 2 min in PBG followed by glass-distilled water, and then poststained with 2% uranyl acetate for 10 min. Finally, the grids with sections were washed 6 × 5 min in PBG and were allowed to air dry before examination under the scanning transmission electron microscope. In the control experiment, the primary antibody was omitted to test for nonspecific secondary antibody binding [Cross-sections of 12-day-old immature grains were immediately cut into small pieces , then washed 2 × 10 min in water. Then the minced gel was washed for 10 min in 200 μL of 50 mM NH4HCO3:ACN (1:1), and we repeated this step until all the color was gone. We then added 10 mM DTT (10 μL 1 M DTT) and 990 μL 50 mM NH4HCO3 to the tube and kept the gels at 56°C for 1 h. After cooling to room temperature, we removed the supernatant, added 50 μL Iodoacetamide (IAM) , and incubated the mixture in the dark for 45 min. After that, we used 25 mM NH4HCO3, 50% ACN, and ACN in this order to wash the strips, and vacuum-dried them for 5 min. Finally, trypsin hydrolysis was conducted at 4°C for 60 min and at 37°C for 16–18 h in this order.The identified GBSSI protein bands identified on the SDS-PAGE gel were cut into small pieces (~3–4 mmm/z). The mass spectrometer was set up to acquire collision-induced dissociation (CID) MS/MS scans after each MS1 scan of the 25 most abundant ions with MSA central losses of m/z 98, 49, and 32.6. For CID, the normalized collision energy was set to 35.For MS analyses, peptides were resuspended in 0.1% formic acid (FA) and analyzed on an LTQ Orbitrap Elite mass spectrometer (Thermo Fisher Scientific) coupled online to an Easy-nLC 1000 (Thermo Fisher Scientific) in the data-dependent mode. The sample was trapped on a 150-μm × 0.5-mm precolumn and eluted from an analytical 75-μm × 150-mm column. Peptides were separated using a linear gradient formed by 2% ACN (acetonitrile) in 0.1% FA (mobile phase A) and 98% ACN in 0.1% FA (mobile phase B), from 3% to 30% of mobile phase B in 90 min. The mass spectrometer was operated with full scan acquisition in the Orbitrap at 24000 Da resolution  for peptides, proteins, and site identification was set to 1%.


This report describes the activities discussed at the 10th meeting of Section II of the Consultative Committee on Standards for the Measurement of Ionizing Radiations  held in May 1989 at Sèvres (France). Topics included present and future international comparisons of activity measurements, the status and possible extension of the International reference system for activity measurements of gamma-ray emitting nuclides, reports from other working groups, accomplishments at the International Bureau of Weights and Measures , and progress at member laboratories. One of the consultative committees of the International Committee of Weights and Measures  which guides and assists the International Bureau of Weights and Measures  in ensuring the uniformity of physical measurements is the Consultative Committee on Standards for the Measurement of Ionizing Radiations  . The vareach pertinent radionuclide. Currently the National Institute of Standards and Technology has received justified requests for over 130 radionuclides, for example [The challenge in radioactivity standards is as much quantity as quality. Although the accuracy required and achieved for specifying the activity of a sample of a radionuclide is usually only of one percent, a standard must be developed for  example . There i−1). Goals of the Radionuclides Section of CCEMRI are to improve measuring methods and better define their uncertainties, to compare results obtained in different countries, and to bring these results into congruence. The 10th meeting made considerable progress towards these goals.Almost all countries have adopted the International System (SI) unit, the becquerel (Bq), specifying the activity of a sample in decays per second  detector can detect at least one radiation most of the time, and the fraction lost can be calculated accurately if the efficiency for different energies is known. A report on experiences in member laboratories is to be published.In addition to maintaining the SIR, and investigating its extension, the BIPM staff participates in the general comparisons and prepares the detailed reports describing the results. They also make fundamental contributions to the development of measuring techniques and their analysis.75Se, with a preliminary value of (16.3±0.3) ms; the development of corrections for circuit dead times in series, with possible mixtures of the two types which further extend when a second pulse arrives during a dead period, or not [Examples presented at this session were the measurement of the half life of a metastable state following the decay of , or not ; and posA final portion of this session, and all recent ones, has been the presentation of written and oral reports from each attending laboratory covering topics of possible general interest not discussed elsewhere in the agenda. These cover not only discoveries and new data, but also trends in the demands and delivery of standards to users.The unusual nature of radioactivity standardization makes international cooperation especially significant. The interchange of ideas about basic standardization during the sessions of the Radionuclides Section of the CCEMRI at BIPM, and about applied radioactivity measurements at associated meetings of the International Committee for Radionuclide Metrology, contributes to both the efficiency and accuracy of such measurements. The examples displayed in this article from the 10th session of the Radionuclides Section illustrate the scope and range of these activities.


The Journal and Authors retract the 28 January 2016 article cited above for the following reasons: Following online criticisms of the published paper, an investigation at the journal has confirmed the manipulation and duplication of data, and a level of image processing that is not compliant with the journal’s policies on image data integrity.Further, a post-publication cross-check screening revealed significant overlap with another manuscript submitted by the authors to another journal. While all manuscripts submitted to Frontiers undergo cross-check screening, the article cited below was in review in parallel with the Frontiers article and thus the overlap was not apparent until publication (Samie et al.,


The recipient had subfebrile fever and leukocytosis post-operatively. A control computed tomography revealed a cuneiform ischemic area, and a foreign body inside the right anterior portal vein branch proximal to this ischemic region. A 10-F Nelaton catheter, 5-cm long, was removed from the portal vein by surgery. Retrospectively, we understood that the portal vein was cut during the back-table procedure and the portal vein catheter was replaced with a larger one for better irrigation. Most probably, the original catheter was cut together with the portal vein, and the tip of the catheter was retained in the portal system and migrated into the liver. As far as we know, such a complication of liver transplantation has never been described previously.Liver transplantation is a technically complex and long surgical procedure. A large quantity of various materials such as catheters, sutures, needles and clips are frequently used during the procedure. These materials may enter in the liver from the vascular or biliary orifices inadvertently. A 50-year-old patient who had hepatic failure due to HBV underwent a deceased-donor liver transplantation. The deceased donor was a 75-year-old HbsAg It is a routine procedure worldwide to count the surgical materials and instruments before closing the abdomen. Despite all these precautions, some pieces may be left in the body cavities -7. Retai+ donor in another transplant center and the local transplant center did not accept this marginal graft. Local transplant team harvested the graft and sent it to our center within nine hours. Back-table procedure was performed in our center and the graft was transplanted to a 50-year-old, HbsAg+ patient who had chronic hepatic failure. There were no intra-operative complications. In the post-operative period, however, an increase in leukocyte count and fever were seen. Abdominal computed tomography on the 9th day revealed a cuneiform ischemic area in the right liver lobe. There was a thin, long foreign body inside the anterior branch of the portal vein supplying this lobe (th day uneventfully. A control computed tomography on day 40 revealed that the necrotic area had regressed. Brain death occurred due to subarachnoid hemorrhage in a 75-year-old, HbsAghis lobe . Removalhis lobe . The porRetrospectively, we understood that the graft portal vein was cut during the back-table procedure and the portal vein catheter was replaced with a larger one for better irrigation. Most probably, the original catheter was cut together with the portal vein, and the tip of the catheter was retained in the portal system and migrated into the liver.Inadvertently retained foreign body would cause significant problems for both patients and health care professionals. It causes morbidity and mortality risk for patients and malpractice lawsuits against health care professionals. Most of the retained foreign bodies consist of surgical gauzes and surgical instruments , 9. Liver transplantation is a multi-staged complex operation including donor hepatectomy, back-table procedure, recipient hepatectomy and implantation. This operation takes more time compared to other surgical operations; many medical staffs participate in the procedure. In the literature, there are some cases where sutures, clips, stents or catheters retained particularly in the bile ducts; all these remnants are usually forgotten during the implantation of the new liver . HoweverIn the case of a suspected foreign body, intra-operative imaging modalities are commonly used. Furthermore, novel techniques such as barcode scanning and radio-frequency identification have not been used widely . A recenIt is advised to extract all foreign materials including irrigation catheters from the donated graft before transporting from a center to another one: first to prevent anyiatrogenic trauma especially to the endothelium and second to prohibit losing the catheters inside the graft.


International Journal of Bipolar Disorders (IJBD), a new, peer-reviewed, open access, online journal. IJBD will publish contributions from the entire range of clinical, psychological and biological research in bipolar disorders. The need for a new journal in bipolar disorders is reflected by an increasing number of research activities around the globe in this disease area. With the help of a distinguished international editorial board of leading researchers from around the world, IJBD aims to help bridge the gap between research findings and clinical practice, as well as to facilitate the dissemination of new research data, with the ultimate goal of improving the care of patients with bipolar disorders. IJBD will be the official journal of the European Network of Bipolar Research Expert Centres (ENBREC), the International Group for the Study of Lithium-Treated Patients , and the German Society for Bipolar Disorders: Deutsche Gesellschaft für Bipolare Störungen (http://www.dgbs.de).I am very pleased to welcome you to the launch of th among the mental disorders  concerning bipolar disorders. IJBD will publish all content online, freely available to researchers worldwide, thereby ensuring maximum dissemination. Together with the Managing Editor Dr. Emanuel Severus, the editorial team and peer-review system, we will ensure that all submitted manuscripts are reviewed fairly and swiftly, and once accepted, published online rapidly. Please participate in


European Clinical Respiratory Journal (ECRJ). The journal is closely associated with the Nordic Respiratory Academy (NORA). Previously, NORA was linked to Clinical Respiratory Journal , before Wiley decided to move CRJ to China.It is with great pleasure that we, the Editors, announce the launch of a new open access respiratory journal: the ECRJ is to provide an international forum where high quality translational studies meet clinical applications. ECRJ aims to publish articles or reviews on clinical or scientific respiratory topics or original research with clinical applications, targeting the readership of both (academic) clinicians and respiratory scientists. The Journal will cover the following topics:Epidemiological data or studies.Preventive strategies.Pathophysiology of inflammatory lung disease – identification of potential future biomarkers and treatment targets.Clinical studies: randomized placebo controlled and observational ‘real-life’ trials; translational research.Novel diagnostic methods, including imaging techniques, physiological tests, and biomarkers.Disease and treatment issues for defined populations, including children and the elderly; self-management.Respiratory intensive and critical care.Updates on the status and advances of general and specific disease areas, including asthma, COPD, cough, interstitial lung disease, cystic fibrosis, infectious lung diseases, tuberculosis, bronchiectasis, occupational and environmental lung disease, OSAS.Progress in smoking intervention and cessation methods.The overall purpose of Translational topics including future targets or biomarkers of disease.Treatment guidelines overview and background discussions.New recommendations.Literature reviews: including year in review, meta analyses.Case reports.Congress proceedings and reports.Additionally, the journal will include an educational section presenting manuscripts or letters to the editor aimed at translating basic science into clinically relevant recommendations. Topics will include, but will not be limited to:CRJ, have decided to join ECRJ. These individuals are active and well-known in their respective fields. Thus, already from the start we have an excellent team of well-experienced people on board. Furthermore, we have been very successful in recruiting excellent international representatives for the different sections, who bring a solid foundation of competence that can guarantee future success.All of the productive editors, who previously worked with ERCJ to steadily become a forum for both clinicians and scientists from NORA and beyond. Based on the rapid flow of high quality submissions so far, the international reputation of the editorial team, and the solid track-record of the previous journal associated with NORA, we believe the Journal is on a fast-track towards being included in PubMed Central. We look forward to your contributions.Our aim is to develop Leif Bjermer Chief EditorDepartment of Respiratory Medicine & AllergologySkåne University HospitalLund, SwedenVibeke Backer Deputy Chief EditorBispebjerg HospitalCopenhagen, DenmarkRonald Dahl Co-EditorDepartment of Respiratory Diseases & AllergyAarhus University HospitalArhus, DenmarkZuzana Diamant Co-EditorDepartment of Respiratory Medicine & AllergologySkåne University Hospital, Lund, SwedenDepartment of General PracticeUniversity Medical Center Groningen and QPS-NLGroningen, The Netherlands


Starch from maize kernels has diverse applications in human and animal diets and in industry and manufacturing. To meet the demands of these applications, starch quantity and quality need improvement, which requires a clear understanding of the functional mechanisms involved in starch biosynthesis and accumulation. In this study, a recombinant inbred line (RIL) population was developed from a cross between inbred lines CI7 and K22. The RIL population, along with both parents, was grown in three environments, and then genotyped using the MaizeSNP50 BeadChip and phenotyped to dissect the genetic architecture of starch content in maize kernels.qSTA9-1) to 10.6 % (qSTA4-1) of the starch variation. The QTL interval was further reduced using the bin-map method, with the physical distance of a single bin at the QTL peak ranging from 81.7 kb to 2.2 Mb. Based on the functional annotations and prior knowledge of the genes in the top bin, seven genes were considered as potential candidate genes for the identified QTLs. Three of the genes encode enzymes in non-starch metabolism but may indirectly affect starch biosynthesis, and four genes may act as regulators of starch biosynthesis.Based on the genetic linkage map constructed using 2,386 bins as markers, six quantitative trait loci (QTLs) for starch content in maize kernels were detected in the CI7/K22 RIL population. Each QTL accounted for 4.7 %  contains supplementary material, which is available to authorized users. Maize is a leading crop worldwide because of its diverse functions as a source for human food and animal feed and as a raw material for industry and manufacturing. With a growing world population and need for biofuel, increasing maize grain yield is necessary to meet the market demand. Starch is the major component of maize kernels, accounting for 70 % of the kernel weight. In addition, starch is increasingly used as a renewable chemical feedstock for the conversion of other products, such as high fructose corn syrup, polymer-based fibers and fuel ethanol . Therefod-glucose, amylose and amylopectin, in the maize endosperm. Although starch metabolism is complex, it is clear that four classes of enzymes, adenosine diphosphate glucose pyrophosphorylases (AGPases), starch synthases (SSs), starch branching enzymes (SBEs) and debranching enzymes (DBEs), play critical roles in starch biosynthesis. Maize mutants have been used to isolate genes encoding key enzymes in starch metabolism, such as Shrunken1 (sh1), Shrunken2 (sh2), Brittle2 (bt2), agpsemzm, agpllzm, Waxy1 (wx1), SS1, Sugary2 (su2), Dull1 (du1), SS2b-2, SS2c, SS3b-1, SS3b-2, SS4, SBEIa, SBEIIa, Amylose extender1 (ae1) and Sugary1 (su1) [sh1 gene encodes the major isoform of sucrose synthase and provides an important link in sucrose-starch conversion reactions, as sucrose synthase catalyzes the reversible reaction between sucrose and uridine diphosphate-glucose [sh2, bt2, agpsemzm and agpllzm encode the large or small subunits of AGPase, which converts glucose-1-phosphate to ADP-glucose, the precursor for starch synthesis [wx1, encoding granule-bound SS I, is solely responsible for amylose production, whereas SS1, Su2, Du1, SS2b-2, SS2c, SS3b-1, SS3b-2 and SS4, encoding four types of soluble SS, are responsible for amylopectin production [SBEIa, SBEIIa and ae1 encode the SBE isoforms Ia, IIa and IIb, respectively [su1 encodes a DBE of the isoamylase type, and mutant su1 kernels contain the highly branched, water-soluble phytoglycogen and constitute the original sweet corns [Starch is deposited as water-insoluble semicrystalline granules, which are chemically comprised of two homopolymers of α-ynthesis –7. wx1, oduction –13. SBEIectively –16, whicet corns . These a3 population, which was derived from a cross of two lines divergently selected for protein content after 76 generations in the Illinois long-term selection experiment [QTL mapping is a classical method for identifying loci for quantitative traits of interest without prior genetic knowledge. A variety of QTLs for the starch content in maize kernels have been identified in different biparental populations since the first study in the Illinois High Protein × Illinois Low Protein Fperiment –32. Amonperiment . This inQTL mapping is firstly suggestive to identify loci for complex quantitative traits, although, the resolution is rather low, often ranging from 10 to 30 cM . IncreasIn this study, a maize CI7/K22 recombinant inbred line (RIL) population was developed and genotyped using the Illumina MaizeSNP50 BeadChip, which contains 56,110 SNPs. The kernel starch contents of this RIL and the parental lines were evaluated after being grown in three environments. The objectives were to (1) construct a high-density genetic linkage map using the inferred bins as markers, (2) dissect the genetic architecture of starch content in maize kernels of the CI7/K22 RIL population, (3) narrow down the position of the identified QTLs using the SNP bin map and (4) mine the candidate genes associated with starch content in the refined QTL interval.P = 0.09). There were moderately positive starch content correlations among the three environments, with correlation coefficients ranging from 0.57 to 0.66  estimate of the starch content was high (82.1 %), indicating that much of the phenotypic starch content variation in the RIL population was genetically determined.The low-starch inbred line CI7 has ~0.1 %, 3.5 % and 7.1 % lower starch content values than K22 in Beijing in 2013, Hainan in 2013 and Neimeng in 2014, respectively. Taken together, no significant difference was observed in the starch content between the two parents, CI7 and K22 , were polymorphic between the two parents. The missing rate of these SNPs ranged from 0 to 15.31 %, with an average of 1.18 %, the heterozygosity ranged from 0 to 15.64 %, with an average of 3.69 % and the minor allele frequency ranged from 0.27 to 0.50, with an average of 0.45 in the CI7/K22 RIL population  to 10.6 % (qSTA4-1). Alleles from K22, the high-starch parent, at all of the mapped loci except qSTA4-1, had increasing effects on the starch content. The largest QTL, qSTA4-1, was located on chromosome 4 and was flanked by PZE104103541 and PZE104106157. The CI7 allele at this locus had an additive effect of 0.54 % for increased starch content. The second largest QTL for starch content, qSTA10-1, located in the genomic region between bins SYN23550 and SYN22965, explained 9.1 % of the phenotypic variation, with an additive effect of 0.50 % on chromosome 10. The next two QTLs for starch content, qSTA5-1 and qSTA5-2, were both located on chromosome 5 and explained 7.7 % and 5.3 % of the phenotypic variation, respectively.Based on a linkage map of 1,719.7 cM, QTLs for starch content were first identified using the BLUP value across the three environments. In total, six QTLs controlling starch content were detected in the CI7/K22 RIL population at an empirical threshold logarithm of odds (LOD) value of 3.1 after 1,000 permutations , indicating that the genetic component of starch content in the CI7/K22 RIL population is mainly characterized by additive gene actions.qSTA1-1) to 2.2 Mb (qSTA5-1), with each bin encompassing 2 (qSTA1-1) to 45 (qSTA10-1) genes, based on the annotated genes in the B73 reference genome Version 5b.60 (http://ensembl.gramene.org/Zea_mays/Info/Index). The functional annotations of all 144 genes indicated that seven genes, ZmGAL (GRMZM2G127123), ZmTPS (GRMZM2G151044), ZmKCS (GRMZM2G569948), ZmWRKY78 (GRMZM2G073272), ZmSnRK1I (GRMZM2G119769), ZmSnRK1 (GRMZM2G157743) and ZmMYB132 (AC206901.3_FG005), were most likely to be the candidate genes for the six QTLs  synthase in the trehalose metabolic pathway, which shares some common intermediate products, such as glucose, with starch metabolism [ZmTPS expression will influence starch metabolism. In addition, T6P, a reactant in the reverse reaction catalyzed by T6P synthase, is a sugar signal that is indispensable for carbohydrate utilization and starch pathway regulation in Arabidopsis [Arabidopsis [ZmTPS was a strong candidate gene for qSTA4-1.For  in milk , 58. Thetabolism . Thus, abidopsis , 61. Leabidopsis . Thus, ZqSTA5-1 was the largest among those of the six identified QTLs and harbored 44 genes in the spanning genomic region  is an alternative and efficient strategy for improving starch quantity and quality when QTLs or genes have been identified. Multiple traits have been improved by MAS in maize, such as head smut resistance , provita linkage –74. The We identified starch-associated QTLs in a RIL population using a high-density linkage map, refined the identified QTLs based on the bin map and subsequently mined their potential causal genes. The six QTLs accounted for 48.6 % of the starch variation in the CI7/K22 RIL population, with only one QTL explaining >10 % of the phenotypic variation. These findings indicate that large-effect QTLs, as well as minor-effect QTLs, contribute to the phenotypic variation in starch content in the CI7/K22 RIL population. Results from this study improve our understanding of the genetic variants that give rise to variation in kernel starch content, as well as of the possible mechanisms that underlie each QTL, and will provide guidance in manipulating starch quantity and quality by molecular breeding or biotechnology-assisted improvement.7 RILs, along with both parents, were grown in a randomized complete block design with one replication in Beijing in 2013, Hainan in 2014 and Neimeng in 2014. Each genotype was grown in a single-row plot having 1 m rows with 0.67 m between rows. In each row, all five ears were self-pollinated and harvested after maturity. Three hundred kernels were bulked for each row, with equal amounts from each harvested ear. Then, 20 representative kernels from each plot were selected from the 300 bulked kernels to measure the starch content.A RIL population consisting of 210 lines was derived from the cross between inbred lines CI7 and K22. CI7 is a high carotenoid and late maturing line introduced from America, which is developed by the USDA-ARS and derived from a backcross of (L317 x 33–16) L317, and K22 is a Chinese elite inbred line derived from a cross between two Chinese inbred lines LK11 and Ye478 . Accordi2) and heat (ethanol). All of the samples were measured with two sub-samples analyzed in parallel, and the average was used for subsequent analyses.The starch content in maize kernels was determined using a fermentable carbohydrate assay as described by Zhou and Bao . In briewww.R-project.org). The linear mixed effect function lmer in the lme4 package of R Version 3.1.1 was fitted to each RIL to obtain the BLUP value for starch content: yi = μ + fi + ei + εi, where yi is the phenotypic value of individual i, μ is the grand mean for all environments, fi is the genetic effect, ei is the effect of different environments and εi is the random error. The grand mean was fitted as a fixed effect, and genotype and environment were considered as random effects. The aov function in R version 3.1.1 was used to estimate the variances of the starch content. The model for the variance analysis was y = μ + αg + βe + ε, where αg was the effect of the gth line, βe was the effect of the eth environment and ε is the error. All of the effects were considered to be random. These variance components were used to calculate the broad-sense heritability as h2 = σ2g/(σ2g + σe2/e) [2g is the genetic variance, σe2 is the residual error and e is the number of environments.All of the statistics were performed using R Version 3.1.1 (+ σe2/e) , where σ6 lines in the CI7/K22 RIL population, together with their parents, were genotyped using the Illumina MaizeSNP50 BeadChip, which contains 56,110 SNPs and covers 19,540 genes [www.maizego.org/Resources.html). Completely co-segregating markers were assigned to a chromosomal bin, and each bin was considered as one marker.All 210 F40 genes . The lea40 genes  was used40 genes  in a Linp < 0.05 [QTL mapping of the starch content was performed using composite interval mapping  implemenp < 0.05 . The conp < 0.05 . To furtp < 0.05 .Arabidopsis or rice linked in the MaizeGDB database (www.maizeGDB.org). Additional protein prediction information was obtained from the InterPro module in the European Bioinformatics Institute database (www.ebi.ac.uk/interpro/).Based on the information available in the Gramene BioMart database (ensembl.gramene.org/biomart), the genes within the refined QTL interval and their functional descriptions were extracted. The function of each gene was further confirmed from orthologs in All supporting data can be found within the manuscript and its additional files.


The correct sentence is: A complete dataset of all original and filtered images is available at the Harvard Dataverse, URL:


PLOS Biology editorial team would like to warmly thank all those individuals who participated in the peer review process this past year at PLOS Biology. During 2015, over 1,200 reviewers from around the world helped evaluate articles submitted to the journal.The Public Library of Science (PLOS) and the PLOS Biology authors, and for helping us to publish a highly valued open access journal.The names of our 2015 reviewers are listed in S1 Reviewer List(PDF)Click here for additional data file.


There are errors in the Funding section. The correct funding information is as follows:http://www.nsfc.gov.cn), Natural Science Foundation of Jiangsu Province (BK2012202) (http://www.jstd.gov.cn/), Chinese Postdoctoral Science Foundation (2013M540518) (http://res.chinapostdoctor.org.cn/BshWeb/index.shtml), Jiangsu Provincial Postdoctoral Science Foundation (1302080C) (http://www.jsbsh.gov.cn/), National 973 Program (Grant No 2010CB428902) (http://www.most.gov.cn/), and Applied Basic Research Project of Suzhou (SYN201306) (http://www.szkj.gov.cn/default.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This work was supported by National Natural Science Foundation of China (NNSFC31400091) (The publisher apologizes for the error.


Triatoma dimidiata, in 2001. At present, 90 complete Hemipteran mitogenomes have been sequenced and annotated. This review examines the history of Hemipteran mitogenomes research and summarizes the main features of them including genome organization, nucleotide composition, protein-coding genes, tRNAs and rRNAs, and non-coding regions. Special attention is given to the comparative analysis of repeat regions. Gene rearrangements are an additional data type for a few families, and most mitogenomes are arranged in the same order to the proposed ancestral insect. We also discuss and provide insights on the phylogenetic analyses of a variety of taxonomic levels. This review is expected to further expand our understanding of research in this field and serve as a valuable reference resource.The study of Hemipteran mitochondrial genomes (mitogenomes) began with the Chagas disease vector,  As one major order of insects, Hemiptera is the largest group of the hemimetabolous insects [Entomologists first suggested that Hemiptera (true bugs) and Homoptera  are two orders according to features of the wing . In 1810s.l.) . The con present ,4,5; the insects . They arTriatoma dimidiata is the vector of Chagas disease, a predominantly chronic disease affecting millions of people [There is great variety within the order Hemiptera, more commonly known as bugs. Hemipterans have evolved an extraordinary range of body forms and lifestyles: some live on land, some live in water, some feed on plants and others are voracious carnivores or scavengers. Therefore, many species of Hemiptera are significant pests of crops and gardens. Some, as many species of aphid, cause direct damage to crop hosts and often kill the entire plants. Additionally, some delphacids cause considerable damage to grain production and have been identified as one cause of rice famine in several Asian countries . Moreovef people .Based on the history of Hemipteran phylogeny research, we propose two controversial questions. First, how many suborders does Hemiptera include? Traditionally, Hemiptera comprised three major groups (including four suborders): Sternorrhyncha , Auchenorrhyncha , and Heteroptera  . PreviouSince the first insect mitogenome was published in 1985 , there hHere, we utilize all the mitogenomes of Hemiptera to analyze their features on the genome level and summarize the rearrangement events for the first time. In addition, all available complete mitogenomes of Hemiptera were used to reconstruct and discuss the phylogeny relationships of this order.Triatoma dimidiata, the vector of Chagas disease, was the first published mitogenome of Hemipterain 2001 [Triatoma dimidiata, Thao et al. [Drosophila yakuba) [ain 2001 . The seqo et al.  reported yakuba) . Subsequ yakuba) ,23,24,25 yakuba) ,27,28, mNilaparvata muiri) to 18,414 bp  and have an average value of 15,733 bp  contains only 18 tRNAs [Most of the mitogenomes (76/90) resemble that of the known ancestral species (. yakuba ) in stru18 tRNAs .Bemisia afer and 86.33% in Aleurodicus dugesii). Species from the suborders Fulgoromorpha, Coleorrhyncha and Heteroptera were all A and C skewed. This was also the case for the species of Cicadomorpha, except for Empoasca vitis. For the suborder Sternorrhyncha, nine species were A and C skewed, including all aphid species. This discovery of all aphid species forming a cluster is similar to the results of previous studies  [All PCGs in the majority of hemipteran mitogenomes were initiated with familiar triplet initiation codons , including the commonly used ATN and some special couplet codons. For instance, in the suborder Coleorrhyncha,  veitchi . Furtheron, ATCA . In factbycidae) . Most PCbycidae) .atp8 had the highest evolutionary rate, followed by nad2, while cox1 appeared to be the lowest , the average rate of synonymous substitutions (Ks), the average ratio of Ka/Ks, and the Jukes-Cantor adjusted Ka/Ks (JKa/JKs) were calculated for each PCG, respectively . The rese lowest . Notably oxidase  and also species . Similar markers ,62. By cetazoans .trnS(AGN), in which the dihydrouridine arm formed a simple loop  and trnV, and between trnV and the control region. The lengths of rrnL and rrnS are determined to be 1192–1260 and 711–766 bp, respectively. These lengths are similar to those of other orders of Insecta [The arrangements of both  Insecta ,66,72,73trnI-trnQ, trnS-nad1, trnE-trnF and rrnS-trnI. The region located between rrnS and trnI, coincided with the A + T-rich region, also called the control region, including the origin of replication and promoters for transcription initiation [There are some non-coding (NC) regions interspersed throughout the hemipteran mitogenomes, thus the mitogenomes of Hemiptera displayed a moderate size variation. Four distinct large NC regions were identified in the following gene pairs of hemipteran mitogenomes: itiation ,74,75. TChauliops fallaxPhilaenus spumarius) [Geisha distinctissima, Sivaloka damnosa, Laodelphax striatella and Laodelphax striatellus) [Alloeorhynchus bakeri) [Philaenus spumariusSchizaphis graminumMost control regions of hemipteran mitogenomes were longer than 1 kb, with high rates of nucleotide substitution and indels, and a variable number of tandem repeats. Generally, one control region of the hemipteran mitogenome includes four parts without order: tandem repeat sequences, sequences of poly(T) stretch, a subregion with high A + T content, and stem-loop structures  , Fulgoroatellus) ,38,39,41 bakeri) , two fratrnE-trnF, trnI-trnQ and trnS-nad1) in three families , and differ in repeat unit sequence and copy number, suggesting that they are highly species-specific  and the transpositions of five gene clusters  between nad4L and trnI [nad2; 2. between nad2 and cox1; 3. between nad4L and nad1; and 4. downstream of rrnL  was chosen representing Auchenorrhyncha, and no taxa of Fulgoromorpha were discussed. Therefore, in the same year, Song and Liang [As mentioned in the introduction, the phylogenic relationship of the Hemiptera has been controversial for many years and two questions remain unanswered. Here, we reviewed the research history of hemipteran phylogenetic relationships based on mitogenomes and combine our phylogenetic analyses to discuss the most reliable results. In 2009, a study clarified the relationships of the three phylogenetically controversial suborders, Auchenorrhyncha, Sternorrhyncha, and Heteroptera . Heteropnd Liang  increasend Liang . In factnd Liang ,41, and nd Liang . The subnd Liang . Speciesnd Liang . Completnd Liang . Cui’s rnd Liang . Meanwhiet al. conducted phylogenomic studies on the mitogenomes of Pentatomomorpha [Under the suborder taxa, the phylogenetic research also was involved. We summarized all the research results of these years . All themomorpha  and Nepomomorpha , and resmomorpha . The intmomorpha ,63), wermomorpha  . However, some relationships have not been resolved based solely on mitogenomes. Nuclear genes evolve more slowly, and are effective for the analysis of deeper phylogenetic relationships. Moreover, some endosymbionts co-evolve with their hosts, and symbiont-derived data, in principle, could be used to reconstruct the evolutionary history of hosts . So, witBothriometopus macrocnemis, GenBank accession number: NC_009983) and Thysanoptera .A total of 90 taxa were sampled in this study . In the The nucleotide sequences of PCGs were translated based on the invertebrate mtDNA genetic code. A + T content were calculated using MEGA version 6.0 . Strand Each of the 13 PCGs of all 92 species were aligned individually using MEGA v6.0  with defGenerally, the complete mitogenomes of Hemiptera were 14–17K bp in size and encoded all 37 genes typical for insects. These genes were arranged in the same order as the proposed ancestral insect, except in a few particular species. Notably, the mitogenomes of three families possessed a large repeat region located at three different positions. We speculate that this region, full of tandem repeats, is another origin of replication. The mitogenomes have been successfully used to reconstruct the phylogenetic relationships within a variety of taxonomic levels of Hemiptera.Future work should focus on four goals. First, the comparative genomics of different categories need more taxon samplings and more mitogenome sequences to further describe the comprehensive characteristics of Hemiptera mitogenomes; Second, the research of various populations and phylogeographic structures of hemipteran species based on mitogenomes require more mitogenome sequences about the same species or similar species; Third, the functional and evolutionary significance of different rearrangement types should be examined to open the view of the evolutionary dynamics of Hemiptera mitogenomes; Finally, phylogenetic inference with more resource data will provide greater insight into the evolution of Hemiptera.


The failure of a kidney transplant is now a common reason for initiation of dialysis therapy. Kidney transplant recipients commencing dialysis have greater morbidity and mortality than transplant-naïve, incident dialysis patients. This study aimed to identify variables associated with survival after graft failure.n = 585). Clinical and blood-derived variables  mismatch, acute rejection episodes, immunosuppression, cardiovascular disease, graft survival, haemoglobin, albumin, phosphate, C reactive protein, estimated glomerular filtration rate (eGFR), rate of eGFR decline, dialysis modality, and access) were collected prospectively and investigated for association with re-transplantation and survival. The association between re-transplantation and survival was explored by modelling re-transplantation as a time-dependent covariate.All recipients of first, deceased donor kidney transplants performed in Northern Ireland between 1986 and 2005 who had a functioning graft at 12 months were included (Median follow-up time was 12.1 years. Recipients with a failing graft (158/585) demonstrated rapid loss of eGFR prior to graft failure, reducing the time available to plan for alternative renal replacement therapy. Median survival after graft failure was 3.0 years. In multivariate analysis, age and re-transplantation were associated with survival after graft failure. Re-transplantation was associated with an 88% reduction in mortality.Optimal management of kidney transplant recipients with failing grafts requires early recognition of declining function and proactive preparation for re-transplantation given the substantial survival benefit this confers. The survival benefit associated with re-transplantation persists after prolonged exposure to immunosuppressive therapy. The proportion of the incident dialysis population with a failed kidney transplant is increasing each year,2. DespiTransplant recipients receive intensive supervision from nephrologists following transplantation and review continues throughout the lifespan of the transplant, albeit at a reduced frequency. It is reasonable to anticipate that these individuals should receive optimal care with regard to management of the complications of progressive chronic kidney disease (CKD) and planning for dialysis. The available evidence suggests that this is not the case. Markers of anaemia, nutrition, inflammation, and mineral bone disease are reportedly worse in the failed renal transplant population than in transplant-naïve patients at the initiation of dialysis,12-14. TKidney transplant failure has ramifications for both transplant recipients and healthcare providers. While there is evidence that there may be sub-optimal management of transplant recipients in the pre-dialysis period, limited data has been published to highlight which modifiable clinical parameters are associated with survival following graft failure. We aimed to address this issue in our study.All recipients of first, deceased donor transplants undertaken between 1986 and 2005 in Northern Ireland who had self-supporting graft function at 12 months were included. Recipients with graft failure within the first year were excluded as they defaulted to their pre-transplant dialysis modality without a prodromal period during which CKD complications could be managed and preparations made for alternative renal replacement therapy (RRT). Individuals whose grafts failed during follow-up at another centre or who returned to dialysis following urgent graft nephrectomy were also excluded. Recipients were followed up until death or August 1, 2012.Clinical data for all recipients and donors is prospectively collected; recorded variables include age, gender, primary renal disease, diabetic status, smoking status, human leukocyte antigen (HLA) mismatch, immunosuppression, acute rejection episodes, cardiovascular disease, graft survival, mode of RRT at graft failure, recipient survival, and cause of death. Primary renal disease is grouped into six categories: glomerulonephritis, chronic pyelonephritis/tubulointerstitial disease, autosomal dominant polycystic kidney disease, diabetic nephropathy, other specified etiologies, and CKD not defined. The diagnosis of cardiovascular disease necessitates physician documentation and objective evidence; for example, a diagnosis of "myocardial infarction" would require clinical documentation with a corresponding electrocardiogram, elevation in cardiac enzymes, or record of confirmatory angiography.Graft failure was defined as the commencement of an alternative mode of RRT. Clinical and blood-derived parameters from the date of graft failure were obtained from a combination of patient records, the laboratory results system, and the regional renal database .Clinical information was collected on dialysis modality and type of access for dialysis: temporary catheter, tunnelled catheter, polytetrafluoroethylene (PTFE) graft, arteriovenous fistula (AVF), or peritoneal dialysis catheter.Estimated glomerular filtration rate (eGFR) at the initiation of dialysis therapy was calculated using the four-variable MDRD equation. The ratSerum haemoglobin, phosphate, albumin, and C reactive protein concentrations were recorded within 1 month of graft failure.In the analysis of graft survival, the factors included in Cox regression analysis were recipient age, primary renal disease, donor age, era of transplantation, HLA mismatch, biopsy-proven acute rejection within 6 months, and type of maintenance immunosuppression.In the analysis of patient survival, re-transplantation was included as a time-dependent covariate in a Cox’s proportional hazards model. In this model, patients contribute follow-up to the "no re-transplantation" group prior to re-transplantation and then switch to the "re-transplantation" group once a second transplant has occurred. If there is subsequent failure of the re-transplant, follow up continues in the latter group. This model reduces the statistical bias which occurs in a standard Cox’s proportional hazard model. For pre-emptive re-transplants, the time to re-transplantation was recorded as 0. Factors included in multivariate analysis were recipient age, gender, primary renal disease, diabetes mellitus, cardiovascular disease, smoking status, anaemia, hyperphosphatemia, and mode of RRT.Time to re-transplantation was also analysed using the Cox’s proportional hazards model with death considered as a competing risk. This method is used when follow-up for the outcome of interest (re-transplantation) is no longer possible because of the occurrence of a competing event (death).SPSS version 20  was used for univariate analyses. Stata release 11  was used for time-dependent covariate and competing-risks survival time analyses.Ethical approval for this study was granted by the Regional Ethics Committee (12/NI/0178).There were 707 first, deceased donor kidney transplants performed between 1986 and 2005. Twelve months after transplantation, 585 recipients had functioning grafts; the demographics of this population are reported in Table There were 162 cases of death-censored graft failure; the median graft survival was 10.4 years (range 1–26 years). Transplant biopsies were performed on 99 recipients with subsequent death-censored graft failure; 10% had late acute rejection, 3% had chronic immunological injury, 23% had interstitial fibrosis/tubular atrophy attributed to CNI toxicity, 22% had recurrence of their primary renal disease, 31% had another histological diagnosis, and 11% were non-diagnostic. Two individuals with graft failure which occurred during follow-up in another centre were not included in further analyses. A further two individuals were excluded because they required urgent graft nephrectomy, one for renal cell carcinoma and the other for refractory malignant hypertension, while maintaining self-supporting graft function , donor age (HR 1.2 (per decade), p = 0.001), and calcineurin inhibitor-based immunosuppression  were strongly associated with graft failure.In multivariate analysis, acute rejection . The mean annual loss of eGFR prior to graft failure was 7.9 mL/min/1.73 m2 (95% CI 7.0–8.8 mL/min/1.73 m2).The eGFR at commencement of alternative RRT was recorded for 143/158 (91%) individuals. The mean eGFR was 9.8 mL/min/1.73 mp = 0.002), but the prevalence of diabetes mellitus  and cardiovascular disease  was comparable between the modalities. Almost half of all recipients who started haemodialysis did so with a temporary catheter. All 31 (34%) recipients with a functioning AVF had had this formed prior to transplantation. The annual loss of eGFR prior to graft failure did not differ between recipients who recommenced dialysis via a temporary catheter and those with alternative access (p = 0.61).Following graft failure, 154 recipients returned to dialysis therapy and four had pre-emptive transplants. The majority of patients (70%) commenced haemodialysis Table ; dialysiSerum haemoglobin, phosphate and albumin concentrations, and the percentage of individuals attaining K/DOQI targets for CKD5 are shown in Table p = 0.7). Graft nephrectomy is not routinely practised but was undertaken in two recipients in the context of refractory acute rejection; one individual had immunosuppression stopped immediately following nephrectomy, while the other was maintained on low dose prednisolone. These individuals are highly sensitised and both have wait-listing times for re-transplantation exceeding 84 months.Immunosuppression was reduced within 12 months following graft failure in 89% of the recipients; 18% were completely weaned from immunosuppressive drugs. Reduction in immunosuppression was not associated with re-transplantation (There were 56 (35%) patients re-transplanted within the follow-up period; 16 were living donor transplants. The median time to re-transplantation was 27 months (range 0–164 months).p <0.001), cardiovascular disease , diabetes mellitus , and commencing dialysis with a temporary catheter  were associated with reduced likelihood of re-transplantation. There was no significant association between HLA mismatch at first transplant , eGFR at graft failure , rate of eGFR decline , commencing peritoneal dialysis , serum haemoglobin , serum phosphate , or serum albumin . In a Cox regression model, only age  remained associated with re-transplantation; the median age at graft failure in recipients who were re-transplanted was 35 years compared to 52 years in those who did not receive a second graft.In a univariate competing risks model, older age (HR 0.7 (per decade), n = 28) of the remaining deaths were attributable to cardiovascular disease, 18% (n = 11) to infection, 15% (n = 9) to malignancy, and the remaining 21% to miscellaneous causes including renal failure (n = 5), sudden cardiac arrest (n = 3), venous thromboembolism (n = 3), respiratory failure secondary to chronic pulmonary disease (n = 1), and haemorrhage (n = 1). For comparison, the causes of death for recipients with functioning grafts were analysed: 29% were attributable to cardiovascular disease, 22% to malignancy, and 21% to infection. In univariate analysis, diabetes mellitus, cardiovascular disease, higher eGFR, and commencing haemodialysis were associated with mortality; these associations were lost after adjustment for confounders. Ascertainment of targets for serum haemoglobin and phosphate at graft failure was not associated with survival. Multivariate analysis demonstrated that recipient age and re-transplantation were strongly associated with survival (Table There were 65 41%) deaths within the follow-up period; the median survival time for these recipients after graft failure was 3.0 years and the median age at death was 62 years. The cause of death was unknown for four individuals; 46% (1% deathsKidney transplantation is transformational for the recipient and cost effective for the healthcare provider,19. TherKidney transplant recipients returning to dialysis have significantly reduced survival compared to both the transplant-naïve dialysis population and those with functioning renal grafts-11. ThisRe-transplantation was the only clearly modifiable factor in this analysis which improved the survival of recipients with kidney transplant failure; after adjustment for multiple covariates, re-transplantation was associated with an 88% reduction in mortality. While this appears intuitive, analysis of the impact of re-transplantation on survival is complex due to the potential confounding from variables which simultaneously influence the likelihood of re-transplantation and survival. It is also essential to model re-transplantation as a time-dependent covariate in this analysis because of the influence of survival itself on the likelihood of re-transplantation. To the best of our knowledge, this is the first report of the impact of re-transplantation in a cohort with kidney transplant failure who had long-term graft survival and follow-up. Ojo et al. reported a significant survival benefit from re-transplantation using similar analysis in a population of kidney transplant recipients with a median graft survival of 1.4 years and follow-up time of 3.8 years. In the Re-transplantation is invariably challenging in this group as these individuals present both technical and immunological difficulties. Transplant recipients may exhibit a more rapid loss of kidney function in the months prior to ESRD than the transplant-naïve CKD population. This stOver the past 40 years, 13% of kidney transplants performed at this centre have been re-transplants. This is comparable to the re-transplantation prevalence elsewhere. In thisEvidence is accumulating that management of CKD complications is unsatisfactory in transplant recipients with graft failure. In this study, targets for the management of anaemia and CKD mineral bone disease were not met. There was no evidence, however, that this influenced the likelihood of re-transplantation or survival. Additionally, the dialysis modality of choice for persons with a failed graft is unknown; 71% of patients in this cohort commenced haemodialysis. This is the largest study to compare survival outcomes between the dialysis modalities,27. TherComprehensive clinical follow-up over 25 years is the first strength of this study. The low level of emigration from Northern Ireland creates an ideal environment for research into long-term transplant outcomes. Secondly, the wealth of prospectively collected data available allows detailed analysis of factors influencing both re-transplantation and survival and facilitates the investigation of how parameters at the time of transplant failure are associated with outcomes. Thirdly, the quantification of the effect of re-transplantation on recipient survival in a cohort with a median graft survival exceeding 10 years is novel and relevant. This is the largest study to date with detailed long-term follow-up of recipients with failed transplants.The small number of recipients could be considered a limitation of this work. While this research lacks the power of a large, registry-based analysis, the detailed and comprehensive follow-up allows meaningful conclusions to be drawn. Secondly, as a result of the historic nature of this cohort, the mean age of the recipients is younger than in the present day. However, it is these individuals who are likely to experience graft failure and require a subsequent kidney transplant during their lifetime. In addition, the maintenance immunosuppressive regimen in the study period is not typical of the modern era. It is possible that recipients with graft failure who were transplanted in a later period may have higher rates of infection and cancer due to a greater cumulative immunosuppressive burden with the use of CNI and induction therapy. Thirdly, information on hypertension and blood pressure control was not consistently available for recipients during the follow-up period. This may have an impact on graft and recipient survival.The substantial progress in kidney transplantation over the past 30 years has enhanced both graft and recipient survival. However, the latter often exceeds the former, and it is increasingly common for transplant recipients to return to dialysis therapy. These individuals are young, have significant comorbidities, and their outcome on dialysis is poor.There are many factors which influence survival after graft failure; some of these are predetermined, such as age, but others may be modified with strategies to minimise and manage complications in transplantation. The single factor which substantially improves survival and which is, at least partly, within the domain of the nephrologist to influence is re-transplantation. Improving outcomes for recipients with failed kidney transplants requires early recognition of inevitable graft failure, assessment and optimisation of comorbid conditions, investigation of the possibility of living kidney donation, and timely re-transplantation if feasible.CKD: chronic kidney disease; RRT: renal replacement therapy; PTFE: polytetrafluoroethylene; AVF: arteriovenous fistula; EGFR: estimated glomerular filtration rate; CNI: calcineurin inhibitor.The authors declare that they have no competing interests.JAM conceived the study, participated in the study design, collected the data, performed the statistical analysis, and drafted the manuscript. CCP participated in the study design and performed the statistical analysis. APM revised the manuscript. AEC collected the data and drafted and revised the manuscript. All authors read and approved the final manuscript.


The frontal eye field region (FEF) of the oculomotor pathways has been intensely studied. The primary goal of this review is to illustrate the phylogenetic displacement of the FEF locus in primate species. The locus is arrayed along the arcuate sulcus in monkeys and abuts into the primary motor strip region in humans. The strengths and limitations of the various functional, anatomical and histological methodologies used to identify such regions are also discussed. Since the earliest studies of the brain as an organ, many criteria have been used to define subtypes and hierarchical organization within and between distinct brain regions. Historically, this has meant describing configurations of multiple brain areas believed to be associated with distinct functions and/or sub-functions according to anatomical landmarks. However, functional classifications have also been widely developed to allow existing definitions of anatomical brain regions to be questioned and reexamined  are a group of simians native to Old World regions including Africa, India and Southeast Asia. Old World monkeys are medium to large in size. Some species are arboreal while others are terrestrial. Cercopithecids are almost exclusively diurnal. Most of the anatomical studies on area 8 have been carried out on Cercopithecidae, which includes the diverse genera of the macaques. It is now more than a century since the oculomotor cortical areas in Cercopithecidae were first discovered and described. The cerebral sulcal pattern is very stable across the whole family Falk, , with anThe oculomotor effect of cortical stimulation described by Ferrier , 1875, BAotus trivarigatus) are lissencephalic anterior to the central sulcus  gyral variations range from no sulcus at all  is close to that of Cercopithecidae with a more accentuated sulcus arcuatus only (Sanides, The Cebidae family of monkeys are mostly diurnal, but one genus, the Aotus, is primarily active at night. The oculomotor cortex of Cebidae has not been studied as widely or over such a long period of time as that of other monkeys or apes. It will be presented here in more detail. Compared to the gyral pattern of Cercopithecidae, the gyral pattern of Cebidae is variable. Owl monkeys (s Figure , as theys Figure , 1987, al Figure , to a sil Figure . The FEFd Akert, . The gyrd Akert,  of CebusSanides,  or with Sanides, . As in tSanides, , 1997. ISanides, .Hominoidea are a branch of Old World tailless anthropoid primates native to Africa and Southeast Asia. In comparison to the Cercopithecidae, major changes have occurred in the cortex of apes, especially in the areas anterior to the central sulcus. There is no sulcus resembling the arcuate sulcus of Cercipithecidae in apes. Differential studies carried out on a large number of chimpanzee brains showed considerable individual variation, particularly in the inferior precentral region (Sherwood et al., agranular (von Bonin and Bailey, The individual variability of cerebral sulcal patterns makes it difficult to examine this idea closely. For, chimpanzees, gorillas and orangutans, the sulcus containing the oculomotor FD is always distant from the motor cortex, is per se (Cheng et al., There are major differences between apes and humans. However, even today, the location of the FEF in humans still raises intriguing problems. The human cerebral sulcal pattern is discernibly different from that of apes. The significant individual gyral variation, sometimes even between one hemisphere and the other, may partly explain the evident discrepancies in historical interpretations, which is particularly noticeable when comparing maps. Histologic studies have shown that the human FEF is not linked to any major sulcus (Pandya and Yeterian, precentral, premotor, and agranular (Figure These imaging studies have tended to characterize the human FEF as mainly r Figure . Accordir Figure , area FBr Figure , area 4 r Figure , betweenr Figure , and in r Figure . Howeverr Figure . Images r Figure  mention,r Figure . An actir Figure . The mear Figure  or imagir Figure  lends suIn animal models, there is a major discrepancy between two major classical anatomical works. For Bailey and von Bonin , macaqueReturning to histoanatomical data, the human FEF, as located by the recent histologic studies, is not located in Brodmann area 8 nor in von Economo FDΓ (Brodmann, In addition, within the striatum, it is also known that in macaques the FEF sends axons to the dorsal part of the caudate nucleus (Künzle and Akert, One point is constant the FEF is always sulcal: to be more precise, it is located on one wall of the cerebral sulcus Figure . This isThe second point is the major change that has occurred between apes and humans. The FEF in apes is composed of a moderately thick and granular layer IV both rostrally and caudally. This granular layer IV becomes almost invisible at the fundus and into the posterior bank, whereas in humans, FEF is pre-central, pre-motor, and agranular. This makes it difficult to conclude that there is topological equivalence between the simian and human FEF position in the agranular—dysgranular—eugranular sequence. Leaving aside the location of the FEF in human, apes and macaques, these discrepancies between cytoarchitectonic classifications, together with the functional delimitations established with the use of fMRI, are raising fundamental questions about the importance of the topological position of cortical areas within the Sanides cytoarchitectonic gradients, but also on the core measures extracted from the fMRI technique by itself.In 2000 Tehovnik and colleagues concluded that “the anatomy of FEFs is an enigma.” In 2015, we find ourselves sharing this view. Major studies in human and animals still need to be performed to reach any other position. Four questions still need to be answered (Tinbergen, How does this displacement of FEF promote selection among primates? For a given species, how does the FEF develop ontogenetically? We believe that a synthesis of the responses to these questions holds the key to understanding the function of the FEF.The 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.


International Journal of Environmnetal Research and Public Health . Therefore, in a 24 h period radioactive plumes can disperse anywhere in the continental United States between 192 to 564 m, assuming…” should read “The continental wide average wind speed at an altitude of 80 meters falls between 8 and 23.5 miles/h [54]. Therefore, in a 24 h period radioactive plumes can disperse anywhere in the continental United States between 192 to 564 miles, assuming...”.Page 4176, The authors wish to make the following amendments to their paper published in c Health :Page 41The authors would like to apologize for any inconvenience caused to readers by these changes.