AML)/myelodysplastic syndrome (MDS) patients who received either a clofarabine/busulfan (CloB2A2) or a fludarabine/busulfan (FB2A2) RIC regimen for allogeneic stem cell transplantation. Between 2009 and 2014, 355 allotransplanted cases were identified from the SFGM‐TC registry as having received either the FB2A2  or the CloB2A2  RIC regimen. In multivariate analysis, FB2A2 was associated with significant lower overall survival  and higher relapse incidence  and a trend for lower leukemia‐free survival . These results were confirmed using a propensity score‐matching strategy. However, when considering AML and MDS patients separately, the benefit of the CLOB2A2 regimen was restricted to AML patients . The better survivals were due to the lower risk of relapse in this CloB2A2 AML subgroup . This retrospective comparison suggests that the CloB2A2 RIC regimen can likely provide longer survival than that awarded by a FB2A2 RIC regimen and may become a new standard of care RIC regimen for allotransplanted AML patients. A prospective phase 3 randomized study is warranted.We have retrospectively compared survivals between acute myeloid leukemia ( In the myeloid setting, allogeneic stem cell transplantation  is indicated as consolidation for acute myeloid leukemia (AML) patients in first complete remission CR1) with intermediate or high‐risk profile   with intRecently, we have reported encouraging results of a clofarabine‐busulfan‐containing RIC regimen in adults with high‐risk AML/MDS in CR at the time of transplant where clofarabine replaced fludarabine as part of the FB2A2 regimen (CloB2A2), demonstrating a 2‐year OS and LFS of 75% and 69%, respectively Clofarabine acts by inhibiting ribonucleotide reductase and DNA polymerase, thereby depleting the amount of intracellular deoxynucleoside triphosphates available for DNA replication. Compared to fludarabine, clofarabine has an increased resistance to deamination and phosphorolysis, and hence better stability as well as higher affinity to deoxycytidine kinase (dCyd), the rate‐limiting step in nucleoside phosphorylation This was a multicenter retrospective study aiming to compare OS and LFS between AML/MDS patients receiving either CloB2A2 or FB2A2 RIC regimen for allo‐SCT, and reported to the SFGM‐TC registry between January 2009 and December 2014. No selection criteria other than those mentioned above were used for this study. Data were collected and investigators were requested to update the main outcomes, especially dates of relapse or death and of last follow‐up. The study was approved by the scientific committee of the SFGM‐TC, and performed according to their guidelines. During the study period, 355 patients from 26 French centers were identified, including 16 AML/MDS patients already reported as part of the previous prospective CLORIC study The FB2A2 consisted of 30 mg/m²/day fludarabine for 5 days (day‐6 to day‐2) combined with 3.2 mg/kg/day busulfan for 2 days (days‐3 and ‐2) and 2.5 mg/kg/day ATG (thymoglobulin) for 2 days (days‐2 and ‐1). In the other subgroup, the first 17 patients received a CloB2A2 regimen according to the previously published schedule As GVHD prophylaxis, cyclosporine (CsA) alone was used in case of related donors in both groups, and for the 16 AML/MDS CloB2A2 patients treated within the previous prospective CLORIC trial 3), status at transplant (first complete remission [CR1] vs. others), type of donor , and cytomegalovirus (CMV) donor/recipient status (‐/‐ vs. others).The primary endpoint of the trial was to compare 2‐year OS and LFS after allo‐SCT between the two groups (CloB2A2 vs. FB2A2). Secondary endpoints were relapse incidence (RI), nonrelapse mortality (NRM), acute and chronic GVHD rates, and comparison of 2‐year OS and LFS between both groups in the setting of AML or MDS patients. Clinical outcomes that were collected included demographic, disease and transplant characteristics, graft‐versus‐host disease (GVHD) status, time to relapse, and survival. FB2A2 patients were considered until December 2013 in order to allow sufficient follow‐up. Quantitative variables are described with median, range, and interquartiles range and were compared by a Wilcoxon rank‐sum test. Categorical variables are described with counts and percent and were compared by Wilcoxon test or Fisher exact test where appropriate. OS was defined as the time between the date of transplant and death. LFS was defined as survival without relapse. Probabilities of OS and LFS were calculated using the Kaplan–Meier estimate. Cumulative incidence functions (CIF) were used to estimate relapse incidence (RI) and nonrelapse mortality (NRM) in a competing risks setting, since death and relapse are competing together. In order to study acute and chronic graft‐versus‐host disease, we considered death and relapse as competing events. Acute and chronic GVHD were diagnosed and graded according to the standard criteria Multivariate analyses were performed using Cox proportional hazard model. Factors differing between two groups in terms of distribution and all factors significantly associated with one of the outcome studied were included in the multivariate analysis.3 vs. others), and CMV seronegativity in donor and recipient versus others. The purpose of the propensity score‐matching strategy was to reduce confounding effects of these variables, and strengthen causal inferences To allow for potential confounding factors between treatments that could influence outcome, propensity score matching was also performed, using the nearest neighbor matching. The following factors were included in the propensity score model: age, diagnosis (AML or MDS), status at transplantation (CR1 vs. others), donor type , WBC at diagnosis , and propensity score analysis was performed using the “MatchIt” package All tests were two‐sided and P = 0.01) in the CloB2A2 group, while there were more recipients with CMV‐positive status in the FB2A2 group . CloB2A2 patients have been transplanted more recently compared to other cases . A 2‐year OS, LFS, RI, and NRM for the whole cohort (n = 355) were 58% (52–64), 52% (47–58), 31% (26–36), and 16% (12–21), respectively.During the study period, 316 AML/MDS patients were identified as having received a FB2A2 RIC regimen  and 39 a CloB2A2 RIC regimen  for allo‐SCT. The characteristics of patients (Table P = 0.03), but no differences between the two groups was observed in terms of 2‐year LFS , 2‐year RI , or 2‐year NRM   as well as the 2‐year incidence of chronic GVHD .The 2‐year OS was significantly higher in the CloB2A2 group , and a CR1 status (P = 0.02) (Table P = 0.04) and use of an unrelated donor (P = 0.03). There were trends for better 2‐year OS and LFS in patients with less than 5000/mm3 WBC at diagnosis . Significantly lower RI was observed in AML (vs. MDS) cases (P = 0.01) or in transplants from unrelated donors (P = 0.01).In univariate analysis, factors associated with significant higher OS were the CloB2A2 regimen (P = 0.04) and a higher risk of relapse  (Table P = 0.08). CR1 status at transplant was associated with better OS , and LFS  while the use of an unrelated donor was associated with better LFS  and lower RI . Also, diagnosis of MDS was the other factor associated with higher RI . Finally, older age (≥60 years) was associated with significant lower OS .In multivariate analysis of the entire cohort, the FB2A2 RIC regimen was independently associated with lower OS  was also observed with this regimen. In the MDS group, neither FB2A2 nor CloB2A2 RIC regimens were associated with OS, LFS, RI, and NRM.In order to reduce confounding effects of variables, and strengthen causal inferences, a propensity score‐matching strategy was used to compare outcomes between the two groups Table . Thirty‐This large retrospective study is the first to compare a standard busulfan/fludarabine‐based RIC regimen (FB2A2) to a new RIC regimen where the fludarabine has been replaced by clofarabine (CLOB2A2) for allo‐SCT in AML/MDS patients. Although there are some limitations in our study , we showed here that the CLOB2A2 RIC regimen is well tolerated and provided significantly better survival for allografted AML patients, with a gain of more than 30% in terms of 2‐year OS and LFS compared to the use of the FB2A2 regimen. Such results seems to be explained by the better antileukemic activity of clofarabine, a second‐generation purine analog, which is known to have an increased resistance to deamination and phosphorolysis, and to induce a direct apoptosis of leukemic cells by activation of caspase 9 OS and LFS were similar when comparing both regimens for MDS patients, a population that showed significantly higher incidence of relapse compared to AML cases. This highlights the fact that MDS and AML patients are two different entities with specific features It should be difficult to improve the results of CLOB2A2 treatment for AML patients . For example, comparison overall of 4 versus 5 days of clofarabine was not associated with improved OS in this cohort (data not shown). Also, increasing clofarabine Unfortunately, subgroup analyses according to molecular status or ELN classification for AML In conclusion, the CloB2A2 RIC regimen can likely provide higher survival compared to the FB2A2 RIC regimen and may become the new standard of care RIC regimen for allotransplanted AML patient. A prospective phase 3 randomized study is urgently warranted.The authors declared no conflict of interest.


NFKB2 mutation in common variable immunodeficiency and isolated adrenocorticotropic hormone deficiency: A case report and review of literature”, which appeared in Volume 95, Issue 40 of Medicine, one of the references in Table [6] should have appeared as Lindsley et al[3].In the article, “


The challenging reliable wafer-scale synthesis of high quality polycrystalline VO2 coatings is demonstrated on 4” Si taking advantage of the oxidative sintering of chemically vapor deposited VO2 films. This approach results in films with a semiconductor-metal transition (SMT) quality approaching that of the epitaxial counterpart. SMT occurs with an abrupt electrical resistivity change exceeding three orders of magnitude with a narrow hysteresis width. Spatially resolved infrared and Raman analyses evidence the self-assembly of VO2 disordered metamaterial, compresing monoclinic (M1 and M2) and rutile (R) domains, at the transition temperature region. The M2 mediation of the M1-R transition is spatially confined and related to the localized strain-stabilization of the M2 phase. The presence of the M2 phase is supposed to play a role as a minor semiconducting phase far above the SMT temperature. In terms of application, we show that the VO2 disordered self-assembly of M and R phases is highly stable and can be thermally triggered with high precision using short heating or cooling pulses with adjusted strengths. Such a control enables an accurate and tunable thermal control of the electrical switching.As a strongly correlated metal oxide, VO Vanadium dioxide VO has seen2 films, essential for high technological applications, remains a challenge as vanadium forms multiple stable oxides like V2O3, V2O5 and V6O1321222O3 or TiO2 substrates or buffer layers24252 films quality are the amplitude of resistivity change and hysteresis width. Ideally, VO2 films show 3–4 orders of magnitude resistivity change with a narrow hysteresis width of ΔT~ 3–4 K. Bulk single crystal offers slightly higher amplitude of resistivity change but is susceptible to breakdown after few cycles of switching between semiconducting and metallic phases23282 films to decrease the density of grain boundaries is not conceivable for practical applications due to the high melting point of this phase (1970 °C). The depression of the melting point, usually observed in nano-crystalline materials2 films attracted a considerable attention owing to their improved morphological advantages and SMT quality. Nevertheless, cost, process conditions, ease of synthesis, morphological control and industrial integration remain limiting challenges for epitaxial growth of VO2. Hence, it is worth investigating ways to grow polycrystalline VO2 films without specific buffer layers, yet still matching the performance of epitaxial or single crystal VO2.Obtaining high quality VO2 films by MOCVD is achieved involving an oxidative sintering step. The investigation of the electrical and optical properties across the SMT reveals the self-assembly of a VO2–disordered metamaterial in which the coalescence and confinement of metallic domains are highly controllable.The synthesis of high quality, electronic grade, wafer-scale VO2 films obtained with ethanol at this temperature range2 characteristic Raman signature (2 films and decrease the density of the grain boundaries.The as-grown films using cyclohexane as a liquid carrier (step 1) are XRD-amorphous , which cignature  but do n2 films. Annealing under vacuum in the absence of oxygen was performed at 600 °C directly in the deposition chamber. As this temperature is far below the melting point (1970 °C) of VO2, no significant sintering took place as shown in 2 to V2O5, that exhibits a lower melting point (690 °C), prior sintering. This approach proves to be successful as displayed in 2 to V2O5 was performed under the O2 partial pressure of 0.01 mbar. The XRD analysis, 2 – V2O5 conversion already at 400 °C. Fixing the temperature at 600 °C was essentially implemented to induce an efficient sintering over a short period (1 h) and to simplify this multi-step process by keeping the substrate temperature constant.Two approaches were implemented to induce the sintering of VO2O5 films undergo reduction to VO2 at the same temperature in the absence of oxygen as shown in 2O5 releases oxygen without significantly affecting the obtained dense morphology  after further annealing under vacuum. Raman spectrum of the crystalline VO2 features an enhanced scattering intensity.XRD and Raman scattering, 2 in the 50–80 °C range whereas Temperature-programmed X- ray diffraction was carried from room temperature up to 130 °C. Contour plots shown in 2 films. The wavelength-dependent total hemispherical reflections in the near infrared region (NIR) are displayed in 101234The optical reflectivity and thermal imaging were acquired as a function of temperature for 500 nm-thick VO2 feature a contrasting thermal emissivity. This contrast was represented in the NIR imaging to spatially resolve the phase transition across the SMT. The surface temperature is captured using a neighboring coated silicon with a thick (4–5 μm) carbon nanotube layer which acts as a perfect black body.Based on the spectroscopic measurements it is clear that the monoclinic and rutile phases of VONIR images in 2 in this range was proposed by H. S. Choi et al.2 is “disordered metamaterial”39In a finite range of temperature (66–69 °C), both semiconducting and metallic phases with contrasting electrical and optical properties co-exist. One of the early descriptions of VOet al.2 in a finite range of temperature features essentially the same kind of physical features as the aforementioned MNP in a dielectric matrix, which strengthens the recent identification of vanadium oxide transition state as “disordered metamaterial”.Yun Zhang The dominance of the metallic phase, The fraction of each phase changes abruptly, 4  conversion during the electrically driven transition, which is in line with static lattice calculations that predict an intermediate phase with a Peierls distortion when approaching the phase transition between M1 and the rutile phases5250Regarding the M2 phase of VOg band shift from 620 cm−1 in M1 to 650 cm−1 in M2et al.3754The presence of M2 would indeed clarify the observed semiconductor behavior after the first order phase transition at 70 °C. Thermal imaging, Unlike nanobeams, such a stress might be randomly localized in polycrystalline films. Not detecting the M2 phase with XRD , where t−1 and M1:620 cm−1), 2 surface to visualize the random distribution of different phases. Each pixel corresponds to a 1 × 1 μm2 analysis area. The red dots in 2. The spectra of the aforementioned colored points in the Raman map are displayed in 2, which is the size of a single pixel in Therefore, Raman mapping was performed at 67.5 °C for both wavenumbers  without any apparent degradation or drift of one state to another. Therefore, the disordered VO2, the metamaterial phase is surprisingly stable over extended periods. Therefore, it is virtually possible to stabilize the system at any point within the hysteresis curve by adjusting the temperature. A practical application of this feature could be a thermally activated electrical switch, which might operate by the supply of short heating and cooling pulses with small amplitudes ΔT. These pulses bring the metamaterial to cycle between resistive “Off” and conductive “On” states while keeping the same background temperature around the SMT value.As noticed during the investigation of the spatial phase distribution within VO2 is displayed in 2 films feature the disordered metamaterial structure. This temperature is applied using a heating stage while monitoring the electrical resistance. The highly resistive semiconducting state is considered as an “off” state. A 3 seconds heating pulse ΔT drives the coalescence of the metallic rutile domains in the metamaterial, a state that is retained after the back stabilization of the temperature at 67 °C. This behavior originates from the difference between the forward and backward transition temperatures due to hysteresis width as illustrated schematically in 2 in the metamaterial state. The amplitude of the thermal pulse activation has a direct impact on the response of VO2 metamaterial as shown in Experimental thermal switching behavior of VO2 electrical switching metamaterial.Using high strength of the thermal activation pulse as shown in 2 disordered metamaterial films operate optimally even after extensive and extended use, which makes it an attractive candidate for highly demanding applications. The attractiveness of such metamaterial will substantially enhance, provided a reliable approach is developed for the tuning of the SMT temperature without scarifying its quality in terms of amplitude, sharpness and hysteresis width.It is worth noting that attaining high switching amplitude while implementing a small thermal activation requires a sharp transition with a minimal hysteresis width. The narrow hysteresis, ΔT = 3 K, obtained in this study is equivalent to single crystal or epitaxial films and is ideal for high performance applications252 film. This multistep process was performed in the same CVD reactor without intermediate handling and air exposure of the samples. The resulting films feature SMT characteristics that match those of epitaxial or bulk VO2 in terms of sharpness and width of the hysteresis. This development paves the way towards the exploration and understanding the behavior of this material. Spatially resolved phase analysis using Raman mapping within the transition regime reveals the self-assembly of VO2 disordered metamaterial that exhibit an outstanding long-term stability. The formation of locally confined M2 intermediate phase during the transition was attributed to the presence of localized strain. The disordered metamaterial was thermally activated to tune the degree of coalescence/confinement of the metallic domains with high precision. Such a control enables a highly accurate and tunable thermal triggering of the electrical switching.Indigenous oxidative sintering approach was implemented in this study to induce an efficient densification of the grown VO−3 mol/l of vanadium (V) oxy-tri-isopropoxide was used as a single-source precursor, which was maintained under nitrogen atmosphere at room temperature before its injection into the evaporation chamber at a frequency of 2 Hz and an adjusted opening time to reach a feeding rate of 1 g/min. The pressure and temperature of the evaporation chamber were maintained at 0.6 mbar and 200 °C during deposition respectively, whereas the walls of the reactor were maintained at 200 °C. During the growth, 500 sccm of nitrogen carrier gas was introduced alongside the precursor injection and the total pressure of the reactor was automatically regulated at 0.6 mbar. The substrate is maintained at 600 °C during the 2 hours of deposition and the subsequent heat treatments.Films of vanadium oxide were deposited on silicon substrates using direct liquid injection MOCVD , which is a stagnation point-flow warm-walled reactor. Cyclohexane solution containing 5 × 10−2 mbar. The sample is then further subjected to annealing at the same temperature under vacuum (~0.6 mbar) acting as a reducing atmosphere for 4 hours, after which the chamber is allowed to cool down. All depositions were carried out on 4-inch silicon wafers without removing the upper native oxide layer that might act as a barrier. Samples were later cut into smaller pieces for analysis purposes. Uniform, high quality VO2 films were observed throughout the wafers in a homogeneous manner.In a second step, an hour long annealing was performed at 600 °C right after the deposition under oxygen partial pressure of 1 × 10X-ray diffraction (XRD), Bruker D8, with CuKα as the X-ray source, was used to identify the crystalline phases of vanadium oxide. Data were collected in the θ−2θ (locked couple) mode from 2θ of 20° to 60° with a step size of 0.02°.Film thickness was measured using an Alpha step d-500 profilometer from KLA-Tencor and FEI Helios Nanolab 650™, Scanning Electron Microscope (SEM). Surface morphology was inspected by SEM at a working distance of 4 mm with an operating voltage of 25 kV.In situ temperature-dependent Raman measurements were performed at ambient air with a Linkam TMS heating stage using fixed heating and cooling ramp at 5 °C/min.Raman spectroscopy was performed using an InVia Raman spectrometer from Renishaw with a 532 nm laser. The electrical resistivity was measured using four-point probe measurements in Van der Pauw configuration. Infrared image analysis was conducted using the FLIR X6580SC thermal camera operating in the 1.5–5.1 μm spectral range with an accurate recording at a frequency of 355 Hz in a full 640 × 512 resolution. Temperature-dependent measurements were performed by placing the sample on a heating stage and cycling the temperature form 40 °C to 80 °C while a thermocouple was placed on the sample to measure the surface temperature. The ramp was fixed at 5 °C/min in the transition range.How to cite this article: Kumar, S. et al. Electrical Switching in Semiconductor-Metal Self-Assembled VO2 Disordered Metamaterial Coatings. Sci. Rep.6, 37699; doi: 10.1038/srep37699 (2016).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Upon publication of the original article , it was 1.) The first column in the body of the table should be labelled "Tissue"2.) The second column of data should be labelled with the animal # and inhaled dose which it received: "marmoset #1 (2.4 × 10^1)"3.) There was a misspelling of one of the tissues in the first column: “Trachbronical LN” should be "Tracheobronchial LN"


PtdIns(3)P binding to Phafin2 occurs with high affinity, triggering minor conformational changes in the protein. Taken together, these studies represent a platform for establishing the structural basis of Phafin2 molecular interactions and the role of the two potentially redundant PtdIns(3)P‐binding domains of the protein in endomembrane compartments.Phafin2 is a phosphatidylinositol 3‐phosphate (PtdIns(3)P) binding protein involved in the regulation of endosomal cargo trafficking and lysosomal induction of autophagy. Binding of Phafin2 to PtdIns(3)P is mediated by both its PH and FYVE domains. However, there are no studies on the structural basis, conformational stability, and lipid interactions of Phafin2 to better understand how this protein participates in signaling at the surface of endomembrane compartments. Here, we show that human Phafin2 is a moderately elongated monomer of ∼28 kDa with an intensity‐average hydrodynamic diameter of ∼7 nm. Circular dichroism (CD) analysis indicates that Phafin2 exhibits an α/β structure and predicts ∼40% random coil content in the protein. Heteronuclear NMR data indicates that a unique conformation of Phafin2 is present in solution and dispersion of resonances suggests that the protein exhibits random coiled regions, in agreement with the CD data. Phafin2 is stable, displaying a melting temperature of 48.4°C. The folding‐unfolding curves, obtained using urea‐ and guanidine hydrochloride‐mediated denaturation, indicate that Phafin2 undergoes a two‐state native‐to‐denatured transition. Analysis of these transitions shows that the free energy change for urea‐ and guanidine hydrochloride‐induced Phafin2 denaturation in water is ∼4 kcal mol AUCanalytical ultracentrifugationCDcircular dichroismDLSdynamic light scattering0ƒ/ƒfrictional ratioGuHClguanidine hydrochloridePtdIns(3)Pphosphatidylinositol 3‐phosphatessedimentation coefficientS20,wsedimentation coefficient under standard conditionsSPRsurface plasmon resonancePleckstrin homology) and C‐terminal FYVE  domains ‐transverse relaxation optimized spectroscopy (TROSY)‐heteronuclear single quantum coherence (HSQC) was performed for the protein sample. Data were processed and analyzed using Topspin 3.2 and NMRpipe.NMR experiments of F339 to F356, CD spectral changes of Phafin2 at 222 nm) against denaturant concentration were analyzed to calculate the Gibbs free energy of unfolding (ΔGH2O0) in the absence of denaturant. To calculate ΔGH2O0 for each spectral analysis, a model in which monomeric native Phafin2 (fN) was converted to a denatured (fD) form without the presence of highly populated intermediates was first considered. This state, known as the equilibrium two‐state is represented as:The transition curves acquired after representing each spectral property  using the relation:R is the universal gas constant  and T is the temperature on the Kelvin scale. The ΔG value varies linearly with denaturant concentration following the equation:x] is the molar concentration of the denaturant and m is the slope of the plot. Thus, linear plots of ΔG versus denaturant concentration were obtained. Data was fitted to the nonlinear least‐squares method using Microsoft Excel  for the calculation of the ΔGH2O0 and m for each experimental condition.Cm, the denaturant concentration at the midpoint of the unfolding transition when ΔG is 0, was estimated. Similarly, the TM of Phafin2 was calculated by following the denaturation of the protein by its CD ellipticity at 222 nm and by determining the temperature at which ΔG is 0 using Eq. The estimation of sn‐glycero‐3‐phosphatidylcholine , or DOPC and dipalmitoyl PtdIns(3)P (1.5%) were dissolved in chloroform/methanol/water (65:35:0.8). The lipid mixture was first dried under N2 and further under vacuum to remove residual chloroform. Phospholipids were resuspended in 20 mM HEPES (pH 7.0) and 100 mM NaCl to a final concentration of 4 mM, sonicated, and extruded for 100‐nm liposome size at 65°C. SPR analysis was performed on a BIAcore X100 instrument with a liposome‐coated L1 sensor chip at room temperature. Typical liposome loading was ∼5,000 RU/channel. Kinetic SPR measurements were performed with the flow rate set at 30 μL/min. Apparent KD values were estimated using the BIAevaluation software, version 2.0 . Experiments determining KD values for PtdIns(3)P were carried out by collecting four independent experiments.Liposomes were prepared as previously described.Supporting InformationClick here for additional data file.


This study assessed whether presenting 3D face stimuli could facilitate children’s facial expression recognition. Seventy-one children aged between 3 and 6 participated in the study. Their task was to judge whether a face presented in each trial showed a happy or fearful expression. Half of the face stimuli were shown with 3D representations, whereas the other half of the images were shown as 2D pictures. We compared expression recognition under these conditions. The results showed that the use of 3D faces improved the speed of facial expression recognition in both boys and girls. Moreover, 3D faces improved boys’ recognition accuracy for fearful expressions. Since fear is the most difficult facial expression for children to recognize, the facilitation effect of 3D faces has important practical implications for children with difficulties in facial expression recognition. The potential benefits of 3D representation for other expressions also have implications for developing more realistic assessments of children’s expression recognition. Understanding others’ feelings from facial expressions is essential for children’s social development and adaptationOne of the key differences between 2D face and 3D face stimuli is the availability of depth cues. In reality, direct social interactions typically occur at a distance, where stereopsis provides strong depth cues through binocular vision. Although 3D representation plays a relatively minor role in adults’ face identity recognition2Studies show that children’s discrimination of facial expression becomes progressively more accurate from early to middle childhood. Infants as young as a few months old have been shown to be able to visually discriminate among facial expressions, as indicated by eye-movement paradigms such as habituation and preferential looking81011131415Over the years, children’s ability to identify facial expressions has been examined in a variety of studies , and 36 were from the third year  of a kindergarten in Beijing. All children had normal vision and no known psychiatric disorders. Informed consent was obtained from the legal guardians of all participating children. The protocol was approved by the Institutional Review Board (IRB) at the Institute of Psychology, Chinese Academy of Sciences. The methods were carried out in accordance with the Declaration of Helsinki.Seventy-one children aged between 3 and 6 participated in the study. Thirty-five of them were from the first year  with 2 expressions (fear and happiness) of 4 intensity levels. These faces were presented in two image formats, either 2D or 3D representations. This amounted to a total of 64 face stimuli (4 models × 2 expressions × 4 intensities × 2 image formats). Two additional models and the same conditions were used in practice trials. The face stimuli were chosen from the BU-3DFE databasehttp://oss.sgi.com/projects/inventor/). They were then displayed with VRVisionIn the 2D image format condition of the current study, the 2D pictorial image was displayed. In the 3D image format condition, the 3D face model with its associated texture was rendered on the screen. The object file format of the 3D models was first converted to Open Inventor file format . The screen resolution was set at 1024 × 768 with 32-bit color. The software for the experimental control was written in Matlab R2012 with Psychophysics Toolbox extensions37p <= 0.5) about the probability of success were conducted on the rating for 2D and 3D images separately. The results showed that children didn’t rate the subjective sense of 3D for the 2D and 3D image formats randomly (p’s < 0.001). They appeared to be able to discriminate 2D and 3D image formats.To confirm that the 3D information could be perceived for the 3D image format, we recruited another sample of 20 kindergarten children to rate the subjective sense of 3D on a 3-point scale  for each of the 64 test face stimuli including both 2D and 3D image formats. Eight practice trials were given before the rating. Binomial tests of a null hypothesis  were executed in a random order.The experimental trials followed immediately after the practice. The 2D and 3D conditions were tested in separate blocks. The order of the two blocks was counterbalanced across age and gender such that half viewed 2D faces first and the other half viewed 3D faces first. The 32 face stimuli in each block were presented in a random order. Each trial began with a 500 ms central fixation, followed by a face on the screen for 8 seconds or until a response was made. This procedure was identical to the practice trials.p’s > 0.05). Outliers in the reaction time were excluded on the basis of a two-standard-deviation cut. The final accuracy data  and reaction time data  of the 71 subjects were subjected to 5-way mixed-design ANOVAs (2 image formats × 2 expressions × 4 intensities × 2 age groups × 2 genders).First we checked the assumptions for ANOVA and confirmed that the residuals were normally distributed and the equal variances can be assumed  = 4.32, p = 0.04, η2p = 0.06). Children’s recognition of facial expression for 3D faces  was significantly faster than that for 2D faces . There was also a main effect of age  = 19.74, p < 0.001, η2p = 0.23). Children in the older age group recognized facial expressions faster  than those the younger group . No other main effects or interaction effects were found in the reaction time data (p’s > 0.06).For reaction time, a main effect of image format was found  = 2.01, p = 0.16, η2p = 0.03) was not significant. The proportion accuracies for 3D faces  and 2D faces  were comparable. There were significant main effects of age  = 20.12, p < 0.001, η2p = 0.23) and intensity  = 7.39, p < 0.001, η2p = 0.25). Performances of the older age group  were more accurate than those of the younger group . Accuracy improved as a function of expression intensity .For accuracy data, the image format effect on accuracy  = 5.58, p = 0.02, η2p = 0.08), as illustrated in F  = 9.68, p < 0.001, η2p = 0.30. Boys recognized fear significantly better with 3D  than 2D  display, while this effect was not significant for girls, F  = 0.09, p = 0.77, η2p = 0.01.These main effects on accuracy were qualified by the significant interactions of image format × expression × gender  = 6.17, p = 0.003, η2p = 0.14) for 2D faces. For 2D image formats, boys recognized happiness  equally as well as girls , whereas they performed significantly worse for fear  than girls .Further simple effect analysis of the three-way interaction on accuracy also revealed a significant simple interaction effects of expression × gender  the reaction time, but not the accuracy (p = 0.62), which is in line with the effect of image format in the subject-based analysis.To evaluate the impact of the variation in the perception of 3Dness on the recognition performance, an item-based regression analysis on accuracy and reaction time with the frequency of each image rated as 3D as a prediction variable was conducted. The results revealed that the frequency of each image rated as 3D could significantly predict . Our results now confirm that 3D information can also lead to faster recognition of facial expressions in kindergarten children and higher accuracy for recognizing difficult emotions for boys. One cause of the facilitating effect in facial expression processing speed may be the additional depth cues that make the expressive features more identifiable. Another contributing factor may be the ecological validity of 3D representations. Children may be more familiar with 3D faces they encounter in real life. Presenting face stimuli in stereopsis resembles real faces more closely. This may be affected by a degree of encoding specificity for 2D and 3D information in face processing. As suggested in the literature, transfer between 2D and 3D representations of faces could compromise identification accuracy even in adultsOur results also confirmed that children’s understanding of specific facial expressions improved with age, that older children recognized facial expressions faster and more accurately. Although the effects of both image format and age were manifested in terms of speed and accuracy, the effects of expression category, expression intensity and children’s gender were only manifested in term of accuracy. It may be speculated that the effect of image format is robust and strong as the effect of age. An alternative explanation is that the reaction time is not a sensitive or reliable index to measure the performance of facial expressions recognition in children. Indeed, our data indicated that the extent of variability of reaction time was far larger than of accuracies in term of coefficient of variation (0.71 vs. 0.16).Recognizing facial expressions is crucial for successful social communication and adaptation. Our finding that 3D representations improve children’s recognition of fearful expressions may apply to children with difficulties in facial expression recognition. It has been shown that higher accuracy for recognizing fearful facial expressions can predict prosocial behaviors42In sum, our findings suggest that, even though 2D images are most common in research on facial expression processing, it may be beneficial to start employing 3D methods so that children’s development in expression recognition can be evaluated more accurately. A 3D approach may also be useful for more effectively training children with expression recognition deficits.How to cite this article: Wang, L. et al. Use of 3D faces facilitates facial expression recognition in children. Sci. Rep.7, 45464; doi: 10.1038/srep45464 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Its synthesis and crystallization was probed using an active machine‐learning algorithm developed by us to explore the crystallization space, the algorithm results were compared with those obtained by human experimenters. The algorithm‐based search is able to cover ca. 9 times more crystallization space than a random search and ca. 6 times more than humans and increases the crystallization prediction accuracy to 82.4±0.7 % over 77.1±0.9 % from human experimenters.The discovery of new gigantic molecules formed by self‐assembly and crystal growth is challenging as it combines two contingent events; first is the formation of a new molecule, and second its crystallization. Herein, we construct a workflow that can be followed manually or by a robot to probe the envelope of both events and employ it for a new polyoxometalate cluster, Na Understanding the supramolecular self‐assembly of complex inorganic molecules poses a difficult problem since it relies on two contingent events.6[Mo120Ce6O366H12(H2O)78]⋅200 H2O (1) {Mo120Ce6} . Importantly, we study how human experimenters approached this specific problem and compare their strategies and performance to our machine‐learning approach.Herein, we design and investigate a new approach for probing the envelope of both the synthesis and the crystallization process of a new polyoxometalate compound with the formula NaSo far, work in this area has been mainly focused on simulations and only a few studies have involved real experiments.Our machine learning approach actively defines new experiments to perform with an aim to improve its model of the system. Such targeted data acquisition strategy allows a reduction in the number of experiments needed to attain the same model quality, thus saving time and financial resources. To our knowledge, it is the first time that such an active data acquisition strategy is applied in this context and compared with human experimenters. Machine learning methods have previously been used as a tool of optimizationWe first introduce the compound that was discovered, the reaction conditions from which it can be isolated and characterized. We then compare our machine‐learning approach against random screening and human experimenters in terms of performance and methodologies for the exploration of the crystallization boundaries 78H12]⋅ca. 200 H2O, but notably was first discovered automatically by our automated chemical robot, see Supporting Information: Experimental Section, Method A. In later experiments we also reproduced the synthesis and crystallization of the compound on the bench, see Supporting Information: Experimental Section, Method B. Compound 1 was characterized by elemental analysis, single‐crystal X‐ray structure analysis, bond valence sum (BVS) calculations, IR and visible‐NIR spectroscopy, redox titrations and thermogravimetry.The new polyoxometalate cluster belongs to the family of lanthanide‐doped molybdenum blues.1 in the unit cell, packed parallel to the crystallographic bc plane giving rise to 1D channels occupied by guest water molecules . The framework of 1 consists of 12 sets of basic building blocks {Mo8}, {Mo2} and {Mo1} units, which are well‐defined in Mo Blue clusters such as the archetypal {Mo154},176},368},2} units substituted by 6 CeIII ions. On the whole, the architecture of 1 is constructed from 12 {Mo8} units, 6 {Mo2} units, 12 {Mo1} units and 6 {Ce(H2O)5} units 5}. Bond lengths of molybdenum atoms coordinated to terminal oxo groups have a Mo=O bond length in the range of 1.554(12)–1.702(9) Å. The symmetric arrangement of 3 CeIII ions on both the upper and lower surfaces of {Mo120Ce6} greatly reduces the symmetry of 1 to D3 as compared with the parent {Mo154} (Dd7 point group). As a result, the wheel displays an irregular ring‐shaped structure with an outer ring diameter of about 31 Å and an inner ring diameter of about 17 Å. A further characteristic of the structure of 1 is the large number of protons resulting from the 24 e− reduction. The overall reduction state of 1 was confirmed using three independent techniques: UV/Vis spectroscopy, redox titration and bond valence sum calculations (BVS), [see Supporting Information for details]. BVS calculations1: [{Mo2}6{Mo1}12{Mo8}12{Ce6}]≡[{MoVI2O5(H2O)2}6{MoVI/V8O26(μ3‐O)2H(H2O)3MoVI/V}12 {CeIII(H2O)5}6]6−.The single‐crystal X‐ray structure analysis reveals four of the dodecameric ring‐shaped clusters To explore the synthetic and crystallization process it is important to define the process of the reaction accurately as shown in Figure 2MoO4⋅2 H2O 1 m, Ce(NO3)3⋅6 H2O 0.1 m, NH2NH2⋅2 HCl 0.25 m and HClO4 1 m were prepared and used as described in the Supporting Information: Experimental Section, Method A. During the experiment both Na2MoO4⋅2 H2O and Ce(NO3)3⋅6 H2O were always added in a 1:1 volume ratio (molar ratio 10:1 respectively). The automated platform mixes, in a reactor, the stock solutions in configurable ratios to a total volume of 15 mL, and allows them to react at 90 °C for 30 min. We then collect a 9 mL sample for crystallization and then use a cleaning protocol to reset the system before the next experiment begins. The crystallization method consists of waiting overnight to allow for crystals to form. Finally, the presence or absence of crystals is checked under illumination with a white light emitting diode (3300–3500 lux at a distance of 5 cm) and the information is added in a database of experiments. It is important to note that under these particular conditions, no other product crystallizes in a time frame longer than one month, see Supporting Information, Table S12. Following this process the initial data set was obtained from previous experiments performed in the platform and is shown in Figure 1). The resulting data set, consisting of 89 points, was provided to each method and served as the initial database and training ground for their subsequent exploration.For the reactions, aqueous stock solutions of Na1). The latter can lead to the observation of other known compounds  or it can lead to the discovery of new chemical species. Figure As described above, we studied three different methods: a machine‐learning algorithm approach, human experimenters and random experiments as a baseline Figure . Each me1), the reagents, the reaction conditions, the platform and the initial set of data. They were not aware of the overall aim of comparing strategies among methods. Each human experimenter was instructed to develop their own strategy given the objective to identify the range of experimental conditions where compound (1) can be isolated. A baseline method is used as control, it consists of selecting experiments at random in the chemical space. This method is thus blind to both the initial and the subsequently collected crystallization information. To determine the differences between methods and their respective overall data acquisition performance we qualitatively analyzed trends in exploration strategies between each method. Then we quantified the number of experiments leading to crystals, as well as the extent of chemical space that was explored by each method. Using this data, it is then possible to compute the effectiveness of respective crystallization models and their predictive power.The machine‐learning approach is based on established active learning algorithm in classification problemsThe difference between human experimenters and the algorithm is illustrated in Figure S28. We can observe the stepwise exploration of human experimenters, starting from the known core of initial data provided and expanding outwards . The limiting factor in their exploration is that when they perform an experiment that yields no‐crystals, they stop after trying only a handful of experiments further than this point. Additionally, human experimenters tend to construct investigations that are more “Cartesian” shown in Figure S28,c, which reflects practical constrains. On the other hand, the algorithm follows a more “polar” approach around the initial set of data  and is not “disturbed” when crystals are not formed in the experiments, allowing a wider area to be covered.Following the results from our experiments, in Figure Additionally, human experimenters can be baited by the absolute number of crystallization points they discover, disregarding how conservative or not their strategy can be. This point is important because a conservative strategy with many small “steps” of exploration can lead to many crystallization points but limits a wider exploration of the chemical space. For example, the second human experimenter performed an impressive 47 experiments leading to crystallization, out of 100  . The quality of the prediction, that is, the percentage of time a crystal prediction is accurate, is expected to increase as more data are collected. Figure 1) in real time. Our “intelligent‐throughput” is powerful since it combines both intuition from machine learning and reliable liquid handling, allowing the system to develop “chemical‐intuition”; we hypothesize this could be a first step to developing a new approach we term chemical intelligence which uses machine learning to explore complex chemical systems. Using this approach we could observe significant differences in the strategies not only between the algorithm and the human experimenters but also between the two human experimenters. These differences can have a significant impact in the ability of exploration and are heavily dependent on the personal and chemical biases of the individual. In the future, we aim to explore how to combine the intuition of the chemists with chemical intelligence to use human–machine teams to identify new phenomena and characterize new chemical systems. We have placed the code onlineIn previous studies the data used to characterize and model crystallization processes were extracted from databases of experiments intended for other research purposes. Here, we coupled the data acquisition process with the modeling of our system, with the aim of characterizing the crystallization boundaries of a new polyoxometalate cluster  should be addressed to the authors.SupplementaryClick here for additional data file.


Saccharomyces cerevisiae, glycerophospholipids are the main membrane lipid constituents. Besides serving as general membrane ‘building blocks’, glycerophospholipids play an important role in determining the physical properties of the membrane, which are crucial for proper membrane function. To ensure optimal physical properties, membrane glycerophospholipid composition and synthesis are tightly regulated. This review will summarize our current knowledge of factors and processes determining the membrane glycerophospholipid composition of the reference eukaryote S. cerevisiae at the level of molecular species. Extrapolating from relevant model membrane data, we also discuss how modulation of the molecular species composition can regulate membrane physical properties.In most eukaryotes, including  DGAT, diacylglycerol acyltransferaseFAS, fatty acid synthaseGPAT, glycerol‐3‐phosphate acyltransferaseGPC, glycerophosphocholineLPAAT, lysoPA acyltransferasePL, phospholipidSFA, saturated fatty acidUFA, unsaturated fatty acidBiological membranes are composed of a complex mixture of lipid molecules, in which proteins are embedded. Technological advances over the last decade, especially in the field of mass spectrometry, have allowed detailed analysis of the cellular lipidome, revealing thousands of different lipid molecular species The proper  membrane lipid composition is important for organization and dynamics of membranes to allow processes such as budding, membrane trafficking, and fusion and fission events Saccharomyces cerevisiae can be divided into three different families, based on their molecular structure: glycerophospholipids , sterols, and sphingolipids. Phospholipids make up most of the lipids of the membrane bilayer and therefore play an important role in determining the physico‐chemical properties of the membrane. This review will focus on the role of bulk phospholipids in determining membrane physico‐chemical parameters, with emphasis on the effects of acyl chain and PL class composition, and using the eukaryote baker's yeast as a reference. Research on membrane lipid housekeeping in yeast has been pivotal in the understanding of lipid homeostasis. We will first briefly introduce phospholipid biosynthesis in yeast  that is converted into malonyl‐CoA (C3) by the acetyl‐CoA carboxylase Acc1p, which is the rate limiting step in acyl‐CoA biosynthesis 2 donor by the fatty acid synthase (FAS) complex consisting of Fas1p and Fas2p, in elongating the growing acyl chain starting from acetyl‐CoA, yielding the main yeast acyl‐CoAs C16:0 and C18:0 and minor amounts of C10:0, C12:0, and C14:0 The bulk synthesis of acyl chains (or fatty acids) starts with acetyl‐CoA  9‐CoA can be elongated to C18:1Δ11‐CoA, also in an Elo1p‐dependent manner C16:0‐CoA, C18:0‐CoA, and C14:0‐CoA to a minor extent can be desaturated by the Δ11 was increased from ± 2.5% to over 10% in a mutant deficient in neutral lipid synthesis compared to the wild‐type, the elongation of C16:1Δ9‐CoA to C18:1Δ11‐CoA was suggested to be relevant for protecting against lipotoxic effects 9 or C18:1Δ9, but not on media containing exogenous C18:1Δ11Triglycerides have been proposed to play a role in fatty acid detoxification by storing toxic acyl chains sn‐glycerol‐3‐phosphate  in the ER , which is synthesized from the chiral water‐soluble precursor sn‐1‐phosphatidylglycerol‐3‐phosphate by Pgs1p PA can be either dephosphorylated to diacylglycerol (DAG) by the PA hydrolase Pah1p (in the ER) via the CDP‐ethanolamine and CDP‐choline pathway, respectively, also known as the Kennedy pathway DAG is the lipid precursor for an alternative route of PE and PC synthesis DAG is also the precursor for the synthesis of the storage lipid triacylglycerol (TAG) by the diacylglycerol acyltransferase (DGAT) Dga1p, which uses acyl‐CoA as acyl chain donor, or by Lro1p that uses a phospholipid as acyl chain donor As a poikilothermic organism, yeast adapts its membrane lipid composition in response to altered growth temperatures in a process known as homeoviscous adaptation in vitro upon temperature variation ACC1 gene affects acyl chain length, as was indicated by in vitro experiments on fatty acid synthesis in which the concentration of its product malonyl‐CoA was varied ACC1 mutant that shows a higher C16/C18 ratio at the nonpermissive temperature 16‐to‐C18 acyl chains in the membrane lipids The acyl chain composition of newly synthesized membrane phospholipids is mainly determined by the extent of desaturation and elongation of the acyl‐CoA pool. The length of the acyl‐CoA species in the acyl‐CoA pool may be regulated by the FAS complex, which was shown to produce different ratios of C16:0‐ to C18:0‐CoA OLE1 gene, which is responsive to temperature, carbon source, and supplementation of exogenous fatty acids OLE1 is regulated by the transcription factors Spt23p and Mga2p, which are both synthesized as 120 kDa proteins (p120) and form homodimers residing in the ER membrane OLE1 expression. The deletion of both SPT23 and MGA2 is synthetically lethal. Single spt23Δ mutants show no alterations in Ole1p levels, but mga2Δ have lower Ole1p levels and therefore lower levels of UFA chains implicating Mga2p as the major player in Ole1p regulation It is widely accepted that the regulation of acyl‐CoA desaturation by Ole1p plays a major role in homeoviscous adaptation in yeast. The activity of Ole1p is regulated at the level of transcription of the via their transmembrane helices Recently Mga2p dimers were proposed to sense lipid packing in vitro enzyme assays, and changes in the lipidome of deletion and overexpression mutants have been used to deduce substrate specificities at the acyl chain level.The substrate specificity of lipid biosynthetic enzymes determines the molecular species profile of synthesized lipids and may have a role in determining the phospholipid molecular species profile (see section in vitro (except for slightly reduced activity towards C18:0‐CoA), its paralog Sct1p was shown to exhibit a strong preference for C16:0‐CoA and C16:1‐CoA In vivo, the deletion of SCT1 was shown to decrease the C16:0 levels in the four major phospholipids PC, PE, PI, and PS, with the largest effect on PC. Interestingly, deletion of GPT2 hardly affects the acyl chain composition of PC, PI, and PS, but does increase the C16:0 and C18:1 levels in PE at the expense of C16:1 et al. SCT1 decreases the cellular C16:0 content by almost 50%, whereas overexpression of SCT1 increases C16:0 levels at the expense of C16:1 and C18:1. Based on these data, it has been hypothesized that Sct1p‐mediated incorporation of C16:0 into PL serves as a sink for C16:0. In line with this hypothesis it was shown that co‐overexpression of OLE1 rescues the growth defect conferred by SCT1 overexpression and the accumulation of C16:0, indicating competition between Sct1p and Ole1p for their shared substrate C16:0‐CoA OLE1 increases the level of C18:1 rather than C16:1 Whereas the GPAT Gpt2p was shown to have little substrate preference 32 PL at the expense of C34 PL Loss of the LPAAT Ale1p does not significantly affect the PL molecular species profile. In contrast, loss of Slc1p causes a general increase in CSCT1 or GPT2 combined with deletion of SLC1 or ALE1, it was shown that deletion of SLC1 in combination with the deletion of either SCT1 or GPT2 has a large effect on the molecular species composition, whereas deletion of ALE1 in combination with SCT1 or GPT2 shows only minor differences de novo synthesis of PL having a more pronounced role in determining the acyl chain at the sn‐2 position versus the absence of a clear‐cut acyl‐CoA substrate specificity for Ale1p may also contribute.In a lipidomics study using four double mutants with deletions of DGA1 show a decrease in C16:0 and C18:1 levels which is compensated by an increase in C16:1 lro1Δare1Δare2Δ). Interestingly it was found that in the quadruple mutant dga1Δlro1Δare1Δare2Δ the total level of C18:1 is increased compared to wild‐type, which is mainly due to the presence of 7.3% C18:1Δ11ARE1 does not decrease the level of C18:1Δ11 and LRO1 or ARE2 only decrease it to 3.3–3.4%. However, the presence of DGA1 reduces the C18:1Δ11 level to wild‐type (0.1%), consistent with Dga1p being responsible for bulk TAG synthesis.The DGAT Dga1p has been proposed to have a substrate specificity for C16:0 and C18:1, based on the observation that yeast cells lacking in vitro and in vivo have been reported for acyl‐CoA synthetases  been reported. This also applies to the PI and PS biosynthetic enzymes Pis1p and Cho1p. However, the routes producing the bulk membrane phospholipids PE and PC were reported to show selectivity at the level of molecular species. In the absence of ethanolamine and choline, yeast is mainly dependent on PS decarboxylation for PE synthesis and subsequent methylation to PC. The mitochondrial enzyme Psd1p is the main PS decarboxylase and produces 70–90% of cellular PE via either the methylation of PE by Cho2p and Opi3p or by the Kennedy pathway were shown to differ in a stable isotope pulse labeling study using D13‐choline and D3‐methionine PCT1, the wild‐type PC molecular species profile cannot be produced by biosynthesis alone, and requires acyl chain remodeling of the PE methylation‐derived PC (see section below).The molecular species profiles of PC synthesized Recently, we reviewed the current knowledge of lipid acyl chain remodeling in yeast via the Kennedy pathway PC can be de‐acylated by a phospholipase A to lysoPC, which can subsequently be de‐acylated to glycerophosphocholine (GPC) by a phospholipase B. PC can also be directly de‐acylated to GPC by a phospholipase B. GPC can either be catabolized to choline and glycerol‐3‐phosphate in vivo by Wagner & Paltauf using the incorporation of exogenous radiolabeled fatty acids cho2∆opi3∆) with a switchable Kennedy pathway (PGAL1‐PCT1) it was shown that cells can survive on exogenous diC8‐PC in the absence of active PC synthesis. Moreover, diC8‐PC was shown to be remodeled to the regular PC species such as 32:2, 32:1, 34:2, and 34:1. However, cell growth is delayed and the content of PC is diminished to less than 10% of total compared to over 40% in the wild‐type, indicating that the uptake of diC8‐PC followed by PC remodeling is not sufficiently efficient to sustain proper PC levels and optimal cell growth The de‐acylation of PC and subsequent re‐acylation of lysoPC or GPC was first demonstrated pct1Δ background newly synthesized PC is mainly diunsaturated as in wild‐type and contains virtually no monounsaturated species. However, the steady‐state PC profile does contain monounsaturated species sn‐1 position of newly synthesized PC contains almost exclusively C16:1, whereas steady‐state PC contains C16:0, C16:1, C18:0, or C18:1 at the sn‐1 position pct1∆ background using the overexpression of SCT1 to increase the level of saturated acyl chains, revealed that the monounsaturated PC species are increased to nearly steady‐state levels at the expense of diunsaturated PC species in approximately 1 doubling time, involving approximately 40% of the newly synthesized PC molecular species PLB1 was shown to slow down this process, indicating a remodeling mechanism via the turnover of PC to GPC. Subsequent acylation of GPC to lysoPC by Gpc1p As mentioned above, in the in vivo. Biophysical studies on model membranes consisting of (mixtures of) well‐defined synthetic lipids or purified lipid extracts have provided much information on how lipid physico‐chemical properties determine membrane physical parameters such as fluidity, bilayer thickness, intrinsic curvature, and lateral pressure profile. It is important to note that most of these parameters are interrelated and therefore a single parameter cannot be modified without affecting the other parameters to some extent. Nevertheless, these studies have enormously contributed to our understanding of the role of lipids in the complex environment of a biological membrane. In the following, we will focus on the various ways in which the phospholipid molecular species profile can affect membrane physical properties and we will discuss possible implications with respect to regulation of membrane lipid composition in vivo.Understanding how physico‐chemical properties of membrane lipids affect membrane properties is key to understanding the importance of the phospholipid molecular species profile for maintaining membrane function in vitro and in vivo. Depending on the temperature, a lipid bilayer can exist in different phases. The two major, biologically relevant phases are the liquid crystalline phase (Lα), a fluid and disordered phase, and the gel phase (Lβ), which forms at lower temperature and is a more ordered and rigid phase. The phase transition temperature (Tm) from the gel to the liquid crystalline phase has been determined for many different lipids, using model membranes composed of pure lipid molecular species.Membrane fluidity is probably the most extensively studied physical property of membranes, both Tm increases with increasing lipid acyl chain length cis‐double bonds in the acyl chains Tm is larger going from a completely saturated lipid species to a monounsaturated species than from a mono‐ to diunsaturated species  phase transition temperature . When mixed with bilayer lipids, type II lipids can be forced to assemble in a bilayer allowing, e.g., mitochondrial membranes to form bilayers despite their very high content of the nonbilayer lipids PE and CL. However, due to the intrinsic curvature of type II lipids, this will induce curvature stress cho2opi3 mutant, PE levels increase and PE takes over as the major membrane PL. In parallel, the proportion of monounsaturated PE species increases at the expense of diunsaturated species, and a shortening of the average acyl chain length is observed. As diunsaturated PE species and PE species with longer acyl chains have stronger nonbilayer propensity, as shown by a lower TH  lateral pressure between the head groups is reduced because of the smaller effective head group volume of the nonbilayer lipids. As a consequence, the lipids will pack more tightly, leading to an increase in the lateral pressure between the acyl chains.The lateral pressure profile of a membrane affects membrane protein structure and stability OLE1 transcriptional regulator Mga2p and the ER stress sensor Ire1p have been elucidated Thorough genetic studies in combination with lipid analysis and lipidomics studies have provided insight into phospholipid biosynthesis and its regulation. However, mechanisms such as the regulation of acyl chain remodeling, the sensing of membrane physico‐chemical properties, and its downstream signaling to the lipid biosynthetic machinery largely remain to be elucidated. Recently, the molecular mechanisms of membrane sensing by the via the Henry regulatory circuit controlled by Opi1p sensing the PA level is well characterized for a set of lipid biosynthetic genes containing UASINO in their promoter Although transcriptional regulation sn‐regioisomers Recent advances in lipidome analysis have provided opportunities to identify lipid characteristics that were previously difficult to distinguish, such as double bond localization and


We observed the superconductor-to-insulator transition by reducing the thickness of Sr2RuO4 single crystals. The appearance of a gap structure in the insulating phase implies local superconductivity. Fractional quantized conductance was observed without an external magnetic field. We found an anomalous induced voltage with temperature and thickness dependence, and the induced voltage exhibited switching behavior when we applied a magnetic field. We suggest that there was fractional magnetic-field-induced electric polarization in the interlayer. These anomalous results are related to topological invariance. The fractional axion angle Θ = π/6 was determined by observing the topological magneto-electric effect in the Bose-insulating phase of Sr2RuO4 nanofilms.The quantum anomaly that breaks the symmetry, for example the parity and the chirality, in the quantization leads to a physical quantity with a topological Chern invariant. We report the observation of a Chern structure in the Bose-insulating phase of Sr We have reported that the current-voltage (I–V) curves in the microscale chiral single domain of Sr2RuO4 with submicron thickness violate parity due to the excitation of the Majorana-Wyle fermions along the one-dimensional chiral edge current21e2/h in two-(or quasi-two-) dimensional chiral superconducting layers, we have investigated electric transport properties by using chiral single domain size Sr2RuO4 with nanoscale thickness2RuO4 thickness to the nanometer range.Layered perovskite Sr2RuO4 systems is the two superconducting phases with Tc ~ 1.5 and 3 K. Although pure Sr2RuO4 single crystals exhibit a Tc of about 1.5 K, enhancement to about 3 K has been reported in Sr2RuO4-Ru eutectic systems2RuO4 without Ru inclusions, an enhanced Tc of around 3 K is observed when measuring uniaxial pressure effects along the c axis2RuO4 single crystals allow access to both topological quantum states and the pairing mechanism itself in chiral p-wave superconductors.One unsolved problem in Sr2RuO4 single crystal nanofilms based on the anomalous transport properties observed for the in-plane and interlayer directions. By reducing the Sr2RuO4 thickness to the nanometer range, we found that a fractional quantum Hall resistance of h/4e2 − h/2e2 occurred as a consequence of the spontaneous Hall current without an external magnetic field. The gap structure below 3 K shows localized superconducting islands connected by tunnel junctions. The anomalous induced voltage and the switching behavior were observed as a function of temperature and thickness under zero bias current for an applied magnetic field parallel to the c axis. The applied magnetic field induced electric polarization in the interlayer of Sr2RuO4 nanofilms. In Sr2RuO4 with a nanoscale thickness, we suggested that the fractional topological magneto-electric effect occurs in three (quasi-two) dimensions, which is characterized by the fractional axion angle (coefficient) Θ = π/6 of the E · B term in the chiral anomaly.In this paper, we report the emergence of a Chern structure in the Bose-insulating phase of Srρxx for various thicknesses of exfoliated Sr2RuO4 films. 2. In general, bulk (thick) superconductors exhibit zero longitudinal resistivity below Tc. We have observed zero resistivity below Tc = 1.59 K for microscale Sr2RuO4 with a thickness of 340 nm, which is consistent with the Tc of bulk Sr2RuO4 crystals15Tc. The result shows that the flow of vortices can be caused by quantum fluctuations of the superconducting phase282RuO4 nanofilms as a result of reducing sample thickness to the nanometer range.Rxy and longitudinal resistance Rxx in sample A with a thickness of 17 nm. With decreasing temperature, the Hall resistance increased with a log T dependence, and reached about 12.1 kΩ below 0.8 K. Interestingly, in the absence of an external magnetic field, we measured a Hall resistance of 12.1 kΩ, which is close to the quantum resistance of h/2e2. A Hall resistance of Rxy = 6.8 kΩ ~ h/4e2 was also observed in sample B . Surprisingly, below 3 K, clear gap structures were observed in both the Hall and the longitudinal conductance spectra. The temperature dependence of the superconducting gap extracted from the coherence peak width in the tunneling spectra is shown in the inset of 2RuO4 systems37383940Tc = 1.5 K reminds us of the pseudo-gap state in cuprate superconductors and the 3 K phase in Sr2RuO4 systems2425262RuO4 nanofilms below 3 K due to the quantum fluctuation of the superconducting phase θ as shown in Vxy as well as Vxx is dependent on the current. The field dependence of the tunneling spectra for sample A at 0.46 K is shown in 2RuO4 single crystal (sample C) shows neither the suppression of Tc nor an enhancement to 3 K  state below 3 K, the anomalous voltage appeared as shown in the inset of V − B characteristics in t was reduced, the induced voltage increased, which is fitted well by the relation V = 1/t. Since spontaneous voltage is related to sample thickness, we can eliminate the contribution of the thermoelectric voltage and a junction at the Au/Sr2RuO4 interface or at a microcrack. Furthermore, the switching behavior of an induced voltage was observed in the region between ±1.0 and ±5.8 T. The solid red line in B − V characteristics. μV and switching behavior under an applied magnetic field as shown in Quantum fluctuations near a quantum critical region bring out the topological properties of systems. To examine the topological magneto-electric coupling in the Bose-insulating phase of SrB − V curves from the measured B − V characteristics. The results for sample A are shown in VSW represents the switching voltage component of the induced voltage. As the magnetic field increases, the anomalous switching voltage VSW increases above ~±1 T. The VSW for the applied magnetic field reaches its maximum value near ±3.5 T, and then decreases. Intriguingly, the switching voltage was clearly observed below 1.5 K. We think that the observation of this anomalous switching voltage is related to the intrinsic properties of the chiral p-wave superconductor Sr2RuO4, because the feature appears below a Tc of about 1.5 K in bulk Sr2RuO4.To analyze the switching phenomena in more detail, we subtract the average 2RuO4. In sample C as shown in V and VSW to vanish, which is consistent with μ0Hc2 in bulk Sr2RuO4. On the other hand, in μ0Hc2 reported for pure bulk Sr2RuO4. To reveal whether or not this anomalous behavior is an intrinsic characteristic of Sr2RuO4, we need to consider the physical properties of the 3 K phase. The 3 K superconductivity in Sr2RuO4-Ru systems induces the enhancement of the upper critical field to Hc3 = 1.7 Hc2B − V characteristics in our nanofilms because we observed the gap structure in a high field of 4 T as shown in We discuss the enhancement of the critical magnetic field in relation to the existence of localized superconducting islands of Srx2−SrxCuO4, which is considered an indication of the charge-cluster glass state2RuO4, the dynamics of the chiral domains generates switching behaviors as a function of magnetic field or time2RuO4 fluctuate in space and time. At present, some possible explanations for the results are conceivable. Below, we discuss in detail a topological interpretation in terms of our results as an interesting possibility.Now let us consider the switching behavior of the resistivity (voltage) in superconducting systems. The Hall resistivity at very low temperature exhibited erratic switching in the vicinity of the quantum superconductor-to-insulator transition in LaE · B in the topological term. First, let us discuss the fractional quantum Hall conductance in a zero magnetic field in Sr2RuO4 nanofilms. From Rxy = 12.1 kΩ and Rxx = 5.3 kΩ for sample A, the sheet Hall conductance 2 layer was determined by using the relation d = 6 Å (=c/2). By considering the number of sheets ns, we represent the Hall conductance as 2RuO4 nanofilms exhibit Hall conductance quantized in the unit of conductance quantum p-wave superconductivity can be developed by the induced CS-term of the effective Lagrangian in topological field theory162RuO4 has yet to be observed experimentally for the following reasons. The Hall resistance in a thick sample becomes smaller than that in a thin film sample, and the observation of the ensemble averaging of the Hall current in multi-chiral domains is complicated. With respect to these issues, an important solution is for the sample to consist of nanoscale thin films of ~10 layers2μm2RuO4 nanofilms, we can observe the fractional quantum Hall conductance near the quantum critical region.To understand the origin of the anomalous behaviors, we address (I) the fractional quantum Hall conductance in the conducting layer without a magnetic field, (II) the fractional magnetic-induced electric polarization in the interlayer, and (III) the integral value of V|/ΔB in 2RuO4 interlayer. We assume that our layered sample is a superconducting bilayer system in order to discuss the possibility of magneto-electric polarization. The capacitance C = εIA/d = 10 fF of the interlayer is estimated, where εI/ε0 ~ 10 is the interlayer dielectric constant, d (=6 Å) is the interlayer distance in Sr2RuO2, and A is the area 0.14 μm2 between the electrodes. We determined the effective electric charge Q∗ ~ 8 e from the induced voltage of |ΔV| = 63 μV. Moreover, we obtained the effective magnetic flux Using the result shown by the fitted slope of |Δ2RuO4 nanofilms to understand the relationship between fractional Hall conductance and electric polarization. The chiral anomaly7p/q with p, q odd integers is predicted by analogy with fractional quantum Hall effects45Below, we consider the topological magneto-electric effect in the Bose-insulating phase of SrE (=ΔV/d) · B represented by the blue square region E · B represented by the red rhombic region E · B is 6(h/e2) at 0.43 K. Similarly, at temperatures below 2.0 K, we estimated the value of E · B in both the square region in a low magnetic field and the rhombic region provided by the voltage switching. We confirmed that the E · B values are the same in the blue and red regions at each temperature. The correspondence of the E · B value is also reproduced in sample C in E · B value. The data points are fitted by an exponential curve. We believe that the E · B value exists in the T = 0, (III) the E · B value is about 12 h/e2, which is comparable to (I) the zero-magnetic-field quantum Hall conductance SΘ, we obtained the fractional angle N is an integer multiple. For the fractional angle Θ = π/6, the quantum Hall conductance 2RuO4 layers using the results of both the fractional Hall conductance and the fractional magneto-electric polarization in the fractional axion angle. Namely, these observations correspond to the fractional Chern structure caused by the quantum anomaly in Sr2RuO4.Furthermore, we discuss the possibility of the fractionalization of the topological Θ-parameter. Using the experimental results, we discuss the integral value 2RuO4 nanofilms by observing the fractional Hall conductance on the surface and the fractional electric polarization in the interlayer. In a zero magnetic field, a quantized fractional Hall resistance was observed in the local superconducting state below 3 K. Under zero bias current, we found the anomalous induced voltage and the switching behavior of the induced voltage for an applied magnetic field parallel to the c axis. The applied magnetic field generated electric polarization in the interlayer of Sr2RuO4. The results suggest the presence of the fractional topological magneto-electric effect in Sr2RuO4 nanofilms. The fractional axion angle Θ = π/6 in the topological Θ-term was also determined.In conclusion, we have detected the emergence of the Chern structure in Bose-insulating Sr2RuO4 thin films, we synthesized Sr2RuO4 single crystals with a solid phase reaction, and selected single crystals with no embedded Ru metal and with homogeneity by observing optical microscope images, chemical composition and crystal orientation2RuO4 single crystal nanofilms were exfoliated on a SiO2(300 nm)/Si substrate. We then fabricated gold electrodes using standard electron beam lithography methods. Scanning electron micrographs of the Sr2RuO4 nanofilms (samples A and B) are shown in 3He refrigerator. All leads were equipped with RC filters (R = 1 kΩ and C = 22 nF). The longitudinal and Hall voltages and the differential conductance were measured with a nanovoltmeter  and a lock-in-amplifier , respectively. The up and down magnetic field sweep rate was 0.102 mT/sec.To obtain nanoscale SrHow to cite this article: Nobukane, H. et al. Chern structure in the Bose-insulating phase of Sr2RuO4 nanofilms. Sci. Rep.7, 41291; doi: 10.1038/srep41291 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


ABA) plays significant roles in integrating environmental signals with embryogenesis, germination, seedling establishment, the floral transition and the adaptation of plants to stressful environments by modulating stomatal movement and stress‐responsive gene expression. ABA signalling consists of ABA perception, signal transduction and ABA‐induced responses. ABA receptors such as members of the PYR/PYL family, group A type 2C protein phosphatases (as negative regulators), SnRK2 protein kinases (as positive regulators), bZIP transcription factors and ion channels are key components of ABA signalling. Post‐translational modifications, including dephosphorylation, phosphorylation and ubiquitination, play important roles in regulating ABA signalling. In this review, we focus on the roles of post‐translational modifications in ABA signalling. The studies presented provide a detailed picture of the ABA signalling network.The plant phytohormone abscisic acid ( The phytohormone abscisic acid (ABA) is a key regulator of plant growth and development and of the responses of plants to biotic and abiotic stresses , which are localized to the cytoplasm, plasma membrane or nucleus /PYR1‐like (PYLs)/regulatory components of ABA receptors (RCAR) family (hereafter referred to as PYR/PYLs), has greatly enhanced our understanding of ABA signalling  and the phosphorylation activity of sucrose nonfermenting 1 (SNF1)‐related protein kinases 2 (SnRK2s) are required for ABA signalling  ligases has been found to be important in ABA perception, ABA signal transduction and the induction of ABA responses. PYR/PRLs, PP2Cs, type 2A protein phosphatases (PP2As), transcription factors and proteins encoded by ABA‐responsive genes are targeted for E3 Ub ligase‐mediated polyubiquitination and degraded by the 26S proteasome. Several types of E3 Ub ligases are involved in ABA signalling. In this review, we focus on recent discoveries related to the post‐translational regulation of ABA signalling.Arabidopsis, which are clustered into 10 groups   double mutant plants exhibit enhanced ABA‐mediated growth inhibition, increased ABA‐responsive gene induction and diminished water loss  has been found to interact with ABI1 and ABI2 during ABA signalling ‐like kinase that can phosphorylate and regulate the activity, stability and subcellular localization of a number of proteins in diverse systems , a single‐subunit RING‐type E3 Ub ligase, interacts directly with the ABA receptors PYR1 and PYL4  1 and RGLG5 have also been demonstrated to be involved in ABA signalling, which belong to RING E3 ligases  can be ubiquitinated and degraded via Ub‐mediated proteolysis. Further, several specific E3 ligases have been discovered  and ABA‐hypersensitive DCAF 1 (ABD1), the substrate receptors in CUL4‐RING E3 ligase complexes, are involved in ABA signalling , a RING‐type E3 ligase, negatively regulates ABA signalling by targeting bZIP transcription factors, including ABI5, ABF1 and ABF3, and the kinase CIPK26 for Ub‐mediated degradation , a C3H2C3‐type RING‐motif protein that functions as an E3 ligase. ABI3 is an unstable protein containing four functional domains: A1, B1, B2 and B3  target a class I homeobox‐leucine zipper transcription factor, ATHB6, for degradation  23, the RAD23/ABI3 complex or DSK2 to promote the association of ABI5 with the protease. ABA may stabilize ABI5 by preventing this association. Clearly, identifying the proteins that interact with RPN10 will be critical in defining how it helps to deliver appropriate cargo to the 26S proteasome  of ABA signalling. Dephosphorylation, phosphorylation and ubiquitination have all been reported to be involved in ABA signalling. After binding to ABA, PYR/PYLs interact physically with group A PP2Cs, disrupting the interaction between PP2Cs and SnRK2s, blocking the dephosphorylation activity of PP2Cs and activating SnRK2s to trigger downstream ABA responses. Multiple substrates of SnRK2s have been identified, including transcription factors, ion channel proteins, a potassium channel protein and a chromatin‐remodelling factor. The ubiquitination of ABA receptors and signalling molecules was recently reported, implying the importance of this modification in ABA signalling. However, certain problems must be addressed in order for us to fully understand the molecular networks involved in ABA signalling.et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., First, studies are needed to dissect the transcriptional, post‐transcriptional and post‐translational regulatory mechanisms of PYR/PYLs. Although it has been shown that PYL4, PYL8 and PYL9 are targeted by DDA1 for degradation by the 26S proteasome, PYR1 and PYL4 are substrates of RSL1, an E3 ubiquitin ligase; thus, the regulation of ABA receptors is far from clear  [grant number 31371222] and Doctoral Fund of Ministry of Education of China (RFDP) [grant number 20132103110004].