A novel single-base deletion of the RUNX Family Transcription Factor 2 gene associated with cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is a rare, autosomal dominant hereditary disorder characterized by skeletal malformations and dental abnormalities. The purpose of this study was to explore the functional role of a novel mutation in the pathogenesis of CCD. Genomic DNA was extracted from peripheral blood mononuclear cells collected from family members of a Chinese patient with CCD. An analysis of their RUNX Family Transcription Factor 2 (RUNX2) gene sequences was performed by PCR amplification and Sanger sequencing. The function of the mutant RUNX2 was studied by bioinformatics, real-time PCR, western blotting, and subcellular localization analysis. Sanger sequencing identified a novel single-base deletion (NM_001024630.4:c.132delG;NP_001019801.3: Val45Trpfs* 99) in the RUNX2 gene present in the Chinese patient with CCD. In vitro, functional studies showed altered protein localization and increased expression of mutant RUNX2 mRNA and mutant Runt-related transcription factor 2 (RUNX2). Luciferase reporter assay demonstrated that the novel RUNX2 mutations significantly increased the transactivation activity of RUNX2 on the osteocalcin gene promoter. In conclusion, we identified a patient with sporadic CCD carrying a novel deletion/frameshift mutation of the RUNX2 gene and performed screening and functional analyses to determine the cause of the CCD phenotype. This study provides new insights into the pathogenesis of CCD.3.

Large scale application of pulse oximeter and auscultation in screening of neonatal congenital heart disease.

PURPOSE: To conduct a retrospective evaluation of a large clinical implementation of combined pulse oximeter (POX) and cardiac auscultation as a fast-screening device for congenital heart disease (CHD). METHODS: Every newborn in a large maternity healthcare center received auscultation and POX screening within 24 hours after delivery. When an abnormal heart murmur or SpO2 level was detected, an echocardiogram was ordered to confirm the diagnosis of CHD. RESULTS: From January 1, 2018 to December 31, 2019, there were 44,147 livebirths at the studied hospital where 498 suspected CHD were identified: 27 newborns by POX screening and 471 by cardiac auscultation. The diagnosis was further confirmed in 458 neonates through echocardiogram. This result put forth an overall diagnosis rate of 92.0%. Cardiac auscultation detected the majority of CHD cases 438 (95.6%) while POX only screened 20 (4.4%) cases. Interestingly, no CHD case was detected by both auscultation examination and POX screening. Auscultation detected most of the common types of CHD, but POX excelled in identifying rare and critical cases. POX screening alone had a very low accuracy of 74.07% in positive predict value (PPV). On the other hand, auscultation functioned well in terms of PPV and negative predict value (NPV) (92.99 and 99.95%, respectively), but the addition of POX improved the overall screening performance resulting in 100% NPV. We also validate the finding with the data 6 months after the study period. CONCLUSION: Our study demonstrated that addition of pulse oximetry to routine cardiac auscultation could be used as an accurate and feasible screening for early screening of CHD in newborns in large-scale clinical practice.

Mapping Trap Dynamics in a CsPbBr3 Single-Crystal Microplate by Ultrafast Photoemission Electron Microscopy.

For versatile lead-halide perovskite materials, their trap states, both in the bulk and at the surface, significantly influence optoelectronic behaviors and the performance of the materials and devices. Direct observation of the trap dynamics at the nanoscale is necessary to understand and improve the device design. In this report, we combined the femtosecond pump-probe technique and photoemission electron microscopy (PEEM) to investigate the trap states of an inorganic perovskite CsPbBr3 single-crystal microplate with spatial-temporal-energetic resolving capabilities. Several shallow trap sites were identified within the microplate, while the deep traps were resolved throughout the surface. The results revealed high-defect tolerance to the shallow traps, while the surface dynamics were dominated by the surface deep traps. The ultrafast PEEM disclosed a full landscape of fast electron transfer and accumulation of the surface trap states. These discoveries proved the excellent electronic properties of perovskite materials and the importance of surface optimization.

Ultrafast Electron Cooling and Decay in Monolayer WS2 Revealed by Time- and Energy-Resolved Photoemission Electron Microscopy.

A comprehensive understanding of the ultrafast electron dynamics in two-dimensional transition metal dichalcogenides (TMDs) is necessary for their applications in optoelectronic devices. In this work, we contribute a study of ultrafast electron cooling and decay dynamics in the supported and suspended monolayer WS2 by time- and energy-resolved photoemission electron microscopy (PEEM). Electron cooling in the Q valley of the conduction band is clearly resolved in energy and time, on a time scale of 0.3 ps. Electron decay is mainly via a defect trapping process on a time scale of several picoseconds. We observed that the trap states can be produced and increased by laser illumination under an ultrahigh vacuum, and the higher local optical-field intensity led to the faster increase of trap states. The enhanced defect trapping could significantly modify the carrier dynamics and should be paid attention to in photoemission experiments for two-dimensional materials.

Vps4b heterozygous mice do not develop tooth defects that replicate human dentin dysplasia I.

BACKGROUND: Vacuolar protein sorting-associated protein 4B (VPS4B) is a member of the ATP enzyme AAA protein family, and is mainly involved in protein degradation and cell membrane fusion. Recently, a dominant mutation in this gene was identified in human dentin dysplasia type I (DD-I). Herein, we report the generation of Vps4b knockout (Vps4b KO) mice; however, the homozygous Vps4b KO mutation was embryonic lethal at the early stages of embryo development, and we therefore report the results of heterozygous mutant mice. RESULTS: Mice heterozygous for Vps4b did not develop tooth defects replicating human DD-I. Immunohistochemistry showed that gene KO was successful, as there was decreased expression of Vps4b in heterozygous mice; hematoxylin and eosin (H&E) staining also showed that the width of the pre-dentin zone was increased in heterozygous mice, although the arrangement of the odontoblasts was not significantly different from wild-type (WT) mice. However, H&E staining showed no obvious abnormalities in the bones of heterozygous mice. Moreover, stereomicroscopic and X-ray radiography results indicated no abnormal manifestations in teeth or bones. Furthermore, statistical analysis of the volume and density of dentin and enamel, as well as skeletal analysis, including the volume and separation of trabecular bone analyzed by micro-CT, all showed no differences between Vps4b heterozygotes and WT mice. In addition, there also were no significant differences in bone or cartilage mineralization as evaluated by Alcian blue-Alizarin red staining. CONCLUSIONS: The heterozygous Vps4b KO mice do not develop tooth defects that replicate human DD-I and this is likely to be due to differences in tooth development between the two species. Consequently, further studies are needed to determine whether mice are an appropriate animal model for human tooth diseases.

Understanding photoluminescence of metal nanostructures based on an oscillator model.

Scattering and absorption properties of metal nanostructures have been well understood based on the classic oscillator theory. Here, we demonstrate that photoluminescence of metal nanostructures can also be explained based on a classic model. The model shows that inelastic radiation of an oscillator resembles its resonance band after external excitation, and is related to the photoluminescence from metallic nanostructures. The understanding based on the classic oscillator model is in agreement with that predicted by a quantum electromagnetic cavity model. Moreover, by correlating a two-temperature model and the electron distributions, we demonstrate that both one-photon and two-photon luminescence of the metal nanostructures undergo the same mechanism. Furthermore, the model explains most of the emission characteristics of the metallic nanostructures, such as quantum yield, spectral shape, excitation polarization and power dependence. The model based on an oscillator provides an intuitive description of the photoluminescence process and may enable rapid optimization and exploration of the plasmonic properties.

[Analysis of DSPP gene mutation in a Chinese pedigree affected with hereditary dentinogenesis imperfecta].

OBJECTIVE: To analyze the clinical phenotype of a Chinese pedigree affected with hereditary dentinogenesis imperfecta and mutation of dentin sialophosphoprotein (DSPP) gene. METHODS: Affected members underwent intraoral photography, dental film and panoramic radiography. Genomic DNA was extracted from peripheral venous blood samples. Coding regions of the DSPP gene were subjected to PCR amplification and Sanger sequencing. Functional effect of the mutation was predicted with SIFT and PolyPhen-2. The tertiary structure of wild type and mutant proteins were predicted by Swiss-Port. RESULTS: A heterozygous c.50C to T (p.P17L) mutation was identified in exon 2 of the DSPP gene in the proband and her father. The same mutation was not found among 200 unrelated healthy controls. The Pro-17 residues and its surrounding positions in DSPP are highly conserved across various species. The mutation was predicted to be damaging to the structure of DSPP protein. CONCLUSION: The c.50C to T (p.P17L) mutation of the DSPP gene probably underlies the disease in this pedigree. Above finding has expanded the spectrum of DSPP gene mutations and provided a basis for genetic counseling and prenatal diagnosis for this family.

[Study on the Fast Quantitative Analysis of the Content of DME Adulterated in LPG].

A new analytical method of analyzing dimethyl ether (DME) content in liquefied petroleum gas (LPG) is proposed in this paper. An unsolved problem about quick detection of the composition of LPG has been settled with this method. A set of precise preparation apparatus for DME/ LPG solution and a set of quickly analytical system of LPG based on near infrared technology were designed. The analytical equipment can be conveniently connected to the sampling cylinder because it can bear 3.5 MPa pressure. Oblique projection algorithm was used to separate the pure spectra of DME from that of the LPG's solutions. The standard curve of the concentration of DME (c) has been built by using the Intensity (I) of pure signal of DME in the LPG solution and the concentrations. The correlation coefficient of the equation is 0.999 4. The result of external validation shows that the relative error is less than 2.0%. The new method has the advantages such as fast, easy and noneed of expensive multivariate modeling.

[Research on Rapid Discrimination of Edible Oil by ATR Infrared Spectroscopy].

A rapid discrimination method of edible oils, KL-BP model, was proposed by attenuated total reflectance infrared spectroscopy. The model extracts the characteristic of classification from source data by KL and reduces data dimension at the same time. Then the neural network model is constructed by the new data which as the input of the model. 84 edible oil samples which include sesame oil, corn oil, canola oil, blend oil, sunflower oil, peanut oil, olive oil, soybean oil and tea seed oil, were collected and their infrared spectra determined using an ATR FT-IR spectrometer. In order to compare the method performance, principal component analysis (PCA) direct-classification model, KL direct-classification model, PLS-DA model, PCA-BP model and KL-BP model are constructed in this paper. The results show that the recognition rates of PCA, PCA-BP, KL, PLS-DA and KL-BP are 59.1%, 68.2%, 77.3%, 77.3% and 90.9% for discriminating the 9 kinds of edible oils, respectively. KL extracts the eigenvector which make the distance between different class and distance of every class ratio is the largest. So the method can get much more classify information than PCA. BP neural network can effectively enhance the classification ability and accuracy. Taking full of the advantages of KL in extracting more category information in dimension reducing and the features of BP neural network in self-learning, adaptive, nonlinear, the KL-BP method has the best classification ability and recognition accuracy and great importance for rapidly recognizing edible oil in practice.

[Rapid Quantitative Analysis of Content of the Additive in Gasoline for Motor Vehicles by Near-Infrared Spectroscopy].

A new rapid quantitative method for the determination of oxygenates and the compounds not included in the national standard in gasoline using near-infrared spectroscopy is raised by this paper. This method combine near-infrared spectroscopy with oblique projection. This experiment choose four different types of gasoline, including reconcile gasoline, FCC refined gasoline, reformed gasoline and desulfurizing gasoline. Prepare series gasoline samples containing different concentrations and different types of compounds. Using FTIR spectrometer to measure those samples and got transmission spectrums. Oblique projection method could separate quantity spectral signal from mixed spectrum signal, and using projection to calculate and analyze the separated signal to obtain the content of measured component. The deviation between this method and the real content is low, the absolute error is less than 0.8 and the relative error is less than 8%. For the actual gasoline samples, compare results of this method with gas chromatography, the absolute error are less than 0.85 and the relative error are less than 6.85%. This method solves the problem of general multivariate calibration methods. It is very significant for the development of rapid detection technology using NIR suitable for on-site and the improvement of the quality of gasoline.

[A correction method of baseline drift of discrete spectrum of NIR].

In the present paper, a new correction method of baseline drift of discrete spectrum is proposed by combination of cubic spline interpolation and first order derivative. A fitting spectrum is constructed by cubic spline interpolation, using the datum in discrete spectrum as interpolation nodes. The fitting spectrum is differentiable. First order derivative is applied to the fitting spectrum to calculate derivative spectrum. The spectral wavelengths which are the same as the original discrete spectrum were taken out from the derivative spectrum to constitute the first derivative spectra of the discrete spectra, thereby to correct the baseline drift of the discrete spectra. The effects of the new method were demonstrated by comparison of the performances of multivariate models built using original spectra, direct differential spectra and the spectra pretreated by the new method. The results show that negative effects on the performance of multivariate model caused by baseline drift of discrete spectra can be effectively eliminated by the new method.

[A new multivariate quantitative method of spectral analysis for multicomponent system].

In the spectral analysis, a large-scale application of the traditional multivariate analysis methods has been limited by both high cost and poor applicability of the calibration models. A new multivariate analysis method was proposed for multicomponent systems in the present paper. Determining MTBE content in gasoline solution by infrared spectroscopy was studied. The spectra of five kinds of gasoline and their 50 narrow distillation fractions were used to build the background library. The oblique projection algorithm was applied to the spectra of MTBE gasoline solution samples to extract the purespectral signal of MTBE in the solution. A unary linear regression curve was built between the pure spectral signals of MTBE and their concentrations with a correlation coefficient of 0.995 2 and an intercept of 0.025. Compared with the orthogonal projection algorithm method and PLS model method, a large amounts of calibration samples and complex model are no longer needed by the new method which is simpler, more accurate and with better applicability.

[Rapid quantitative analysis of hydrocarbon composition of furfural extract oils using attenuated total reflection infrared spectroscopy].

A set of rapid analysis system for hydrocarbon composition of heavy oils was designed using attenuated total reflection FTIR spectrometer and chemometrics to determine the hydrocarbon composition of furfural extract oils. Sixty two extract oil samples were collected and their saturates and aromatics content data were determined according to the standard NB/SH/T0509-2010, then the total contents of resins plus asphaltenes were calculated by the subtraction method in the percentage of weight. Based on the partial least squares (PLS), calibration models for saturates, aromatics, and resin+asphaltene contents were established using attenuated total reflection FTIR spectroscopy, with their SEC, 1.43%, 0.91% and 1.61%, SEP, 1.56%, 1.24% and 1.81%, respectively, meeting the accuracy and repeatability required for the standard. Compared to the present standard method, the efficiency of hydrocarbon composition analysis for furfural extract oils is significantly improved by the new method which is rapid and simple. The system could also be used for other heavy oil analysis, with excellent extension and application foreground.

[Study on rapid quantitative analysis of the active ingredient in ABC extinguishing agent and type identification of extinguishing agent powders using near infrared spectroscopy].

A new quantitative method to determine the NH4H2PO4 in ABC powder extinguishing agent and to distinguish between ABC and BC powder extinguishing agents using near infrared diffuse reflectance spectroscopy is proposed. A PLS calibration model for the NH4H2PO4 content in extinguishing agent powder was established, with RMSECV = 2.1, RMSEP = 2.4. An identification model for ABC and BC powder extinguishing agents was built by SIMCA and the identification accuracy rate is 100%. This method, compared to the present standard method, has the characteristics of rapidness and easy operation, whichis fit for the quantitative analysis and type distinguishing of the fire products on site.

Imaging and Controlling Photonic Modes in Perovskite Microcavities.

Perovskite microcavities have excellent photophysical properties for integrated optoelectronic devices, such as nanolasers. Imaging and controlling the photonic modes within the cavity are fundamentally important to understand and develop applications. Here, photoemission electron microscopy (PEEM) is used to image the photonic modes within optical microcavities with a nanometer-scale spatial resolution. From a CsPbBr3 microcavity, hybrid mode patterns are observed. Spatial frequency spectrum analysis on the patterns uncovers the characteristic cavity modes, which are modeled with transverse magnetic (TM) and transverse electric (TE) waves, and assigned to exciton-polariton modes. Based on this understanding, the light focus in a designed microcavity is imaged in real space and controlled by the light field polarization. The study confirms that the cavity modes in perovskites can be effectively observed by the PEEM technique under resonant excitation, which, in turn, promotes the design of optoelectronic devices based on perovskite microcavities.

Spectromicroscopy and imaging of photoexcited electron dynamics at in-plane silicon pn junctions.

The ultrafast spatiotemporal imaging of photoexcited electrons is essential to understanding interfacial electron dynamic processes. We used time- and energy-resolved photoemission electron microscopy (PEEM) to investigate the photoexcited electron dynamics at multiplex in-plane silicon pn junctions. We found that the measured kinetic energy of photoelectrons from n-type regions is higher than that from p-type regions owing to different work functions. Interestingly, the kinetic energy of outer n-type regions is higher than that of inner n-type regions, which is caused by the reverse bias induced by photoemission. Time-resolved PEEM results reveal different evolution rates of hot electrons in different doping regions. The rise time of the n-type (outer n-type) regions is faster than that of the p-type (inner n-type) regions. So, closed doping patterns can influence the electron spectra and dynamics at the micro-nano scale. These results help us to understand the ultrafast dynamics of carriers at in-plane interfaces and optimize optoelectronic integrated devices with complex heterojunctions.

Steering valley-polarized emission of monolayer MoS2 sandwiched in plasmonic antennas.

Monolayer transition metal dichalcogenides have intrinsic spin-valley degrees of freedom, making it appealing to exploit valleytronic and optoelectronic applications at the nanoscale. Here, we demonstrate that a chiral plasmonic antenna consisting of two stacked gold nanorods can modulate strongly valley-polarized photoluminescence (PL) of monolayer MoS2 in a broad spectral range at room temperature. The valley-polarized PL of the MoS2 using the antenna can reach up to ~47%, with approximately three orders of PL magnitude enhancement within the plasmonic nanogap. Besides, the K and K' valleys under opposite circularly polarized light excitation exhibit different emission intensities and directivities in the far field, which can be attributed to the modulation of the valley-dependent excitons by the chiral antenna in both the excitation and emission processes. The distinct features of the ultracompact hybrid suggest potential applications for valleytronic and photonic devices, chiral quantum optics, and high-sensitivity detection.

In situ scattering of single gold nanorod coupling with monolayer transition metal dichalcogenides.

We investigated in situ the interaction between a single gold nanorod and monolayer transition metal dichalcogenides (TMDCs) by atomic force microscopy nanomanipulation and single-particle spectroscopy. We observed that the resonant scattering peak of the hybrid redshifted, the full width at half maximum of the scattering resonance narrowed and the scattering intensity increased compared with those of the same nanorod before coupling with monolayer TMDCs. These results were understood with the aid of finite-difference time-domain simulations, the Fano model, and the classical oscillator model. Also, the spectral features varied with the distance between the nanorod and TMDCs, and the interaction was mainly attributed to the resonant energy transfer effect. Our findings clarify the influence of TMDCs on the plasmonic resonance and contribute to a deeper understanding of the plasmon exciton interaction. These results are beneficial for the optimization of plasmonic nanostructure-TMDC hybrids and their corresponding applications.

Hybrid Metal-Dielectric Nano-Aperture Antenna for Surface Enhanced Fluorescence.

A hybrid metal-dielectric nano-aperture antenna is proposed for surface-enhanced fluorescence applications. The nano-apertures that formed in the composite thin film consist of silicon and gold layers. These were numerically investigated in detail. The hybrid nano-aperture shows a more uniform field distribution within the apertures and a higher antenna quantum yield than pure gold nano-apertures. The spectral features of the hybrid nano-apertures are independent of the aperture size. This shows a high enhancement effect in the near-infrared region. The nano-apertures with a dielectric gap were then demonstrated theoretically for larger enhancement effects. The hybrid nano-aperture is fully adaptable to large-scale availability and reproducible fabrication. The hybrid antenna will improve the effectiveness of surface-enhanced fluorescence for applications, including sensitive biosensing and fluorescence analysis.

Whole exome sequencing identifies an AMBN missense mutation causing severe autosomal-dominant amelogenesis imperfecta and dentin disorders.

Tooth development is a complex process that involves precise and time-dependent orchestration of multiple genetic, molecular, and cellular interactions. Ameloblastin (AMBN, also named "amelin" or "sheathlin") is the second most abundant enamel matrix protein known to have a key role in amelogenesis. Amelogenesis imperfecta (AI [MIM: 104500]) refers to a genetically and phenotypically heterogeneous group of conditions characterized by inherited developmental enamel defects. The hereditary dentin disorders comprise a variety of autosomal-dominant genetic symptoms characterized by abnormal dentin structure affecting either the primary or both the primary and secondary teeth. The vital role of Ambn in amelogenesis has been confirmed experimentally using mouse models. Only two cases have been reported of mutations of AMBN associated with non-syndromic human AI. However, no AMBN missense mutations have been reported to be associated with both human AI and dentin disorders. We recruited one kindred with autosomal-dominant amelogenesis imperfecta (ADAI) and dentinogenesis imperfecta/dysplasia characterized by generalized severe enamel and dentin defects. Whole exome sequencing of the proband identified a novel heterozygous C-T point mutation at nucleotide position 1069 of the AMBN gene, causing a Pro to Ser mutation at the conserved amino acid position 357 of the protein. Exfoliated third molar teeth from the affected family members were found to have enamel and dentin of lower mineral density than control teeth, with thinner and easily fractured enamel, short and thick roots, and pulp obliteration. This study demonstrates, for the first time, that an AMBN missense mutation causes non-syndromic human AI and dentin disorders.