Neural Correlates of Analogical Reasoning on Syntactic Patterns.

Analogical reasoning is central to thought and learning. However, previous neuroscience studies have focused mainly on neural substrates for visuospatial and semantic analogies. There has not yet been research on the neural correlates of analogical reasoning on syntactic patterns generated by the syntactic rules, a key feature of human language faculty. The present investigation took an initial step to address this paucity. Twenty-four participants, whose brain activity was monitored by fMRI, engaged in first-order and second-order relational judgments of syntactic patterns as well as simple and complex working memory tasks. After scanning, participants rated the difficulty of each step during analogical reasoning; these ratings were related to signal intensities in activated regions of interest using Spearman correlation analyses. After prior research, differences in activation levels during second-order and first-order relational judgments were taken as evidence of analogical reasoning. These analyses showed that analogical reasoning on syntactic patterns recruited brain regions consistent with those supporting visuospatial and semantic analogies, including the anterior and posterior parts of the left middle frontal gyrus, anatomically corresponding to the left rostrolateral pFC and the left dorsolateral pFC. The correlation results further revealed that the posterior middle frontal gyrus might be involved in analogical access and mapping with syntactic patterns. Our study is the first to investigate the process of analogical reasoning on syntactic patterns at the neurobiological level and provide evidence of the specific functional roles of related regions during subprocesses of analogical reasoning.

Non-invasive diagnosis of primary Sjögren's syndrome using ultrasonography and transcriptome biomarkers.

Diagnosing primary Sjögren's syndrome (pSS) is difficult due to clinical heterogeneity and the absence of non-invasive specific biomarkers. To develop non-invasive pSS diagnosis methods that integrate classic clinical indexes, major salivary gland ultrasonography (SGUS), and gene expression profiles shared by labial gland and peripheral blood, we conducted a study on a cohort of 358 subjects. We identified differentially expressed genes (DEGs) in glands and blood that were enriched in defense response to virus and type I interferon production pathways. Four upregulated DEGs common in glands and blood were identified as hub genes based on the protein-protein interaction networks. A random forest model was trained using features, including SGUS, anti-SSA/Ro60, keratoconjunctivitis sicca tests, and gene expression levels of MX1 and RSAD2. The model achieved comparable pSS diagnosis accuracy to the golden standard method based on labial gland biopsy. Our findings implicate this novel model as a promising diagnosis technique of pSS.

Pump-probe strategy for instantaneous 2D detection of CH3 in flames using a single laser.

Visualization of the reaction zone of flames using CH radicals as markers is restricted by the low concentration of CH in fuel-lean conditions. To address this, methyl radicals (CH3) are employed as a substitution of CH in premixed methane/air flames. A pump-probe method was adopted with the pump laser photolyzing CH3 and the probe laser detecting the photolyzed CH (X2Π) fragments. Laser excitation scans were performed to ensure that the fluorescence detected was from CH only. Visualization of the reaction zone of flames was accomplished by a CH3 photofragmentation laser-induced fluorescence technique in fuel-lean conditions (the equivalence ratio of 0.4), where CH planar laser-induced fluorescence did not work in both laminar and turbulent jet flames. The proposed pump-probe method of CH3 can be used to visualize the reaction zone of hydrocarbon combustion under both fuel-lean and fuel-rich conditions with a superior signal-to-noise ratio.

A Statistical Framework for Mapping Risk Genes from De Novo Mutations in Whole-Genome-Sequencing Studies.

Analysis of de novo mutations (DNMs) from sequencing data of nuclear families has identified risk genes for many complex diseases, including multiple neurodevelopmental and psychiatric disorders. Most of these efforts have focused on mutations in protein-coding sequences. Evidence from genome-wide association studies (GWASs) strongly suggests that variants important to human diseases often lie in non-coding regions. Extending DNM-based approaches to non-coding sequences is challenging, however, because the functional significance of non-coding mutations is difficult to predict. We propose a statistical framework for analyzing DNMs from whole-genome sequencing (WGS) data. This method, TADA-Annotations (TADA-A), is a major advance of the TADA method we developed earlier for DNM analysis in coding regions. TADA-A is able to incorporate many functional annotations such as conservation and enhancer marks, to learn from data which annotations are informative of pathogenic mutations, and to combine both coding and non-coding mutations at the gene level to detect risk genes. It also supports meta-analysis of multiple DNM studies, while adjusting for study-specific technical effects. We applied TADA-A to WGS data of ∼300 autism-affected family trios across five studies and discovered several autism risk genes. The software is freely available for all research uses.

Stereoscopic high-speed imaging of iron microexplosions and nanoparticle-release.

In this work, the combustion behavior of seeded iron particles (d50 = 70 µm) in a laminar diffusion flame was studied in a modified Mckenna flat-flame burner. Two high speed cameras in stereo configuration allowed 3D position and 3D velocity measurements of burning iron particles as well as 3D evaluation of particle microexplosions. Microexplosive processes are important since it can affect both combustion stability and formation of product components. The observed microexplosions happened before particle extinction resulting in change of trajectories, velocities, radiation intensities and fragmentation into smaller particles. It was observed for the first time that fragments of these microexplosions tend to produce planar structures. A frequent release phenomenon was observed during the iron particle combustion using magnified thermal radiation imaging and high-speed shadowgraphy. This release phenomenon was indirectly confirmed with scanning electron microscopy of combust products, revealing multiple cracked particle shells and hollow structures. Black body radiation characteristics was observed indicating the release being in condensed phase and emission spectroscopy identified FeO as intermediate species during combustion. The observed release is believed to mainly consist of iron-oxide nanoparticles formed in the homogenous reaction between vapor iron and oxidizers.

Distinct genetic patterns of shared and unique genes across four neurodevelopmental disorders.

Neurodevelopmental disorders, including autism spectrum disorder (ASD), intellectual disability (ID), developmental disorders (DD) and epileptic encephalopathy (EE), have a strong clinical comorbidity, which indicates a common genetic etiology across various disorders. However, the underlying genetic mechanisms of comorbidity and specificity remain unknown across neurodevelopmental disorders. Based on de novo mutations, we compared systematically the functional characteristics between shared and unique genes under these disorders, as well as the spatiotemporal trajectory of development in brain and common molecular pathways of all shared genes. We observed that shared genes present more constrained against functional rare genetic variation, and harbor more pathogenic rare variants than do unique genes in each disorder. Furthermore, 71 shared genes formed two clusters related to synaptic transmission, transcription regulation and chromatin regulator. Particularly, we also found that two core genes STXBP1 and SCN2A, that were shared by the four neurodevelopmental disorders showed prominent pleiotropy. Our findings shed light on the shared and specific patterns across neurodevelopmental disorders and will enable us to further comprehend the etiology and provide valuable information for the diagnosis of neurodevelopmental disorders.

Nonrandom occurrence of multiple de novo coding variants in a proband indicates the existence of an oligogenic model in autism.

PURPOSE: Elucidating the genetic architecture underlying autism spectrum disorder (ASD) will aid in the understanding of its genetic etiology and clinical diagnosis. METHODS: A comprehensive set of coding de novo variants (DNVs) from 4504 trios with ASD and 3012 control/sibling trios from several large-scale sequencing studies were collected and combined. Multiple in-depth analyses including DNVs burden, clinical phenotypes, and functional networks underlying the combined data set were used to evaluate the nonrandom occurrence of multiple extreme DNVs (loss-of-function and damaging missense variants) in the same patients. RESULTS: We observed a significant excess of multiple extreme DNVs among patients with ASD compared with controls. Meanwhile, patients with ASD carrying 2+ extreme DNVs had significantly lower IQs than patients carrying 0 or 1 DNV. Moreover, much closer functional connectivity than expected was observed among 2 or more genes with extreme DNVs from the same individuals. In particular, we identified 56 key genes as more confident ASD genes compared with other known ASD genes. In addition, we detected 23 new ASD candidate genes with recurrent DNVs, including VIP, ZWILCH, MSL2, LRRC4, and CAPRIN1. CONCLUSIONS: Our findings present compelling statistical evidence supporting an oligogenic model and provide new insights into the genetic architecture of ASD.

Trio-based exome sequencing arrests de novo mutations in early-onset high myopia.

The etiology of the highly myopic condition has been unclear for decades. We investigated the genetic contributions to early-onset high myopia (EOHM), which is defined as having a refraction of less than or equal to -6 diopters before the age of 6, when children are less likely to be exposed to high educational pressures. Trios (two nonmyopic parents and one child) were examined to uncover pathogenic mutations using whole-exome sequencing. We identified parent-transmitted biallelic mutations or de novo mutations in as-yet-unknown or reported genes in 16 probands. Interestingly, an increased rate of de novo mutations was identified in the EOHM patients. Among the newly identified candidate genes, a BSG mutation was identified in one EOHM proband. Expanded screening of 1,040 patients found an additional four mutations in the same gene. Then, we generated Bsg mutant mice to further elucidate the functional impact of this gene and observed typical myopic phenotypes, including an elongated axial length. Using a trio-based exonic screening study in EOHM, we deciphered a prominent role for de novo mutations in EOHM patients without myopic parents. The discovery of a disease gene, BSG, provides insights into myopic development and its etiology, which expands our current understanding of high myopia and might be useful for future treatment and prevention.

Dual-laser-induced Breakdown Thermometry via Sound Speed Measurement：A New Procedure for Improved Spatiotemporal Resolution.

Measurement of acoustic waves from laser-induced breakdown has been developed as gas thermometry in combustion atmospheres. In the measurement, two laser-induced breakdown spots are generated and the local gas temperature between these two spots is determined through the measurement of the sound speed between them. In the previous study, it was found that the local gas breakdown can introduce notable system uncertainty, about 5% to the measured temperature. To eliminate the interference, in present work, a new measurement procedure was proposed, where two individual laser pulses with optimized firing order and delay time were employed. With the new measurement procedure, the system uncertainty caused by local gas breakdown can be largely avoided and the temporal and spatial resolutions can reach up to 0.5 ms and 10 mm, respectively. The improved thermometry, dual-laser-induced breakdown thermometry (DLIBT), was applied to measure temperatures of hot flue gases provided by a multijet burner. The measured temperatures covering the range between 1000 K and 2000 K were compared with the ones accurately obtained through the two-line atomic fluorescence (TLAF) thermometry with a measurement uncertainty of ~3%, and a very good agreement was obtained.

Quantitative SO2 Detection in Combustion Environments Using Broad Band Ultraviolet Absorption and Laser-Induced Fluorescence.

Spectrally resolved ultraviolet (UV) absorption cross sections of SO2 in combustion environments at temperatures from 1120 to 1950 K were measured for the first time in well-controlled conditions through applying broad band UV absorption spectroscopy in specially designed one-dimensional laminar flat flames. The temperature was observed to have a significant effect on the absorption cross-section profiles at wavelength shorter than 260 nm, while at the longer wavelength side, the absorption cross-section profiles have much less dependence on temperature. The absorption cross section at 277.8 nm with a value of 0.68 × 10-18 cm2/molecule was suggested for the evaluation of the SO2 concentration because of the weak dependence on temperature. To make spatially resolved measurements, laser-induced fluorescence (LIF) of SO2 excited by a 266 nm laser was investigated. Spectrally resolved LIF signal was analyzed at different temperatures. The LIF signal showed strong dependence on temperature, which can potentially be used for temperature measurements. At elevated temperatures, spatially resolved LIF SO2 detection up to a few ppm sensitivity was achieved. Combining UV broad band absorption spectroscopy and LIF, highly sensitive and spatially resolved quantitative measurements of SO2 in the combustion environment can be achieved.

Ultraviolet Absorption Cross Sections of KOH and KCl for Nonintrusive Species-Specific Quantitative Detection in Hot Flue Gases.

An understanding of potassium chemistry in energy conversion processes supports the development of complex biomass utilization with high efficiency and low pollutant emissions. Potassium exists mainly as potassium hydroxide (KOH), potassium chloride (KCl), and atomic potassium (K) in combustion and related thermochemical processes. We report, for the first time, the measurement of the ultraviolet (UV) absorption cross sections of KOH and KCl at temperatures between 1300 K and 1800 K, using a newly developed method. Using the spectrally resolved UV absorption cross sections, the concentrations of KOH and KCl were measured simultaneously. In addition, we measured the concentrations of atomic K using tunable diode laser absorption spectroscopy, both at 404.4 and 769.9 nm. The 404.4 nm line was utilized to expand the measurement dynamic range to higher concentrations. A constant amount of KCl was seeded into premixed CH4/air flames with equivalence ratios varied from 0.67 to 1.32, and the concentrations of KOH, KCl, and atomic K in the hot flue gas were measured nonintrusively. The results indicate that these techniques can provide comprehensive data for quantitative understanding of the potassium chemistry in biomass combustion/gasification.

Correction: Nonrandom occurrence of multiple de novo coding variants in a proband indicates the existence of an oligogenic model in autism.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Instantaneous one-dimensional equivalence ratio measurements in methane/air mixtures using femtosecond laser-induced plasma spectroscopy.

Equivalence ratio is one of the most significant parameters in combustion flow fields. In this paper, femtosecond laser-induced plasma spectroscopy (FLIPS) technique for instantaneous one-dimensional local equivalence ratio measurements were performed. By measuring the spatially resolved spectra of FLIPS, we found that the spectral peak area ratios of CH (431 nm)/N2 (337 nm), CH (431 nm)/N2 (357 nm), and CH (431 nm)/O (777 nm) can be utilized to achieve one-dimensional local equivalence ratio measurements. Among them, the CH peak at ~431 nm and the O peak at ~777 nm are strong enough to be used to achieve single-shot measurements, which is important to turbulent flow fields. Furthermore, systematic experiments were performed by using FLIPS in both laminar and turbulent flow fields. The FLIPS technique features the abilities of instantaneous one-dimensional quantitative measurements, high spatial resolution, and no Bremsstrahlung interference.

Enhancement of femtosecond laser-induced plasma fluorescence using a nanosecond laser.

We demonstrate the enhancement of femtosecond (fs) laser-induced filaments in air and nitrogen flow fields using a nanosecond (ns) laser. With the ns laser being imposed on the filaments, the length and the emission intensity of the filaments were largely increased. Temporally resolved spectra of the enhanced filaments were obtained. The results show that the ns laser enhanced the short-lifetime fluorescence of nitrogen, which comes from the transition processes of N2 +(B2Σu + - X2Σg +), N2(B3Пg - A3Σu +) and N2(C3Пu - B3Пg). However, it had little effect on the long-lifetime chemiluminescence, which mainly comes from reactions such as N2(A3Σu +) + N2(A3Σu +) → N2(X1Σg +, v = 0) + N2(B3Пg). A possible explanation of this phenomenon is given, and this phenomenon might have potential applications in instantaneous one-dimensional measurements of various species in gas flow fields.

Ammonia measurements with femtosecond laser-induced plasma spectroscopy.

Femtosecond laser-induced plasma spectroscopy for in situ ammonia (NH3) measurements was demonstrated in NH3/N2 mixtures. When a femtosecond laser at 800 nm was focused at the flow field, the parent NH3 molecules would be photolyzed to generate electronics excited NH fragments, and then indirect measurements of NH3 could be realized by detecting the NH fluorescence (A3Π-X3Σ-) at 336 nm. A detection limit of 205 ppm was achieved. This work is the first attempt, to the best of our knowledge, for ammonia measurements with a femtosecond laser, and the results are useful for the development of ammonia diagnostics.

Femtosecond laser-induced plasma spectroscopy for combustion diagnostics in premixed ammonia/air flames.

Ammonia (NH3) is a sustainable fuel with excellent emission characteristics. Hence, it is important to develop diagnostic techniques for NH3 combustion. In this paper, femtosecond laser-induced plasma spectroscopy (FLIPS) was performed in premixed NH3/air flames. The plasma emission spectra induced by the femtosecond laser in the flame and the chemiluminescence spectra of the flame itself were both measured. Through calibration, we found that the spectral intensity ratio of NH (336 nm)/N2 (337 nm) could be used for equivalence ratio measurements in NH3 combustion flow fields. This work is the first attempt at using a femtosecond laser-based technique for NH3 combustion diagnostics.

mirDNMR: a gene-centered database of background de novo mutation rates in human.

De novo germline mutations (DNMs) are the rarest genetic variants proven to cause a considerable number of sporadic genetic diseases, such as autism spectrum disorders, epileptic encephalopathy, schizophrenia, congenital heart disease, type 1 diabetes, and hearing loss. However, it is difficult to accurately assess the cause of DNMs and identify disease-causing genes from the considerable number of DNMs in probands. A common method to this problem is to identify genes that harbor significantly more DNMs than expected by chance, with accurate background DNM rate (DNMR) required. Therefore, in this study, we developed a novel database named mirDNMR for the collection of gene-centered background DNMRs obtained from different methods and population variation data. The database has the following functions: (i) browse and search the background DNMRs of each gene predicted by four different methods, including GC content (DNMR-GC), sequence context (DNMR-SC), multiple factors (DNMR-MF) and local DNA methylation level (DNMR-DM); (ii) search variant frequencies in publicly available databases, including ExAC, ESP6500, UK10K, 1000G and dbSNP and (iii) investigate the DNM burden to prioritize candidate genes based on the four background DNMRs using three statistical methods (TADA, Binomial and Poisson test). As a case study, we successfully employed our database in candidate gene prioritization for a sporadic complex disease: intellectual disability. In conclusion, mirDNMR (https://www.wzgenomics.cn/mirdnmr/) can be widely used to identify the genetic basis of sporadic genetic diseases.

Filamentary anemometry using femtosecond laser-extended electric discharge - FALED.

We demonstrate a non-contact spatiotemporally resolved comprehensive method for gas flow velocity field measurement: Filamentary Anemometry using femtosecond Laser-extended Electric Discharge (FALED). A faint thin plasma channel was generated in ambient air by focusing an 800-nm laser beam of 45 fs, which was used to ignite a pulsed electric discharge between two electrodes separated over 10 mm. The power supplier provided a maximum voltage up to 5 kV and was operated at a burst mode with a current duration of less than 20 ns and a pulse-to-pulse separation of 40 µs. The laser-guided thin filamentary discharge plasma column was blowing up perpendicularly by an air jet placed beneath in-between the two electrodes. Although the discharge pulse was short, the conductivity of the plasma channel was observed to sustain much longer, so that a sequence of discharge filaments was generated as the plasma channel being blown up by the jet flow. The sequential bright thin discharge filaments can be photographed using a household camera to calculate the flow velocity distribution of the jet flow. For a direct comparison, a flow field measurement using FLEET [Appl. Opt. 50, 5158 (2011)] was also performed. The results indicate that the FALED technique can provide instantaneous nonintrusive flow field velocity measurement with good accuracy.

mirVAFC: A Web Server for Prioritizations of Pathogenic Sequence Variants from Exome Sequencing Data via Classifications.

Exome sequencing has been widely used to identify the genetic variants underlying human genetic disorders for clinical diagnoses, but the identification of pathogenic sequence variants among the huge amounts of benign ones is complicated and challenging. Here, we describe a new Web server named mirVAFC for pathogenic sequence variants prioritizations from clinical exome sequencing (CES) variant data of single individual or family. The mirVAFC is able to comprehensively annotate sequence variants, filter out most irrelevant variants using custom criteria, classify variants into different categories as for estimated pathogenicity, and lastly provide pathogenic variants prioritizations based on classifications and mutation effects. Case studies using different types of datasets for different diseases from publication and our in-house data have revealed that mirVAFC can efficiently identify the right pathogenic candidates as in original work in each case. Overall, the Web server mirVAFC is specifically developed for pathogenic sequence variant identifications from family-based CES variants using classification-based prioritizations. The mirVAFC Web server is freely accessible at https://www.wzgenomics.cn/mirVAFC/.

Comprehensive CO detection in flames using femtosecond two-photon laser-induced fluorescence.

We demonstrate a femtosecond two-photon laser-induced fluorescence (fs-TPLIF) technique for sensitive CO detection, using a 230 nm pulse of 9 µJ and 45 fs. The advantages of fs-TPLIF in excitation of molecular species were analyzed. Spectra of CO fs-TPLIF were recorded in stable laminar flames spatially resolved across the flame front. A hot band (1, n) together with the conventional band (0, n) of the B→A transitions were observed in the burned zone and attributed to the broadband nature of the fs excitation. The CO fs-TPLIF signal recorded across the focal point of the excitation beam shows a relatively flat intensity distribution despite of the steep laser intensity variation, which is beneficial for CO imaging in contrast to nanosecond and picosecond TPLIF. This phenomenon can be explained by photoionization, which over the short pulse duration dominates the population depletion of the excited B state due to the high peak power, but only contributes in total a negligible X state depletion due to the low pulse energy. Single-shot CO fs-TPLIF images in methane/air flames were recorded by imaging the broadband fluorescence. The results indicate that fs-TPLIF is a promising tool for CO imaging in flames.