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Abstract Ultrafast lasers have become powerful tools in various fields, and increasing their fundamental repetition rates to the gigahertz (GHz) level holds great potential for frontier scientific and industrial applications. Among various schemes, passive mode-locking in ultrashort-cavity fiber laser is promising for generating GHz ultrashort pulses (typically solitons), for its simplicity and robustness. However, its pulse energy is far lower than the critical value of the existing theory, leading to open questions on the mode-locking mechanism of GHz fiber lasers. Here, we study the passive mode-locking in GHz fiber lasers by exploring dynamic gain depletion and recovery (GDR) effect, and establish a theoretical model for comprehensively understanding its low-threshold mode-locking mechanism with multi-GHz fundamental repetition rates. Specifically, the GDR effect yields an effective interaction force and thereby binds multi-GHz solitons to form a counterpart of soliton crystals. It is found that the resulting collective behavior of the solitons effectively reduces the saturation energy of the gain fiber and permits orders of magnitude lower pulse energy for continuous-wave mode-locking (CWML). A new concept of quasi-single soliton defined in a strongly correlated length is also proposed to gain insight into the dynamics of soliton assembling, which enables the crossover from the present mode-locking theory to the existing one. Specifically, two distinguishing dynamics of Q-switched mode-locking that respectively exhibit rectangular- and Gaussian-shape envelopes are theoretically indicated and experimentally verified in the mode-locked GHz fiber laser through the measurements using both the standard real-time oscilloscope and emerging time-lens magnification. Based on the proposed criterion of CWML, we finally implement a GDR-mediated mode-locked fiber laser with an unprecedentedly high fundamental repetition rate of up to 21 GHz and a signal-to-noise ratio of 85.9 dB.

Abstract Background Gliomas are recognized as the most frequent type of malignancies in the central nervous system, and efficacious prognostic indicators are essential to treat patients with gliomas and improve their clinical outcomes. The chemokine (C‐C motif) ligand 2 (CCL2) is a promising predictor for glioma malignancy and progression. However, at present, the methods to evaluate CCL2 expression level are invasive and operator‐dependent. Objective It was expected to noninvasively predict CCL2 expression levels in malignant glioma tissues by magnetic resonance imaging (MRI)‐based radiomics and assess the association between the developed radiomics model and prognostic indicators and related genes. Methods MRI‐based radiomics was used to predict CCL2 expression level using data obtained from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA) databases. A support vector machine (SVM)‐based radiomics model and a logistic regression (LR)‐based radiomics model were used to predict the radiomics score, and its correlation with CCL2 expression level was analyzed. Results The results revealed that there was an association between CCL2 expression level and the overall survival of cases with gliomas, and bioinformatics correlation analysis showed that CCL2 expression level was highly correlated with disease‐related pathways, such as mTOR signaling pathway, cGMP‐PKG signaling pathway, and MAPK signaling pathway. Both SVM‐ and LR‐based radiomics data robustly predicted CCL2 expression level, and radiomics scores could also be used to predict the overall survival of patients. Moreover, the high/low radiomics scores were highly correlated with the known glioma‐related genes, including CD70, CD27, and PDCD1. Conclusion An MRI‐based radiomics model was successfully developed, and its clinical benefits were confirmed, including the prediction of CCL2 expression level and patients' prognosis.

Dissipative soliton molecules (DSMs) are of great interest for studying the complexity of nonlinear optical problems as they can map with the matter molecules for making interdisciplinary analogies. In contrast to strongly bound DSMs that have a short time separation between the bound solitons, the complex dynamics and underlying binding mechanism of loosely bound soliton molecules (LBSMs) with orders of magnitude longer time separation remain open questions. To this end, here, we explore real-time spectroscopy using a dispersive temporal interferometer (DTI) to visualize the dynamics of LBSMs in a mode-locked fiber laser and unveil their underlying phase-evolving mechanism. The DTI enables fringe-resolved spectroscopy in real time of the LBSM’s evolution by creating duplicates of the LBSM that results in a much closer time separation between the individual solitons of the LBSM. The real-time evolution of the LBSM’s phase exhibits a diverging sliding landscape, which is theoretically and experimentally proved to be closely associated with gain dynamics. Based on the understanding of its phase dynamics, we finally demonstrate programmable phase-encoding modulation of the LBSM through gain control. These efforts not only shed light on understanding the mechanism of long-range interactions in LBSMs but also provide an alternative approach for all-optical information processing.

Abstract Background Low-pass genome sequencing (LP GS) has shown distinct advantages over traditional methods for the detection of mosaicism. However, no study has systematically evaluated the accuracy of LP GS in the detection of mosaic aneuploidies and copy number variants (CNVs) in prenatal diagnosis. Moreover, the influence of sequencing depth on mosaicism detection of LP GS has not been fully evaluated. Methods To evaluate the accuracy of LP GS in the detection of mosaic aneuploidies and mosaic CNVs, 27 samples with known aneuploidies and CNVs and 1 negative female sample were used to generate 6 simulated samples and 21 virtual samples, each sample contained 9 different mosaic levels. Mosaic levels were simulated by pooling reads or DNA from each positive sample and the negative sample according to a series of percentages (ranging from 3 to 40%). Then, the influence of sequencing depth on LP GS in the detection of mosaic aneuploidies and CNVs was evaluated by downsampling. Results To evaluate the accuracy of LP GS in the detection of mosaic aneuploidies and CNVs, a comparative analysis of mosaic levels was performed using 6 simulated samples and 21 virtual samples with 35 M million (M) uniquely aligned high-quality reads (UAHRs). For mosaic levels > 30%, the average difference (detected mosaic levels vs. theoretical mosaic levels) of 6 mosaic CNVs in simulated samples was 4.0%, and the average difference (detected mosaic levels vs. mosaic levels of Y chromosome) of 6 mosaic aneuploidies and 15 mosaic CNVs in virtual samples was 2.7%. Furthermore, LP GS had a higher detection rate and accuracy for the detection of mosaic aneuploidies and CNVs of larger sizes, especially mosaic aneuploidies. For depth evaluation, the results of LP GS in downsampling samples were compared with those of LP GS using 35 M UAHRs. The detection sensitivity of LP GS for 6 mosaic aneuploidies and 15 mosaic CNVs in virtual samples increased with UAHR. For mosaic levels > 30%, the total detection sensitivity reached a plateau at 30 M UAHRs. With 30 M UAHRs, the total detection sensitivity was 99.2% for virtual samples. Conclusions We demonstrated the accuracy of LP GS in mosaicism detection using simulated data and virtual samples, respectively. Thirty M UAHRs (single-end 35 bp) were optimal for LP GS in the detection of mosaic aneuploidies and most mosaic CNVs larger than 1.48 Mb (Megabases) with mosaic levels > 30%. These results could provide a reference for laboratories that perform clinical LP GS in the detection of mosaic aneuploidies and CNVs.

Abstract Most variations in the human genome refer to single-nucleotide variation (SNV), small fragment insertions and deletions, and genomic copy number variation (CNV). Many human diseases including genetic disorders are associated with variations in the genome. These disorders are often difficult to be diagnosed because of their complex clinical conditions, therefore, an effective detection method is needed to facilitate clinical diagnosis and prevent birth defects. With the development of high-throughput sequencing technology, the method of targeted sequence capture chip has been extensively used owing to its high throughput, high accuracy, fast speed, and low cost. In this study, we designed a chip that potentially captured the coding region of 3043 genes associated with 4013 monogenic diseases, with an addition of 148 chromosomal abnormalities that can be identified by targeting specific regions. To assess the efficiency, a strategy of combining the BGISEQ500 sequencing platform with the designed chip was utilized to screen variants in 63 patients. Eventually, 67 disease-associated variants were found, 31 of which were novel. The results of the evaluation test also show that this combined strategy complies with the requirements of clinical testing and has proper clinical application value.

Abstract Observing the dynamics of 3D soliton molecules can hold great opportunities for unveiling the mechanism of molecular complexity and other nonlinear problems. In spite of this fantastic potential, real-time visualization of their dynamics occurring on femtosecond-to-picosecond time scales is still challenging, particularly when high-spatiotemporal-resolution and long-term observation are required. In this work, we observe the real-time speckle-resolved spectral-temporal dynamics of 3D soliton molecules for a long time interval using multispeckle spectral-temporal measurement technology. Diverse real-time dynamics of 3D soliton molecules are captured for the first time, including the speckle-resolved birth, spatiotemporal interaction, and internal vibration of 3D soliton molecules. Further studies show that nonlinear spatiotemporal coupling associated with a large average-chirp gradient over the speckled mode profile plays a significant role in these dynamics. These efforts may shed new light on decomposing the complexity of 3D soliton molecules, and create an analogy between 3D soliton molecules and chemical molecules.

To address the structural concerns of a 12.0 m-span landing assembled single-tube frame (LASF) for Chinese solar greenhouses subjected to snow loads, the internal forces and deformations of LASF and its reinforced counterpart (RLASF) were numerically simulated to determine the ultimate bearing capacities (Lu) and the failure loads (Lf). During the simulations, steel tubes were modeled as beam188 elements and cables as link180 elements. The frame constraints and the connections were assumed to be fixed supports and rigid, respectively. The loads were determined according to the Chinese standard (GB51183-2016). Simulations revealed that the LASF and RLASF primarily withstand bending moments and are prone to strength failures under snow loads. Both exhibited lower Lu and Lf under non-uniform snow loads than under uniform snow loads. The results also indicated that crop loads could deteriorate the structural safety of the LASF and RLASF. Lu and Lf were found to be proportional to the section modulus of the tubes. The effects of wind loads and initial geometry imperfections on Lf of the LASF and RLASF can be neglected. Furthermore, the RLASF exhibited higher Lf compared to the LASF. Steel usage of the RLASF could be further reduced by replacing circular tubes with rectangular tubes, making the RLASF a feasible option for constructing Chinese solar greenhouses.

IntroductionDue to the shortage of land and water resource, optimization of systems for production in commercial greenhouses is essential for sustainable vegetable supply. The performance of lettuce productivity and the economic benefit in greenhouses using a soil-based system (SBS) and a hydroponic production system (HPS) were compared in this study.MethodsExperiments were conducted in two identical greenhouses over two growth cycles (G1 and G2). Three treatments of irrigation volumes (S1, S2, and S3) were evaluated for SBS while three treatments of nutrient solution concentration (H1, H2, and H3) were evaluated for HPS; the optimal levels from each system were then compared.Results and discussionHPS was more sensitive to the effects of environmental temperature than SBS because of higher soil buffer capacity. Compared with SBS, higher yield (more than 134%) and higher water productivity (more than 50%) were observed in HPS. We detected significant increases in ascorbic acid by 28.31% and 16.67% and in soluble sugar by 57.84% and 32.23% during G1 and G2, respectively, compared with SBS. However, nitrate accumulated in HPS-grown lettuce. When the nutrient solution was replaced with fresh water 3 days before harvest, the excess nitrate content of harvested lettuce in HPS was removed. The initial investment and total operating cost in HPS were 21.76 times and 47.09% higher than those in SBS, respectively. Consideration of agronomic, quality, and economic indicators showed an overall optimal performance of the H2 treatment. These findings indicated that, in spite of its higher initial investment and requirement of advanced technology and management, HPS was more profitable than SBS for commercial lettuce production.

A two-channel, time–wavelength interleaved photonic analog-to-digital converter (PADC) system with a sampling rate of 10.4 GSa/s was established, and a concise method for measuring and data correcting the channel sampling timing walk-off of PADCs for signal recovery was proposed. The measurements show that for the two RF signals of f1 = 100 MHz and f2 = 200 MHz, the channel sampling timing walk-off was 12 sampling periods, which results in an ENOB = −0.1051 bits for the 100 MHz directly synthesized signal, while the ENOB improved up to 4.0136 bits using shift synthesis. In addition, the peak limit method (PLM) and normalization processing were introduced to reduce the impacts of signal peak jitter and power inconsistency between two channels, which further improve the ENOB of the 100 MHz signal up to 4.5668 bits. All signals were analyzed and discussed in both time and frequency domains. The 21.1 GHz signal was also collected and converted using the established two-channel PADC system with the data correction method, combining the PLM, normalization, and shift synthesis, showing that the ENOB increased from the initial −0.9181 to 4.1913 bits, which demonstrates that our method can be effectively used for signal recovery in channel-interleaved PADCs.

To address the issues of excessive heat loss from the roofs of multi-span greenhouses and high energy consumption for heating during winter production, we propose an approach for the external insulation of the roof of multi-span glass greenhouses and have developed an external insulation system (EIS) to practice this approach. The system achieved full coverage of the greenhouse roof through mechanized unfurling and furling of external thermal blankets, thereby achieving energy-saving insulation. This paper describes the overall design and working method of the EIS, providing detailed design and structural parameters for critical components such as the traction rope transmission mechanism and the rail-type sealing structure. Through a system verification experiment, the specifications of the traction rope were determined and the rationality of the EIS’s thermal blanket unfurling and furling time was confirmed. An insulation performance experiment indicated that the average heat flux of the greenhouse roof covered with the external thermal blanket over 14 continuous nights was 54.2 W/m2, compared with 198.6 W/m2 for a single-layer glass roof. Covering the roof with the external thermal blanket reduced heat loss from the glass roof by 72.7%. The average heat flux of the roof of the Venlo-type multi-span greenhouse with double-layer internal insulation was 99.9 W/m2 during the same period, indicating that the heat loss from the roof using external insulation was only 50.3%. This study provides a novel thermal insulation approach and an energy-saving system for multi-span greenhouses.

Vertical farming (VF) is an emerging cultivation frame that maximizes total plant production. However, the high energy-consuming artificial light sources for plants growing in the lower and middle layers significantly affect the sustainability of the current VF systems. To address the challenges of supplementary lighting energy consumption, this study explored and optimized the structural design of cultivation frames in VF using parametric modeling, a light simulation platform, and a genetic algorithm. The optimal structure was stereoscopic, including four groups of cultivation trough units in the lower layer, two groups in the middle layer, and one group in the upper layer, with a layer height of 685 mm and a spacing of 350 mm between the cultivation trough units. A field experiment demonstrated lettuce in the middle and lower layers yielded 82.9% to 92.6% in the upper layer. The proposed natural light stereoscopic cultivation frame (NLSCF) for VF was demonstrated to be feasible through simulations and on-site lettuce cultivation experiments without supplementary lighting. These findings confirmed that the NLSCF could effectively reduce the energy consumption of supplemental lighting with the ensure of lettuce’s regular growth. Moreover, the designing processes of the cultivation frame may elucidate further research on the enhancement of the sustainability and efficiency of VF systems.

The effects of optical sampling pulse power, RF power, and electronic back-end bandwidth on the performance of time- and wavelength-interleaved photonic analog-to-digital converter (PADC) with eight-channel 41.6 GHz pulses have been experimentally investigated in detail. The effective number of bits (ENOB) and peak-to-peak voltage (Vpp) of converted 10.6 GHz electrical signals were used to characterize the effects. For the 1550.116 nm channel with 5.2 G samples per second, an average pulse power of 0 to −10 dBm input to the photoelectric detector (PD) has been tested. The Vpp increased with increasing pulse power. And the ENOB for pulse power −9~−3 dBm was almost the same and all were greater than four. Meanwhile, the ENOB decreased either when the pulse power was more than −2 dBm due to the saturation of PD or when the pulse power was less than −10 dBm due to the non-ignorable noise relative to the converted weak signal. In addition, RF powers of −10~15 dBm were loaded into the Mach–Zehnder modulator (MZM). The Vpp increased with the increase in RF power, and the ENOB also showed an increasing trend. However, higher RF power can saturate the PD and induce greater nonlinearity in MZM, leading to a decrease in ENOB, while lower RF power will convert weak electrical signals with more noise, also resulting in lower ENOB. In addition, the back-end bandwidths of 0.2~8 GHz were studied in the experiments. The Vpp decreased as the back-end bandwidth decreased from 8 to 3 GHz, and remained nearly constant for the bandwidth between the Nyquist bandwidth and the subsampled RF signal frequency. The ENOB was almost the same and all greater than four for a bandwidth from 3 to 8 GHz, and gradually increased up to 6.5 as the back-end bandwidth decreased from the Nyquist bandwidth to 0.25 GHz. A bandwidth slightly larger than the Nyquist bandwidth was recommended for low costs and without compromising performance. In our experiment, the −3 to −5 dBm average pulse power, about 10 dBm RF power, and 3 GHz back-end bandwidth were recommended to accomplish both a high ENOB more than four and large Vpp. Our research provides a solution for selecting optical sampling pulse power, RF power, and electronic back-end bandwidth to achieve low-cost and high-performance PADC.

Abstract Sepsis, caused by uncontrollable infection and inflammatory response, leads to more than 30 million infected patients and results in high morbidity worldwide every year. Currently, no efficient approaches have been developed for sepsis therapy due to antimicrobial resistance and inflammatory storm. Here, we report macrophages loaded with aggregated carbon dots (ACDs) in the lysosome, termed MCDs, to treat sepsis in immunosuppressive mice. The ACDs are constructed by negative CDs and amine‐abundant polyethyleneimine (PEI), enabling them to bear the strong antibacterial ability and enhanced photoluminescent efficacy. The ACDs are specifically located in the macrophage lysosomes, efficiently enhancing the multidrug‐resistant bacteria‐killing ability of MCDs. More importantly, the MCDs possess superior anti‐inflammatory effects such as reducing the number of pro‐inflammatory (M1) and stimulating anti‐inflammatory (M2) macrophages. These effects upregulate the inflammatory cytokines (TNF‐α, IL‐1β, IL‐4, and IL‐10), ultimately resulting in increased sepsis survival. Our work provides an intelligent approach to overcoming multidrug‐resistant bacteria‐induced infection from sepsis patients and paves a new avenue on employing nanoparticle‐loaded cells for combating inflammation‐related infection.

In this work, we present a high-power, high-repetition-rate, all-fiber femtosecond laser system operating at 1.5 $\unicode{x3bc}$ m. This all-fiber laser system can deliver femtosecond pulses at a fundamental repetition rate of 10.6 GHz with an average output power of 106.4 W – the highest average power reported so far from an all-fiber femtosecond laser at 1.5 $\unicode{x3bc}$ m, to the best of our knowledge. By utilizing the soliton-effect-based pulse compression effect with optimized pre-chirping dispersion, the amplified pulses are compressed to 239 fs in an all-fiber configuration. Empowered by such a high-power ultrafast fiber laser system, we further explore the nonlinear interaction among transverse modes LP01, LP11 and LP21 that are expected to potentially exist in fiber laser systems using large-mode-area fibers. The intermodal modulational instability is theoretically investigated and subsequently identified in our experiments. Such a high-power all-fiber ultrafast laser without bulky free-space optics is anticipated to be a promising laser source for applications that specifically require compact and robust operation.

Abstract Background The American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) presented technical standards for interpretation and reporting of constitutional copy-number variants in 2019 (the standards). Although ClinGen developed a web-based CNV classification calculator based on scoring metrics, it can only track and tally points that have been assigned based on observed evidence. Here, we developed AutoCNV (a semiautomatic automated CNV interpretation system) based on the standards, which can automatically generate predictions on 18 and 16 criteria for copy number loss and gain, respectively. Results We assessed the performance of AutoCNV using 72 CNVs evaluated by external independent reviewers and 20 illustrative case examples. Using AutoCNV, it showed that 100 % (72/72) and 95 % (19/20) of CNVs were consistent with the reviewers’ and ClinGen-verified classifications, respectively. AutoCNV only required an average of less than 5 milliseconds to obtain the result for one CNV with automated scoring. We also applied AutoCNV for the interpretation of CNVs from the ClinVar database and the dbVar database. We also developed a web-based version of AutoCNV (wAutoCNV). Conclusions AutoCNV may serve to assist users in conducting in-depth CNV interpretation, to accelerate and facilitate the interpretation process of CNVs and to improve the consistency and reliability of CNV interpretation.

Abstract Triple-negative breast cancer (TNBC) is one of the most daunting diseases, low toxicity and efficient approaches are in urgent demand. Herein, we developed degradable mesoporous manganese carbonate nanocubes (MnCO3 NCs), incorporated with survivin shRNA-expressing plasmid DNA (iSur-pDNA) and riboflavin (Rf), namely MRp NCs, for synergistic TNBC therapy. The MnCO3, itself, could generate O2 and CO2 under H2O2 and thus relieve the hypoxia and acidic tumor microenvironment (TME). Furthermore, the MnCO3 NCs exhibited high Rf loading capacity and iSur-pDNA delivery ability after polyethyleneimine modification. Specifically, MRp NCs decompose in TME, meanwhile they deprived the endogenous expression of survivin gene and significantly amplified the generation of reactive oxygen species after exposure to LED light, resulting in serious tumor destruction. The multifunctional MRp NCs with LED light-driven characters are able to provide a high efficiency, low toxicity and promising strategy for TNBC therapy.

A 1.5 μm ultralow‐noise single‐frequency fiber laser (SFFL) is realized based on a delay fiber phase‐locked method and the nonlinear amplification effect of a semiconductor optical amplifier (SOA). Via feedback locking of the phase jitter signal, the phase noise achieves the minimum value of −160 dB rad Hz−1/2 m−1 with a maximum reduction of 50 dB. Meanwhile, SOA reduces the intensity noise by a maximum of 65 dB, making it near the shot‐noise limit for frequencies above 40 kHz. To demonstrate this state‐of‐art SFFL with ultralow‐noise property, a high‐resolution fiber‐optic dynamic strain sensing based on a fiber‐based Michelson interferometer (FMI) is performed. As a result, the strain resolution reaches 26 fε Hz−1/2 in the 30–200 Hz band, which is improved by almost three orders of magnitude than that realized by a free‐running SFFL. To the best of the knowledge, this is the first time to achieve such a high‐resolution fiber‐optic dynamic strain sensor in the low‐frequency range utilizing the FMI system. This high‐resolution fiber‐optic strain sensing has promising applications in geophysics and biophotonics. Moreover, this ultralow‐noise SFFL is competitive for sophisticated applications, such as precise absolute distance measurement, quantum key distribution, and generating squeezed light.

ObjectiveIntraoperative hemorrhage represents a major risk during endoscopic intraventricular surgery. There are very few publications describing the maintenance of hemostasis during conventional endoscopic intraventricular surgery. Here, we designed a new mini-tubular port to combine intra- and extra-endoscopic techniques for endoscopic intraventricular surgery. With this new methodology, complicated techniques can be performed more efficiently with improved bleeding control.MethodsThe new mini-tubular port consists of an outer sheath and an obturator. The sheath is a thin-walled transparent cylinder that is 0.35 mm thick, 10 mm in diameter, and 90 mm in length. In this report, we describe the use of the mini-tubular port on 36 patients receiving endoscopic intraventricular surgery.ResultsThe study enrolled 36 patients, with a median age of 45 years (range: 0–72 years), of which 19 were male and 17 were female. Pure ETV (endoscopic third ventriculostomy) was performed in 20 patients and pure biopsy was performed in 2. ETV and biopsy were performed in five patients, ETV and the removal of cysticerci were performed in five, cyst fenestration was performed in one, ETV and cyst fenestration were performed in two, and ETV and shunt removal were performed in one patient. Two patients received microscopic surgery following endoscopic surgery during the same operation. A total of 17 patients (47%) underwent extra-endoscopic techniques. The median Karnofsky Performance Status (KPS) score of the patients prior to surgery was 50, while the median KPS score of the patients after one month of surgery was 80; these scores were significantly different (P

Observing 3D dissipative solitons is very challenging since their formation is stochastically and not repeatable. Here, the authors report the real-time multispeckle spectral-temporal observation of dissipative solitons in an optical fiber and analyze their long term evolution.

ObjectiveIt is well known that accurate location of the leak in the operation is crucial for repairing cerebrospinal fluid leakage. The study aims to investigate the application of intraoperative injection of normal saline through lumbar drainage in repairing complex leaks.MethodsThe fistulas of all patients with CSF leak were located by computed tomography cisternography (CTC) or heavy T2 magnetic resonance imaging (MRI) before surgery. Before anesthesia, the patient underwent lumbar drainage implantation, and then 20 ml of normal saline was slowly injected through the lumbar drainage to observe the patient's response. The surgical approach was designed based on the preoperative imaging data. When the operation was near to the suspected fistula, normal saline was injected through lumbar drainage (20 ml each time) to confirm the leak location. After CSF leak repair, saline was injected again to confirm whether the repair was successfully.ResultOf the 5 patients with complex leaks, 4 cases were repaired by transnasal endoscopy method, and 1 case was repaired by transnasal endoscopy method and epidural method. A total of 7 leaks were found during the operation. During the operation, 40–120 ml of normal saline was injected through lumbar drainage. Cauda equina neuralgia was developed in patients who received 120 ml normal saline, which was relieved by intrathecal injection of dexamethasone. During the follow-up of 3 months, 1 case suffered from brain abscess, which was controlled by vancomycin. There was no recurrence of rhinorrhea.ConclusionIntraoperative injection of normal saline through lumbar drainage can not only better expose the complex leak but also check the repair effect of the leak during transnasal endoscopic repair, which is effective and avoids side effects.

Due to three-dimensional, stochastic and non-repeatable transitions of dissipative solitons, it is challenging to monitor their full dynamics. Here, the authors resolve the dynamics by wavelength and along two spatial dimensions with up to trillions of frames per second using compressed ultrafast photography.

Raman-scattering microscopy: Fiber laser reduces the bulk An extremely stable fiber laser makes the high-resolution imaging technique of coherent Raman scattering (CRS) microscopy more practical for use in hospitals. CRS employs two pulsed laser beams to probe human tissues, providing structural and chemical information without the need for chemical labelling. However, current CRS systems require bulky laser systems that are impractical for clinical use. Now, Thomas Huser at Bielefeld University in Germany, with coworkers in Hong Kong (Kenneth K. Y. Wong) and the USA (Xiaoming Wei), have demonstrated CRS imaging using a compact pulsed fiber laser that provides excellent stability over a wide frequency range. Their system produced fast, high contrast images of living human cells and mouse tissues including the kidney and brain. Moreover, the fiber-based laser beam could easily be connected to other optical imaging systems such as endoscopes, to acquire images inside the body.

In this paper, we propose the motion recurring pattern analysis (MRPA) method for the lossless representation of a motion database at the segment level instead of the motion degree of freedom (DOF) level. First, we concatenate all the motions into a long sequence in the motion database, and we discover similar posture paths by building a matching trellis structure based on the randomized k-d tree. Second, horizontal segments of paths are suitably refined, based on a self-organizing map, to obtain the optimized segmentation for maximum compression gains. Third, by using the path as a connection agent, these segments are clustered into a forest of trees. With this forest structure, we obtain the prediction residuals (the differences between the nonroot branches and their parents), and the differences between neighboring residuals are encoded under floating-point compression. Relative to previous lossless compression methods, our approach can achieve a higher compression ratio with comparable decompression time costs.

Drip fertigation systems are a new technology to alleviate water shortages and improve fertilizer use efficiency. Emitter clogging is the main obstacle to their application. However, few efficient, safe, and environmentally friendly methods are available to alleviate clogging. In this study, we explored the effects of magnetized water irrigation on emitter clogging at different fertilization levels. Field experiments were conducted to study the patterns and clogging characteristics of drip irrigation systems during two planting seasons. The results showed that with an increase in fertilizer application, clogging of the emitter was aggravated. Magnetization treatment effectively relieved emitter clogging, which increased the average discharge variation rate (Dra) by 4.1–29.0% and 2.6–64.4%, respectively, and decreased the dry weight (DW) of the clogging substance by 14.0–64.6% and 15.0–75%, respectively, in the two planting seasons, compared with that of the non-magnetization treatment. The composition of the main clogging substances was estimated using X-rays; the results showed that quartz, silicate, and carbonate were the dominant substances that induced emitter clogging. Magnetization treatment can reduce the content of clogging substances and is thus a possible mechanism to alleviate clogging. Our study demonstrated that water magnetization treatment is an effective, chemical-free treatment method with great potential for clogging control in drip fertigation systems.

Strain sensors that can work sustainably and continuously without any external power supply are highly desirable for future wearable and implantable devices. Herein, a self‐powered stretchable strain sensor based on the integration of mechanoluminescent phosphors with an elastomer optical fiber is proposed and developed. This mechanoluminescent optical fiber is capable of emitting light just driven by external strain, without the need of an external light source or electric power. The strain‐induced emitted light can be collected and guided along the mechanoluminescent optical fiber. The sensor exhibits linear strain response up to 50% and high‐accuracy strain measurement (±1%). Moreover, this optical fiber strain sensor displays consistent signals over 10 000 stretch–release motion cycles, which demonstrates the good durability of the sensor. Due to the excellent light confinement of the elastomer optical fiber, this strain sensor is demonstrated in both bright‐ and dark‐field measurements, wearable gloves, and an implantable sensing device, thereby demonstrating potential as a promising technology for future self‐powered optical sensor systems.

In order to quantitatively describe the energy dissipation law of jointed rock mass, we obtained the jointed cores in laboratory conditions using marble from the roof and floor of Jinchanghe Lead–zinc mine in Baoshan. The dissipative degree of stress wave in marble jointed rock mass is measured by introducing quality factor Qs parameter. Based on the experimental principle of Split Hopkinson Pressure rod loading device (SHPB), we proposed a three-wave energy method of incident wave, reflected wave and projected wave for calculating jointed rock samples’ quality factor Qs based on stress wave energy. Using the SHPB test system for multiple specimens taken from the same piece of rock mass shock compression experiment, the three groups of specimens under different loading conditions gained incident wave and reflected wave and transmission wave experimental data, using the method of stress wave energy to deal with stress wave data, and calculate the joint sample maximum storage energy, dissipation energy and Qs quality factors. The results show that: ① The non-destructive breaking time–history strain of Dali rock mass under impact load is obtained by SHPB dynamic test system; combined with the deformation energy and dissipation energy calculation principle of quality factor, six groups of Qs experimental values are obtained. Although the Qs experimental values are discrete, the overall deviation is small with an average of 43.07. ② AUTODYN-Code was used to simulate the damage and fracture characteristics of rock mass with different quality factors under explosive dynamic load. The results showed that the radius of rock mass compression shear damage area gradually increased with the increase in porosity, but it was not obvious.

The light intensity is low in haze weather, and the facility is in a weak light environment for a long time. As a functional film, light conversion film (LCF) can improve the light conversion performance and is conducive to regulating the environment in the facility to promote crop growth. It can be seen from the test that the light transmittance of LCF under visible light conditions (400–780 nm) is 8.67% higher than that of ordinary film (OF), with stronger light transmittance. In the red–orange light band (600–700 nm), the LCF is 1.3% higher than that of the OF. Through the detection of irradiance, it was found that the irradiance was outdoor environment > LCF > OF in any weather. A two-year greenhouse experiment was conducted to study the effect of LCF on the whole growth process of facility agriculture (environment-soil-crop) under weak light. It is found that LCF reduces the air humidity by 0.47~2.83%; it has an obvious warming effect on the surface soil of greenhouse, and it is linearly correlated with temperature. In terms of crop growth, LCF significantly (p < 0.05) increased the photosynthetic rate at heading stage, and finally increased the yield, total soluble sugar and reduction-type Vitamin C by 8.97–39.53%, 9.22–30.14%, and 1.41–21.09%, respectively. In addition, considering the frequent haze weather in North China, the use of LCF can improve air temperature, CO2 concentration, photosynthetically active radiation (PAR), and soil temperature, and it can effectively deal with the challenge of weak light. In conclusion, LCF can improve the facility environment and improve crop yield and quality, indicating that the implementation of LCF has potential benefits in solving crop yield reduction and quality decline in haze weather. In addition, as the main component of LCF, rare earth materials are a new type of clean energy, which can effectively promote the sustainable development of the agricultural ecosystem.

Despite the steadily increasing area under protected agriculture there is a current lack of knowledge about the effects of the insect-proof screen (IPS) on microclimate and crop water requirements in arid and semi-arid regions. Field experiments were conducted in two crop cycles in Ningxia of Northwest China to study the impact of IPS on microclimate, reference evapotranspiration (ET0) and growth of Chinese Flowering Cabbage (CFC). The results showed that IPS could appreciably improve the microclimate of the CFC field in the two crop cycles. During the first crop cycle (C1), compared with no insect-proof screen (NIPS) treatment, the total solar radiation and daily wind speed under the IPS treatment were reduced by 5.73% and 88.73%. IPS increased the daily average air humidity, air, and soil temperature during C1 by 11.84%, 15.11% and 10.37%, respectively. Furthermore, the total solar radiation and daily wind speed under the IPS treatment during the second crop cycle (C2) were markedly decreased by 20.45% and 95.73%, respectively. During C2, the daily average air temperature and air humidity under the IPS treatment were increased slightly, whereas the daily average soil temperature was decreased by 4.84%. Compared with NIPS treatment, the ET0 under the IPS treatment during C1 and C2 was decreased by 6.52% and 21.20%, respectively, suggesting it had great water-saving potential when using IPS. The plant height, leaf number and leaf circumference of CFC under the IPS treatment were higher than those under the NIPS treatment. The yield under the IPS treatment was significantly increased by 36.00% and 108.92% in C1 and C2, respectively. Moreover, irrigation water use efficiency (IWUE) was significantly improved under the IPS treatment in the two crop cycles. Therefore, it is concluded that IPS can improve microclimate, reduce ET0, and increase crop yield and IWUE in arid and semi-arid areas of Northwest China.

The knowledge of crop water requirements is critical for agricultural water conservation, especially for accurate irrigation decision making in the greenhouse. Investigating the water demand pattern of the tomato in the solar greenhouse environment and constructing an appropriate irrigation decision-making model are urgently needed to improve irrigation water use efficiency. We designed four irrigation-level treatments: 100% ET0 (T1), 85% ET0 (T2), 70% ET0 (T3), and 55% ET0 (T4), and conducted a two-vegetation-season tomato planting trial under drip irrigation conditions in a solar greenhouse. The Pearson’s correlation coefficient method analyzed the intrinsic linkage and influence between soil–crop–environment and tomatoes’ water demand patterns. Indicators suitable for irrigation decision making in greenhouse tomatoes were selected, and regression functions were constructed for environmental and crop physiological parameters by combining path analysis and multiple regression methods. Finally, a fusion irrigation decision-making model was constructed by introducing a distance function in the Dempster–Shafer (D–S) theory primary probability assignment (BPA) synthesis algorithm and combining it with a triangular affiliation function. The results showed that: (1) the soil coefficient of variation was shallow > middle > deep, and tomatoes absorbed water mainly in the 0–60 cm soil layer; (2) the crop stem flow rate, net photosynthetic rate, and transpiration rate were positively correlated with irrigation water and had the highest correlation with net radiation, relative humidity, and relative humidity, with correlation coefficients of 0.9441, 0.9441, and 0.7679, respectively; (3) the constructed decision model had a significantly lower value of uncertainty than other methods, while the highest decision value could reach over 0.99, which achieved the best decision accuracy compared to other algorithms.

Cerebral cavernous malformations (CCMs) are vascular lesions that predominantly occur in the brain. CCMs can be sporadic or hereditary in an autosomal dominant manner. The genes harboring variants of familial CCMs (FCCMs) include CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. In this study, we identified a novel CCM1/KRIT1 mutation in a Chinese family with FCCMs. This family consists of 20 members, and 6 of them had been diagnosed with CCMs. The proband patient is a 17-year-old female who has suffered from CCM-related intracranial hemorrhage four times. Magnetic resonance imaging (MRI) revealed four lesions in the different brain regions and one lesion has progressively enlarged. The pathological histology confirmed CCMs. Whole exome sequencing revealed a novel deletion mutation (c.1635delA) within exon 15 of CCM1/KRIT1 gene in the proband patient, her mother, and her uncle who had CCMs. This frameshift mutation led to a premature termination codon (PTC) at nucleotides 1652–1654. We also detected that the CCM1 mRNA levels in the blood lymphocytes of the family members with CCMs were reduced by 46.4% compared to that in healthy controls. Collectively, our results suggested that the CCM1 mutation could potentially be a causative factor for FCCMs in the Chinese family and the reduction of CCM1 mRNA expression in the blood lymphocytes of the patients might be a potential biomarker for the diagnosis and prognosis of CCMs. Our findings expanded the spectrum of CCM mutations and helped to guide genetic counseling and early genetic diagnosis for at-risk family members.

BackgroundFamilial adenomatous polyposis (FAP) is an autosomal dominant disorder characterized primarily by the development of numerous adenomatous polyps in the colon and a high risk for colorectal cancer. FAP is caused by germline mutations of the adenomatous polyposis coli (APC) gene. The proband in this family was a 39-year-old female patient with the pathologic diagnosis of adenomatous polyps, and then a five-generation kindred with FAP was characterized in the following years. This article identified an APC mutation, and demonstrated the practical use of APC-linked STR markers, which could be used to reduce misdiagnosis of prenatal diagnosis or preimplantation genetic diagnosis resulted from contamination or allele drop-out.MethodsNext-generation sequencing (NGS) was used to identify the possible APC mutations in an affected individual from a family with autosomal dominant colon cancer. Targeted sequencing then used to identify additional related individuals with the mutation. Three short tandem repeat (STR) loci, D5S299, D5S134, and D5S346, were used for PCR-based microsatellite analysis of the APC gene in the extended family.ResultsWe identified an APC: p.W553X mutation. The STR haplotype at the APC locus, A1B4C1, was shared by all clinically affected individuals with the APC: p.W553X mutation. In addition, the APC: p.D1822V variant was observed in 40% affected individuals and in two unaffected individuals.ConclusionWe described a protein truncation mutation, APC: p.W553X; demonstrated the value of APC-linked STR markers (D5S299, D5S134, and D5S346) haplotypes; and suggested the potential role of these haplotypes in detecting loss of heterozygosity of the APC gene.

Syndactyly is one of the most frequent hereditary limb malformations with clinical and genetical complexity. Autosomal dominant syndactyly type IV (SD4) is a rare form of syndactyly, caused by heterozygous mutations in a sonic hedgehog (SHH) regulatory element (ZRS) which resides in intron 5 of the LMBR1 gene on chromosome 7q36.3. SD4 is characterized by complete cutaneous syndactyly of the fingers, accompanied by cup-shaped hands due to flexion of the fingers and polydactyly. Here, for the first time, we reported a large Chinese family from Fujian province, manifesting cup-shaped hands consistent with SD4 and intrafamilial heterogeneity in clinical phenotype of tibial and fibulal shortening, triphalangeal thumb-polysyndactyly syndrome (TPTPS). We identified a novel duplication of ∼222 kb covering exons 2–17 of the LMBR1 gene in this family by sub-exome target sequencing. This case expands our new clinical understanding of SD4 phenotype and again confirms the feasibility to detect copy number variation by sub-exome target sequencing.

Leber congenital amaurosis (LCA) is a group of severe congenital retinal diseases. Variants in the guanylate cyclase 2D gene (GUCY2D), which encodes guanylate cyclase 1 (ROS-GC1), are associated with LCA1 and account for 6%-21% of all LCA cases. In this study, one family with LCA1 was recruited from China. A combination of next generation sequencing and Sanger sequencing was used to screen for disease-causing mutations. We found three novel mutations (c.139delC, p.Ala49Profs*36; c.835G>A, p.Asp279Asn and c.2783G>A, p.Gly928Glu) in the GUCY2D gene. Proband III-2 carries mutations c.139delC and c.2783G>A, which are inherited from the heterozygous mutation carriers, II-2 (c.139delC) and II-3 (c.2783G>A) that possess c.139delC and c.2783G>A. Additionally, II-8 carries heterozygous mutation c.835G>A. Sanger sequencing was used to confirm the presence of the three novel mutations in other family members. Mutation c.139delC results in a truncated protein. Mutations c.835G>A and c.2783G>A significantly reduce the catalytic activity of ROS-GC1. Our findings highlight the gene variants range of LCA. Moreover, HPLC-coupled tandem mass spectrometry (HPLC-MS/MS) was used to analyze the concentration of 3',5'-cyclic guanosine monophosphate (cGMP), suggesting that HPLC-MS/MS is an effective alternative method to evaluate the catalytic activity of wild-type and mutant ROS-GC1.

Aiming to solve the problems of poor performance and low stability in the automatic clip-feeding of a grafting machine, an automatic clip-feeding mechanism with a precise single-clip discharge mechanism was designed, and a clip-feeding performance test was carried out. Taking the grafting clip of the 2TJGQ-800 type of vegetable-grafting robot as the research object, the clamping-force analysis model of the grafting clip was constructed by ABUQUS finite-element analysis software, and the variation law of clamping force, steel wire diameter, and opening deformation, as well as the calculation equation of clamping force, were obtained. The grafting clip model was verified by mechanical test, and test results showed that the grafting clip with a steel wire diameter of 0.7 mm proved safe and reliable for grafted cucumber and watermelon seedlings; the grafting clip with steel wire diameter of 0.8 mm had a risk of producing injury to grafted cucumber and watermelon seedlings when clamping. The method of single-clip discharge in the inclined discharging slideway was put forward, and the components for clip discharge and clip pushing were designed. The critical thrust for sending out the grafting clip in the clip-feeding slideway was 0.603 N after analyzing the force status of the grafting clip in the clip-feeding slideway. Test results showed that the success rate of automatic clip-feeding reached 98.67% when inclination angle of row-discharging slideway was 50° and the thrust of clip-pushing cylinder (input air pressure of 0.4 MPa) was 8.04 N, which met the technical requirements of mechanical grafting. The inclination of the grafting clip and the damaged clip in the feeding slideway is the main reason for the failure of clip-feeding. The research results can provide theoretical and design references for the innovative research of the automatic clip-feeding mechanism of grafting robots.

To characterize key odorants in scallion pancake (SP), volatiles were extracted by solvent extraction-solvent assisted flavor evaporation. A total of 51 odor-active compounds were identified by gas chromatography-olfactometry (GC-O) and chromatography–mass spectrometry (GC-MS). (Z/E)-3,6-Diethyl-1,2,4,5-tetrathiane was detected for the first time in scallion food. Application of aroma extract dilution analysis to extracts showed maltol, methyl propyl disulfide, dipropyl disulfide and 2-pentylfuran had the highest flavor dilution (FD) factor of 4096. Twenty-three odorants with FD factors ≥ 8 were quantitated, and their odor active values (OAVs) were calculated. Ten compounds with OAVs ≥ 1 were determined as the key odorants; a recombinate model prepared from the key odorants, including (E,E)-2,4-decadienal, dimethyl trisulfide, methyl propyl disulfide, hexanal, dipropyl trisulfide, maltol, acetoin, 2-methylnaphthalene, 2-pentylfuran and 2(5H)-furanone, successfully simulated the overall aroma profile of SP. The changes in odorants during storage were investigated further. With increasing concentrations and OAVs during storage, hexanal became an off-flavor compound.

Global climate change has noticeable influences on the water vapor redistribution in China, which is embodied by the fact that both wetting and drying tendencies were observed across China. This poses the necessity to monitor and understand the water vapor evolution in China. However, observations of water vapor from different techniques are subjected to systematic biases, different spatiotemporal resolutions and coverages, and different accuracy, which would hamper their joint use, potentially leading to contradictory conclusions when using different techniques. Data fusion is a promising way to address this problem. Some scholars have proposed several methods to fuse multi-source PWV data in China region, such as the enhanced spatial and temporal adaptive reflectance fusion model, the hybrid PWV fusion model, and the linear calibration model. Although these models can produce PWV products with improved accuracy, they still have some shortcomings, such as no consideration for spatial or temporal variations in bias or inevitably impose some biases inaccurate information since assumptions made for interpolations are imperfect. In this study, we use the high-quality Global Navigation Satellite System (GNSS) precipitable water vapor (PWV) to calibrate and optimize the Moderate-resolution Imaging Spectroradiometer (MODIS) and the European Centre for Medium-Range Weather Forecasts ReAnalyses 5 (ERA5) PWV in 2018–2019 through a Generalized Regression Neural Network (GRNN) at annual, quarterly, and monthly timescales. Validation results demonstrate that modifying the MODIS and ERA5 PWV at the monthly timescale results in the best accuracy. In the monthly experiment, the average bias, standard deviation (STD), and root mean square (RMS) error of modified MODIS PWV are 0.0 mm, 2.6 mm, and 2.6 mm, respectively. The percentage improvement is as high as 50% in terms of RMS compared to the original MODIS PWV. It becomes 0.0 mm, 1.7 mm, and 1.7 mm for the modified ERA5 PWV and the percentage improvement is 40%. Since the biases among different products are well-calibrated and the accuracy of MODIS and ERA5 PWV is improved to the same level of GNSS PWV, we can fuse them by simply merging them. Finally, we generate a new product of PWV in China with a temporal resolution of 1 day, a spatial resolution better than 31 km, and an accuracy better than 2.7 mm, which will serve as a high-quality product for investigating the water vapor redistribution under a changing climate.

In this work, the lacunary Keggin-type phosphotungstates of [PW9O34]9- (PW9) clusters were loaded onto the g-C3N4 nanosheets (NSs) to synthesize the phosphotungstate clusters-decorated 2D heterojunction photocatalysts by using the electrostatic-force driven self-assembly process. The surface charge polarity of g-C3N4 NSs was changed from a negative to a positive charge through the acidizing treatment. The positively-charged g-C3N4 NSs allowed the negatively-charged PW9 clusters to be adsorbed and deposited onto the g-C3N4 NSs, forming the PW9/g-C3N4 heterojunction NSs. The as-synthesized samples were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, and UV-VIS absorption spectra, respectively. The photocatalytic activity tests indicated that, upon simulated sunlight irradiation, the photocatalytic H2-generation rate of PW9/g-C3N4 heterojunction NSs (~23.8 μmol h−1) was ~3.3 times higher than that of the pure g-C3N4 NSs (~7.3 μmol h−1). The enhanced photocatalytic activity of PW9 cluster-decorated g-C3N4 NSs could be attributed to the enhanced separation process of the photoinduced charge-carriers, due to the Z-scheme-mediate charge transfer behavior across their hetero-interface.

Exploiting the promising third near-infrared optical window (1600–1870 nm) for deep bioimaging is largely underdeveloped, mostly because of the lack of stable femtosecond laser sources in leveraging the less scattering loss and locally reduced water absorption. In this letter, we demonstrate the fiber chirped pulse amplification of a short wavelength mode-locked thulium-doped fiber laser (TDFL) at 1785 nm. The mode-locked TDFL (via nonlinear polarization rotation) operates stably at the soliton pulsing regime with a fundamental repetition rate of 46.375 MHz. Utilizing a two-stage fiber amplifier incorporated along the pulse chirping fiber, the power of the laser pulse is boosted up to 690 mW. After dechirping with a diffraction grating pair, laser pulse with a duration of 445 fs, pulse energy of 5.7 nJ, and peak power of 12 kW is achieved. Higher power can be achieved by exploiting low-loss high power fiber components at this special wavelength range.

This work presents an experimental study that focused on the meso-damage evolution of cemented waste rock-tailing backfill (CWRTB) under triaxial compression using the in situ X-ray computed tomography (CT) technique. Although numerous investigations have studied the magnitude of the strength of CWRTB material, the mesoscopic damage evolution mechanisms under triaxial deformation are still poorly understood. Artificial CWRTB samples with a waste rock proportion of 30% were prepared by mixing tailings, waste rock, cement, and water. A specific self-developed loading device was used to match the CT machine to real-time CT scanning for the CWRTB sample. A series of 2D CT images were obtained by performing CT imaging at five key points throughout the test and from three positions in the sample. The CT values, for the purpose of meso-damage evolution in CWRTB, were identified. The results showed that the axial stress–strain curve presented strain hardening characteristics. The CT data revealed the inhomogeneous damage field inside the CWRTB sample and the most severely damaged regions that were usually located at the waste block-tailings paste interfaces. The changes in CT values for the different regions of interest (ROI) revealed the complicated interactions between the waste blocks and the tailings paste matrix. The meso-structural changes, formation of the localized bands, and the associated stress dilatancy phenomenon were strongly influenced by the interactions between the waste blocks and tailing paste.

[This corrects the article DOI: 10.1371/journal.pone.0133636.].

Cemented waste rock backfill (CWRB), which is a mixture of tailings, waste rock, cement, and water, is subjected to combination actions in underground mining operations and has been widely used in deep resource mining. While the strength requirement and macroscopic deformation behaviors of CWRB have been well studied, the mesoscopic damage evolution mechanisms are still not well understood. In this work, a CWRB sample with a waste rock proportion of 30% was studied with a uniaxial compression test under tomographic monitoring, using a 450 kV industrial X-ray computed tomography (CT). Clear CT images, CT value analysis, crack identification, and extraction reveal that CWRB damage evolution is extremely inhomogeneous and affected by the waste rock size, shape, and distribution. Furthermore, the crack initiation, propagation, and coalescence behaviors are limited to the existing waste rocks. When deformation grows to a certain extent, the cracks demonstrate an interlocking phenomenon and their propagation paths are affected by the waste rocks, which may improve the ability to resist compressive deformation. Volumetric dilatancy caused by the damage and cracking behavior has closed a link with the meso-structural changes, which are controlled by the interactions between the waste rocks and the cemented tailing paste.

Targeted next-generation sequencing (NGS) is a cost-effective approach for rapid and accurate detection of genetic mutations in patients with suspected genetic disorders, which can facilitate effective diagnosis.We designed a capture array to mainly capture all the coding sequence (CDS) of 2,181 genes associated with 561 Mendelian diseases and conducted NGS to detect mutations. The accuracy of NGS was 99.95%, which was obtained by comparing the genotypes of selected loci between our method and SNP Array in four samples from normal human adults. We also tested the stability of the method using a sample from normal human adults. The results showed that an average of 97.79% and 96.72% of single-nucleotide variants (SNVs) in the sample could be detected stably in a batch and different batches respectively. In addition, the method could detect various types of mutations. Some disease-causing mutations were detected in 69 clinical cases, including 62 SNVs, 14 insertions and deletions (Indels), 1 copy number variant (CNV), 1 microdeletion and 2 microduplications of chromosomes, of which 35 mutations were novel. Mutations were confirmed by Sanger sequencing or real-time polymerase chain reaction (PCR).Results of the evaluation showed that targeted NGS enabled to detect disease-causing mutations with high accuracy, stability, speed and throughput. Thus, the technology can be used for the clinical diagnosis of 561 Mendelian diseases.

A series of experimental flow tests for artificial block-in-matrix-soils (bimsoils) samples with various slenderness ratios were performed to study the Non-Darcy groundwater flow characteristics. The variations of seepage velocity, permeability coefficient, critical sample height, and non-Darcy flow factor for samples against slenderness ratios were investigated. A servo-controlled flow testing system that was developed by the authors was adopted to conduct the flow test. Cylindrical bimsoil samples (50 mm diameter and various heights) with staggered rock block percentages (RBPs) (30, 40, 50, and 60%, by mass) were prepared by compaction tests to roughly insure the same porosity of the soil matrix. The testing results show that flow the distance has a strong influence on the flow characteristics of bimsoil, and the relationship between the permeability coefficient and slenderness ratio is proposed. In addition, the critical sample height to eliminate the slenderness effect was determined, and the relationship between the critical sample height and RBP was established. Moreover, the responses of non-Darcy flow were studied by using an index of non-Darcy βfactor, which reveals the internal mechanism of the effect of flow distance on groundwater flow characteristics. The research results can be useful to the prediction of flow piping disaster for geological body made up of bimsoils.

Identification of gene variants plays an important role in research on and diagnosis of genetic diseases. A combination of enrichment of targeted genes and next-generation sequencing (targeted DNA-HiSeq) results in both high efficiency and low cost for targeted sequencing of genes of interest.To identify mutations associated with genetic diseases, we designed an array-based gene chip to capture all of the exons of 193 genes involved in 103 genetic diseases. To evaluate this technology, we selected 7 samples from seven patients with six different genetic diseases resulting from six disease-causing genes and 100 samples from normal human adults as controls. The data obtained showed that on average, 99.14% of 3,382 exons with more than 30-fold coverage were successfully detected using Targeted DNA-HiSeq technology, and we found six known variants in four disease-causing genes and two novel mutations in two other disease-causing genes (the STS gene for XLI and the FBN1 gene for MFS) as well as one exon deletion mutation in the DMD gene. These results were confirmed in their entirety using either the Sanger sequencing method or real-time PCR.Targeted DNA-HiSeq combines next-generation sequencing with the capture of sequences from a relevant subset of high-interest genes. This method was tested by capturing sequences from a DNA library through hybridization to oligonucleotide probes specific for genetic disorder-related genes and was found to show high selectivity, improve the detection of mutations, enabling the discovery of novel variants, and provide additional indel data. Thus, targeted DNA-HiSeq can be used to analyze the gene variant profiles of monogenic diseases with high sensitivity, fidelity, throughput and speed.