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Hematopoiesis is a process of constitutive regeneration whereby hematopoietic stem and progenitor cells (HSPCs) replenish mature blood cells. During maturation and aging, HSPCs shift their output to support the demands of prenatal development and postnatal maturation both at homeostasis and in response to stress. How HSPC ontogeny changes throughout life is unknown; studies to date have largely focused on specific individual ages, particularly at single cell resolution. Here, we performed single cell RNA-seq of human HSPCs from early prenatal development into mature adulthood. We observed shifts in HSPC transcriptional states and differentiation trajectories over time. We identified age-specific gene expression patterns throughout human maturation and developed methods for identifying, prospectively purifying, and functionally validating age-specific HSC states. Together, our findings define the temporal maturation of human HSPCs and uncover principles applicable to age-biased blood diseases.SummarySingle cell RNA sequencing reveals that the mechanisms of human hematopoietic stem and progenitor cell (HSPC) fate commitment change over a lifetime from gestation to mature adulthood.

Fumed silica is prepared by flame pyrolysis, where silicon halide is combusted in an oxygen-hydrogen flame, resulting in finely dispersed and thermally stable silicon dioxide. Because of its unique physical and chemical properties, including high porosity, large pore volumes, large specific area, and high chemical activity, fumed silica is widely used in rubbers, plastics, adhesives, paints, and printing inks for reinforcement, as well as in thixotropy, anti-setting, and anti-sagging applications. These functional properties of fumed silica are related to the silanol group on its surface. However, there is no accurate and convenient test method to determine the silanol group content on the surface of fumed silica. This work explores a novel method to determine the silanol group content on the surface of fumed silica by chemical reaction-headspace gas chromatography (HS-GC). Theoretically, by this method, the silanol group can rapidly react with the Grignard reagent and generate methane, the amount of which can be determined accurately by GC analysis. GC analysis was conducted using a headspace flask as a closed reactor to transform the silanol group into a volatile component through a chemical reaction, so as to realize the accurate determination of silica hydroxyl. The amount of methane produced in the reaction was directly proportional to the content of silanol groups on the surface of fumed silica. Therefore, the silanol group content was calculated using the chemical reaction equation. Before the experiment, fumed silica was dried for 2 h in an oven at 105 ℃ to remove adsorbed moisture. The dried fumed silica sample was then reacted with the Grignard reagent dispersed in toluene in an airtight reaction bottle. Toluene was used as a dispersion agent to promote contact and reaction between the fumed silica sample and Grignard reagent. The methane produced by the reaction was injected into a gas chromatograph for separation and further detected using a flame ionization detector (FID). Methane was quantified from the peak areas of the GC signals using the external standard method, and the silanol content in the sample was obtained. Simultaneously, factors influencing the outcome of the method, such as the dosage of the Grignard reagent and reaction time with it, were optimized by a comparison test. Accordingly, 2.0 mL of 0.3 mol/L Grignard reagent and a reaction time of 15 min were found to be optimal for testing. The test results showed that there was good linear correlation between the content of the silanol group and the GC signals, with a correlation coefficient of 0.9990. The limit of detection was 0.30 mg/g, and the limit of quantification was 1.00 mg/g. The relative standard deviation of reproducibility was less than 3%. Based on an interlaboratory test conducted by four laboratories on five samples with different silanol group contents, the repeatability limit (r) was less than 2.5%, and the reproducibility limit (R) was less than 6.5%. Compared with the traditional chemical method, the method involving HS-GC presents distinct advantages in terms of lower reagent consumption, high sensitivity, good stability, and reliability. It is suitable for the rapid detection of the silanol group content on the surface of fumed silica, and can aid in the quality control of fumed silica during its production and application. This method has important theoretical and practical significance for developing accurate methods to determine silica hydroxyl in the silicon industry for standards and the optimization of industrial technology. This study serves as a foundation to standardize and promote the rapid development of silicon material-related industries.

The non-uniform distribution of the heat flux commonly occurs in systems where vapor-liquid phase changes, such as nuclear reactors, and aerospace thermal control systems. This poses a great challenge on the study of pressure drop, heat transfer coefficient, and flow pattern prediction. In addition, flow patterns and heat transfer characteristics are usually affected by differences in fluid properties (viscosity, density, and surface tension), thermodynamic conditions (pressure, temperature), and geometric dimensions. At present, most of the researches on non-uniform heat flux are concentrated in systems with pure working fluids. However, compared to the pure working fluid, the mixed working fluid, particularly the zeotropic working fluid can improve the cycle efficiency and has great application potential, chiefly due to the temperature glide. There are few studies on the two-phase flow pattern and heat transfer characteristics of the zeotropic working fluid under non-uniform heat flux. Aiming at the problem of vapor-liquid phase change of zeotropic working fluid under non-uniform heat flux boundary conditions, a two-phase flow boiling experimental system in a horizontal tube with a 10 mm inner diameter under non-uniform heat flow was established. The studied zeotropic working fluid is R245fa/R134a with a mass fraction of 0.7:0.3. Experiments were performed at conditions where the mass flux ranges from 175 to 373 kg/(m2 s), while the heat flux ranges from 9.95 to 47.57 kW/m2. Using a high-speed camera and image processing technology, the gray values of the observed bubble flow, plug flow, stratified flow, and annular flow were analyzed, and the flow patterns under both non-uniform and uniform heat flux were demonstrated. Effects of the vapor quality, mass flux, heat flux and saturation temperature on the two-phase heat transfer coefficient were analyzed. And on the basis of experimental data, the prediction accuracy of four commonly used correlations was evaluated. The results show that the gray value of bubble flow and plug flow fluctuate widely, while the gray value fluctuation range of stratified flow and annular flow is relatively small. The typical flow pattern under non-uniform heat flux is the same as flow pattern under uniform heat flux. With the same amount of the additional heat, under the condition of non-uniform heat flux, the initial vapor quality of annular flow is advanced, and the proportion of the annular flow is larger than the non-annular flow. The main reason for this phenomenon is that the flow instability caused by non-uniform heat flux accelerates the transition of intermittent flow to annular flow. In addition, the heat transfer coefficient changes little at the lower vapor quality, and the heat transfer coefficient of the intermittent flow region is independent of vapor quality. In the annular flow region with higher vapor quality, the heat transfer coefficient increases with the increase of vapor quality. The heat transfer coefficient increases with the increase of mass flux and heat flux. The saturation temperature has little effect on the heat transfer coefficient in the convection boiling region and has a certain influence in the nucleate boiling region. Furthermore, the prediction ability of the four correlations is poor in the non-annular flow region. Relatively, the prediction accuracy of the Sun & Mishima correlation is the highest in the annular flow region.

Shield tunneling prior to the shafts excavation is an efficient and economical method in the construction of the heat-supplying shield tunnel. Combining the first large cross-section heat-supplying shield tunnel project in China, the characteristics of the construction method are analyzed, and the control measures of segment joints deformation are put forward. Based on the site conditions, the numerical analysis model including interface element is established, and the control effect of the measures is analyzed and evaluated. Through on-site monitoring, the change law of longitudinal stress and joints deformation in different construction stages are measured. Based on the numerical analysis model, the effects of tunnel depth, stratum and grouting reinforcement area on joints deformation are analyzed. The results show that: the deformation of segment joints can be divided into two stages in the project of shield tunneling prior to the shafts excavation: shaft excavation and segments removal, and the segments removal is the main factor. According to the results of numerical calculation and on-site monitoring, the control measures of longitudinal tension lining and retightening bolt, priority to pouring concrete in the bottom of tunnel and secondary grouting behind lining can control the loss of longitudinal stress, and reduce the joints deformation. The maximum deformation of segment joints is 3.51 mm, which meets the waterproofing requirements of shield tunnels. In the project of shield tunneling prior to the shafts excavation, the deformation control of the top segment joints should be strengthened in the shallow tunnel, while for the deep tunnel, which should be strengthened of the bottom segment joints. When the tunnel passes through the stratum with larger resilience modulus, the deformation of the bottom joints will be larger. Grouting reinforcement of surrounding soil can reduce the loss of longitudinal stress and the joints deformation effectively.

Studying individuals at increased genetic risk for schizophrenia may generate important theories regarding the emergence of the illness. In this investigation, genetic high-risk individuals (GHR, n = 37) were assessed with functional magnetic resonance imaging and compared to individuals in the first episode of schizophrenia (FESZ, n = 42) and healthy comparison subjects (HCS, n = 59). Measures of functional connectivity and the amplitude of low-frequency fluctuation (ALFF) were obtained in a global, data-driven analysis. The functional connectivity measure, termed degree centrality, assessed each voxel's connectivity with all the other voxels in the brain. GHR and FESZ displayed increased degree centrality globally and locally. On ALFF measures, GHR were indistinguishable from HCS in the majority of areas but resembled FESZ in insula, basal ganglia and hippocampus. FESZ evidenced reduced amplitude of the global neural signal as compared to HCS and GHR. Results support the hypothesis that schizophrenia diathesis involves functional connectivity and ALFF abnormalities. In addition, they further an emerging theory suggesting that increased connectivity and metabolism may be involved in schizophrenia vulnerability and early stages of the illness.

A new series of 3,6-diaryl-1H-pyrazolo[3,4-b]pyridine compounds have been discovered as potent anaplastic lymphoma kinase (ALK) inhibitors. The 4-hydroxyphenyl in the 6-position of 1H-pyrazolo[3,4-b]pyridine were crucial and a fluorine atom substitution could give promising inhibitory activity. The IC50 of compound 9v against ALK was up to 1.58 nM and a binding mechanism was proposed.

A synthesis of cephalostatin 1 from hecogenin is described in detail. The gram-scale synthesis of south part features a Baeyer–Villiger oxidation of hecogenin to 16,20-diol, a selective oxidation of C16 OH with Dess–Martin periodinane, a Rh(I)-catalyzed C15 C16 double bond shift to C14 C15 position, and a Hg(OAc)2-mediated spiroketal formation from cyclic enol ethers with alkenyl side chain at 2-position. Key transformations in the synthesis of north part, also on gram scale, include an abnormal Baeyer–Villiger oxidation of hecogenin to the corresponding dinorcholanic lactone, where a catalytic amount of iodine acts as a traceless and catalytic switch, an umpolung of steroidal 22-aldehyde to forge C22 C23 bond with good stereochemical control, a cascade spiroketal-forming process to establish DEF rings in one operation, and a selective oxidation of C3 OH. There are also other noteworthy transformations that, although not used in our final route, are valuable and could be applied to other syntheses, including: intra- or intermolecular SN2′ processes of C14-heteroatom-substituted C15 C16 alkenes, an unprecedented rearrangement of β-adduct of D-ring dienes and singlet oxygen, a chelation-controlled methylallylation of C23 aldehyde, and so on.

The pre-peak loading stages of rock in compression tests are divided into four stages (i.e., crack closure, elastic deformation, stable crack growth and unstable crack growth) by identifying the Crack Closure stress (CC), Crack Initiation stress (CI), and crack damage stress. A new method for determining the CC and CI is presented in this paper and compared with previous methods. The new method is called “Continuous Strain Deviation” (CSD), and it solves two problems associated with other methods: 1) determining the limits for the elastic range in laboratory data, and 2) identifying where crack closure or initiation occurs from the subtle changes in the stress-strain data. Starting from an initial point corresponding to 30% to 40% UCS, the proposed algorithm provides a distinct indicator for CC and CI. The CC and CI for Badaling granite and Aspo diorite are determined with the proposed method, results from which are similar to other methods. Sensitivity analyses of the CSD method show that stable CC and CI values could be estimated using any initial point from 30% to 40% UCS. Comparison studies show that the CSD method predicts a smaller stress range and gives a more distinct indicator for both CC and CI.

The parabolic trough collector (PTC) is one of the most mature technologies to harvest solar energy for heat applications. However, the non-uniform heat flux distribution on the outer surface of absorber tube can lead to a high local temperature and a large temperature gradient on the tube wall, thus resulting into many issues, such as the degradation of the selective coating, the vacuum loss, the deformation of the absorber tube, and even the breakage of the glass envelope. These issues pose great challenges for the safety and high-efficiency operation of PTC systems. The corresponding effective solution is to increase the uniformity of the heat flux distribution on the absorber tube. Based on this purpose, how to quantify the uniformity of heat flux distribution is of great significance for the design of the parabolic trough collector. In this work, the existing uniformity indexes in engineering are summarized and compared. It is found that there are three problems in the related studies: (1) Some indexes are unbounded, which makes it difficult to compare uniformity of different distribution types; (2) some indexes are dimensioned, and its difficult to compare uniformity of different physical quantities distribution; (3) for most of the existing indexes, only the value of physical quantity is considered, while the spatial distribution characteristic of physical quantity is ignored. This phenomenon makes the description of uniformity incomprehensive. In view of this, a new uniformity index is proposed to consider both the value and spatial position of physical quantity by decoupling uniformity index into uniformity index of value and uniformity index of spatial position. The uniformity index of value is to quantify the dispersion degree of a set of data values from the average, and the uniformity index of spatial position is to quantify the amount of dispersion of data values in different spatial zones. The effectiveness of the proposed uniformity index is verified by evaluating the uniformity of three different distributions. Compared with existing uniformity indexes, the proposed index has a better ability to distinguish the uniformity of the distribution. Thereafter, the proposed uniformity index is employed to evaluate the uniformity of heat flux distribution in four typical types of PTC. The obtained results show that the proposed uniformity index can quickly and accurately evaluate the uniformity of heat flux distributions in PTC. Furthermore, due to the characteristics of strict boundedness and dimensionless, the proposed index can be easily applied as the guidance of PTC design and optimization.

Objective: The purpose of this meta-analysis was to summarize the prevalence and risk factors of mental health problems among healthcare workers during the COVID-19 pandemic.Methods: We applied an optimized search strategy across the PubMed, EMBASE, Scopus, PsycINFO, and four Chinese databases, with hand searching supplemented to identify relevant surveys. Studies were eligible for inclusion if they were published in peer-reviewed literature and used a validated method to assess the prevalence and risk factors of mental health problems among healthcare workers during the COVID-19 pandemic. Heterogeneity was quantified using Q statistics and the I2 statistics. The potential causes of heterogeneity were investigated using subgroup analysis and meta-regression analysis. Sensitivity analysis was performed to examine the robustness of the results.Results: We pooled and analyzed data from 20 studies comprising 10,886 healthcare workers. The prevalence of depression, anxiety, insomnia, post-traumatic stress symptoms, phobia, obsessive–compulsive symptoms, and somatization symptoms was 24.1, 28.6, 44.1, 25.6, 35.0, 16.2, and 10.7%, respectively. Female and nurses had a high prevalence of depression and anxiety. Frontline healthcare workers had a higher prevalence of anxiety and a lower prevalence of depression than the those in the second-line. Furthermore, the proportion of moderate–severe depression and anxiety is higher in the frontline. Additionally, four studies reported on risk factors of mental health problems.Conclusions: In this systematic review, healthcare workers have a relatively high prevalence of depression, anxiety, insomnia, post-traumatic stress symptoms, phobia, obsessive–compulsive symptoms, and somatization symptoms during the COVID-19 pandemic, and focus should be on the healthcare workers at high risk of mental problems. Mental health problems in healthcare workers should be taken seriously, and timely screening and appropriate intervention for the high-risk group are highly recommended.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020179189.

Background: The aim of this study was to report the clinical features and mutations in a patient with autosomal-inherited Alport syndrome (AS).Methods: We examined the clinical data, mutation analysis results, and family tree of a patient with autosomal-inherited AS, who had nephrotic syndrome as her first manifestation.Results: The proband was a girl of 11 months who presented with nephritic and nephrotic syndromes including gross hematuria but had a normal renal function. Her treatment course was complicated by steroid resistance and a poor response to cyclosporine A and cyclophosphamide pulse therapy. Renal biopsy was performed 2 years after disease onset; light microscopy showed glomerular segmental mesangio-proliferative lesions, and type IV collagen staining showed the loss of the α3 chain in the glomerular and tubular basement membrane (GBM and TBM) and α5 chain loss in the GBM. Electron microscopy showed uneven GBM thickness, with the dense basement membrane (BM) layer obviously delaminated and torn, showing a typical “lace-like” change. The segmental BM was loosened and widened. Her father did not develop microscopic hematuria until 10 years later, while her grandmother had asymptomatic hematuria and proteinuria when the proband was diagnosed. We detected a new COL4A4 mutation in the proband, namely c.1715delG (p.G572Vfs * 81) in exon 24. Her father and grandmother carried the same mutation, but her mother and sister did not.Conclusions: We found a new potentially pathogenic mutation of COL4A4 in a patient with autosomal-inherited AS, which presented as nephrotic syndrome in infancy.

An overhead transmission line system is a typical wind-sensitive structure with high flexibility, light weight, and low structural damping. Wind-induced dynamic reaction of the transmission...

To achieve high device performance and high reliability for the gallium nitride (GaN)-based high electron mobility transistors (HEMTs), efficient heat dissipation is important but remains challenging. Enormous efforts have been made to transfer a GaN device layer onto a diamond substrate with a high thermal conductivity by bonding. In this work, two GaN-diamond bonded composites are prepared via modified surface activated bonding (SAB) at room temperature with silicon interlayers of different thicknesses (15 nm and 22 nm). Before and after post-annealing process at 800 oC, thermal boundary conductance (TBC) across the bonded interface including the interlayer and the stress of GaN layer are investigated by time-domain thermoreflectance and Raman spectroscopy, respectively. After bonding, the 15 nm Si interlayer achieved a higher TBC. The post-annealing significantly increased the TBC of both interfaces, while the TBC of 22 nm silicon interlayer increased greater and became higher than that of 15 nm. Detailed investigation of the microstructure and composition of the interfaces were carried out to understand the difference in interfacial thermal conduction. The obtained stress was no more than 230 MPa for both before and after the annealing, and this high thermal stability of the bonded composites indicates that the room temperature bonding can realize a GaN-on-diamond template suitable for further epitaxial growth or device process. This work brings a novel strategy of SAB followed by high-temperature annealing to fabricate a GaN-on-diamond device with a high TBC.

High-risk forms of B-acute lymphoblastic leukemia (B-ALL) remain a therapeutic challenge. Leukemia-initiating cells (LICs) self-renew and spark relapse and therefore have been the subject of intensive investigation; however, the properties of LICs in high-risk B-ALL are not well understood. Here, we use single-cell transcriptomics and quantitative xenotransplantation to understand LICs in MLL-rearranged (MLL-r) B-ALL. Compared with reported LIC frequencies in acute myeloid leukemia (AML), engraftable LICs in MLL-r B-ALL are abundant. Although we find that multipotent, self-renewing LICs are enriched among phenotypically undifferentiated B-ALL cells, LICs with the capacity to replenish the leukemic cellular diversity can emerge from more mature fractions. While inhibiting oxidative phosphorylation blunts blast proliferation, this intervention promotes LIC emergence. Conversely, inhibiting hypoxia and glycolysis impairs MLL-r B-ALL LICs, providing a therapeutic benefit in xenotransplantation systems. These findings provide insight into the aggressive nature of MLL-r B-ALL and provide a rationale for therapeutic targeting of hypoxia and glycolysis.

Vortioxetine hydrobromide is a common clinical medication for major depressive disorder (MDD). However, it remains unclear whether vortioxetine hydrobromide acts by affecting the structure and composition of gut microbiota. Here, we analyzed fecal samples from 28 healthy controls (HCs) and 26 patients with MDD before treatment with vortioxetine hydrobromide, at 4 weeks after treatment, and at 8 weeks after treatment. High-throughput pyrosequencing showed that, according to the Chao1 and Shannon indices, fecal bacterial α-diversity was higher in the patients with MDD than in the HCs (p < 0.05), but no significant differences were observed after vortioxetine hydrobromide treatment (p > 0.05). PCoA results revealed that the gut microbiota composition was significantly different between the MDD groups and HCs. Proteobacteria and Actinobacteria were strongly increased, whereas Firmicutes were significantly reduced in the MDD group compared with the HCs. After treatment with vortioxetine hydrobromide, Firmicutes were significantly increased, and the proportion of Bacteroidetes decreased. Most notably, Lachnospira, Roseburia, and Faecalibacterium were negatively correlated with the severity of depressive symptoms. Taken together, our data indicate changes in the fecal microbiota composition in MDD patients compared with HCs, and vortioxetine hydrobromide may treat MDD through regulation of the gut microflora.

High hardness and corrosion resistance of SiC (silicon carbide) bulk materials have always been a difficult problem in the processing of an all-SiC piezoresistive pressure sensor. In this work, we demonstrated a SiC sealing cavity structure utilizing SiC shallow plasma-etched process (&le, 20 &mu, m) and SiC&ndash, SiC room temperature bonding technology. The SiC bonding interface was closely connected, and its average tensile strength could reach 6.71 MPa. In addition, through a rapid thermal annealing (RTA) experiment of 1 min and 10 mins in N2 atmosphere of 1000 &deg, C, it was found that Si, C and O elements at the bonding interface were diffused, while the width of the intermediate interface layer was narrowed, and the tensile strength could remain stable. This SiC sealing cavity structure has important application value in the realization of an all-SiC piezoresistive pressure sensor.

The classification, risk stratification, and treatment selection of patients with hematologic malignancies are heavily influenced by recurrent molecular alterations determined by next-generation sequencing (NGS).1-5 Peripheral blood (PB) and bone marrow (BM) are generally considered equivalent sample sources, especially if similarly involved by disease, but large studies comparing the mutational profiles of paired PB and BM samples (ie, taken from the same patient at the same time point of their disease history) have not been performed.6,7 We report a retrospective analysis of 164 patients from a single institution with suspected or known hematologic diseases for whom both PB and BM NGS was performed.

In this paper, we explored a method to remove the contamination and impurities left on SiC surface after plasma-etched process. The stubborn contamination is resulting from fluorochemical caused by plasma-etched process, residue left after stripping Ni metal mask, Ni–O compounds formed by the metal mask with SiC Si surface oxide film and carbon-containing contamination introduced by the process environment. By adding a layer of SiO2 mask between SiC and the original metal mask together with ultrasonic cleaning and oxygen plasma cleaning process, the sample surface roughness was effectively reduced from 1.090 to 0.055 nm. Moreover, this method supplies a valuable reference for solving the problem of surface contamination caused by plasma etched.

In very jointed rock masses, the ground arch developed around the underground opening is an arch-shaped structure to maintain the excavation stability, and the rock bolting has been attributed as one of the dominant approaches to enhance the arching effect. Through 2D finite element method (FEM), numerical studies were performed to investigate the arching effect and the importance of rock bolting. Based on the distribution of the mean stress σm, the boundary of the ground arch is determined without several limitations existed in other methods and the artificial arching effect of rock bolting could be assessed directly. Impacts of the cover depth Ht, the tunnel span D, the in situ stress ratio k, and the rock mass strength (frictional strength ϕ) were first revealed. The enhancement provided by the rock bolting were then directly evaluated through the artificial ground arch. The formation of the artificial arch is carefully studied considering the bolt spacing and the bolt length. Results show that σm could be used as a reliable indicator to assess the arching effect. Rock bolting reinforces the surrounding rock mass and contributes to the formation of the sub-arch therein. With enough reinforcement, the sub-arch overlaps each other and a global artificial arch could form to enhance the arching effect.

The vascular adventitia contains numerous cell types including fibroblasts, adipocytes, inflammatory cells, and progenitors embedded within a complex extracellular matrix (ECM) network. In response to vascular injury, adventitial progenitors and fibroblasts become activated and exhibit increased proliferative capacity and differentiate into contractile cells that remodel the ECM. These processes can lead to vascular fibrosis and disease progression. Our previous work established that the ECM protein aortic carboxypeptidase-like protein (ACLP) promotes fibrotic remodeling in the lung and is activated by vascular injury. It is currently unknown what controls vascular adventitial cell differentiation and if ACLP has a role in this process. Using purified mouse aortic adventitia Sca1+ progenitors, ACLP repressed stem cell markers (CD34, KLF4) and upregulated smooth muscle actin (SMA) and collagen I expression. ACLP enhanced myocardin-related transcription factor A (MRTFA) activity in adventitial cells by promoting MRTFA nuclear translocation. Sca1 cells from MRTFA-null mice exhibited reduced SMA and collagen expression induced by ACLP, indicating Sca1 cell differentiation is regulated in part by the ACLP-MRTFA axis. We determined that ACLP induced vessel contraction and increased adventitial collagen in an explant model. Collectively these studies identified ACLP as a mediator of adventitial cellular differentiation, which may result in pathological vessel remodeling.

Discontinuous defect in the rockmass is a key influential factor in controlling the strength behavior, and how to estimate the anisotropic strength and scale effect on the defected rockmass is the remaining challenging focus in engineering application. In the present study, intact tuff samples cored from the Xiabeishan tunnel engineering in situ are conducted by experiment tests (i.e., uniaxial compression test, triaxial compression test, and Brazilian tensile test) to obtain the corresponding mechanical parameters. Results from the numerical simulations using the particle flow code (PFC) by the flat-jointed model (FJM) are performed to match the macroparameters from experimental results. It is observed that numerical results have good agreement with the macroscopic mechanical parameters of intact samples including UCS, BTS, triaxial compression strength, and corresponding deformation parameters. Finally, a series of uniaxial and confining compression tests are conducted by using a synthetic rockmass (SRM) method which is coupled with the discrete element method (DEM) and discrete fracture network (DFN). Then, the anisotropy and scale effects on the strength characteristics of the defected rockmass are investigated. The results show that defects have a vital effect on the failure mode and strength behavior of the rockmass in the research region. The strength parameters are changed with the specimen size. The REV size of the considered defected rockmass is regarded as 5 × 10 m, and this size is also influenced by the confinement level. The anisotropy of macroscopic strength parameters is found in the considered defected rockmass, whose stress-strain curves and failure modes are also discussed.

Wind tunnel studies are conducted to investigate the wind load effect of a representative single-column-supported two-plate billboard structure. Firstly, synchronous pressure measurement on the billboard of a rigid model in wind tunnel is carried out. The alongwind, acrosswind and torsional loads at different wind directions are analyzed. Simplified pressure distributions causing alongwind and torsional loads at the most unfavorable wind directions are presented. Secondly, an aeroelastic model test is conducted and the response at the base of supporting column is obtained from force balance measurement. The measured responses are also compared with the analytical predictions to validate the effectiveness of analytical approach. This analysis sheds new insight on the aerodynamic admittance function and aerodynamic damping. A simplified approach for the analysis of torsional response is introduced in terms of effective eccentricity coefficient. This study provides comprehensive wind load testing data and analytical approach for prediction of wind-induced response of two-plate billboard structures.

Background/Aims: Reactive oxygen species (ROS) contribute to the dysfunction of serum lipoproteins, which triggers lipid metabolism abnormalities in the development of atherosclerosis and hypertension. Myeloperoxidase (MPO) is involved in ROS modifications, triggering lipid peroxidation and aldehyde formation. However, the relationship between the entirety of the MPO reaction system and oxidative modification of serum lipoproteins in atherosclerotic patients with hypertension remains unclear. Methods: We measured MPO activity (peroxidation and chlorination), 4-hydroxynonenal-modified low-density lipoprotein (HNE-LDL), malondialdehyde-modified low-density lipoprotein (MDA-LDL), H 2 O 2 , reduced glutathione (GSH), and oxidized glutathione (GSSG) using a corresponding commercial kit in atherosclerotic patients with hypertension and healthy participants. We used Spearman’s correlation analysis to investigate the correlation between MPO activity and the levels of these oxidative and anti-oxidative stress-related indices and performed response surface regression to investigate the relationship between the MPO reaction system and the levels of HNE-LDL, MDA-LDL, and the GSH/GSSG ratio. Results: Our results showed no association between the levels of MPO peroxidation activity, MPO chlorination activity, H 2 O 2 , and Cl - and those of HNE-LDL, MDA-LDL, GSH, and GSSG, and the GSH/GSSG ratio in healthy participants. In addition, no effects of the peroxidation reaction system of MPO (PRSM) and the chlorination reaction system of MPO (CRSM) on GSH/GSSG were found in this investigation. However, we found that the PRSM rather than the CRSM correlated with progressive low-density lipoprotein (LDL) modifications by HNE-LDL and MDA-LDL in atherosclerotic patients with hypertension. Conclusion: The PRSM rather than the CRSM correlated with progressive LDL modifications via reactive aldehydes in atherosclerotic patients with hypertension. Further investigation is warranted to evaluate whether the PRSM may serve as a potential index for monitoring LDL function in atherosclerosis and hypertension.

Polycomb group (PcG) proteins are a well-studied group of chromatin modifiers belonging to one of two distinct multi-protein complexes: Polycomb repressive complex 1 (PRC1) and PRC2. With definitive hematopoiesis, PRCs contribute to many aspects of fetal and adult blood formation. However, it is largely unknown how many of the age-specific effects of PRCs in hematopoiesis are regulated. Here, we show that the definitive hematopoietic stem and progenitor cell (HSPC) compartment is remodeled from the fetus to the neonate and into young adulthood coordinated with changes in mature blood cell output. This process is in part dependent on the PRC1 component Cbx2, which is regulated by the heterochronic Lin28b/let-7 axis. First, we quantified various population of definitive hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) using midgestation fetal liver (FL, embryonic day 14.5 (E14.5)), newborn bone marrow (BM, postnatal day 0-1), or young adult (postnatal age 6 to 8 weeks) BM. The lymphoid biased multipotent progenitor 4 (MPP4, ~0.9-fold) declined as the mice matured and aged. We also found erythroid-biased MPP2 diminished (~0.7-fold) while myeloid-biased MPP3 increased (~1.7-fold) with maturation. Using isolated long-term (LT) HSCs from these three stages, we found that E14.5 FL (~8.0-fold) and neonatal LT-HSC (~4.0-fold) showed more rapid B-cell reconstitution compared to young adult LT-HSCs upon transplantation. We found that many of these effects were regulated by Lin28b/let-7. Next, we aimed to determine the downstream mediators of Lin28/let-7's effect on HSPCs maturation. By interrogating gene regulatory subnetworks differentially active across mouse HSPC maturation and mining these subnetworks for predicted let-7 target transcripts, we found Cbx2 enriched in E14.5 FL (P=0.003) and adult HSPCs ectopically expressing LIN28B relative to wild-type adult HSPCs. In cell-based assays, we confirmed that let-7 microRNAs directly regulated CBX2 protein levels. Thus, the Lin28b/let-7 axis governs CBX2 protein levels, leading us to hypothesize that this axis exerts its wide-ranging effects on hematopoietic maturation by regulating PRC1 by controlling Cbx2 levels. As CBX2's developmental stage-specific functions have not been investigated, we generated Cbx2-/-embryos and investigated definitive FL hematopoiesis. We observed skewing of myeloerythorid progenitors to an adult-like myeloid-predominant distribution in Cbx2-/- embryos (P=0.0002), and B-cells in Cbx2-/- neonatal spleens were diminished (P=0.04). We further examined this effect using transplanted Cbx2-/- MPP4 from E14.5 FL which resulted in a decreased donor derived B-lymphoid output compared to wild-type littermates (~0.7-fold). To understand the functional role of Cbx2/PRC1 in juvenile hematopoiesis, we next investigated the role of Cbx2 in maintaining histone H2A monoubiquitinylation (H2AK119Ub) - the histone modification placed by PRC1 - in FL HSPCs. In Cbx2-/- FL HSPCs, the global distribution of H2AK119Ub localization did not change, but several specific H2AK119Ub peaks were altered. We observed differential H2AK119Ub abundance associated with a candidate enhancer within the Erg gene, suggestive of control of Erg expression by Lin28b/let-7/Cbx2. We confirmed that this enhancer activated transcription from a minimal promoter (~8-fold). Erg expression was increased in perinatal spleens of Cbx2-/- mice compared to Cbx2+/+ littermates (~4-fold). Moreover, we found that Cbx2 could repress ERG expression as well as other master HSPC transcription factors. Overall, our findings show that the Lin28b/let-7-axis controls developmental stage-specific hematopoietic output through PRC1-mediated chromatin remodeling. These findings demonstrate a key mechanism by which HSPCs alter their properties during developmental maturation with relevance to age-skewed blood disorders. Disclosures No relevant conflicts of interest to declare.

This paper addresses analysis of dynamic buffeting response of a hinged transmission line (conductor) under nonstationary wind excitations. The nonstationary wind speed is characterized by deterministic time-varying mean and stochastic fluctuating components. The wind load on the conductor is quantified using quasi-steady theory. The wind-induced response of the conductor is decomposed into deterministic time-varying mean and stochastic dynamic components. The time-varying mean response is determined by nonlinear static analysis with an analytical solution. The stochastic dynamic response is determined through quasi-static analysis in terms of influence function around the time-varying mean equilibrium. A closed-form formulation is presented for calculating time-varying standard derivation of response. The cumulative distribution function of the extreme response over a given time duration is then calculate using mean upcrossing rate theory of nonstationary random process. The effectiveness and accuracy of the proposed analytical framework are verified through response time history analysis using a nonlinear finite element model. The response characteristics of conductor under various nonstationary winds are examined through a parametric study.

This study addresses the estimation of buffeting response of overhead conductor based on random vibration theory with closed-form formulations. Special attention is placed on the determination of static deformation with consideration of geometric nonlinearity, and its influence on the dynamic modal properties, aerodynamic modal damping and buffeting response. The dynamic response around the static equilibrium is separated into background and resonant components, which are calculated by using influence function and modal analysis, respectively. The aerodynamic modal damping ratios are estimated in closed-form formulations in which the influence of static swing of the conductor plane is explicitly accounted. Example studies presented in this study illustrate the accuracy and effectiveness of this linear buffeting analysis framework through comparison with nonlinear finite element model (FEM) analysis in the time domain. The importance of consideration of static deformation is revealed for the prediction of alongwind displacement and tension, especially, the resonant response component. The contributions of modal responses to various resonant responses are also examined.

Background and purpose Autoimmune disorders are growing alarmingly high in prevalence across the globe. Autoimmune encephalitis has had a dramatic impact on the medical field, effectually altering diagnostic and treatment paradigms in regard to neuropsychiatric disorders. Our primary goal in conducting this study was to analyze the clinical characteristics of autoimmune encephalitis patients, with special focus on psychiatric presentations, in the West China Hospital and report patient prognoses after immunotherapy. Methods Data for patients admitted to the West China Hospital with autoimmune encephalitis diagnoses from 2015 to 2016 were collected and the corresponding clinical features were analyzed. Results We ultimately included 70 patients with autoimmune encephalitis: 56 (80%) anti-NMDAR encephalitis patients, 8 (11%) LGI1 antibody encephalitis patients, and 6 (9%) GABAbR antibody encephalitis patients. The median age of the 70 patients was 33 years, 40% were female, and the initial symptoms in 31 patients (44%) were psychiatric in nature. Psychiatric disturbance appeared in 58 patients (83%) during inpatient treatment, after which 57 patients (81%) recovered. Conclusions Many patients with autoimmune encephalitis present psychotic symptoms; psychiatric symptoms typically appear before neurological features emerge. Timely diagnosis and treatment may yield favorable prognosis.

Co $$^+$$ ions with multiple energies from 50 to 380 keV were implanted into ZnO single crystals up to a total dose of $$1.25\times 10^{17}\,\hbox {cm}^2$$ . The implanted samples were annealed in open air for 30 min between 200 and 1100 $$^{\circ }$$ C. All the samples before and after implantation and annealing were characterized by X-ray diffraction (XRD), Raman scattering and positron annihilation measurements. XRD and Raman scattering measurements indicate that Co implantation induces severe lattice damage, and after annealing the damage recovers gradually. No Co clusters or Co-related second phase was observed in the implanted samples. Doppler broadening of positron annihilation radiation measurements using a slow positron beam reveals a large number of vacancy clusters introduced by Co implantation. After annealing up to 1000 $$^{\circ }$$ C, almost all the defects induced by implantation are removed. The implanted samples show clear ferromagnetism measured at 5 K. It shows very slight decrease after annealing at 700 $$^{\circ }$$ C and becomes much weaker after annealing at 1000 $$^{\circ }$$ C. The origin of ferromagnetism is most probably due to substitution of Co $$^+$$ ions at Zn lattice sites. However, it is apparent that the decrease in magnetization after annealing is consistent with the vacancy recovery process, indicating that the ferromagnetism in Co-implanted ZnO is mediated by defects such as Zn vacancy (V $$_{Zn}$$ ) or vacancy clusters. First principles calculations also support that Zn-related monovacancies and vacancy clusters can enhance the ferromagnetism in Co-doped ZnO.

Objective: To describe a case of leucine-rich, glioma inactivated 1 antibody-encephalitis presenting with psychosis. Methods: Case report. Results: A young man with leucine-rich, glioma inactivated 1-antibody encephalitis initially presented with acute psychotic symptoms, short-term memory loss and faciobrachial dystonic seizures. Magnetic resonance imaging revealed hippocampal lesions. Electroencephalography revealed frontotemporal slowing of background activity. Conclusion: Increased awareness of leucine-rich, glioma inactivated 1-antibody encephalitis may promote early recognition and treatment.

Depositional microfacies identification plays a key role in the exploration and development of oil and gas reservoirs. Conventionally, depositional microfacies are manually identified by geologists based on the observation of core samples. This conventional method for identifying depositional microfacies is time-consuming, and only the depositional microfacies in a few wells can be identified due to the limited core samples in these wells. In this study, the support vector machine (SVM) algorithm is proposed to identify depositional microfacies automatically using well logs. The application of SVM includes the following steps: First, the depositional microfacies are determined manually in several wells with core samples. Then, the training sets used in the SVM algorithm are extracted from the well logs. Finally, a quantitative discrimination model based on the SVM algorithm is established to realize the classification of depositional microfacies. Field application shows that this innovative and constructive solution can be effectively used in uncored wells to identify depositional microfacies with a rate of accuracy approaching 84%. It overcomes the limitation of the conventional manual method which greatly contributes to the cost-saving of core analysis and improves the sustainable profitability of oil and gas exploration.

We have investigated the dry etching of Al0.12GaAs/Al0.9GaAs Distributed Bragg Reflectors (DBRs) using photoresist mask in Inductively Coupled Plasma system with Cl2/BCl3/Ar chemistry. Resultant etch rate/etch profiles are studied as a function of ICP process parameters and photoresist mask sidewall profile. The vertical and inclined sidewalls were obtained via controlling mixing gas proportion. Enhancing physical effect in etching, photoresist mask patterns could transfer to etched substrate. In the end, controllable sidewall profile, smooth etch surface and repeatable process of Al0.12GaAs/Al0.9GaAs DBRs etching were achieved.

Surface passivation in InP-based High Electron Mobility Transistors (HEMTs) plays an important role in reducing or eliminating their surface effects which limit both direct-current (DC) and radio-frequency (RF) performances. In the present work, effect of surface passivation was studied using an ultra-thin 20 nm PECVD Si 3 N 4 layer. In DC performance, after passivation, its maximum transconductance ( g m , MAX ) is increased up to 1200 mS/mm. It is found that, by scaling the thickness of Si 3 N 4 layer, the increase in C gd after passivation can be effectively limited verified by small-signal modeling. As a result, S -parameter measurements demonstrate an increase in extracted f max up to 450 GHz after passivation. The results show that, by using an ultra-thin Si 3 N 4 surface passivation, its RF performance can be improved in InP-based HEMTs.

Molecular biological research into wood development and formation has been the focus in recent years, but the pace of discovery of related genes and their functions in the control of wood properties has been slow. The microarray technique—with its advantages of high throughput capacity, sensitivity, and reliability over other tools developed for investigating genes expression patterns—is capable of rapidly assaying thousands of genes. In this study, a cDNA microarray prepared from two cDNA libraries of developing poplar xylem tissues was used to assay gene expression patterns in immature xylem tissues at different heights from the main stem of Populus deltoides (15 years old), which was confirmed to have distinct wood properties (microfibrillar angle, woody density) by X-ray. Two hundred seventy-four transcripts with differential expression profiles between the chips were screened out, and the individual clones were subjected to 5′ sequencing. Using bioinformatic analysis, we identified candidate genes that may influence poplar wood properties, many of which belong to various regulatory and signal transduction gene families, such as zinc finger protein transcription factor, DNA-binding transcription factor, ethylene response factors, and so on. The results suggest that these genes may regulate enzymes involved in wood formation. Further work will be performed to clone these genes and determine how they influence poplar wood properties.

Leukemia stem cells (LSCs) are the subset of leukemic cells that drive leukemia progression, resist therapy, and remain latent to spark disease relapse. LSCs are quantified by efficiency of xenografting immunodeficient mice, a measurement that is predictive of leukemia outcome. Although LSCs have been previously thought to be rare and phenotypically primitive, recent data indicate that LSCs may actually be heterogeneous. Here, we use single-cell transcriptomics combined with limiting dilution xenotransplantation to dissect the ontogeny of MLL-rearranged B-lymphoblastic leukemia (MLL-r B-ALL), an aggressive form of childhood leukemia. Compared to acute myeloid leukemia (AML), LSCs are abundant in MLL-r B-ALL. Recapitulating the unique clinical behavior of this form of leukemia, MLL-r B-ALL cells undergo a B-lymphoid to myeloid lineage switch under chemotherapy pressure consistent with primitive, multipotent transcriptional programs present in LSCs. Although we identify rare, chemotherapy-resistant, primitive LSCs, we also observe LSCs emerging from more differentiated populations. These facultative LSCs self-renew and possess the capability to replenish the full cellular diversity of MLL-r B-ALL. Using CITE-seq, we find that stem cell programs can be fully uncoupled from immunophenotype in MLL-r B-ALL. In mechanistic studies, we find that the phenotypically differentiated LSCs that drive bottom-up reconstitution of the leukemic cellular ontogeny bear signatures of MYC activation and oxidative phosphorylation. We confirm recruitment of these pathways in actively reconstituting, phenotypically differentiated LSCs, and define a pathway by which MYC rewires metabolism in MLL-r B-ALL LSCs. We find that MYC is required for LSC plasticity in vitro and in vivo. Targeting oxidative metabolism impairs LSC engraftment, identifying a potential therapeutic intervention. We conclude that the high LSC content and dual lineage and LSC plasticities of MLL-r B-ALL contribute to its chemotherapy resistance and persistently poor outcomes. Disclosures Shalek: Honeycomb Biotechnologies: Consultancy, Current equity holder in publicly-traded company; Cellarity: Consultancy, Current equity holder in publicly-traded company; Repertoire Immune Medicines: Consultancy, Current equity holder in publicly-traded company; Merck: Consultancy; Orche Bio: Consultancy, Current equity holder in publicly-traded company; Dahlia Biosciences: Consultancy, Current equity holder in publicly-traded company.

In this work, experiments were carried out to compare the phase separation performance of double branching T-junction with that of single branching T-junction. The inlet and outlet branches of double T-junction were arranged horizontally with the inner diameter of 8 mm. R134a was used as the working fluid. The inlet mass flow rate (mass flux) was set at 10, 15, 20, 25 g s−1 (199, 298, 398, 497 kg m−2 s−1) and the inlet quality was set at 0.3, 0.5, 0.7 respectively in the experiment of single T-junction. It is concluded that the inlet mass flux has little influence on phase separation while the phase separation efficiency drops sharply with the increase of inlet quality, which is consistent with the conclusions in literature. The experimental data is also compared with the predicted values generated by theoretical models based on air-water and it is found that there is no model suitable for refrigerants. Furthermore, a comparative study between single T-junction and double T-junction was carried out from two perspectives: separation performance comparison of different branches and comparison between single and double T-junctions. The results show that the double T-junction performance is greatly affected by inlet quality and mass split ratio of the first branch, and not always higher than that of single T-junction for horizontal arrangement. Finally, predicting equations of outlet quality of double T-junction are correlated based on experimental data, which have a high predicting accuracy under the high mass split ratio conditions.

A Rh(III)-catalyzed aldehyde C–H bond functionalization of salicylaldehydes with arylboronic acids has been developed, with features of mild reaction condition and high efficiency. Furthermore, the functionalized 2-hydroxybenzophenone could be subject to divergent synthesis of heterocycles.

An Fe-catalyzed reductive coupling of unactivated alkenes with β-nitroalkenes has been developed. The reaction proceeds through a radical pathway, with β-nitroalkenes serving as the vinylating reagents and the nitro group being cleaved in the process. Therefore, this method provides a viable synthetic approach to valuable secondary- and tertiary-alkylated styrene derivatives. Furthermore, control experiments were conducted and a plausible mechanism is proposed.

We present and demonstrate a self-aligned pocket well (SPW) structure used in planar bulk MOSFETs with a metal gate length of 25 nm and an effective channel length less than 20 nm. The SPW features a retrograde doping profile in vertical direction and a doping profile self-aligned with drain/extension in lateral direction. A novel process, called replacement spacer gate (RSG), is designed to avoid challenges in gate patterning and high- $k$ metal gate filling. Planar bulk pMOSFETs, with SPW and halo doping, respectively, were simulated and fabricated adopting the RSG process. Due to its retrograde feature, the SPW can achieve low drain-induced barrier lowering (DIBL) along with low $V_{T}$ . Compared with halo doping with the same $V_{{T,{\rm sat}}}$ at $V_{\rm DD} = 0.8$ V, despite no $I_{\mathrm{{\scriptscriptstyle ON}}}$ enhancement, the SPW reduces DIBL by 45% and enhances $I_{\rm EFF}$ by 18%. Compared with halo doping with the same $I_{\mathrm{{\scriptscriptstyle OFF}}} = 100$ nA/ $\mu \text{m}$ at $V_{\rm DD} = 0.8$ V, the SPW structure reduces DIBL by 16%, enhances $I_{\mathrm{{\scriptscriptstyle ON}}}$ by 5%, and improves $I_{\rm EFF}$ by 30%. In addition, with the self-aligned feature, the SPW does not deteriorate junction band-to-band tunneling (BTBT) leakage in comparison with halo doping. Otherwise, 20 times larger BTBT leakage will emerge due to the profile overlap between retrograde doping and drain/extension doping.