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Process safety groups in the pharmaceutical industry are important components of active pharmaceutical ingredient development through its life cycle, from discovery to commercial manufacturing. The pharmaceutical process safety laboratory staff conduct a series of tests to identify chemically unstable reagents, intermediates, solvents, reaction mixtures, and high-energy reactions to ensure that the proposed operating conditions provide a sufficient safety margin from the onset of undesired and potentially catastrophic thermal decomposition. Across several pharmaceutical companies, the methods used for these assessments and how results and conclusions are made are widespread (vide infra). A working group was created with members from several pharmaceutical companies within the International Consortium for Innovation and Quality in Pharmaceutical Development, with the goal of precompetitive collaboration and to understand each of the participating companies’ procedures and assessment regarding process safety. Each company was invited to provide input using a blind survey format. This was done in the interest of making this knowledge accessible for the participating companies and the wider community of other pharma and chemical companies, and even academic institutions in the US and throughout the world. In this second article, we focus on instruments used to characterize thermal hazards in process safety laboratories. Detailed information on how these instruments are used and how all the instruments work together in process safety assessments at each stage of development is discussed.

Landslides are severe disasters that occur in mountainous areas, and can cause enormous losses. Nanxia expressway is located in the north mountainous region of Guangxi. A landslide occurred near the Yanlai overhead bridge built along the expressway. Investigations have shown that the landslide significantly affected the pier. Additionally, the occurrence of joints with the slope at a slight angle is dangerous, and the highly weathered sandstone increases the risk of landslide, particularly during heavy rainfall. In this study, a retaining wall combined with an anchor-stake was used to reinforce a slope and improve its safety during the rainy season. In the implemented stability measure, the quantity and consequently the cost of materials is lower compared with other methods. The slope was stable and safe during the subsequent overhead bridge operation. Based on the observed performance, it is concluded that the retaining wall combined with the anchor-stake efficiently and economically reinforces the slope against small landslides.

Organic light emitters based on multiresonance-induced thermally activated delayed fluorescent materials have great potential for realizing efficient, narrowband organic light-emitting diodes (OLEDs). However, at high brightness operation, efficiency roll-off attributed to the slow reverse intersystem crossing (RISC) process hinders the use of multiresonance-induced thermally activated delayed fluorescent materials in practical applications. Here we report a heavy-atom incorporating emitter, BNSeSe, which is based on a selenium-integrated boron–nitrogen skeleton and exhibits 100% photoluminescence quantum yield and a high RISC rate (kRISC) of 2.0 × 106s−1. The corresponding green OLEDs exhibit excellent external quantum efficiencies of up to 36.8% and ultra-low roll-off character at high brightnesses (with very small roll-off values of 2.8% and 14.9% at 1,000 cd m−2and 10,000 cd m−2, respectively). Furthermore, the outstanding capability to harvest triplet excitons also enables BNSeSe to be a superior sensitizer for a hyperfluorescence OLED, which shows state-of-the-art performance with a high excellent external quantum efficiency of 40.5%, power efficiency beyond 200 lm W−1, and luminance close to 20,0000 cd m−2.

Human infection with Chlamydia psittaciis rare but difficult to recognize. We report an outbreak of psittacosis among poultry processing workers in China. We applied metagenomic next-generation sequencing and identified Chlamydia psittacireads from samples of all seven patients, four of which were subsequently confirmed by PCR. Epidemiological results suggested that the poultry processed in the factory was the possible source of human infection.

We demonstrate a high-efficiency on-chip one-dimensional metalens for three-dimensional (3D) light focusing. The metalens consists of a one-dimensional dielectric nano-antenna array, which scatters the evanescent wave of a nano-waveguide into free space and focuses this scattered light into a 3D ring. The corresponding phase profile of the metalens is controlled by the relative locations of antennas in the array. Through antenna-waveguide distance optimization, the designed metalens only scatters 1.5% of propagation light into free space and 55% of the scattered energy is focused into the 3D ring. When we use the antennas with an optimized shape, 50.18% of the focused energy is concentrated in a circular arc of the ring, which subtends an angle of 48°. This high-efficiency on-chip one-dimensional metalens is promising for non-invasive optical signal detection in photonic integrated chips.

The hazard assessment of a telescoped Miyaura borylation and Suzuki coupling reaction employing bis(pinacolato)diboron (BisPin), used in the developmental synthesis of an intermediate for abemaciclib, led to the observation of hydrogen being generated. Quantitative headspace GC and solution 11B NMR were used to show that the rapid decomposition of the excess BisPin from the borylation under the aqueous basic conditions of the Suzuki reaction was responsible for H2generation. The moles of H2observed were found equal to the BisPin excess, which is rationalized by mass balance and a stoichiometric reaction. The possible generation of the stoichiometric levels of H2should be considered in hazard assessments of this class of reaction. Kinetic and process modeling was used to minimize the risk upon scale-up, and results for commercial manufacturing batches are presented, which showed good agreement with the lab scale data. Furthermore, the hydrogen evolution potentials of other common borylating agents including bisboronic acid (BBA) and pinacol borane were demonstrated.

Quantum mechanical (QM) applications to predict heat of reaction (ΔHr) and thermal stability of strained aminocarbocylic salts, diazo compounds, and nitroalkanes for early phase thermal hazard risk assessment is presented. We provide examples on the use of explicit solvation to predict accurate ΔHr. Based on the QM calculations, the criticality class of a copper-catalyzed C–N coupling reaction is determined according to Stoessel’s reaction criticality class and the predictions are consistent with RC1 calorimetric experiment. We emphasize that to predict accurate ΔHr, it is important to consider the roles of reagents and solvents in QM calculations rather than simply considering the bond formation and bond breaking steps involved with reactants and products. Further, the use of predicted ΔHrfor salt formation is applied to predict the thermal stability of bromoacetylene azetidine compounds to establish structure–stability relationship which would be useful to identify stable salt intermediates for safe reaction design. A strong correlation between ΔHrand the left limit of the DSC onset temperature (Tinit, °C) of the of exothermic peak is identified (Tinit= −2.85 ΔHr− 99.5). We propose that this model can be used as a prediction tool for novel azetidine salts to provide an estimate of thermal stability before synthesis. In this paper, for the first time we report molecular electrostatic potential (MESP) descriptor for the prediction of Tinitof diazo compounds. The deepest MESP minimum (Vmin) on the diazo group is considered as a probe to quantify the variation in structural effects. A strong correlation between Vminand Tinitis found which would provide a new way of interpreting the thermal stability of novel diazo molecules just based on chemical structure. Further, the applicability of Vminis verified on another set of compounds (nitroalkanes) and a good correlation is obtained. The structure–stability relationships that involves Vmincan be a useful QM descriptor for thermal stability prediction of a variety of molecules.

A cattle pangenome representation was created based on the genome sequences of 898 cattle representing 57 breeds. The pangenome identified 83 Mb of sequence not found in the cattle reference genome, representing 3.1% novel sequence compared with the 2.71-Gb reference. A catalog of structural variants developed from this cattle population identified 3.3 million deletions, 0.12 million inversions, and 0.18 million duplications. Estimates of breed ancestry and hybridization between cattle breeds using insertion/deletions as markers were similar to those produced by single nucleotide polymorphism–based analysis. Hundreds of deletions were observed to have stratification based on subspecies and breed. For example, an insertion of a Bov-tA1 repeat element was identified in the first intron of the APPL2gene and correlated with cattle breed geographic distribution. This insertion falls within a segment overlapping predicted enhancer and promoter regions of the gene, and could affect important traits such as immune response, olfactory functions, cell proliferation, and glucose metabolism in muscle. The results indicate that pangenomes are a valuable resource for studying diversity and evolutionary history, and help to delineate how domestication, trait-based breeding, and adaptive introgression have shaped the cattle genome.

Developing organic thermally activated delayed fluorescence (TADF) emitters with high efficiency and narrowband emissions is crucial and challenging for high-quality organic light-emitting diodes (OLEDs). Here, three multiresonance TADF emitters DPACzBN1, DPACzBN2, and DPACzBN3 are designed via a peripheral decoration strategy and synthesized through a lithium intermediate cascade borylation reaction (15% yield for DPACzBN1) or a more efficient lithium-free direct borylation reaction (45% yield for DPACzBN2 and 75% yield for DPACzBN3). All the emitters exhibit a similar blue emission with small full-width at half maximum (fwhm) values as low as 20 nm in toluene solutions. The introduction of the diphenylamino moiety into the parent molecule DPACzBN1 can not only maintain the high photoluminescence quantum yields over 90% but also narrow the bandwidth and enhance the rate constant of the reverse intersystem crossing process, as well as suppress the spectral broadening in devices. Benefiting from the excellent TADF properties and good inhibition of spectral broadening, TADF OLEDs based on DPACzBN3 achieve the highest maximum external quantum efficiency of 27.7% and the smallest fwhm of 24 nm among the three emitters.

The large-scale manufacture of complex synthetic peptides is challenging due to many factors such as manufacturing risk (including failed product specifications) as well as processes that are often low in both yield and overall purity. To overcome these liabilities, a hybrid solid-phase peptide synthesis/liquid-phase peptide synthesis (SPPS/LPPS) approach was developed for the synthesis of tirzepatide. Continuous manufacturing and real-time analytical monitoring ensured the production of high-quality material, while nanofiltration provided intermediate purification without difficult precipitations. Implementation of the strategy worked very well, resulting in a robust process with high yields and purity.

The neutral salt spray test was carried out on TSZ410 stainless steel welded joints, and its corrosion behavior was studied using metallurgical microscope, scanning electron microscope, X-ray diffractometer, energy-dispersive spectrometer, electrochemical workstation, and weight-loss analysis. The results showed that after salt spray test for 128 days, there was obvious corrosion at the matrix while there was no visible corrosion at the weld seam and fusion area. The structure of the weld seam was not changed, indicating its good corrosion resistance. [ABSTRACT FROM AUTHOR]

The synthesis of the highly energetic pharmaceutical intermediate 4-methyl-1,2,5-oxadiazole-3-carboxylic acid via cyclization of (2E,3E)-butane-2,3-dione dioxime followed by selective oxidation of the resulting 3,4-dimethyl-1,2,5-oxadiazole was developed to support the sample production for clinical trials. Rigorous process safety evaluations revealed many potential safety risks associated with the involved highly energetic compounds and the high exothermicity of the oxidation reaction. A continuous flow process was developed for the synthesis of 3,4-dimethyl-1,2,5-oxadiazole to mitigate the potential safety risks associated with the thermal instability of starting material (2E,3E)-butane-2,3-dione dioxime and product 3,4-dimethyl-1,2,5-oxadiazole. A much safer process for the highly exothermic oxidation of 3,4-dimethyl-1,2,5-oxadiazole involving portion-wise addition of potassium permanganate was developed to avoid accumulation of reactive chemicals. The desired product was isolated as N-methyl morpholine 4-methyl-1,2,5-oxadiazole-3-carboxylate to avoid handling of potentially explosive 4-methyl-1,2,5-oxadiazole-3-carboxylic acid in its solid form. The developed process was successfully scaled up to afford a total of 93.52 kg of N-methyl morpholine 4-methyl-1,2,5-oxadiazole-3-carboxylate to support the production of a drug substance.

ABSTRACTZika virus (ZIKV) is an emerging arthropod-borne flavivirus that, upon infection, results in teratogenic effects and neurological disorders. ZIKV infections pose serious global public health concerns, prompting scientists to increase research on antivirals and vaccines against the virus. These efforts are still ongoing as the pathogenesis and immune evasion mechanisms of ZIKV have not yet been fully elaborated. Currently, no specific vaccines or drugs have been approved for ZIKV; however, some are undergoing clinical trials. Notably, several strategies have been used to develop antivirals, including drugs that target viral and host proteins. Additionally, drug repurposing is preferred since it is less costly and takes less time than other strategies because the drugs used have already been approved for human use. Likewise, different platforms have been evaluated for the design of vaccines, including DNA, mRNA, peptide, protein, viral vectors, virus-like particles (VLPSs), inactivated-virus, and live-attenuated virus vaccines. These vaccines have been shown to induce specific humoral and cellular immune responses and reduce viremia and viral RNA both in vitroand in vivo. Importantly, most of these vaccines have entered clinical trials. Understanding the viral disease mechanism will provide better strategies for developing therapeutic agents against ZIKV. This review provides a comprehensive summary of the viral pathogenesis of ZIKV and current advancements in the development of vaccines and drugs against this virus.

To explore the enhancement features of early hepatocellular carcinoma (HCC, including well‐differentiated HCC and high‐grade dysplastic nodules with a focus of HCC) and high‐grade dysplastic nodules (HGDNs) on contrast‐enhanced ultrasound (CEUS), correlated with the histopathologic findings. This retrospective study enrolled 81 patients with 85 pathologically confirmed hepatic lesions (69 early HCCs and 16 HGDNs). All of the hepatic lesions were examined by CEUS with SonoVue (Bracco SpA, Milan, Italy) before surgery or biopsy. The enhancement features of early HCCs and HGDNs were evaluated and compared with histopathologic findings. Thirty‐eight (55.1%) early HCCs showed arterial‐phase hyperenhancement (APHE). The major enhancement pattern of early HCCs was APHE without portal venous/late‐phase wash‐out (20 of 69 [29.0%]). Eight (11.6%) early HCCs manifested APHE. Wash‐out was observed in 30 (43.5%) early HCCs. Sixteen (23.2%) early HCCs showed very‐late wash‐out (>120 seconds). Wash‐out was not observed in all HGDNs. Of the 16 HGDNs, arterial‐phase isoenhancement without portal venous/late‐phase wash‐out was the major enhancement pattern (n = 7 [43.8%]). The degree of CD34 expression of sinusoidal endothelial cells was more diffuse in early HCCs than in HGDNs (56.5% versus 12.5%; P= .001). Arterial‐phase enhancement patterns of early HCCs on CEUS were correlated with the degree of CD34 expression (P= .039). Enhancement patterns were significantly different between early HCCs and HGDNs on CEUS. Diffuse CD34 expression of sinusoidal endothelial cells in early HCC was correlated with APHE on CEUS.

Various models have been applied to predict the trend of the epidemic since the outbreak of COVID‐19. In this study, we designed a dynamic graph model, not for precisely predicting the number of infected cases, but for a glance of the dynamics under a public epidemic emergency situation and of different contributing factors. We demonstrated the impact of asymptomatic transmission in this outbreak and showed the effectiveness of city lockdown to halt virus spread within a city. We further illustrated that sudden emergence of a large number of cases could overwhelm the city medical system, and external medical aids are critical to not only containing the further spread of the virus but also reducing fatality. Our model simulation showed that highly populated modern cities are particularly vulnerable and lessons learned in China could facilitate other countries to plan the proactive and decisive actions. We shall pay close attention to the asymptomatic transmission being suggested by rapidly accumulating evidence as dramatic changes in quarantine protocol are required to contain SARS‐CoV‐2 from spreading globally. Author summary:We designed a dynamic graph model for a glance of the dynamic under the COVID‐19 pandemic by considering a transportation model as the center. We illustrated that the asymptomatic transmission is the dominating factor contributing to the outbreak and city lockdown is the most effective way to halt virus spread. In addition, the external medical aids are able to effectively reduce the fatality rate when the city medical system is overwhelmed.

Monitoring pH is of great importance in a diverse range of fields ranging from the industrial and agricultural to environmental and biomedical fields. Herein we introduce and demonstrate a sensing scheme that utilizes a pH-sensitive ligand, citric acid (CA), to modulate a cascaded energy transfer process in Ce3+-sensitized fluoride nanocrystals (NCs), resulting in a change of emission to provide pH sensing over a broad range from 3 to 10. The ligand modulates cascaded energy transfer from Ce3+to Gd3+and then to activators (Tb3+, Eu3+, and Mn2+) in the pH values from 3 to 10. The decreased energy transfer efficiency from Ce3+to Gd3+ions by a pH-responsive electronegativity alteration of the ligand at higher pH activates the sensing capability. All of the sensing properties are completely reversible and independent of sensor concentrations in the ratiometric analysis. Our findings provide a new promising pH sensing design based on inorganic fluoride NCs.

Background: Recent state-of-the-art sequencing technologies enable the investigation of challenging regions in the human genome and expand the scope of variant benchmarking datasets. Herein, we sequence a Chinese Quartet, comprising two monozygotic twin daughters and their biological parents, using four short and long sequencing platforms (Illumina, BGI, PacBio, and Oxford Nanopore Technology). Results: The long reads from the monozygotic twin daughters are phased into paternal and maternal haplotypes using the parent–child genetic map and for each haplotype. We also use long reads to generate haplotype-resolved whole-genome assemblies with completeness and continuity exceeding that of GRCh38. Using this Quartet, we comprehensively catalogue the human variant landscape, generating a dataset of 3,962,453 SNVs, 886,648 indels (< 50 bp), 9726 large deletions (≥ 50 bp), 15,600 large insertions (≥ 50 bp), 40 inversions, 31 complex structural variants, and 68 de novo mutations which are shared between the monozygotic twin daughters. Variants underrepresented in previous benchmarks owing to their complexity—including those located at long repeat regions, complex structural variants, and de novo mutations—are systematically examined in this study. Conclusions: In summary, this study provides high-quality haplotype-resolved assemblies and a comprehensive set of benchmarking resources for two Chinese monozygotic twin samples which, relative to existing benchmarks, offers expanded genomic coverage and insight into complex variant categories.

High oil and protein content make tetraploid peanut a leading oil and food legume. Here we report a high-quality peanut genome sequence, comprising 2.54 Gb with 20 pseudomolecules and 83,709 protein-coding gene models. We characterize gene functional groups implicated in seed size evolution, seed oil content, disease resistance and symbiotic nitrogen fixation. The peanut B subgenome has more genes and general expression dominance, temporally associated with long-terminal-repeat expansion in the A subgenome that also raises questions about the A-genome progenitor. The polyploid genome provided insights into the evolution of Arachis hypogaeaand other legume chromosomes. Resequencing of 52 accessions suggests that independent domestications formed peanut ecotypes. Whereas 0.42–0.47 million years ago (Ma) polyploidy constrained genetic variation, the peanut genome sequence aids mapping and candidate-gene discovery for traits such as seed size and color, foliar disease resistance and others, also providing a cornerstone for functional genomics and peanut improvement.

To study the clinical effect on old ankle injury treated with collateral bloodletting at ashipoint combined with the external application of Sānqī (三七 Radix et Rhizoma Notoginseng) powder.

The extraction of core phases through seismic interferometry is important for exploring the seismic structure of the Earth's inner core because it can provide an unprecedented data coverage. However, low signal‐to‐noise ratios and uncertainties in phase arrivals hinder the application of seismic interferometry. With three arrays from the China Regional Seismic Network, South America, and the western United States, we simulate coda interferometry using the one‐dimensional synthetic coda of large earthquakes (magnitude ≥ 7.0) from 2005 to 2012. Compared with the cross correlations of real coda (10,000–40,000 s after earthquakes), the similarities among the simulated waveforms of the core phases (PKIKP, PKIIKP, PKPab, PKIKP2, and PKIIKP2) indicate that reverberations at first‐order discontinuities constitute the major source for coda interferometry. Relative to synthesized Green's functions, the core phases derived from coda interferometry provide reliable phase information but varying amplitudes. In particular, the slownesses are generally consistent with the theoretical calculations, thereby confirming the extracted phases. The simulations prefer the 15‐ to 50‐s period band and indicate that the earthquake distribution has an insignificant effect on the retrieval of core phases at small distances (0–8°). Coda interferometry is scarcely affected by white noise, but it is influenced by the attenuation of the inner core. Experiments on focal mechanisms further suggest that coda signals from dip‐slip earthquakes mainly contribute to the reconstruction of the core phases (except for the simulated PKPab). Core phases are extracted and confirmed through simulations of coda interferometryReverberations at first‐order discontinuities from large earthquakes are the major source to reconstruct the core phasesThe retrieval of core phases is dependent on frequency band and focal mechanism but not significantly affected by source heterogeneities

This study was designed to evaluate the effects of drilling through the growth plate and using adipose-derived stem cells (ADSCs) and bone morphogenetic protein-2 (BMP-2) to treat femoral head epiphyseal ischemic necrosis, which can be done in juvenile rabbits. Passagefour bromodeoxyuridine (BrdU)-labeled ADSCs were cultured, assayed with MTT to determine their viability and stained with alizarin red dye to determine their osteogenic ability. Two-month-old, healthy male rabbits (1.2 to 1.4 kg, n=45) underwent ischemic induction and were randomly divided into five groups (group A: animal model control; group B: drilling; group C: drilling & ADSCs; group D: drilling & BMP-2; and group E: drilling & ADSCs & BMP-2). Magnetic resonance imaging (MRI), X-ray imaging, hematoxylin and eosin staining and BrdU immunofluorescence detection were applied 4, 6 and 10 weeks after treatment. Approximately 90% of the ADSCs were labeled with BrdU and showed good viability and osteogenic ability. Similar results were observed in the rabbits in groups C and E at weeks 6 and 10. The animals of groups C and E demonstrated normal hip structure and improved femoral epiphyseal quotients and trabecular areas compared with those of the groups A and B (P<0.01). Group D demonstrated improved femoral epiphyseal quotients and trabecular areas compared with those of groups A and B (P<0.05). In summary, drilling through the growth plate combined with ADSC and BMP-2 treatments induced new bone formation and protected the femoral head epiphysis from collapsing in a juvenile rabbit model of femoral head epiphyseal ischemic necrosis.

With the development of molecular biology technology, the discovery of microRNAs (miRNAs) has provided new ideas for the diagnosis, treatment, and prognosis of lung cancer and laid a foundation for the study of this malignancy. To assess the potential prognostic value of miR-92a as a new biomarker in non-small cell lung cancer (NSCLC) via clinical evaluation, a total of 100 patients with NSCLC admitted to the Respiratory and Intensive Care Department of Suining Central Hospital in Sichuan Province between August 2007 and April 2020 were retrospectively analyzed. The correlation between miR-92a expression and prognosis of patients with NSCLC was also evaluated in the present study. The expression level of miR-92a was measured by PT-PCR and in situ hybridization. Chi-square test was adopted to explore the relationship of miR-92a expression and clinical features. Kaplan–Meier survival curves were plotted to delineate the overall survival rate of patients with NSCLC. Cox regression analysis was performed to evaluate the prognostic significance of miR-92a expression in NSCLC. The miR-92a expression in NSCLC tissue samples was significantly higher than that in normal lung tissues (P< .001) and significantly correlated with the Eastern Cooperative Oncology Group score, histological type, and distant metastasis (P< .05). Survival curve revealed that patients with NSCLC and high miR-92a expression had relatively higher mortality than those with low PAK4 expression (P= .001). Cox regression analysis explained that miR-92a expression was associated with the prognosis of patients with NSCLC (HR = 1.8, 95% CI: 1.0–3.2, P= .036). In summary, miR-92a was highly expressed in NSCLC tissues and could act as a prognostic factor for patients with NSCLC. These results illustrate that miR-92a expression plays an important role in the invasion and metastasis of NSCLC, and miR-92a can be used as a new biomarker to determine the prognosis of this cancer.

We have previously studied a series of room temperature ionic liquids (RTILs) based on 1-ethyl-3-methylimidazolium ([emim]+) and tetra-alkylphosphonium ([P222n]+) cations with different aprotic heterocyclic anions (AHAs). It has been found that many of the AHA ILs exhibit very good conductivity for their viscosities. The results provide insight into the design of ILs with enhanced dynamics that may be suitable for electrolyte applications (1, 2). Lithium salts based on the bis(trifluoromethylsulfonyl)imide ([TFSI]-), bis(fluorosulfonyl)imide ([FSI]-) and tetrafluoroborate ([BF4]-) anions have been extensively studied in lithium salt/IL mixtures for such applications (3-18). Here we will further explore how the addition of lithium AHA salts, compared to the popular [TFSI]-, [FSI]- and [BF4]--based ones, affects the transport properties of the RTILs in order to evaluate the feasibility of using these AHA ILs for lithium-ion battery applications. In particular, we investigate the viscosity and ionic conductivity, as well as anion, cation and lithium diffusivity, as measured by Pulse-Gradient-Spin-Echo NMR spectroscopy.

This work investigates the ability of LIBS to produce quality spectra from small particles of concrete demolition waste using single-shot spectra collected in open air. The 2–8 mm materials are rounded river gravel, green glass shards, and plastic flakes. Considered are focal length, air, moisture, laser energy, and laser incidence angle (LIA). The research methodology is an experimental study using the so-called observation depth(OD)and spectral abundanceas quality indicators. The relation between ablation volume, breakdown threshold, optical signal strength, and OD is captured in a simplified model to provide a better understanding of the dependence of the spectra on the LIA and material positioning in the laser beam. A 100 mm lens provided a compromise between spectral abundance, level of air interference and achievable OD. The study indicates LIBS can yield good quality data, even in cases of up to 3 mm surface roughness. Surface moisture did raise the percentage of bad spectra from an average 4% to 18%, but overall LIBS is still capable of providing quality data under challenging conditions.

Gallbladder adenoma is a pre-cancerous neoplasm and needs surgical resection. It is difficult to differentiate adenoma from other gallbladder polyps using imaging examinations. The study aimed to illustrate characteristics of contrast-enhanced ultrasound (CEUS) and its diagnostic value in gallbladder adenoma.

The Earth’s solid inner core exhibits strong anisotropy, with wave velocity dependent on the direction of propagation due to the preferential alignment of iron crystals. Variations in the anisotropic structure, laterally and with depth, provide markers for measuring inner-core rotation and offer clues into the formation and dynamics of the inner core. Previous anisotropy models of the inner core have assumed a cylindrical anisotropy in which the symmetry axis is parallel to the Earth’s spin axis. An inner part of the inner core with a distinct form of anisotropy has been suggested, but there is considerable uncertainty regarding its existence and characteristics. Here we analyse the autocorrelation of earthquake coda measured by global broadband seismic arrays between 1992 and 2012, and find that the differential travel times of two types of core-penetrating waves vary at low latitudes by up to 10 s. Our findings are consistent with seismic anisotropy in the innermost inner core that has a fast axis near the equatorial plane through Central America and Southeast Asia, in contrast to the north–south alignment of anisotropy in the outer inner core. The different orientations and forms of anisotropy may represent a shift in the evolution of the inner core.

This paper has introduced a kind of method which can simulate the echo signal of radar receiver by the use of the Digital Radio Frequency Memory (DRFM) and Programable Logic Device (PLD).With the realization of actual circuit,the echo simulator can produce intermediate frequency and video signals.Therefore,with the help of the echo simulator, we can raise the detection ability of radar receiver system considerably. The structure of the simulator is simple but its function is great.The echo simulator can simulate intermediate frequency signals of radar receiver system for the first time.So the simulator can locate where isn’t work well of the radar receive system.

The dynamic target echo intermediate-frequency signal source can be used to detecting and repairing receiving system, signal processing system, display system of conventional radar. The output frequency which conducted by the signal source can be adjusted. The range of output signal frequency basically covers different types of radar, which has important practical application value on the maintenance of radar. The dynamic target echo intermediate-frequency signal source is make up of source processing unit, intermediate-frequency unit, monitoring unit, the time reference source, input and output driver board and power supply pulse generation. Pulse processing unit in the signal source is in the core status.

This study investigates the influence of material nonlinear in slender reinforced concrete (RC) columns dynamic second-order effects under seismic load. The stiffness reduction coefficient is adopted in this paper. To identify the significance of various effects in terms of the dynamic second-order effects of the slender RC columns, nonlinear dynamic analyses are conducted for different periods and stability coefficients of simulated models with rare occurrence earthquake. On the basis of the obtained numerical results, the influence of material nonlinear for dynamic second-order effects are reviewed.

In order to ensure the dimensional accuracy of housing with small fillets, various forming factors have been analyzed in this paper based on finite element simulation. Through the analysis of the forming factors, the principle of die angle selection, the proper reverse drawing height in sizing process, sequence of sizing and applications of local sheet bulk metal forming in housing production were put forward, and some forming laws of housing with small fillets were concluded.

The production method of a driving axles used in gearbox is presented in this paper. A five-stage cold extrusion technology for forming the driving axle was made. First, simulations based on thermal-mechanical coupling finite element model were performed with Deform_2D. During the forming process, the concave appeared at the shaft end. And its formation mechanism was studied. Then the forming rules were obtained. Corresponding experiments were carried out and quality forging was achieved. Simulation and experimental results both indicate that the five-stage cold extrusion technology was feasible.

The morphologies of triblock copolymer/homopolymer blend films confined between two neutral hard walls were studied via MC simulations on a simple cubic lattice. For ABA/A and ABA/B blend films, the effects of φh(the volume fraction of the homopolymer) and Mh/Mb(the ratio of the molecular mass of the homopolymer to that of the corresponding blocks) on the morphologies were investigated in detail. For both ABA/A and ABA/B blend films, a higher φhor Mh/Mbwould result in stronger macrophase separation between the triblock copolymer and homopolymer. For ABA/C blend films, Mh/Mbhardly influences the morphologies of homopolymer domains regardless of whether the homopolymer C is more compatible with block A or with block B. Compared to AB/A and AB/C blend films, the morphologies of ABA/A (or ABA/B) and ABA/C blend films are much more irregular. The simulated results in this work show good consistency with experiments and other simulations.

The transport of the overdamped Brownian particles in a spatially periodic potential subject to the threevalue Poissonian noise in the stationary state is considered. We show that for the spatially periodic potential, no matter whether it is asymmetric, or is symmetric, flux can be induced. But the mechanism is different. The former is the common action of broken reflection symmetry and transition among three-value Poissonian noise in a cyclic way; the latter is single behavior of transition among three-value Poissonian noise in a cyclic way.

In this paper, we study the transport of the system with the additive temporal-spatial noise, by two models, i.e., a spatial asymmetry model and a spatial symmetry model. The study shows that the correlation of the additive noise with the space and the spatial asymmetry are ingredients for the transport.

The transport of a spatially periodic system with infinite globally coupled oscillators driven by temporal-spatial noises is investigated. The probability current shows that the correlation of the multiplicative noises with the space, the spatial asymmetry, and the coupling among the different oscillators are ingredients for the transport of particles. It is a new phenomenon that the correlation of the multiplicative noises with the space can induce the nonzero flux.

Expression of the high‐affinity receptor on basophils and mast cells is modulated by immunoglobulin E (IgE) antibody. Recent studies have shown that modulation occurs through interaction of IgE with the receptor itself, but the mechanisms underlying this control are not understood. Taking both a theoretical and experimental approach, we examined several competing models that focus on whether there is IgE‐regulated loss, IgE‐regulated synthesis, or both regulated loss and synthesis of the Fc receptor for IgE (FcɛRI). We report that removing IgE from occupied FcɛRI resulted in an accelerated loss only in the unoccupied receptor, with no loss of occupied receptors and no loss of total receptors when all receptors were occupied. Together with previous studies, these results establish that there was IgE‐regulated loss of receptors. An examination of synthetic rates of FcɛRIα using pulse‐labeling with 35S‐methionine indicated no difference in synthetic rates in the presence or absence of IgE. Similarly, the presence or absence of IgE had no influence on the levels of mRNA for either α, β, or γ subunits of FcɛRI. Using model simulations, we found that regulated‐synthesis models could be distinguished from regulated‐loss/constant‐synthesis models on the basis of the relationship between starting FcɛRI densities and changes in density after culture for 1 week in the absence of IgE. Experimental data from this type of study fit a regulated‐loss model that did not include regulation of synthesis. Taken together, these results suggest that IgE regulates cell surface expression of FcɛRI only by regulating the rate that receptor is lost from the cell surface.

Background:Disialoganglioside GD3 is expressed on the surface of selected cell types. Anti-GD3 mAb administered to human subjects with malignant melanoma produces signs and symptoms of immediate hypersensitivity reactions. Objective:The expression of GD3 by human mast cells was assessed during mast cell development in vitro and in samples of lung and skin. Methods:GD3 on tissue- and in vitro–derived mast cells was analyzed after double labeling of cells for tryptase (G3 mAb) or Kit (YB5.B8 mAb) and GD3 (R24 mAb). Glycolipids in extracts of fetal liver–derived mast cells were examined by using high-performance thin-layer chromatography. Results:Flow cytometry showed that the percentage of GD3+cells increased in parallel to Kit+cells during the recombinant human stem cell factor–dependent development of fetal liver–derived mast cells. Double-labeling experiments showed that GD3+cells were also surface Kit+and granule tryptase positive, identifying them as mast cells in preparations of lung-, skin-, fetal liver–, and cord blood–derived cells. The major acidic glycolipid detected was NeuAcα2-8NeuAcα2-3Galβ1-4Glcβ1-1′Cer (GD3). Among peripheral blood leukocytes, only basophils and about 10% of the T cells were labeled with anti-GD3 mAb. Anti-GD3 mAb–conjugated magnetic beads were used to purify mast cells to greater than 90% purity from dispersed skin cells enriched to approximately 12% purity by means of density-dependent sedimentation but were less proficient for dispersed human lung mast cells, most likely because of other cell types that express GD3. Conclusion:GD3 is expressed on the surface of developing human mast cells in parallel to tryptase in secretory granules and, like Kit, can serve as a target for their enrichment by immunoaffinity techniques. (J Allergy Clin Immunol 2001;107:322-30.)

The rational design and synthesis of highly-efficient cathode catalysts are of importance to high-performance lithium-oxygen batteries (LOBs). In this work, We use crab shell waste as a carbon source through carbonization, activation, and sol-gel method to synthesize activated functional carbon (AFC) and fabricate CoPt/AFC catalyst for Li-O2batteries. The as-prepared AFC possesses abundant hydroxyl (OH‒) and amino (NH2‒) groups as the link bridge for enhancing the metal-support interaction. Revealed by the density functional theory calculations, the tuned adsorption for intermediates and reduced overpotentials for both oxygen reduction and evolution reactions (ORR and OER) are achieved on such the composite structure. Experimentally, CoPt nanoparticles are evenly distributed on the surface of OH‒ and NH2‒ functionalized porous carbon through the sol-gel method. The abundant pore structures in the resultant catalyst (CoPt/AFC) can provide sufficient room for depositing discharge products. Moreover, the side reactions are effectively suppressed, as evidenced by the in-situ Raman spectra. As a result, the LOBs with the CoPt/AFC cathode present excellent electrochemical performances with a high discharge specific capacity of 8.25 mAh cm−2, a low overpotential of 0.47 V, and good cycling stability of 156 cycles.

ABSTRACTIn recent years, black testa peanut (Arachis hypogaeaL.) has been favored because of its nutritional value and health function. To explore the genetic basis of peanut testa color, high-throughput sequencing technology was used to sequence the transcriptome of black testa peanut ‘ZH9ʹ and pink testa peanut ‘ZH8.ʹ Over 18 million high-quality reads were assembled into 49,404–52,578 genes for these two cultivars using a combined assembly strategy. Totally, 4,122 differentially expressed genes (DEGs) were identified between ZH8 and ZH9, among which 1317 (32%) were up-regulated and 2805 (68%) were down-regulated. KEGG analysis showed that the pathways of anthocyanin biosynthesis, isoflavonoid biosynthesis, flavone and flavonol biosynthesis, and phenylpropanoid biosynthesis were in the top 20 differentially expressed genes enriched pathways. Further analysis showed that the formation of the black color of ZH9 testa was mainly due to the reduction of lignin biosynthesis and isoflavonoid biosynthesis, and as a result, more substrate flow to anthocyanin biosynthesis. The up-regulation of all genes associated with DFR, a key enzyme determining flavonoid synthesis or anthocyanin synthesis in the flavonoid metabolic pathway, is also a strategy for increasing dihydroflavonol, a substrate for anthocyanin and flavonol biosynthesis. In addition, we identified three up-regulated R2R3MYB transcription factors associated with anthocyanin biosynthesis in ZH9. Finally, we verified the expressions of 15 genes that encode key enzymes and transcription factors using quantitative real-time PCR (qRT-PCR).

Soft soil was widely distributed in the coastal area, and the key characters were high water content and low capacity. Cement Mixing Pile (CMP) is an effective method to treat soft soil foundation. While CMP construction quality was difficult to control and it was of different reinforce effect for different geology origin. In this paper, five geology origins have been divided for the littoral area, lagoon area, alluvial area (Yangtse River), alluvial area (Ancient Yellow River) and lacustrine area. CMP, used in 26 expressways which were constructed during the period of 2008 - 2016, has been divided two-part (Upper & Lower part) to test the construction quality of CMP through Standard Penetration Test (SPT), Unconfined Compaction Strength (UCS) and Cement Mixing Pile Quality Designation (CMPQD). Results show that geology origins have great influence on the construction quality of CMP at the same construction maintenance condition. Depth has a significant effect on UCS of the lower part of CMP while the little effect on UCS of the upper part. Construction quality of long CMP was more difficult to control than short CMP. The high quality of the upper part may cause the unqualified lower part evaluated as qualified or good, which may lead to some engineering accidents.