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Evaluation of Cr, Mn, Fe, Zn and Se in humans is challenged by the potentially high within-individual variability of these elements in biological specimens, which are poorly characterised. This study aimed to evaluate their within-day, between-day and between-month variability in spot samples, first-morning voids and 24-h collections. A total of 529 spot urine samples (including eighty-eight first-morning voids and 24-h collections) were collected from eleven Chinese adult men on days 0, 1, 2, 3, 4, 30, 60 and 90 and analysed for these five elements using inductively coupled plasma-MS. Intraclass correlation coefficients (ICC) were utilised to characterise the reproducibility, and their sensitivity and specificity were analysed to assess how well a single measurement classified individuals’ 3-month average exposures. Serial measurements of Zn in spot samples exhibited fair to good reproducibility (creatinine-adjusted ICC = 0·47) over five consecutive days, which became poor when the samples were gathered months apart (creatinine-adjusted ICC = 0·33). The reproducibility of Cr, Mn, Fe and Se in spot samples was poor over periods ranging from days to months (creatinine-adjusted ICC = 0·01–0·12). Two spot samples were sufficient for classifying 60 % of the men who truly had the highest (top 33 %) 3-month average Zn concentrations; for Cr, Mn, Fe and Se, however, at least three specimens were required to achieve similar sensitivities. In conclusion, urinary Cr, Mn, Fe, Zn and Se concentrations showed a strong within-individual variability, and a single measurement is not enough to efficiently characterise individuals’ long-term exposures.
We assessed inheritance of resistance to sugarcane brown rust (Puccinia melanocephala) in selfing F1 populations of wild sugarcane germplasm Erianthus rockii ‘Yundian 95-19’ and E. rockii ‘Yundian 95-20’. We tested parent and selfing F1 individuals for the brown rust resistance gene, Bru1, that has been shown to confer resistance to brown rust in sugarcane. The Bru1 gene was not detected in E. rockii ‘Yundian 95-19’, E. rockii ‘Yundian 95-20’ or their selfing F1 individuals, and we found there was segregation of resistance in the two selfing F1 populations (segregation ratio: 3:1). The results confirmed resistance in E. rockii ‘Yundian 95-19’ and E. rockii ‘Yundian 95-20’ to sugarcane brown rust is controlled by a novel, single dominant gene.
Dalian, China, is a city free of rabies in recent 20 years, but the annual cost for rabies vaccination still brings an economic burden on society and individuals. We did a retrospective descriptive analysis to analyse the reason for this and try to find some ways to resolve it. A total of 10 028 post-exposure prophylaxis (PEP) cases were recorded from January 2016 to December 2017. According to the exposure grades, 32 cases were grade I; 7712 cases were grade II; 2284 cases were grade III. All the patients in the cases were injured by pet dogs without abnormal clinical signs, and 80% of them were home pet dogs. Fifty-two per cent of the pet dogs were vaccinated. All the dogs survived during the PEP vaccination period. The data showed that a considerable proportion of people who did not have exposure risk for rabies had received vaccination. The underlying reasons included social, medical and personal factors. So here we proposed to replace the current ‘five-course’ intramuscular injection with intradermal injection method in the cities free of rabies in China, this can not only achieve effective vaccination but also save resources and eliminate the fear of rabies from victims. Meanwhile we should strengthen communication on rabies knowledge and make a routine evaluation of rabies surveillance system to improve understanding of the risk for rabies from biting animals.
The performance of immune system is vital for defending the body from pathogens, and it plays a crucial role in health homoeostasis. In a previous study, we have shown that LFP-20, a twenty-amino acid antimicrobial peptide in the N terminus of porcine lactoferrin, modulated inflammatory response in colitis. Here, we further investigated the effects of LFP-20 on immune homoeostasis to elucidate the mechanism of its anti-inflammation action. A lipopolysaccharide (LPS)-triggered systemic inflammatory response mice model was established. On the basis of observed mucosal lesions and apoptosis in small intestine, we found increased macrophage and neutrophil infiltration in ileum after LPS stimulation. Expectedly, LFP-20 pre-treatment attenuated the LPS-mediated immune disorders in ileum. Moreover, the flow cytometry results indicated pre-treatment with LFP-20 sustained the balance of CD3+CD8+ T cells, B cells and natural killer cells in LPS-triggered immune disturbance. Simultaneously, we demonstrated LFP-20 modulated the secretion of both activated Th1-related IL-12p70, interferon-γ, TNF-α and Th2-related IL-4, IL-5 and IL-6. Furthermore, we found LFP-20 facilitated a balanced Th1 and Th2 response, which triggered cellular defence mechanisms and induced B cells to produce opsonising antibodies belonging to certain IgG subclasses to defend against LPS stimulation. Collectively, our study indicated pre-treatment with LFP-20 could defend against LPS-triggered systemic inflammatory response in mice via modulating immune homoeostasis.
This paper presents a novel balanced-to-balanced power divider (PD) based on a simple and compact three-line coupled structure for the first time. By bisecting the proposed symmetrical structure, the differential mode (DM) and the common mode (CM) equivalent circuits can be obtained for analysis. The DM equivalent circuit exhibits a three-line in-phase power dividing response, and then a resistor is added between the two outputs for achieving good isolation. Meanwhile, the CM equivalent circuit shows a three-line all-stop response so that the CM suppression in this design does not need to be considered. Accordingly, the detailed design procedure of the DM PD is given. For demonstration, a prototype centered at 1.95 GHz is designed, fabricated, and measured. The simulated and measured results with good agreement are presented, showing low DM loss and wideband CM suppression.
OBJECTIVES/SPECIFIC AIMS: Prostate cancer (PCa) is the most common noncutaneous malignancy in men in the United States. A significant fraction of advanced PCa treated with androgen deprivation therapy experience relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). The PCa tumor microenvironment is comprised of a complex mixture of epithelial and stroma cell types engaged in multifaceted heterotypic interactions functioning to maintain tumor growth and immune evasion. We recently uncovered the important role played by myeloid-derived suppressor cells (MDSCs) to mediate tumor immune evasion in aggressive PCa (Wang, Lu et al., Cancer Discovery, 2016). Immune checkpoint blockade (ICB) has elicited durable therapeutic responses across a number of cancer types. However, the impact of ICB on mCRPC has been disappointing, which may signal the need to combine mechanistically-distinct ICB agents and/or override immunosuppression in the tumor microenvironment. Our objective is to determine if robust immunotherapy responses in mCRPC may be elicited by the combined actions of ICB agents together with targeted agents that neutralize MDSCs yet preserve T cell function. METHODS/STUDY POPULATION: We created a novel embryonic stem cell-based chimeric mouse model of mCRPC engineered with signature mutations to study the response to single and combination immunotherapy. The efficacy studies were followed with detailed mechanistic investigation and clinical validation. RESULTS/ANTICIPATED RESULTS: Consonant with early stage clinical trials experience, anti-CTLA4 or anti-PD1 monotherapy failed to impact disease progression. Similarly, modest anti-tumor activity was observed with combination ICB as well as monotherapy with targeted agents including Cabozantinib (tyrosine kinase inhibitor), Dactolisib (PI3K/mTOR inhibitor), and Dasatinib (tyrosine kinase inhibitor). In contrast, mCRPC primary and metastatic disease showed robust responses to dual ICB treatment together with either Cabozantinib or Dactolisib, but not with Dasatinib which impaired T cell infiltration in the tumor. Detailed intratumoral immune profiling with mass cytometry (CyTOF) showed that combined ICB and Cabozantinib or Dactolisib was associated with significant depletion of MDSCs. Cabozantinib and Dactolisib blocked the PI3K signaling activity in MDSCs and reduced their immunosupppresive activity. Mechanistically, the combination efficacy was due to the upregulation of IL-1RA and suppression of MDSC-promoting cytokines secreted by mCRPC cells. DISCUSSION/SIGNIFICANCE OF IMPACT: We demonstrated that an antibody cocktail targeting CTLA4 and PD1 was insufficient to generate effective anti-tumor response, but combination of ICB with targeted therapy that inactivates PI3K signaling displayed superior synergistic efficacy through impairing MDSCs in the tumor microenvironment. These observations illuminate a clinical path hypothesis for combining ICB with MDSC-targeted therapies in the treatment of mCRPC. Importantly, conclusions from the study on PCa may have implications in combination immunotherapy for aggressive breast cancer which is also largely resistant to immune checkpoint blockade and replete with immunosuppressive myeloid cells.
In this paper, we construct the first examples of complex surfaces of general type with arbitrarily large geometric genus whose canonical maps induce non-hyperelliptic fibrations of genus
, and on the other hand, we prove that there is no complex surface of general type whose canonical map induces a hyperelliptic fibrations of genus
if the geometric genus is large.
To optimise patients’ outcomes and gain insight into transmitted drug resistance (TDR) among human immunodeficiency virus (HIV)-1 treatment-naive patients in Beijing, the prevalence of TDR was assessed. Demographic and clinical data of 1241 treatment-naive patients diagnosed between April 2014 and February 2015 were collected. TDR was defined using the Stanford University HIV drug resistance mutations database. The risk factors were evaluated by multi-logistic regression analysis. Among 932 successfully amplified cases, most were male (96.78%) and infected through men having sex with men (91.74%). Genotype were CRF01_AE (56.44%), B (20.60%), CRF07_BC (19.96%), C (1.61%) and other genotypes (1.39%). The overall prevalence of TDR was 6.12%. Most frequent mutations occurred in non-nucleoside reverse transcriptase inhibitors (NNRTIs) (3.11%), followed by protease inhibitors (PIs) (2.25%) and nucleoside reverse transcriptase inhibitors (NRTIs) (1.32%). Furthermore, HIV-1 genotype was associated with high risk of resistance, in which genotype C and other genotype may have higher risk for resistance. The prevalence among treatment-naive patients in Beijing was low. Resistance to NNRTIs was higher than with PIs or NRTIs. Continuous monitoring of regional levels of HIV-1 TDRs would contribute to improve treatment outcomes and prevent failures.
Excited by the great success of metal halide perovskites in the optoelectronic and electro-optic fields and the interesting emerging physics (Rashba splitting, quantum anomalous hall effect) of layered metal halides, metal halides have recently been attracting significant attentions from both research and industrial communities. It is shown that most progresses have been made when these materials are obtained at reduced dimensions. Among several growth methods, vapor phase epitaxy has been demonstrated with a universal control on morphology, phase, and composition. We thus believe that a thorough understanding on the physical properties and on the growth of general metal halide compounds at reduced dimensions would be very beneficial in the study of recent perovskites and layered metal halide materials. This review covers the physical properties of most studied metal halides and summarizes the vapor phase epitaxial growth knowledge collected in the past century. We hope that this comprehensive review could be helpful in designing new physical properties and in planning growth parameters for emerging metal halide crystals.
In the analysis of the interaction between external periodic excitation and unsteady separated flow in controlling the flow separation, a new nonlinear approximate model has been established. This model is used to describe the typical chaotic and coherent characteristics of a separated flow such as small- or large-scale vortices, the injection, and the dissipation of the kinetic energy based on a simulation of a simplified cross-direction motion of free shear flows. This study presents an appropriate treatment to simulate the external periodic excitation and uses the maximum Lyapunov exponent to evaluate the degree of flow ordering in the different control states. The results of the nonlinear model are compared with experimental and numerical results, showing that the nonlinear model could be used to effectively explain the behaviours of chaotic flows and investigate the rules for controlling separated flows. In addition, as shown in the nonlinear approximate model, the self-synchronization of unsteady flow separation and periodic excitation has been analysed. Initially, the research provided an explanation of the self-synchronization mechanism, which cites that the effects of the separated flow control are independent of the phase difference between the periodic excitation and the unsteady flow. The characteristics of unsteady separated flow control have also been presented in this model, where the corresponding large eddy simulation (LES) was used for separated flows in a curved diffuser. The proper orthogonal decomposition (POD) method was used to analyse the difference between separated vortical structures with or without periodic excitation. The results showed that the model and the simulation had the same mechanism of flow control as for the separated flows. The periodic excitation transforms the original chaotic flow into a relatively ordered flow and decreases the magnitude of the chaotic unstable vortices, rather than completely eliminating the vortices, while flow mixing is reduced, inducing less energy loss.
Toxoplasmosis is a serious zoonoses disease and opportunistic, and can be life-threatening. Dexamethasone (DEX) is widely used in the clinic for treatment of inflammatory and autoimmune diseases. However, long-term use of DEX is often easy to lead to acute toxoplasmosis in patients, and the potential molecular mechanism is still not very clear. The aims of this study were to investigate the effect of DEX on proliferation of Toxoplasma and its molecular mechanisms, and to establish the corresponding control measures. All the results showed that dexamethasone could enhance the proliferation of Toxoplasma gondii tachyzoites. After 72 h of DEX treatment, 566 (±7) tachyzoites were found in 100 host cells, while only 86 (±8) tachyzoites were counted from the non-treated control cells (P < 0·01). Gas chromatography (GC) analysis showed changes in level and composition of fatty acids in DEX-treated host cells, and T. gondii. Fish oil was added as a modulator of lipid metabolism in experimental mice. It was found that mice fed with fish oil did not develop the disease after infection with T. gondii, and the structure of fatty acids in plasma changed significantly. The metabolism of fatty acid in the parasites was limited, and the desaturase gene expression was downregulated. These results indicate that the molecular mechanism of dexamethasone to promote the proliferation of T. gondii may be that dexamethasone induces the change of fatty acids composition of tachyzoites and host cells. Therefore, we recommend supplementation of fatty acid in immunosuppressive and immunocompromised patients in order to inhibit toxoplasmosis.
China makes a unique and vital contribution to maintaining global and regional waterbird diversity and conservation. Despite considerable historical conservation efforts, the continued loss of waterbird diversity and abundance necessitates a contemporary review of Chinese sites of conservation significance. The Ecological Protection Red Line (EPRL) was proposed by China’s Central Government in 2013 to protect areas providing crucial ecosystem services and provides the opportunity for such a review to enhance waterbird conservation in China. By incorporating various sources of data, surveys and information, we identified a suite of sites of waterbird conservation significance in China, following the Ramsar Site Criteria/Important Bird and Biodiversity Area (IBA) Criteria. In total, we identified 422 sites, of which the existing 286 IBA sites formed the basis of the site safeguard network. Altogether, these sites of waterbird conservation significance constitute over 727,000 km2 (7.6% of China’s land surface). Over half of the area of these sites is outside China’s national nature reserves, thus confirming the importance and urgency of including them in the EPRL for the effective conservation of waterbird sites. We suggest that this assessment of sites of waterbird importance offers a useful model to apply to other taxa, such as terrestrial birds and mammals.
The composite Li-ion battery anode material of Fe2SiO4, Fe3O4, Fe3C (Fe-Si-O) and carbon nanotubes was prepared by a simple one-step reaction between ferrocene and tetraethyl orthosilicate. When cycled at 100 mA g-1, this material exhibited ever-increasing capacities and reached 588 mAh g-1 at the 280th cycle. At 500 mA g-1, a reversible capacity of 350 mAh g-1 was retained for 600 cycles. Compared with Fe3O4 materials, the Fe-Si-O/CNT exhibited superior long-term high-rate performance, which could mainly result from its enhanced stability and conductivities by introducing silicates and CNTs during the one-step synthesis.
The motion and rotation of an ellipsoidal particle inside square tubes and rectangular tubes with the confinement ratio R/a∈(1.0,4.0) are studied by the lattice Boltzmann method (LBM), where R and a are the radius of the tube and the semi-major axis length of the ellipsoid, respectively. The Reynolds numbers (Re) up to 50 are considered. For the prolate ellipsoid inside square and rectangular tubes, three typical stable motion modes which depend on R/a are identified, namely, the kayaking mode, the tumbling mode, and the log-rolling mode are identified for the prolate spheroid. The diagonal plane strongly attracts the particle in square tubes with 1.2≤R/a<3.0. To explore the mechanism, some constrained cases are simulated. It is found that the tumbling mode in the diagonal plane is stable because the fluid force acting on the particle tends to diminish the small displacement and will bring it back to the plane. Inside rectangular tubes the particle will migrate to a middle plane between short walls instead of the diagonal plane. Through the comparisons between the initial unstable equilibrium motion state and terminal stable mode, it is seems that the particle tend to adopt the mode with smaller kinetic energy.
Dissimilar joints of advanced 9Cr/CrMoV have been successfully welded by narrow gap submerged arc welding using multi-layer and multi-pass techniques. The objective of our study is to establish the correlation between impact toughness and microstructural characteristics of the welded joints. Impact toughness tests were conducted in a wide range of temperature from −60 °C to 80 °C for different regions in the dissimilar joints. The fracture appearance transition temperature of base metal of 9Cr, CrMoV and weld metal were tested as 23 °C, −9 °C and −2 °C respectively, which all satisfied the service requirement. Optical microscope and scanning electron microscope revealed that weld metal and base metal of CrMoV comprised martensite and bainite while 9Cr was composed of lath martensite. The low toughness in the latter region arose from large grains with excessive carbide precipitates. Nonuniform microstructure in the heat-affected zone of 9Cr side caused different crack propagation paths and subsequently led to large variations of absorbed energy. When crack propagates along carbon-enriched zone in heat affected zone, the absorbed energy was 48 J. With crack deviating far from carbon-enriched zone, the absorbed energy increased to 147 J. Examination on fracture surfaces revealed the typical brittle fracture appearance in 9Cr and inter-granular fracture mode in heat-affected zone of 9Cr side when crack propagated along carbon-enriched zone.
The present study was performed to identify the genotype of a hypertrophic cardiomyopathy family and investigate the clinicopathogenic characteristics and prognostic features of relevant genetic abnormalities. Target sequence capture sequencing was performed to screen for pathogenic alleles in a 32-year-old female patient (proband). Sanger sequencing was carried out to verify the results. Sanger sequencing was also performed on other family members to identify allele carriers. A survival analysis was carried out using published literature and our findings. We found that the proband and her son harboured a Gly716Arg sequence variant of the β-myosin heavy chain. Neither the proband’s father nor the mother were carriers of this sequence variant; thus, the mutation was classified as “de novo”. Further survival analysis revealed that female patients appear to have a longer life expectancy compared with males. Our study may provide an effective approach for the genetic diagnosis of hypertrophic cardiomyopathy.
A 100-J-level Nd:glass laser system in nanosecond-scale pulse width has been constructed to perform as a standard source of high-fluence-laser science experiments. The laser system, operating with typical pulse durations of 3–5 ns and beam diameter 60 mm, employs a sequence of successive rod amplifiers to achieve 100-J-level energy at 1053 nm at 3 ns. The frequency conversion can provide energy of 50-J level at 351 nm. In addition to the high stability of the energy output, the most valuable of the laser system is the high spatiotemporal beam quality of the output, which contains the uniform square pulse waveform, the uniform flat-top spatial fluence distribution and the uniform flat-top wavefront.
In this paper we study the Oort conjecture concerning the non-existence of Shimura subvarieties contained generically in the Torelli locus in the Siegel modular variety
. Using the poly-stability of Higgs bundles on curves and the slope inequality of Xiao on fibered surfaces, we show that a Shimura curve
is not contained generically in the Torelli locus if its canonical Higgs bundle contains a unitary Higgs subbundle of rank at least
. From this we prove that a Shimura subvariety of
type is not contained generically in the Torelli locus when a numerical inequality holds, which involves the genus
, the dimension
, the degree
of CM field of the Hermitian space, and the type of the symplectic representation defining the Shimura subdatum. A similar result holds for Shimura subvarieties of
type, defined by spin groups associated to quadratic spaces over a totally real number field of degree at least
subject to some natural constraints of signatures.
We studied the effects of four non-nutrient environmental factors (temperature, salinity, irradiance and pH) on the growth inhibition of the macroalgae Ulva pertusa (Chlorophyta) upon the microalgae Heterosigma akashiwo (Rhaphidophyta). Experiments were conducted in single-factor incubation and various two-factor combination experiments in which temperature (10, 15, 25 and 30°C), salinity (10, 20, 30 and 40 g kg−1 water), irradiance (20, 100, 200 and 400 μmol m−2 s−1), and pH (5.5, 7, 8.5 and 10) were varied systematically. The growth rates of U. pertusa and H. akashiwo and the rate of microalgal growth inhibition were altered significantly by changing some of the non-nutrient factors in both the single-factor and the two-factor experiments. The optimal growth conditions for U. pertusa were 20–25°C, salinity of 30 g kg−1, irradiance level of 200–400 μmol m−2 s−1, and pH 8.5–10; optimal conditions for H. akashiwo growth were 25°C, 30 g kg−1, 100 μmol m−2 s−1 and pH 8.5, respectively. The growth inhibitory influence of U. pertusa on H. akashiwo was strongest at 25°C with low salinity (10 g kg−1), high irradiance (400 μmol m−2 s−1) and high alkalinity (pH = 10). The results of this study may be helpful in the development of methods for using green macroalgae to control the proliferation of microalgae in harmful algal blooms (HABs). In particular, these findings provide guidance regarding optimum levels of non-nutrient environmental factors in confined areas, such as aquaculture factories.