Electron Bunch Train Excited Higher-Order Modes in a Superconducting RF Cavity

Higher-order mode (HOM) based intra-cavity beam diagnostics has been proved effectively and conveniently in superconducting radio-frequency (SRF) accelerators. Our recent research shows that the beam harmonics in the bunch train excited HOM spectrum, which have much higher signal-to-noise ratio than the intrinsic HOM peaks, may also be useful for beam diagnostics. In this paper, we will present our study on bunch train excited HOMs, including the theoretic model and recent experiments carried out based on the DC-SRF photoinjector and SRF linac at Peking University.Comment: Supported by National Natural Science Foundation of China (11275014

SnoRNA Snord116 (Pwcr1/MBII-85) Deletion Causes Growth Deficiency and Hyperphagia in Mice

Prader-Willi syndrome (PWS) is the leading genetic cause of obesity. After initial severe hypotonia, PWS children become hyperphagic and morbidly obese, if intake is not restricted. Short stature with abnormal growth hormone secretion, hypogonadism, cognitive impairment, anxiety and behavior problems are other features. PWS is caused by lack of expression of imprinted genes in a ∼4 mb region of chromosome band 15q11.2. Our previous translocation studies predicted a major role for the C/D box small nucleolar RNA cluster SNORD116 (PWCR1/HBII-85) in PWS. To test this hypothesis, we created a ∼150 kb deletion of the >40 copies of Snord116 (Pwcr1/MBII-85) in C57BL/6 mice. Snord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation

An Efficient Orthogonal Polynomial Method for Auxetic Structure Analysis with Epistemic Uncertainties

Traditional approaches used for analyzing the mechanical properties of auxetic structures are commonly based on deterministic techniques, where the effects of uncertainties are neglected. However, uncertainty is widely presented in auxetic structures, which may affect their mechanical properties greatly. The evidence theory has a strong ability to deal with uncertainties; thus, it is introduced for the modelling of epistemic uncertainties in auxetic structures. For the response analysis of a typical double-V negative Poisson’s ratio (NPR) structure with epistemic uncertainty, a new sequence-sampling-based arbitrary orthogonal polynomial (SS-AOP) expansion is proposed by introducing arbitrary orthogonal polynomial theory and the sequential sampling strategy. In SS-AOP, a sampling technique is developed to calculate the coefficient of AOP expansion. In particular, the candidate points for sampling are generated using the Gauss points associated with the optimal Gauss weight function for each evidence variable, and the sequential-sampling technique is introduced to select the sampling points from candidate points. By using the SS-AOP, the number of sampling points needed for establishing AOP expansion can be effectively reduced; thus, the efficiency of the AOP expansion method can be improved without sacrificing accuracy. The proposed SS-AOP is thoroughly investigated through comparison to the Gaussian quadrature-based AOP method, the Latin-hypercube-sampling-based AOP (LHS-AOP) method and the optimal Latin-hypercube-sampling-based AOP (OLHS-AOP) method

Anisotropy-Based Adaptive Polynomial Chaos Method for Hybrid Uncertainty Quantification and Reliability-Based Design Optimization of Structural-Acoustic System

The evaluation of objective functions and component reliability in the optimisation of structural-acoustic systems with random and interval variables is computationally expensive, especially when strong nonlinearity exhibits between the response and input variables. To reduce the computational cost and improve the computational efficiency, a novel anisotropy-based adaptive polynomial chaos (ABAPC) expansion method was developed in this study. In ABAPC, the anisotropy-based polynomial chaos expansion, namely the retained order of polynomial chaos expansion (PCE) differs from each variable, is used to construct the initial surrogate model instead of first-order polynomial chaos expansion in conventional methods. Then, an anisotropy-based adaptive basis growth strategy was developed to reduce the estimation of the coefficients of the polynomial chaos expansion method and increase its computational efficiency. Finally, to solve problems with probabilistic and interval parameters, an adaptive basis truncation strategy was introduced and implemented. Using the ABAPC method, the computational cost of reliability-based design optimisation for structural-acoustic systems can be efficiently reduced. The effectiveness of the proposed method were demonstrated by solving two numerical examples and optimisation problems of a structural-acoustic system

Anisotropy-Based Adaptive Polynomial Chaos Method for Hybrid Uncertainty Quantification and Reliability-Based Design Optimization of Structural-Acoustic System

The evaluation of objective functions and component reliability in the optimisation of structural-acoustic systems with random and interval variables is computationally expensive, especially when strong nonlinearity exhibits between the response and input variables. To reduce the computational cost and improve the computational efficiency, a novel anisotropy-based adaptive polynomial chaos (ABAPC) expansion method was developed in this study. In ABAPC, the anisotropy-based polynomial chaos expansion, namely the retained order of polynomial chaos expansion (PCE) differs from each variable, is used to construct the initial surrogate model instead of first-order polynomial chaos expansion in conventional methods. Then, an anisotropy-based adaptive basis growth strategy was developed to reduce the estimation of the coefficients of the polynomial chaos expansion method and increase its computational efficiency. Finally, to solve problems with probabilistic and interval parameters, an adaptive basis truncation strategy was introduced and implemented. Using the ABAPC method, the computational cost of reliability-based design optimisation for structural-acoustic systems can be efficiently reduced. The effectiveness of the proposed method were demonstrated by solving two numerical examples and optimisation problems of a structural-acoustic system

Embryonic Origin and Subclonal Evolution of Tumor-Associated Macrophages Imply Preventive Care for Cancer.

Macrophages are widely distributed in tissues and function in homeostasis. During cancer development, tumor-associated macrophages (TAMs) dominatingly support disease progression and resistance to therapy by promoting tumor proliferation, angiogenesis, metastasis, and immunosuppression, thereby making TAMs a target for tumor immunotherapy. Here, we started with evidence that TAMs are highly plastic and heterogeneous in phenotype and function in response to microenvironmental cues. We pointed out that efforts to tear off the heterogeneous camouflage in TAMs conduce to target de facto protumoral TAMs efficiently. In particular, several fate-mapping models suggest that most tissue-resident macrophages (TRMs) are generated from embryonic progenitors, and new paradigms uncover the ontogeny of TAMs. First, TAMs from embryonic modeling of TRMs and circulating monocytes have distinct transcriptional profiling and function, suggesting that the ontogeny of TAMs is responsible for the functional heterogeneity of TAMs, in addition to microenvironmental cues. Second, metabolic remodeling helps determine the mechanism of phenotypic and functional characteristics in TAMs, including metabolic bias from macrophages ontogeny in macrophages functional plasticity under physiological and pathological conditions. Both models aim at dissecting the ontogeny-related metabolic regulation in the phenotypic and functional heterogeneity in TAMs. We argue that gleaning from the single-cell transcriptomics on subclonal TAMs origins may help understand the classification of TAMs population in subclonal evolution and their distinct roles in tumor development. We envision that TAM-subclone-specific metabolic reprogramming may round-up with future cancer therapies

An Effective Degumming Technology for Ramie Fibers Based on Microbial Coculture Strategy

Microbial treatment of natural fibers is a preferred alternatives in ramie degumming process as compared to conventional chemical degumming technology with alkaline treatment at high temperature. Usually, it is difficult to degrade the noncellulosic components of ramie bast completely with a single strain in the mono-culturing degumming system. Microbial coculture strategy has been widely used in biotechnology, especially in the degradation of biological materials. In the present study, five strains for ramie degumming were identified as Dickeya dadantii strain DCE-01, Bacillus subtilis strain 1101, Bacillus sp. B6, Bacillus cereus strain B7, and Bacillus cereus strain B8 by sequencing of 16 S rRNA genes. Enzymatic activities characterization, ramie degumming experiments with mono-culturing systems, and the evaluation of strain compatibility showed that group DCE-01/B7 were the most suitable pairs for the construction of bacterial coculturing system. After preliminary optimization of coculturing fermentation condition, the weight loss weight ratio of ramie fibers was 27%, which was increased 13.6% and 8.9% while compared to mono-culturing systems of strain B7 and DCE-01 respectively. These data highlighted the benefit of microbial coculture strategy in the application of ramie degumming process, and indicated a higher-efficiency alternative for the microbial degumming in the textile industry

CIRP attenuates acute kidney injury after hypothermic cardiovascular surgery by inhibiting PHD3/HIF-1α-mediated ROS-TGF-β1/p38 MAPK activation and mitochondrial apoptotic pathways

Abstract Background The ischemia–reperfusion (IR) environment during deep hypothermic circulatory arrest (DHCA) cardiovascular surgery is a major cause of acute kidney injury (AKI), which lacks preventive measure and treatment. It was reported that cold inducible RNA-binding protein (CIRP) can be induced under hypoxic and hypothermic stress and may have a protective effect on multiple organs. The purpose of this study was to investigate whether CIRP could exert renoprotective effect during hypothermic IR and the potential mechanisms. Methods Utilizing RNA-sequencing, we compared the differences in gene expression between Cirp knockout rats and wild-type rats after DHCA and screened the possible mechanisms. Then, we established the hypothermic oxygen–glucose deprivation (OGD) model using HK-2 cells transfected with siRNA to verify the downstream pathways and explore potential pharmacological approach. The effects of CIRP and enarodustat (JTZ-951) on renal IR injury (IRI) were investigated in vivo and in vitro using multiple levels of pathological and molecular biological experiments. Results We discovered that Cirp knockout significantly upregulated rat Phd3 expression, which is the key regulator of HIF-1α, thereby inhibiting HIF-1α after DHCA. In addition, deletion of Cirp in rat model promoted apoptosis and aggravated renal injury by reactive oxygen species (ROS) accumulation and significant activation of the TGF-β1/p38 MAPK inflammatory pathway. Then, based on the HK-2 cell model of hypothermic OGD, we found that CIRP silencing significantly stimulated the expression of the TGF-β1/p38 MAPK inflammatory pathway by activating the PHD3/HIF-1α axis, and induced more severe apoptosis through the mitochondrial cytochrome c-Apaf-1-caspase 9 and FADD-caspase 8 death receptor pathways compared with untransfected cells. However, silencing PHD3 remarkably activated the expression of HIF-1α and alleviated the apoptosis of HK-2 cells in hypothermic OGD. On this basis, by pretreating HK-2 and rats with enarodustat, a novel HIF-1α stabilizer, we found that enarodustat significantly mitigated renal cellular apoptosis under hypothermic IR and reversed the aggravated IRI induced by CIRP defect, both in vitro and in vivo. Conclusion Our findings indicated that CIRP may confer renoprotection against hypothermic IRI by suppressing PHD3/HIF-1α-mediated apoptosis. PHD3 inhibitors and HIF-1α stabilizers may have clinical value in renal IRI