In klystron amplifiers, spurious oscillations caused by the backstreaming electrons from collector may lead to unacceptable instabilities in experiments. To facilitate the fast and accurate analysis ...of such types of self-oscillations, rather than performing time-consuming particle-in-cell (PIC) simulations, the small signal theory to predict threshold conditions of spurious oscillations in klystrons has been further developed and implemented into the klystron computer code KlyC. If spurious oscillation occurs, the frequency and Q of the oscillation mode in a small signal regime can also be predicted. The effectiveness of the proposed threshold prediction method has been demonstrated through benchmarking against PIC codes, showing great agreement with result discrepancies at the several percentage level, while numerical computation time for small signal models is significantly (at least three orders of magnitude) faster than executed in the PIC simulations.
The 2014/15 influenza season was the second season of roll-out of a live attenuated influenza vaccine (LAIV) programme for healthy children in England. During this season, besides offering LAIV to ...all two to four year olds, several areas piloted vaccination of primary (4-11 years) and secondary (11-13 years) age children. Influenza A(H3N2) circulated, with strains genetically and antigenically distinct from the 2014/15 A(H3N2) vaccine strain, followed by a drifted B strain. We assessed the overall and indirect impact of vaccinating school age children, comparing cumulative disease incidence in targeted and non-targeted age groups in vaccine pilot to non-pilot areas. Uptake levels were 56.8% and 49.8% in primary and secondary school pilot areas respectively. In primary school age pilot areas, cumulative primary care influenza-like consultation, emergency department respiratory attendance, respiratory swab positivity, hospitalisation and excess respiratory mortality were consistently lower in targeted and non-targeted age groups, though less for adults and more severe end-points, compared with non-pilot areas. There was no significant reduction for excess all-cause mortality. Little impact was seen in secondary school age pilot only areas compared with non-pilot areas. Vaccination of healthy primary school age children resulted in population-level impact despite circulation of drifted A and B influenza strains.
Drought is one of the major natural disasters in the Loess Plateau of China. We aimed to reveal drought occurrence regularity, relations between different magnitudes of drought and precipitation ...intensity changes. Based on Chinese climate divisions and digital elevation model graphs of the Loess Plateau region, our study area was divided into five subregions by means of cluster analysis of the region’s meteorological stations using a self-organizing map neural network. Utilizing daily precipitation data from 72 stations for the 1961–2012 period, and using the number of consecutive days without precipitation as the drought level evaluation, the frequency and differing magnitudes of drought occurrences in each season were analyzed. In addition, the first precipitation intensity after a drought period was analyzed using a Pearson type III frequency curve. Precipitation frequency changes following drought occurrences with different magnitudes in each subregion were analyzed, and the relationship between rainfall intensity and different drought magnitudes was observed, as was the relationship between rainfall intensity and the number of drought occurrences. The results of our study indicate that, first, changes in drought levels in the region within and between years are not obvious, but that changes are significant between decades. Moreover, drought frequency in subregions I, IV and V of our study was higher than in areas II and III. Second, as the drought level increased, the probability of heavy rainstorms and extraordinary rainstorms in the Loess Plateau region became lower, and the frequency of spatial changes at different precipitation intensities varied. The frequency of different precipitation intensities in subregions I, II, IV and V initially showed a decreasing trend, but, with continued development of drought and when extraordinary drought occurred, moderate and heavy rain became an increasing trend, with the frequency of rainstorms and heavy rainstorms decreasing at first, then becoming the same. The probability of moderate and heavy rain in subregion III showed a decreasing trend; that of rainstorms, heavy rainstorms and extraordinary rainstorms initially decreased then became the same. Third, while the frequency of drought occurrences in the Loess Plateau region for the 1961–2012 period showed an increasing trend overall, the extent of the increase differed among the different subregions.
The COP9 signalosome (CSN) is an evolutionarily conserved multisubunit protein complex, which controls protein degradation through deneddylation and inactivation of cullin-RING ubiquitin E3 ligases ...(CRLs). Recently, the CSN complex has been linked to the NF-κB signaling pathway due to its association with the IKK complex. However, how the CSN complex is regulated in this signaling pathway remains unclear. Here, we have carried out biochemical experiments and confirmed the interaction between the CSN and IKK complexes. In addition, we have determined that overexpression of IKKα or IKKβ leads to enhanced phosphorylation of CSN5, the catalytic subunit for CSN deneddylase activity. Mutational analyses have revealed that phosphorylation at serine 201 and threonine 205 of CSN5 impairs CSN-mediated deneddylation activity in vitro. Interestingly, TNF-α treatment not only enhances the interaction between CSN and IKK but also induces an IKK-dependent phosphorylation of CSN5 at serine 201, linking CSN to TNF-α signaling through IKK. Moreover, TNF-α treatment affects the CSN interaction network globally, especially the associations of CSN with the proteasome complex, eukaryotic translation initiation factor complex, and CRL components. Collectively, our results provide new insights into IKK-mediated regulation of CSN associated with the NF-κB signaling pathway.
Per- and polyfluoroalkyl substances (PFAS) remain controversial due to their high persistency and potential human toxicity. Although occupational exposure to PFAS has been widely investigated, the ...implications of PFAS occurrence in the general population remain to be unraveled. Considering that serum from most people contains PFAS, the aim of this study was to characterize the lipidomic profile in human serum from a general cohort (n = 40) with residual PFAS levels. The geometric means of ∑PFAS (11.8 and 4.4 ng/mL) showed significant differences (p < 0.05) for the samples with the highest (n = 20) and lowest (n = 20) concentrations from the general population respectively. Reverse-phase liquid chromatography coupled to drift tube ion mobility and high-resolution mass spectrometry using dual polarity ionization was used to characterize the lipid profile in both groups. The structural elucidation involved the integration of various parameters, such as retention time, mass-to-charge ratio, tandem mass spectra and collision cross section values. This approach yielded a total of 20 potential biomarkers linked to the perturbed glycerophospholipid metabolism, energy metabolism and sphingolipid metabolism. Among these alterations, most lipids were down-regulated and some specific lipids (PC 36:5, PC 37:4 and PI O-34:2) exhibited a relatively strong Spearman correlation and predictive capacity for PFAS contamination. This study could support further toxicological assessments and mechanistic investigations into the effects of PFAS exposure on the lipidome.
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•LC-IM-MS-based untargeted lipidomics was applied to investigate the serum of a general cohort with residual PFAS.•Annotation of 20 potential biomarkers with the integration of RT, m/z, CCS values, and tandem mass spectra•Some specific lipids with a relatively strong Spearman correlation and predictive capacity for PFAS contamination
Electrical energy storage (EES) exploiting secondary battery technologies is ideal for large-scale energy storage needs due to the rapid growth in proliferation of renewable energy sources and the ...emerging markets of grid-scale battery applications. Sodium-ion batteries (SIBs), a more sustainable EES option alternative to lithium-ion batteries (LIBs), have attracted intensive interests over the past decade, because of the natural abundance, evenly geographical-distributed Na-source, significantly low cost, and environmental benignity. Polyanionic compounds offer an appealing combination of rich structural diversity, superior ionic conductivity, high structural and thermal stability, and convenient storage/handling, making them competitive and attractive candidate electrode materials for next generation energy storage systems. In this review, recent advancements made regarding polyanion-type electrodes used for SIBs are summarized, elaborating their intrinsic structural characteristics, electrochemical properties, and corresponding sodium-storage mechanisms. Furthermore, we highlight the recent achievements in the lab-scale Na-ion full-cell prototypes that consist of polyanion-type compounds as one or both working electrodes. Last but not least, challenges and outlooks on further optimization of the structure and the electrochemical performance of polyanion-type electrode materials for SIBs are also presented to provide some insights to facilitate the practical realization of sodium-ion technologies.
Objective
To compare the clinicoradiologic features of tumours with echinoderm anaplastic lymphoma kinase (
ALK
) rearrangements, epidermal growth factor receptor (
EGFR
) mutations, or wild type ...(WT) for both genes in a cohort of patients with lung adenocarcinoma to identify useful characteristics of different gene statuses.
Methods
In 346 lung adenocarcinoma patients,
ALK
rearrangements were confirmed with fluorescence in situ hybridisation, and
EGFR
mutations were determined by pyrosequencing assay. Patients were divided into three groups:
ALK
rearrangement (ALK+ group,
n
= 48),
EGFR
mutation (EGFR+ group,
n
= 166), and WT for both genes (WT group,
n
= 132). Chest computed tomography (CT) examinations were performed in all patients. The percentages of ground-glass opacity volume (pGGO) and tumour shadow disappearance rate (TDR) were measured using semi-automated nodule assessment software.
Results
The pGGO was significantly lower in the ALK+ group (25.1 % ± 24.3) than in the EGFR+ group (37.2 % ± 25.7,
p
< 0.001) and the WT group (36.1 % ± 24.6,
p
= 0.001). The TDR in the ALK+ group (17.3 % ± 25.1) was significantly lower than in the EGFR+ group (26.8 % ± 24.9,
p
= 0.002) and the WT group (25.7 % ± 24.6,
p
= 0.003).
Conclusions
Solid pattern with lower incidence of lobulated border, finely spiculated margins, pleural retraction, and bubble-like lucency on CT imaging are the main characteristics of
ALK
rearrangement tumours.
Key Points
•
EGFR/ALK testing is recommended for lung adenocarcinoma patients for EGFR/ALK-targeted TKI therapy
.
•
EGFR /ALK testing is restricted by limited tissue samples and cost pressures
.
•
Lower pGGO and TDR are the main clinicoradiological characteristics of ALK+ tumours
.
•
pGGO and TDR are predictive factors for selecting patients for ALK/EGFR testing
.
Objective
To give a new insight into the mechanism of ApoE dysregulation and microRNA‐1908 in Alzheimer's disease (AD).
Methods
Plasma ApoE levels were measured in 20 AD patients and 20 healthy ...controls. THP‐1 was maintained in RPMI1640 with 10% fetal bovine serum. Quantitative real‐time polymerase chain reaction was performed to detect 13‐microRNA and ApoE mRNA in cultured cell lines. Enzyme‐linked immunosorbent assay was used to measure human ApoE in the plasma or culture medium of cell lines and also used to quantify the human Aβ42 in the culture medium of cell lines.
Results
We found plasma ApoE level reduced in AD patients (2.28 vs 3.78 μg/mL, P < .001), and microRNA‐1908 was up‐regulated in AD patients and was negatively associated with plasma ApoE (r = −0.32, P = .012). In human macrophage cell line THP‐1 and astrocytoma cell line U87, microRNA‐1908 could inhibit the mRNA and protein levels of ApoE by targeting its 3′untranslated region. Consistently, microRNA‐1908 inhibits the ApoE‐mediated Aβ clearance.
Conclusions
Our study provides new insight into the mechanism of ApoE dysregulation in AD patients, and microRNA‐1908 might be a therapeutic target for AD treatment.
A thermal lattice BGK model with doubled populations is proposed to simulate the two-dimensional natural convection flow in porous media (porous metals). The accuracy of this method is validated by ...the benchmark solutions. The detailed flow and heat transfer at the pore level are revealed. The effects of pore density (cell size) and porosity on the natural convection are examined. Also the effect of porous media configuration (shape) on natural convection is investigated. The results showed that the overall heat transfer will be enhanced by lowering the porosity and cell size. The square porous medium can have a higher heat transfer performance than spheres due to the strong flow mixing and more surface area.
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