We describe 14 yr of public data from the Parkes Pulsar Timing Array (PPTA), an ongoing project that is producing precise measurements of pulse times of arrival from 26 millisecond pulsars using the 64-m Parkes radio telescope with a cadence of approximately 3 weeks in three observing bands. A comprehensive description of the pulsar observing systems employed at the telescope since 2004 is provided, including the calibration methodology and an analysis of the stability of system components. We attempt to provide full accounting of the reduction from the raw measured Stokes parameters to pulse times of arrival to aid third parties in reproducing our results. This conversion is encapsulated in a processing pipeline designed to track provenance. Our data products include pulse times of arrival for each of the pulsars along with an initial set of pulsar parameters and noise models. The calibrated pulse profiles and timing template profiles are also available. These data represent almost 21 000 h of recorded data spanning over 14 yr. After accounting for processes that induce time-correlated noise, 22 of the pulsars have weighted root-mean-square timing residuals of $<\!\!1\,\mu\text{s}$ in at least one radio band. The data should allow end users to quickly undertake their own gravitational wave analyses, for example, without having to understand the intricacies of pulsar polarisation calibration or attain a mastery of radio frequency interference mitigation as is required when analysing raw data files.

In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.

Flexibility is one of the important mechanical performance parameters of stent. The flexibility of tapered stents, especially self-expanding tapered stents, remains unknown. In this study, we developed a new selfexpanding tapered stent for tapered arteries and performed a numerical investigation of stent flexibility by using finite element method. The effect of stent design parameters, including taper and link space width, on stent flexibility was studied. The flexibility of the proposed stent was also compared with that of traditional cylindrical stents. Results show that the tapered stent is more flexible than the traditional cylindrical stent. Furthermore, the flexibility of the tapered stent increases with increasing stent taper and stent link space width. The increase in the stent link space width can contribute to the reduction in the peak stress. Therefore, tapered stents with high link space width will improve the stent flexibility. This work provides useful information for improvement of stent design and clinical selection.

The role of adiponectin and leptin signalling pathways has been suggested to play important roles in the protective effects of energy restriction (ER) on mammary tumour (MT) development. To study the effects of ER on the methylation levels in adiponectin receptor 1 (AdipoR1) and leptin receptor overlapping transcript (Leprot) genes using the pyrosequencing method in mammary fat pad tissue, mouse mammary tumour virus-transforming growth factor-α (MMTV-TGF-α) female mice were randomly assigned to ad libitum (AL), chronic ER (CER, 15 % ER) or intermittent ER (3 weeks AL and 1 week 60 % ER in cyclic periods) groups at 10 weeks of age until 82 weeks of age. The methylation levels of AdipoR1 in the CER group were higher than those in the AL group at week 49/50 (P < 0·05), while the levels of methylation for AdipoR1 and Leprot genes were similar among the other groups. Also, the methylation levels at CpG2 and CpG3 regions of the promoter region of the AdipoR1 gene in the CER group were three times higher (P < 0·05), while CpG1 island of Leprot methylation was significantly lower compared with the other groups (P < 0·05). Adiponectin and leptin gene expression levels were consistent with the methylation levels. We also observed a change with ageing in methylation levels of these genes. These results indicate that different types of ER modify methylation levels of AdipoR1 and Leprot in different ways and CER had a more significant effect on methylation levels of both genes. Epigenetic regulation of these genes may play important roles in the preventive effects of ER against MT development and ageing processes.

Small intestinal epithelium homeostasis involves four principal cell types: enterocytes, goblet, enteroendocrine and Paneth cells. Epidermal growth factor (EGF) has been shown to affect enterocyte differentiation. This study determined the effect of dietary EGF on goblet, enteroendocrine and Paneth cell differentiation in piglet small intestine and potential mechanisms. Forty-two weaned piglets were used in a 2 × 3 factorial design; the major factors were time post-weaning (days 7 and 14) and dietary treatment (0, 200 or 400 µg/kg EGF supplementation). The numbers of goblet and enteroendocrine cells were generally greater with the increase in time post-weaning. Moreover, the supplementation of 200 µg/kg EGF increased (P < 0.01) the number of goblet and enteroendocrine cells in villus and crypt of the piglet small intestine as compared with the control. Dietary supplementation with 200 µg/kg EGF enhanced (P < 0.05) abundances of differentiation-related genes atonal homologue 1, mucin 2 and intestinal trefoil factor 3 messenger RNA (mRNA) as compared with the control. Piglets fed 200 or 400 µg/kg EGF diet had increased (P < 0.05) abundances of growth factor-independent 1, SAM pointed domain containing ETS transcription factor and pancreatic and duodenal homeobox 1 mRNA, but decreased the abundance (P < 0.01) of E74 like ETS transcription factor 3 mRNA as compared with the control. Animals receiving 400 µg/kg EGF diets had enhanced (P < 0.05) abundances of neurogenin3 and SRY-box containing gene 9 mRNA as compared with the control. The mRNA abundance and protein expression of lysozyme, a marker of Paneth cell, were also increased (P < 0.05) in those animals. As compared with the control, dietary supplementation with 200 µg/kg EGF increased the abundance of EGF receptor mRNA and the ratio of non-phospho(p)-β-catenin/β-catenin (P < 0.05) in villus epithelial cells at days 7 and 14. This ratio in crypt epithelial cells was higher (P < 0.05) on the both 200 and 400 µg/kg EGF groups during the same period. Our results demonstrated that dietary EGF stimulated goblet, enteroendocrine and Paneth cell differentiation in piglets during the post-weaning period, partly through EGFR and Wnt/β-catenin signalling.

Some studies have shown that the excessive metabolic heat production is the primary cause for dead chicken embryos during late embryonic development. Increasing heat shock protein (HSP) expression and adjusting metabolism are important ways to maintain body homeostasis under heat stress. This study was conducted to investigate the effects of in ovo injection (IOI) of vitamin C (VC) at embryonic age 11th day (E11) on HSP and metabolic genes expression. A total of 320 breeder eggs were randomly divided into normal saline and VC injection groups. We detected plasma VC content and rectal temperature at chick’s age 1st day, and the mRNA levels of HSP and metabolic genes in embryonic livers at E14, 16 and 18, analysed the promoter methylation levels of differentially expressed genes and predicted transcription factors at the promoter regions. The results showed that IOI of VC significantly increased plasma VC content and decreased rectal temperature (P < 0.05). In ovo injection of VC significantly increased heat shock protein 60 (HSP60) and pyruvate dehydrogenase kinase 4 (PDK4) genes expression at E16 and PDK4 and secreted frizzled related protein 1 (SFRP1) at E18 (P < 0.05). At E16, IOI of VC significantly decreased the methylation levels of total CpG sites and −336 CpG site in HSP60 promoter and −1137 CpG site in PDK4 promoter (P < 0.05). Potential binding sites for nuclear factor-1 were found around −389 and −336 CpG sites in HSP60 promoter and potential binding site for specificity protein 1 was found around −1137 CpG site in PDK4 promoter. Our results suggested that IOI of VC increased HSP60, PDK4 and SFRP1 genes expression at E16 and 18, which may be associated with the demethylation in gene promoters. Whether IOI of VC could improve hatchability needs to be further verified by setting uninjection group.

We present a new method to combine cold gas kinematics with the stellar kinematics modelled with the Schwarzschild orbit-superposition technique, and its application to the lenticular galaxy NGC 2974. The combination of stellar and cold gas kinematics significantly improves the constraints on the measured dark matter profile: assuming a generalised NFW halo profile, we find a cuspy inner halo slope for NGC 2974.

In this paper, a novel single-cavity triangular substrate-integrated waveguide (TSIW) dual-band filter loading a complementary triangular split ring resonator (CTSRR) is proposed, which has three transmission zeros (TZs) in the stopband in total. The dual-band response is achieved by the CTSRR and the degenerate modes of the TSIW cavity. In order to control the TZs, we propose two adjustment techniques, shift feeding technique and adding via perturbation. In addition, the CTSRR etched on the surface can produce a new TZ in the upper first-passband. Finally, a dual-band filter with three TZs is simulated, fabricated, and measured. There is a good agreement between the simulated results and measured ones.

Force-feeding was considered as a traditional high-efficiency approach to improve growth performance and accelerate fat deposition of Pekin ducks. However, force-feeding is a serious violation of international advocacy on animal welfare, because it can induce serious injuries to animals, such as damages to the digestive tract, effects on immunity and even severe oxidative stress. Therefore, it is urgent to stop force-feeding. The aim of this study was to determine the effects of force feeding on immune function, digestive function and oxidative stress in the mucosa of duodenum and jejunum of Pekin ducks. A total of 500 ducks were randomly divided into two groups. The control group was allowed to feed freely on a basal diet. The experimental group was force-fed by inserting a plastic feeding tube 8 to 10 inches long down the esophagus for 6 days. Compared with the control group, there was a significant (P<0.05) increase in serum diamine oxidase, d-lactic acid, endotoxin and corticosterone levels in the force-feeding group. The crypt depth in duodenum and jejunum showed significant differences (P<0.05) between the two groups and the intestinal villus epithelium cell was severely damaged in force-feeding group. Similarly, the activities of digestive enzymes as well as the levels of immune function in the duodenal and jejunal mucosa in the force-feeding group were significantly higher than the control group (P<0.05). However, there was a significant decrease in the superoxide dismutase, glutathione peroxidase and catalase levels with a marked increase in malondialdehyde level in duodenal and jejunal mucosa (P<0.05). In summary, at the end of the fattening period with force-feeding for 6 days, Pekin ducks experienced an adverse effect on the integrity of their duodenal and jejunal mucosa epithelium cell as well as their immune function and antioxidant capacity of Pekin ducks but also had improvement in digestive enzyme activities.

We propose a statistical model for homogeneous turbulence undergoing distortions, which improves and extends the MCS model by Mons, Cambon & Sagaut (J. Fluid Mech., vol. 788, 2016, 147–182). The spectral tensor of two-point second-order velocity correlations is predicted in the presence of arbitrary mean-velocity gradients and in a rotating frame. For this, we numerically solve coupled equations for the angle-dependent energy spectrum ${\mathcal{E}}(\boldsymbol{k},t)$ that includes directional anisotropy, and for the deviatoric pseudo-scalar  $Z(\boldsymbol{k},t)$ , that underlies polarization anisotropy ( $\boldsymbol{k}$  is the wavevector, $t$ the time). These equations include two parts: (i) exact linear terms representing the viscous spectral linear theory (SLT) when considered alone; (ii) generalized transfer terms mediated by two-point third-order correlations. In contrast with MCS, our model retains the complete angular dependence of the linear terms, whereas the nonlinear transfer terms are closed by a reduced anisotropic eddy damped quasi-normal Markovian (EDQNM) technique similar to MCS, based on truncated angular harmonics expansions. And in contrast with most spectral approaches based on characteristic methods to represent mean-velocity gradient terms, we use high-order finite-difference schemes (FDSs). The resulting model is applied to homogeneous rotating turbulent shear flow with several Coriolis parameters and constant mean shear rate. First, we assess the validity of the model in the linear limit. We observe satisfactory agreement with existing numerical SLT results and with theoretical results for flows without rotation. Second, fully nonlinear results are obtained, which compare well to existing direct numerical simulation (DNS) results. In both regimes, the new model improves significantly the MCS model predictions. However, in the non-rotating shear case, the expected exponential growth of turbulent kinetic energy is found only with a hybrid model for nonlinear terms combining the anisotropic EDQNM closure and Weinstock’s return-to-isotropy model.

Hypoimmunity and numerous stresses are two major challenges in broiler industry. Nutrient intervention at the specific time of embryonic stage is a feasible way to improve animal performance. This study was conducted to investigate the possible effects of in ovo feeding (IOF) of vitamin C at embryonic age 15th day (E15) on growth performance, antioxidation and immune function of broilers. A total of 240 broiler fertile eggs were randomly divided into two groups (0 and 3 mg injected dose of vitamin C at E15), and new-hatched chicks from each treatment were randomly allocated into six replicates with 10 chicks per replicate after incubation. The results indicated that in ovo vitamin C injection improved the hatchability (P < 0.05) and increased immunoglobulin M (IgM) (at the broiler’s age 1st day, D1), IgG and IgM concentrations (D21), as well as lysozyme activity (D21, P < 0.05) and total antioxidant capacity (D42, P < 0.01) in plasma of broilers. On D21, the splenic expression level of DNA methyltransferase 1 (DNMT1) was up-regulated in vitamin C (VC) group, whereas interleukin (IL)-6, interferon-γ, ten-eleven translocation protein 1 and thymine-DNA glycosylase were down-regulated (P < 0.05). On D42, in ovo vitamin C injection up-regulated splenic expression levels of DNMT1, DNA methyltransferase 3B (DNMT3B) and growth arrest and DNA-damage-inducible protein beta (P < 0.05), whereas down-regulated splenic expression levels of IL-6, tumour necrosis factor-α and methyl-CpG-binding domain protein 4 (P < 0.05). Our findings suggested that IOF of 3 mg vitamin C at E15 could improve, to some extent, the antioxidant activity and immune function in plasma, corresponding with the lower expression of pro-inflammatory cytokines in spleen. However, IOF of vitamin C leading to the changes in the expression of DNA methyltransferases and demethylases may suggest an increased trend of DNA methylation level in spleen and whether DNA methylation variation is associated with the lower expression of pro-inflammatory cytokines in spleen warrants future study.

In the 2015 review paper ‘Petawatt Class Lasers Worldwide’ a comprehensive overview of the current status of high-power facilities of ${>}200~\text{TW}$ was presented. This was largely based on facility specifications, with some description of their uses, for instance in fundamental ultra-high-intensity interactions, secondary source generation, and inertial confinement fusion (ICF). With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification (CPA), which made these lasers possible, we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed. We are now in the era of multi-petawatt facilities coming online, with 100 PW lasers being proposed and even under construction. In addition to this there is a pull towards development of industrial and multi-disciplinary applications, which demands much higher repetition rates, delivering high-average powers with higher efficiencies and the use of alternative wavelengths: mid-IR facilities. So apart from a comprehensive update of the current global status, we want to look at what technologies are to be deployed to get to these new regimes, and some of the critical issues facing their development.

Hepatitis E is an important zoonosis that is prevalent in China. Hepatitis E virus (HEV) is a pathogen that affects humans and animals and endangers public health in China. In this study, the detection of HEV epidemics in swine in Sichuan Province, China, was carried out by nested real-time PCR. A total of 174 stool samples and 160 bile samples from swine in Sichuan Province were examined. In addition, software was used to analyse the biological evolution of HEV. The results showed that within 2 years of swine HEV (SHEV) infection in China, SHEV was first detected in Sichuan Province. HEV was endemic in Sichuan; the positive rate for pig farms was 11.1%, and the total positive sample rate was 10.5%. The age of swine with the highest positive rate (17.9%) was 5–9 weeks. The examined swine species in order of highest to lowest HEV infection rates were Chenghua pig, Large White, Duroc, Pietrain, Landrace and Hampshire. Nucleotide and amino acid sequence analysis showed that the HEV epidemic in swine in Sichuan Province was related to genotype IV, which had the highest homology to HEV in Beijing. Sichuan strains have greater variation than Chinese representative strains, which may indicate the presence of new HEV strains.

Plant nitrogen (N) links with many physiological progresses of crop growth and yield formation. Accurate simulation is key to predict crop growth and yield correctly. The aim of the current study was to improve the estimation of N uptake and translocation processes in the whole rice plant as well as within plant organs in the RiceGrow model by using plant and organ maximum, critical and minimum N dilution curves. The maximum and critical N (Nc) demand (obtained from the maximum and critical curves) of shoot and root and Nc demand of organs (leaf, stem and panicle) are calculated by N concentration and biomass. Nitrogen distribution among organs is computed differently pre- and post-anthesis. Pre-anthesis distribution is determined by maximum N demand with no priority among organs. In post-anthesis distribution, panicle demands are met first and then the remaining N is allocated to other organs without priority. The amount of plant N uptake depends on plant N demand and N supplied by the soil. Calibration and validation of the established model were performed on field experiments conducted in China and the Philippines with varied N rates and N split applications; results showed that this improved model can simulate the processes of N uptake and translocation well.

Vessel flexure can be triggered naturally by surgical operation, heart pulsation and body movement. It may affect the mechanical behavior of the stent and the existence of a stent may in turn cause vessel injury. In the present study, the finite element method is employed to study the interaction between stent and vessel during vessel flexure. Two- and four-link stents made of stainless steel 316L and magnesium alloy WE43 are considered. Results indicate that longitudinal deformation of the stent can be caused by vessel flexure, and the higher levels of stress exist in the link struts. The existence of the stent could induce significant stress concentration and straightened deformation on vessel wall in the course of vessel flexure. Stents with more links or made of harder materials show greater anti-deformation capability, thus inducing a more severe stress concentration and straightened deformation on the vessel wall. The bending direction also affects the mechanical performance of the vessel-stent system. The results obtained could provide useful information for better stent designs and clinical decisions.

To investigate the effects of soybean isoflavone (SI) on immunity in infectious bursal disease virus (IBDV)-infected broilers, chicks were fed the same basal diet supplemented with 0 (non-infected control), 0 (infected control), 10, 20 or 40 mg/kg SI for 44 days. At 21 days old, chickens were inoculated with bursal infectious dose causing 50% morbidity of the IBDV BC 6/85 strain by the eye-drop and nasal route (except for non-infected controls). Results showed that, over 1–23 days post-infection (dpi), there was a significant interaction between SI supplementation level and time: high-level SI supplementation increased peripheral T lymphocyte proliferation, percentages of CD3+, CD4+ and CD8+ T lymphocytes, CD4+ to CD8+ ratio, serum concentrations of IgA, IgM and IgG, and IBDV antibody titres. Except for serum IgA and IgM, these variables increased over time with far higher values at 23 dpi than earlier. Compared with non-infected controls, IBDV inoculation decreased peripheral T lymphocyte proliferation at 3 dpi, percentages of CD3+, CD4+ and CD8+ T lymphocytes, and serum IgG, IgM concentration at 23 dpi, and increased IBDV antibody titres at 7, 15 and 23 dpi. Supplemental SI quadratically increased peripheral T lymphocyte proliferation, CD4+ to CD8+ ratio and serum IgA concentration at 3 dpi, percentages of CD3+, CD4+ and CD8+ T lymphocytes at 3 and 23 dpi, and serum IgM concentration and IBDV antibody titres at 23 dpi. These results indicate that dietary SI improved cellular and humoral immunity of IBDV-infected birds and may enhance resistance of Yellow-feathered broilers to infectious diseases.

Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector (RRV). RRVs selectively infect cancer cells due to innate and adaptive immune response defects in cancers that allow virus replication, and the requirement for cell division for virus integration into the genome. Toca 511 spreads through tumors, stably delivering an optimized yeast cytosine deaminase gene that converts the prodrug Toca FC (investigational, extended-release 5-FC) into 5-FU within the tumor microenvironment. 5-FU kills infected dividing cancer cells and surrounding tumor, myeloid derived suppressor cells, and tumor associated macrophages, resulting in long-term tumor immunity in preclinical models. Data from a Phase 1 resection trial showed six durable CRs and extended mOS compared to historical controls. The FDA granted Breakthrough Therapy Designation for Toca 511 & Toca FC in the treatment of patients with rHGG. Toca 5 is an international, randomized, open-label Phase 3 trial (NCT02414165) of Toca 511 & Toca FC versus SOC in patients undergoing resection for first or second recurrence of rHGG. Patients will be stratified by IDH1 status, KPS, and geographic region. Primary endpoint is OS, and secondary endpoints are durable response rate, durable clinical benefit rate, duration of durable response, and 12-month survival rate. Key inclusion criteria are histologically proven GBM or AA, tumor size ≥1cm and ≤5cm, and KPS ≥70. Immune monitoring and molecular profiling will be performed. Approximately 380 patients will be randomized. An IDMC is commissioned to review the safety and efficacy data which includes 2 interim analyses. Enrollment is ongoing.

This study was designed to explore the association between undernutrition in the growth period and cardiovascular risk factors in a middle-aged Chinese population. A total of 1756 subjects, aged 45–60 years, were invited to participate in the Hefei Nutrition and Health Study and divided into three groups according to their self-reported animal food intake in the growth period. Group 1, Group 2 and Group 3 were defined as undernutrition, nutritional improvement and the good nutrition group, respectively. In the three groups, the subjects in Groups 1 and 2 had more oil and salt intake (P<0.001), and less eggs and milk intake (P<0.001), when compared with the subjects in Group 3. After adjusting for age, education, smoking status and other confounding factors, it was found that male participants who experienced nutritional improvement before age 18 had higher risk of hypertension [odds ratio (OR)=1.68; 95% confidence intervals (CI): 1.05, 2.69] than those with good nutrition, and female participants with undernutrition (OR=1.52; 95% CI: 1.01, 2.29) and nutritional improvement (OR=1.68; 95% CI: 1.04, 2.69) before age 18 had a higher risk of hypertension than those with good nutrition. For diabetes, obesity, hypercholesterolemia and hypertriglyceridemia, our results did not found difference among the three groups both in male and female. Our findings indicated that nutritional deficiency in childhood was associated with bad dietary behaviors and a significantly increased risk of hypertension in middle age. Therefore, early adequate nutrition is very important for the prevention of non-communicable diseases later.