Establishment of a Reverse Genetics System for Studying Human Bocavirus in Human Airway Epithelia

Human bocavirus 1 (HBoV1) has been identified as one of the etiological agents of wheezing in young children with acute respiratory-tract infections. In this study, we have obtained the sequence of a full-length HBoV1 genome (including both termini) using viral DNA extracted from a nasopharyngeal aspirate of an infected patient, cloned the full-length HBoV1 genome, and demonstrated DNA replication, encapsidation of the ssDNA genome, and release of the HBoV1 virions from human embryonic kidney 293 cells. The HBoV1 virions generated from this cell line-based production system exhibits a typical icosahedral structure of approximately 26 nm in diameter, and is capable of productively infecting polarized primary human airway epithelia (HAE) from the apical surface. Infected HAE showed hallmarks of lung airway-tract injury, including disruption of the tight junction barrier, loss of cilia and epithelial cell hypertrophy. Notably, polarized HAE cultured from an immortalized airway epithelial cell line, CuFi-8 (originally derived from a cystic fibrosis patient), also supported productive infection of HBoV1. Thus, we have established a reverse genetics system and generated the first cell line-based culture system for the study of HBoV1 infection, which will significantly advance the study of HBoV1 replication and pathogenesis.This work was supported by PHS R21 grant AI085236 and PHS R01 grant AI070723 from NIAID (J Qiu) and PHS R01 grant HL108902 from NHLBI (J Engelhardt)

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Spectral decomposition of susceptibility artifacts for spectral-spatial radiofrequency pulse design

Susceptibility induced signal loss is a limitation in gradient echo functional MRI. The through-plane artifact in axial slices is particularly problematic due to the inferior position of air cavities in the brain. Spectral-spatial RF pulses have recently been shown to reduce signal loss in a single excitation. The pulses were successfully demonstrated assuming a linear relationship between susceptibility gradient and frequency, however, the exact frequency and spatial distribution of the susceptibility gradient in the brain is unknown. We present a spiral spectroscopic imaging sequence with a time-shifted RF pulse that can spectrally decompose the through-plane susceptibility gradient for spectral-spatial RF pulse design. Maps of the through-plane susceptibility gradient as a function of frequency were generated for the human brain at 3T. We found that the linear relationship holds well for the whole brain with an optimal slope of −1.0μT/m/Hz

Effect of feed quantity on breakage degree of ore particles subjected to high voltage pulses

The effect of spatial arrangement of feed sample on the breakage degree of high voltage pulse breakage (HVPB) product was investigated by varying the number of feed particles discharged simultaneously inside a processing vessel. Two kinds of hard porphyry copper ores were treated using the commercial HVPB tester SELFRAG Lab and a custom-made unit respectively. The results indicate that, at given electrode gap and specific energy, the fineness (t10) of HVPB product increases with feed quantity, while the pre-weakening degree (CAb) of HVPB product decreases with feed quantity. A new index of equivalent product fineness (t10e), which reflects the combined effect of\ua0t10\ua0and\ua0CAb, is employed to represent the overall breakage degree of HVPB product. It is found that the value of\ua0t10e\ua0has a positive relation with the feed quantity of HVPB tests. The effect of feed quantity on ore behaviour in HVPB is attributed to the influence of particles bed volume on breakdown strength and the negative effect of water gap between ore particles and top electrode. Finally, it is recommended to take feed quantity into consideration in HVPB studies to obtain comparative testing results, and to select the most appropriate breakage degree indexes from\ua0t10,\ua0CAb\ua0and\ua0t10e\ua0according to research aim. Particularly, electrode gap just filled by feed particles is preferred to optimize the over breakage degree of ore particles

Growth behavior of iron grains during deep reduction of copper slag

The change in granularity of iron grains in copper slag during coal-based deep reduction was identified using optical microscopy and the Image J analysis software. The growth behavior of iron grains was investigated based on the Hillert dynamic model. The results indicate that the granularity and sphericity of iron grains are strongly affected by the reduction time and temperature during the deep reduction process. It is found that in isothermal condition, the growth rate of iron granularity increases with time exhibiting an S-shape characteristic. Meanwhile, in non-isothermal condition, the growth rate of iron granularity increases exponentially with temperature. When the reduction temperature is in the range of ~1423–1573 K and the reduction time was in the range of ~30–180 min, the grain growth kinetic parameters are calculated as follows: growth index n = 1.424 ± 0.07855, apparent activation energy Q = 116.17 kJ∙mol, and pre-exponential factor as 20,839.38

Single-shot echo-planar imaging with Nyquist ghost compensation:interleaved dual echo with acceleration (IDEA) echo-planar imaging (EPI)

Echo planar imaging is most commonly used for BOLD fMRI, owing to its sensitivity and acquisition speed. A major problem with EPI is Nyquist (N/2) ghosting, most notably at high field. EPI data are acquired under an oscillating readout gradient and hence vulnerable to gradient imperfections such as eddy current delays and off-resonance effects, as these cause inconsistencies between odd and even k-space lines after time reversal. We propose a straightforward and pragmatic method herein termed Interleaved Dual Echo with Acceleration (IDEA) EPI: Two k-spaces (echoes) are acquired under the positive and negative readout lobes, respectively, by performing phase blips only before alternate readout gradients. From these two k-spaces, two almost entirely ghost free images per shot can be constructed, without need for phase correction. The doubled echo train length can be compensated by parallel imaging and/or partial Fourier acquisition. The two k-spaces can either be complex-averaged during reconstruction, which results in near-perfect cancellation of residual phase errors, or reconstructed into separate images. We demonstrate the efficacy of IDEA EPI and show phantom and in vivo images at both 3 and 7 Tesla

Analysis of magnetic particle agglomeration structure and interaction forces between magnetic particles

Chain-like and diamond-shaped magnetic particle agglomeration (MPA) commonly forming in a weak magnetic field are simulated based on the finite element method (FEM), and the effects of particle diameter, magnetic field strength, particle relative magnetic permeability, and particle number in magnetic particle chains (MPCs) and diamond-shaped MPA on the strength of MPA are analysed in detail. The results show that magnetic forces on the centre contact points (CCPs) of MPA are positively correlated with the particle diameter, magnetic field strength, particle relative magnetic permeability, and particle number. In addition, the forces on the CCPs of the MPCs (N=2) have a square relationship with the particle diameter and magnetic field strength and have a power relationship of 1.25 with the particle relative magnetic permeability. The forces on each contact point decrease slowly from the centre to both ends in the MPCs and then rapidly decrease to one value (approximately 0.779 times the forces on the CCPs). As for the diamond-shaped MPA, with the increase in the angle α between the magnetic field and axis of diamond-shaped MPA, the force magnitude of the particle entrained parallelly in the diamond-shaped MPA shows a trend of a “cosine curve” shape and the minimum value is 2109 times that of the entrained particle’s gravity. The angle θ between the direction of the force and the negative X-axis shows a trend of a “sine curve” shape. When α = 25º and 155º, the angle θ of the force on the entrained particle reaches an extreme value, that is, θ = 21.87º. Only if the angle θ reaches 30º can the particle entrained parallelly escape from the diamond-shaped MPA. Thus, the diamond-shaped MPA remains in a stable state and it is difficult to disperse MPA by changing the direction of the magnetic field

Effect of high voltage pulse treatment on the surface chemistry and floatability of chalcopyrite and pyrite

The effect of high voltage pulse (HVP) treatment on the surface chemistry and flotation behaviour of chalcopyrite and pyrite were investigated using single mineral. The results indicated that the effect of HVP treatment on pyrite was more significant than chalcopyrite, both in terms of size reduction degree and flotation behaviour. Despite the stronger resistance to mechanical breakage than chalcopyrite, the proportion of −0.053 mm product of pyrite was higher than chalcopyrite for 12.2 per cent in average after HVP treatment of different pulse numbers. The flotation recovery of chalcopyrite was only slightly reduced after HVP treatment of 130 pulse discharges. However, under the same test conditions, the flotation recovery of pyrite was reduced by 64.1 per cent in average. The flotation behaviour of the two single minerals were in agreement with their surface oxidation behaviour in HVP treatment. XPS analysis and EDTA extraction suggested that chalcopyrite surface had only partially oxidized by HVP treatment; whereas pyrite was deeply oxidized with a large amount of S element converted to be sulphate radicals. The relative permittivity of pyrite, chalcopyrite and water was 33.5, 78.1 and 80 respectively, which led to a ratio of electrical field strength inside pyrite, chalcopyrite and water theoretically being 2.39:1.02:1. As a result, pyrite particles had stronger capability to attract electrical breakdown channel than chalcopyrite, and subjected to more severe size reduction and surface oxidation under the same conditions. On the other hand, the slight surface oxidation of chalcopyrite particles was hypothesized to be caused by the active species (OH, H2O2, etc.) formed during pulse discharge