Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions ...in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer's theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.
This study investigates the differences in the microstructure, defects and mechanical behavior of porous structures from a β-type Ti24Nb4Zr8Sn manufactured by electron beam melting (EBM) and ...selective laser melting (SLM). The phases, size and shape of melt pool, volume and distribution of defects are analyzed and correlated to the compressive mechanical and fatigue properties. Due to different powder bed temperatures, the microstructure of EBM and SLM samples consists of α+β phases and a single β phase, respectively. The faster cooling rate during SLM promotes the formation of fine β dendrites, which leads to a higher compressive strength (50 ± 0.9 MPa) and lower Young's Modulus (0.95 ± 0.05 GPa) in comparison to the EBM parts (45 ± 1.1 MPa and 1.34 ± 0.04 GPa respectively). The large defects present within solid strut are likely a result of tin vaporization. The tin vapor is more easily trapped during the SLM process due to a smaller laser spot size and a faster cooling rate. This results in a 10 times increase in the number of defects. These defects have a limited influence on both the static properties and low stresses level fatigue strength, but it causes a reduced and variable fatigue life at high stresses level.
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Ti–6Al–4V reticulated meshes with different elements (cubic, G7 and rhombic dodecahedron) in Materialise software were fabricated by additive manufacturing using the electron beam ...melting (EBM) method, and the effects of cell shape on the mechanical properties of these samples were studied. The results showed that these cellular structures with porosities of 88–58% had compressive strength and elastic modulus in the range 10–300MPa and 0.5–15GPa, respectively. The compressive strength and deformation behavior of these meshes were determined by the coupling of the buckling and bending deformation of struts. Meshes that were dominated by buckling deformation showed relatively high collapse strength and were prone to exhibit brittle characteristics in their stress–strain curves. For meshes dominated by bending deformation, the elastic deformation corresponded well to the Gibson–Ashby model. By enhancing the effect of bending deformation, the stress–strain curve characteristics can change from brittle to ductile (the smooth plateau area). Therefore, Ti–6Al–4V cellular solids with high strength, low modulus and desirable deformation behavior could be fabricated through the cell shape design using the EBM technique.
Cell-free DNA (cfDNA) in human plasma is a class of biomarkers with many current and potential future diagnostic applications. Recent studies have shown that cfDNA molecules are not randomly ...fragmented and possess information related to their tissues of origin. Pathologies causing death of cells from particular tissues result in perturbations in the relative distribution of DNA from the affected tissues. Such tissue-of-origin analysis is particularly useful in the development of liquid biopsies for cancer. It is therefore of value to accurately determine the relative contributions of the tissues to the plasma DNA pool in a simultaneous manner. In this work, we report that in open chromatin regions, cfDNA molecules show characteristic fragmentation patterns reflected by sequencing coverage imbalance and differentially phased fragment end signals. The latter refers to differences in the read densities of sequences corresponding to the orientation of the upstream and downstream ends of cfDNA molecules in relation to the reference genome. Such cfDNA fragmentation patterns preferentially occur in tissue-specific open chromatin regions where the corresponding tissues contributed DNA into the plasma. Quantitative analyses of such signals allow measurement of the relative contributions of various tissues toward the plasma DNA pool. These findings were validated by plasma DNA sequencing data obtained from pregnant women, organ transplantation recipients, and cancer patients. Orientation-aware plasma DNA fragmentation analysis therefore has potential diagnostic applications in noninvasive prenatal testing, organ transplantation monitoring, and cancer liquid biopsy.
Quaternary Ti–(20–26)Nb–(2–8)Zr–(3.5–11.5)Sn (wt%) alloys were investigated to evaluate the effects of Zr and Sn on Young's modulus and superelasticity of Ti–Nb-based alloys. X-ray diffraction ...analysis showed that solution-treated alloys have β
+
α″, β
+
ω, α″
+
ω, α″, or β microstructures. Zr and Sn increase the lattice parameters of the β phase; for orthorhombic α″ matensite, they increase the lattice parameter
a but decrease both
b and
c. The martensitic start temperature of the α″ is depressed by Zr and Sn additions, whereas the formation of athermal ω is dependent on Zr and Sn contents. Differential scanning calorimetry (DSC) measurements show that 1
wt% of Nb, Zr or Sn addition decreases the martensitic start temperature by 17.6, 41.2 or 40.9
K, respectively, due to their negative effect on lattice parameter ratios of the martensite (
c/
a and
b/
a). Tensile tests were used to evaluate Young's modulus and superelasticity of the solution-treated alloys. Of the studied alloys Ti–24Nb–4Zr–7.5Sn with single β microstructure has the lowest Young's modulus of 52
GPa and recoverable elastic strain of about 2% at room temperature after cyclic strain.
Additive manufacturing technique is a promising approach for fabricating cellular bone substitutes such as trabecular and cortical bones because of the ability to adjust process parameters to ...fabricate different shapes and inner structures. Considering the long term safe application in human body, the metallic cellular implants are expected to exhibit superior fatigue property. The objective of the study was to study the influence of cell shape on the compressive fatigue behavior of Ti-6Al-4V mesh arrays fabricated by electron beam melting. The results indicated that the underlying fatigue mechanism for the three kinds of meshes (cubic, G7 and rhombic dodecahedron) is the interaction of cyclic ratcheting and fatigue crack growth on the struts, which is closely related to cumulative effect of buckling and bending deformation of the strut. By increasing the buckling deformation on the struts through cell shape design, the cyclic ratcheting rate of the meshes during cyclic deformation was decreased and accordingly, the compressive fatigue strength was increased. With increasing bending deformation of struts, fatigue crack growth in struts contributed more to the fatigue damage of meshes. Rough surface and pores contained in the struts significantly deteriorated the compressive fatigue strength of the struts. By optimizing the buckling and bending deformation through cell shape design, Ti-6Al-4V alloy cellular solids with high fatigue strength and low modulus can be fabricated by the EBM technique.
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•Ti-6Al-4V meshes with different cell shapes were fabricated by EBM technique.•The fatigue behavior of these meshes was strongly influenced by the cell shapes.•The fatigue mechanism is the interaction of cyclic ratcheting and crack growth.•Cyclic ratcheting dominated the compressive fatigue processes of these meshes.•Fatigue properties can be improved by optimizing buckling and bending deformations.
Abstract Studies have suggested that maternal infection/inflammation maybe a major risk factor for neurodevelopmental brain damage. In the present study, we evaluated the effects of prenatal exposure ...to a low level of inflammatory stimulation lipopolysaccharide (LPS) repeatedly on spatial learning and memory performances in rat offspring's lifetime. Sixteen pregnant Sprague–Dawley rats were randomly divided into two groups. The rats in the LPS group were treated i.p. with LPS (0.79 mg/kg) at gestation day 8, 10 and 12; meanwhile the rats in the control group were treated with saline. After delivery, the rat offspring at 3- (young), 10- (adult) and 20-mon-old (aged) were allocated. Spatial learning and memory abilities were tested by Morris water maze. The structure of hippocampal CA1 region was observed by light microscopy. The expression of synaptophysin (SYP) and glial fibrillary acidic protein (GFAP) in hippocampal CA1 region were measured by immunohistochemistry. Results showed that the rat offspring of LPS group needed longer escape latency and path-length in the Morris water maze and presented a significant neuron loss, decreased expression of SYP, increased expression of GFAP in CA1 region in histological studies. All these changes were more significant with the age increasing. These findings support the hypothesis that maternal systemic inflammation may alter the state of astrocytes in rat offspring for a long time, the alteration may affect neurons and synapse development in neural system, increase the neurons' vulnerability to environment especially as the age increasing, at last result in distinct learning and memory impairment.
Abstract
Ion Cyclotron Range of Frequencies (ICRF) heating and Neutral Beam Injection (NBI) can have synergy due to the acceleration of NBI beam ions by ICRF wave fields at their harmonics. To ...understand the influence of ICRF-NBI synergy on fast ion distribution and plasma performance, dedicated experiments and TRANSP simulations have been carried out on EAST. The simulation results are consistent with the experimental results. They show that the ICRF-NBI synergy not only accelerates the NBI beam ions with energy lower than 80 keV to energy larger than 300 keV, but also generates fusion neutrons with energy larger than 3 MeV. Moreover, ICRF-NBI synergy improves the plasma performance by increasing the poloidal beta, plasma stored energy, core ion temperature, total neutron yield and kinetic pressure. In a typical H-mode plasma with 1.0 MW NBI and 1.5 MW ICRF power, it was observed that ICRF-NBI synergy increases the poloidal beta, plasma stored energy, core ion temperature and neutron yield by ∼35%, 33%, 22% and 80%, respectively. Various parameter scans show that the ICRF-NBI synergetic effects can be enhanced by decreasing the minority ion concentration or the distance between the harmonic resonance and magnetic axis, or by increasing the ICRF heating power or NBI beam energy. Consequently, this leads to a generation of fast ions with higher energy. For instance, the maximum energy of the fast ion tail increases from 300 to 600 keV as n(H) decreases from 5% to 0.1%.
This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer.
In this phase III, ...double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.
Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 95% confidence interval (CI), 10.9-not evaluable versus 5.4 (95% CI, 3.7-5.7) months hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001, and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%).
Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.
•Chinese patients with platinum-sensitive recurrent ovarian cancer received maintenance niraparib (n = 177) or placebo (n = 88).•Median PFS was longer for niraparib versus placebo: 18.3 versus 5.4 months (HR = 0.32; 95% CI, 0.23-0.45; P < 0.0001).•Niraparib had a similar PFS benefit for 249 patients receiving individualized dosing based on bodyweight and platelet count.•Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively.•In the niraparib group, Grade ≥3 platelet count decreased/thrombocytopenia occurred in 11.3% of patients.
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