To dissect the antibiotic role of nanostructures from chemical moieties belligerent to both bacterial and mammalian cells, here we show the antimicrobial activity and cytotoxicity of ...nanoparticle-pinched polymer brushes (NPPBs) consisting of chemically inert silica nanospheres of systematically varied diameters covalently grafted with hydrophilic polymer brushes that are non-toxic and non-bactericidal. Assembly of the hydrophilic polymers into nanostructured NPPBs doesn't alter their amicability with mammalian cells, but it incurs a transformation of their antimicrobial potential against bacteria, including clinical multidrug-resistant strains, that depends critically on the nanoparticle sizes. The acquired antimicrobial potency intensifies with small nanoparticles but subsides quickly with large ones. We identify a threshold size (d
~ 50 nm) only beneath which NPPBs remodel bacteria-mimicking membrane into 2D columnar phase, the epitome of membrane pore formation. This study illuminates nanoengineering as a viable approach to develop nanoantibiotics that kill bacteria upon contact yet remain nontoxic when engulfed by mammalian cells.
Effective bonding between adherents plays a key role in retrofitting concrete structures in civil engineering using fibre-reinforced polymers (FRPs). To ensure structural safety, it is critical to ...develop design codes, which account for uncertainties of materials, the environment, and load, to estimate bond behaviour under long-term exposure to harsh environments. Therefore, a reliability analysis was performed to study the bond behaviour of FRP⁻concrete interface under wet⁻dry cycles and sustained loading. Thirty double-lap, shear-bonded carbon FRP (CFRP)⁻concrete composite specimens were tested after wet⁻dry cycles and sustained loading exposure. The fracture energy
of the bond behavior between CFRP and concrete was directly obtained from the measured local bond-slip curves. Five widely used test methods were adopted to verify the possible distribution types of
. Based on the best fit distribution of
, a reliability index
was then calculated for the specimens. The effects of wet⁻dry exposure and sustained loading on
were analysed separately. The effects of the mean and standard deviation of the load on
were compared. It was found that the mean had a greater impact on reliability than the standard deviation, but neither changed the regulation of the exponential reduction of
with increasing wet⁻dry cycle time. Their impact was significant for a small number of wet⁻dry cycles but insignificant for more than 4000 wet⁻dry cycles.
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Membrane proteins can be reconstituted in polymer-encased nanodiscs for studies under near-physiological conditions and in the absence of detergents, but traditional styrene-maleic acid copolymers ...used for this purpose suffer severely from buffer incompatibilities. We have recently introduced zwitterionic styrene-maleic amide copolymers (zSMAs) to overcome this limitation. Here, we compared the extraction and reconstitution of membrane proteins into lipid nanodiscs by a series of zSMAs with different styrene:maleic amide molar ratios, chain sizes, and molecular weight distributions. These copolymers solubilize, stabilize, and support membrane proteins in nanodiscs with different efficiencies depending on both the structure of the copolymers and the membrane proteins.
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Styrene-maleic acid copolymers allow for solubilization and reconstitution of membrane proteins into nanodiscs. These polymer-encased nanodiscs are promising platforms for studies of membrane ...proteins in a near-physiologic environment without the use of detergents. However, current styrene-maleic acid copolymers display severe limitations in terms of buffer compatibility and ensued flexibility for various applications. Here, we present a new family of styrene-maleic acid copolymers that do not aggregate at low pH or in the presence of polyvalent cations, and can be used to solubilize membrane proteins and produce nanodiscs of controlled sizes.
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Elevated temperature exposure has a negative effect on the performance of the matrix resin in Carbon Fiber Reinforced Plastics (CFRP) plates, whereas limited quantitative research focuses on the ...deteriorations. Therefore, 30 CFRP specimens were designed and tested under elevated temperatures (10, 30, 50, 70, and 90 °C) to explore the degradations in tensile properties. The effect of temperature on the failure mode, stress-strain curve, tensile strength, elastic modulus and elongation of CFRP plates were investigated. The results showed that elevated temperature exposure significantly changed the failure characteristics. When the exposed temperature increased from 10 °C to 90 °C, the failure mode changed from the global factures in the whole CFRP plate to the successive fractures in carbon fibers. Moreover, with temperatures increasing, tensile strength and elongation of CFRP plates decreases gradually while the elastic modulus shows negligible change. Finally, the results of One-Way Analysis of Variance (ANOVA) show that the degradation of the tensile strength of CFRP plates was due to the impact of elevated temperature exposure, rather than the test error.
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We report here a green chemistry method to conjugate hydrophobic payloads (Lilial as a prototype) highly efficiently (35.8 wt %) with (1→4)-2-amino-2-deoxy-β-d-glucan (i.e., chitosan) via Schiff base ...bond formation in an ionic liquid, which renders chitosan easily dissolvable in common organic solvents and amenable to further functional modifications. As an example, thermoresponsive poly(N-isopropylacrylamide) was grafted to the chitosan−Lilial conjugate. The graft copolymer self-assembled in water at neutral pH into core−shell nanocarriers with a favorable size distribution (d ∼ 142 ± 60 nm) for intravenous administration. Under conditions of enhanced temperature and acidity (T = 37 °C, pH = 4.5) mimicking endosomal or lysosomal uptake, the nanocarriers fell apart and formed reversed micelles with greatly reduced sizes (d ∼ 8 ± 3 nm) favoring clearance by renal filtration, and 70% Lilial molecules were liberated within 30 h through hydrolytic cleavage of the exposed Schiff base conjugation. This smart stimuli-responsive drug release profile reveals a viable approach in the development of chitosan-based nanocarriers for intravenous administration of hydrophobic pharmaceuticals.
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Magic-angle spinning nuclear magnetic resonance is well suited for the study of membrane proteins in the nativelike lipid environment. However, the natural cellular membrane is invariably more ...complex than the proteoliposomes most often used for solid-state NMR (SSNMR) studies, and differences may affect the structure and dynamics of the proteins under examination. In this work we use SSNMR and other biochemical and biophysical methods to probe the structure of a seven-transmembrane helical photoreceptor, Anabaena sensory rhodopsin (ASR), prepared in the Escherichia coli inner membrane, and compare it to that in a bilayer formed by DMPC/DMPA lipids. We find that ASR is organized into trimers in both environments but forms two-dimensional crystal lattices of different symmetries. It favors hexagonal packing in liposomes, but may form a square lattice in the E. coli membrane. To examine possible changes in structure site-specifically, we perform two- and three-dimensional SSNMR experiments and analyze the differences in chemical shifts and peak intensities. Overall, this analysis reveals that the structure of ASR is largely conserved in the inner membrane of E. coli, with many of the important structural features of rhodopsins previously observed in ASR in proteoliposomes being preserved. Small, site-specific perturbations in protein structure that occur as a result of the membrane changes indicate that the protein can subtly adapt to its environment without large structural rearrangement.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Multiple moderate-resolution crystal structures of human aquaporin-1 have provided a foundation for understanding the molecular mechanism of selective water translocation in human cells. To gain ...insight into the interfacial structure and dynamics of human aquaporin-1 in a lipid environment, we performed nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulations. Using magic angle spinning solid-state NMR, we report a near complete resonance assignment of the human aquaporin-1. Chemical shift analysis of the secondary structure identified pronounced deviations from crystallographic structures in extracellular loops A and C, including the cis Y37–P38 bond in loop A, as well as ordering and immobilization of loop C. Site-specific H/D exchange measurements identify a number of protected nitrogen-bearing side chains and backbone amide groups, involved in stabilizing the loops. A combination of molecular dynamics simulations with NMR-derived restraints and filtering based on solvent accessibility allowed for the determination of a structural model of extracellular loops largely consistent with NMR results. The simulations reveal loop stabilizing interactions that alter the extracellular surface of human AQP1, with possible implications for water transport regulation through the channel. Modulation of water permeation may occur as a result of rearrangement of side chains from loop C in the extracellular vestibule of hAQP1, affecting the aromatic arginine selectivity filter.
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Rate of penetration (ROP) is affected by many factors (i.e. rock properties, drilling parameters), and the increase of ROP is required to meet the needs of modern drilling operations. This paper ...presents a methodology to increase ROP by developing targeted impact drilling plans according to classify rock mechanic parameters of the different formations. In this paper, rock mechanic parameters are calculated based on well logging data, and the results are clustered according to unsupervised clustering algorithm. Then, the clustering data are used as the material parameters for numerical simulation, and the rock-breaking performance of polycrystalline diamond compact (PDC) cutter in different formations under determined impact load and, cutting velocity is discussed as well as the coupling of these two factors. It is shown that the crushing volume of the rock clustering from upper softer formations can be significantly increased by coupling impact load and higher cutting velocity while maintaining the lower specific energy consumption. In the cluster rock of harder formations which needs maximum mechanical energy to break, impact load can greatly reduce its specific energy consumption. However, after increasing the cutting velocity, the specific energy increases greatly while the rock crushing volume increases insignificantly, which is not expected in the drilling. According to simulation results, the paper developed two ROP enhancement modes, using impact drilling mode (Drilling Pipe+ Axial Impact Hammer+ Bit) in well interval of harder volcanic rock formations drilling while high-speed rotary impact mode (Drilling Pipe+ Positive Displacement Motor+ Axial Impact Hammer+ Bit) drills the well interval of upper softer formations. The feasibility of these modes has been verified by field experiments. The figures show that compared with offset well which drilled by positive displacement motor (PDM), high-speed rotary impact drilling increases ROP by 48.44% on average in three trips in the well interval of upper softer formations. Meanwhile, conventional impact drilling mode has the strongest ROP improving ability in the well interval of harder volcanic rock formations, reaching 113.45% in the fourth trip, and also has the advantage of saving PDM rental costs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Oil and gas resources covered under gravel layer have had much attention. The mechanical behaviors and failure mechanism of conglomerate, main component of gravel layer, are still unclear for the ...complex distribution characteristics in gravel size, shape, and content. A numerical model considering gravel particles distributed randomly was established to study the effect of gravel distribution characteristics using a discrete element method. Results indicate that increasing the gravel size or content, or overlapping of the particles can reduce the number of independent gravel blocks, thus enhancing the heterogeneity of conglomerate and changing the failure types and crack development trend. The failure strength shows a parabolic trend with rising gravel content, while the elastic modulus increases linearly, causing the ability of specimen to resist deformation to improve. The mutual extrusion brings about the increase of failure strength rapidly and the reversal of peak strain and Poisson’s ratio when gravel content is over 70%. The cohesion and internal friction angle show a parabolic tendency, based on which the strength prediction model of conglomerate considering gravel content was established with high precision. This work provides a kind of numerical method for studying the physical and mechanical characteristics of the strongly heterogeneous rock considering the components.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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