Towards small-molecule CXCR3 ligands with clinical potential

The CXCR3 chemokine receptor was first discovered in 1996 and has been shown to play an important role in several diseases, most of which are related to inflammation. This review describes in detail the development of small CXCR3 ligands and their therapeutic potential. Classes of CXCR3 antagonists with strikingly variable core structures have emerged. Some of these compounds have confirmed the beneficial role of CXCR3 antagonism in animal models of disease. One of the compounds, AMG487, progressed to Phase II clinical trials but has been withdrawn because of lack of efficacy. New antagonist classes are being developed to reveal the full therapeutic potential of CXCR3.     

The use of long-chain plant polyprenols as a means to modify the biological properties of new biodegradable polyurethane scaffolds for tissue engineering. A pilot study

Microporous membranes for tissue engineering were produced from new biodegradable polyurethane based on hexamethylene diisocyanate, poly(ε-caprolactone) diol and 1,4:3,6-dianhydro-d-sorbitol. The interconnected pores had an average size in the range of 5–100 μm. The tensile strength at break, the Young’s modulus and elongation at break of the membranes were 3.2 ± 0.3 MPa, 25.2 ± 1.5 MPa and 190 ± 12%, respectively, while nonporous foils from the same polymers had a tensile strength at break of 40 ± 2 MPa, a Young’s modulus of 91 ± 6 MPa, and an elongation at break of 370 ± 10%. The membranes were incubated for 10 days in a 2.65 vol% solution of long-chain plant polyprenol in n-hexane to promote their interaction with cells and tissues. The polyprenol was isolated from leaves of Magnolia cobus and was a mixture of prenol-10 and prenol-11. The prenol-impregnated membranes and nonimpregnated membranes (control) were tested in cell culture to assess whether impregnation has a beneficial effect on cell-material interaction. The cells used in the test were chondrocytes isolated from the articular-epiphyseal cartilage of leg bones of 5-day-old inbred LEW rats. The time of culture was 2 and 5 weeks. Both, the nonimpregnated and impregnated polyurethane membranes supported attachment and growth of rat chondrocytes. The cells firmly attached to the surface of the microporous membranes, invaded the pores and maintained the round shape characteristic for chondrocyte-like-morphology. Abundant fibrillar extracellular matrix produced by the cells resembled the network formed by chondrocytes in vivo. The cells produced relatively more extracellular matrix in the membranes impregnated with polyprenol than in the control membranes. Impregnation of polyurethane scaffolds with biologically active amphiphilic polyprenols may be a route to facilitate the cell–material interaction.     

Theoretical consideration of the effect of porosity on thermal conductivity of porous materials

The thermal conductivity of porous materials is theoretically studied in connection with nanoporous materials used in recent semiconductor devices. The effects of porosity and pore size on the thermal conductivity are discussed. The thermal conductivity of insulating materials is determined by the heat capacity of phonons, the average phonon velocity and the phonon mean free path. We investigate the porosity dependence of these quantities, especially by taking into account phonon scatterings by pores, and present an expression for the thermal conductivity as a function of porosity. Our model consideration predicts that the thermal conductivity of nanoporous materials depends on the ratio of the pore size R _p to the phonon mean free path for zero-porosity, l ₀. The thermal conductivity for l ₀/R _p > 1 decreases steeply with increasing porosity because of effective phonon scatterings by pores. On the other hand, the thermal conductivity for l ₀/R _p < 0.1 decreases moderately with increasing porosity because phonon scatterings by pores are no longer effective. On the basis of the present theoretical consideration, we discuss the principal factor dominating the porosity dependence of thermal conductivity in nanoporous materials. We also discuss how one can design nanoporous materials with lower or higher thermal conductivity.     

Influence of cement content and environmental humidity on asphalt emulsion and cement composites performance

Asphalt and cement concrete are the most popular materials used in the construction of roads, highways, bridge deck surface layers and pavements in airports and other areas with heavy wheel roads. Whereas asphalt possesses, compared to concrete, the advantages of a short curing period, high skid resistance and easy maintenance, it also shows lower fatigue durability, ravelling and rutting due to repeated concentrated loads and susceptibility to temperature changes and moisture. On the other hand, concrete pavements are initially more expensive, have lower driving comfort and are susceptible to cracking due to volume changes and to salt damage. A material with low-environmental impact and with advantages of both asphalt and concrete may be obtained by combining bitumen emulsions and a cementitious material. In this paper, cold asphalt mixtures with different amounts of cement were tested with Marshall stability tests. Selected mixtures were also cured at different environmental relative humidity (35, 70 and 90 % RH). By monitoring the mass of the specimens and estimating the water bound by the cement, the total water remaining in the mixtures was calculated. Details of the microstructure in the mixtures were examined with X-ray microtomography. According to the results of the present study, cement contributes to the hardening of cold asphalt mixtures both by creating cement paste bridges between the aggregates and by removing water from the mixtures through cement hydration. Asphalt and cement composites appear to be promising materials for implementation in real pavements, although their rate of hardening needs to be improved further.     

Stochastic generation of particle structures with controlled degree of heterogeneity

The recently developed void expansion method (VEM) allows for an efficient generation of porous packings of spherical particles over a wide range of volume fractions. The method is based on a random placement of the structural particles under addition of much smaller “void-particles” whose radii are repeatedly increased during the void expansion. Thereby, they rearrange the structural particles until formation of a dense particle packing and introduce local heterogeneities in the structure. In this paper, microstructures with volume fractions between 0.4 and 0.6 produced by VEM are analyzed with respect to their degree of heterogeneity (DOH). In particular, the influence of the void- to structural particle number ratio, which constitutes a principal VEM-parameter, on the DOH is studied. The DOH is quantified using the pore size distribution, the Voronoi volume distribution and the density-fluctuation method in conjunction with fit functions or integral measures. This analysis has revealed that for volume fractions between 0.4 and 0.55 the void-particle number allows for a quasi-continuous adjustment of the DOH. Additionally, the DOH-range of VEM-generated microstructures with a volume fraction of 0.4 is compared to the range covered by microstructures generated using previous Brownian dynamics simulations, which represent the structure of coagulated colloidal suspensions. Both sets of microstructures cover similarly broad and overlapping DOH-ranges, which allows concluding that VEM is an efficient method to stochastically reproduce colloidal microstructures with varying DOH.     

Temperature-dependent 2-D to 3-D growth transition of ultra-thin Pt films deposited by PLD

During the growth of thin metal films on dielectric substrates at a given deposition temperature T_d, the film’s morphology is conditioned by the magnitude and asymmetry of up- and downhill diffusion. Any severe change of this mechanism leads to a growth instability, which induces an alteration of the thin film morphology. In order to study this mechanism, ultrathin Pt films were deposited via pulsed laser deposition onto yttria-stabilized zirconia single crystals at different deposition temperatures. The morphological evolution of Pt thin films has been investigated by means of scanning electron microscopy, atomic force microscopy and standard image analysis techniques. The experimentally obtained morphologies are compared to simulated thin film structures resulting from a two-dimensional kinetic Monte Carlo approach. Two main observations have been made: (i) thin Pt films deposited onto ZrO₂ undergo a growth transition from two-dimensional to three-dimensional growth at T_d > 573 K. The growth transition and related morphological changes are a function of the deposition temperature; and (ii) a critical cluster size of i¹ = 4 in combination with an asymmetric Ehrlich–Schwoebel barrier favoring the uphill diffusion of atoms allows for a computational reproduction of the experimentally obtained film morphologies.     

香港太古广场

精选理由简洁大方的设计糅合了自然、温暖及柔和的元素,呈现出不一样的现代风格。错落有致的陈设将改造后太古广场的休闲、前卫与标新立异的时尚表现得酣畅淋漓。可以说,香港太古广场在Thomas Heatherwick手里获得了新生。     

Physical Virology: Direct Measurement of Phage phi29 Stiffness Provides Evidence of Internal Pressure (Small 15/2012)

A 3D AFM topography rendition of a phage phi29 (red) adsorbed on mica (blue) is shown by P. J. de Pablo and coworkers, where part of the viral DNA (yellow) has been ejected through the tail. The phi29 bacteriophage translocates part of its DNA into the host by releasing the elastic energy arising from the internal pressure created during the DNA-packing process. Pushing with the AFM tip on the phage enables the direct measurement of the stiffness to estimate its internal pressure, just as a tyre may be pressed with fingers.     

A descriptive model of information problem solving while using internet

This paper presents the IPS-I-model: a model that describes the process of information problem solving (IPS) in which the Internet (I) is used to search information. The IPS-I-model is based on three studies, in which students in secondary and (post) higher education were asked to solve information problems, while thinking aloud. In-depth analyses of the thinking-aloud protocols revealed that the IPS-process consists of five constituent skills: (a) defining information problem, (b) searching information, (c) scanning information, (d) processing information, and (e) organizing and presenting information. Further, the studies revealed that regulation skills prove to be crucial for the on-going IPS-process. The IPS-I-model depicts the constituent skills, regulation skills, and important conditional skills. The model gives an initial impetus for designing IPS-instruction.