Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumour-burdened lymph nodes after intravenous and subcutaneous administration in rats

The current study sought to explore whether the subcutaneous administration of lymph-targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumour activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumour-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumour growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumour-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumour activity, possibly suggesting constrained drug release at the site of action.

Experimental studies of cold-formed steel hollow section columns at elevated temperatures

This paper reports the details of an experimental study of cold-formed steel hollow section columns at ambient and elevated temperatures. In this study the global buckling behaviour of cold-formed Square Hollow Section (SHS) slender columns under axial compression was investigated at various uniform elevated temperatures up to 700℃. The results of these column tests are reported in this paper, which include the buckling/failure modes at elevated temperatures, and ultimate load versus temperature curves. Finite element models of tested columns were also developed and their behaviour and ultimate capacities at ambient and elevated temperatures were studied. Fire design rules given in European and American standards including the Direct Strength Method (DSM) based design rules were used to predict the ultimate capacities of tested columns at elevated temperatures. Elevated temperature mechanical properties and stress-strain models given in European steel design standards and past researches were used with design rules and finite element models to investigate their effects on SHS column capacities. Comparisons of column capacities from tests and finite element analyses with those predicted by current design rules were used to determine the accuracy of currently available column design rules in predicting the capacities of SHS columns at elevated temperatures and the need to use appropriate elevated temperature material stress-strain models. This paper presents the important findings derived from the comparisons of these column capacities.

Local buckling studies of cold-formed steel compression members at elevated temperatures

Cold-formed steel members have been widely used in residential and commercial buildings as primary load bearing structural elements. They are often made of thin steel sheets and hence they are more susceptible to local buckling. The buckling behaviour of cold-formed steel compression members under fire conditions is not fully investigated yet and hence there is a lack of knowledge on the fire performance of cold-formed steel compression members. Current cold-formed steel design standards do not provide adequate design guidelines for the fire design of cold-formed steel compression members. Therefore a research project based on extensive experimental and numerical studies was undertaken to investigate the local buckling behaviour of light gauge cold-formed steel compression members under simulated fire conditions. First a series of 91 local buckling tests was conducted at ambient and uniform elevated temperatures up to 700oC on cold-formed lipped and unlipped channels. Suitable finite element models were then developed to simulate the behaviour of tested columns and were validated using test results. All the ultimate load capacity results for local buckling were compared with the predictions from the available design rules based on AS/NZS 4600, BS 5950 Part 5, Eurocode 3 Parts 1.2 and 1.3 and the direct strength method (DSM), based on which suitable recommendations have been made for the fire design of cold-formed steel compression members subject to local buckling at uniform elevated temperatures.

Cyclic Salinity Model for deposition of large-scale coal deposits

Existing field data for Rangal coals (Late Permian) of the Bowen Basin, Queensland, Australia, are inconsistent with the depositional model generally accepted in the current geological literature to explain coal deposition. Given the apparent unsuitability of the current depositional model to the Bowen Basin coal data, a new depositional model, here named the Cyclic Salinity Model, is proposed and tested in this study.

Influence of pipe length and flow rate on nano-particle deposition in laminar circular pipe flows

The Lagrangian particle tracking provides an effective method for simulating the deposition of nano- particles as well as micro-particles as it accounts for the particle inertia effect as well as the Brownian excitation. However, using the Lagrangian approach for simulating ultrafine particles has been limited due to computational cost and numerical difficulties. The aim of this paper is to study the deposition of nano-particles in cylindrical tubes under laminar condition using the Lagrangian particle tracking method. The commercial Fluent software is used to simulate the fluid flow in the pipes and to study the deposition and dispersion of nano-particles. Different particle diameters as well as different pipe lengths and flow rates are examined. The results show good agreement between the calculated deposition efficiency and different analytic correlations in the literature. Furthermore, for the nano-particles with higher diameters and when the effect of inertia has a higher importance, the calculated deposition efficiency by the Lagrangian method is less than the analytic correlations based on Eulerian method due to statistical error or the inertia effect.

Anthropogenic nitrogen deposition predicts local grassland primary production worldwide

Humans dominate many important Earth system processes including the nitrogen (N) cycle. Atmospheric N deposition affects fundamental processes such as carbon cycling, climate regulation, and biodiversity, and could result in changes to fundamental Earth system processes such as primary production. Both modelling and experimentation have suggested a role for anthropogenically altered N deposition in increasing productivity, nevertheless, current understanding of the relative strength of N deposition with respect to other controls on production such as edaphic conditions and climate is limited. Here we use an international multiscale data set to show that atmospheric N deposition is positively correlated to aboveground net primary production (ANPP) observed at the 1-m2 level across a wide range of herbaceous ecosystems. N deposition was a better predictor than climatic drivers and local soil conditions, explaining 16% of observed variation in ANPP globally with an increase of 1 kg N·ha-1·yr-1 increasing ANPP by 3%. Soil pH explained 8% of observed variation in ANPP while climatic drivers showed no significant relationship. Our results illustrate that the incorporation of global N deposition patterns in Earth system models are likely to substantially improve estimates of primary production in herbaceous systems. In herbaceous systems across the world, humans appear to be partially driving local ANPP through impacts on the N cycle.

Numerical investigation of aerosol particle transport and deposition in realistic lung airway

Different human activities like combustion of fossil fuels, biomass burning, industrial and agricultural activities, emit a large amount of particulates into the atmosphere. As a consequence, the air we inhale contains significant amount of suspended particles, including organic and inorganic solids and liquids, as well as various microorganism, which are solely responsible for a number of pulmonary diseases. Developing a numerical model for transport and deposition of foreign particles in realistic lung geometry is very challenging due to the complex geometrical structure of the human lung. In this study, we have numerically investigated the airborne particle transport and its deposition in human lung surface. In order to obtain the appropriate results of particle transport and deposition in human lung, we have generated realistic lung geometry from the CT scan obtained from a local hospital. For a more accurate approach, we have also created a mucus layer inside the geometry, adjacent to the lung surface and added all apposite mucus layer properties to the wall surface. The Lagrangian particle tracking technique is employed by using ANSYS FLUENT solver to simulate the steady-state inspiratory flow. Various injection techniques have been introduced to release the foreign particles through the inlet of the geometry. In order to investigate the effects of particle size on deposition, numerical calculations are carried out for different sizes of particles ranging from 1 micron to 10 micron. The numerical results show that particle deposition pattern is completely dependent on its initial position and in case of realistic geometry; most of the particles are deposited on the rough wall surface of the lung geometry instead of carinal region.

Optimized multilayer indium-free electrodes for organic photovoltaics

Flexible multilayer electrodes that combine high transparency, high conductivity, and efficient charge extraction have been deposited, characterised and used as the anode in organic solar cells. The anode consists of an AZO/Ag/AZO stack plus a very thin oxide interlayer whose ionization potential is fine-tuned by manipulating its gap state density to optimise charge transfer with the bulk heterojunction active layer consisting of poly(n-3- hexylthiophene-2,5-diyl) and phenyl-C61-butyric acid methyl ester (P3HT:BC61BM). The deposition method for the stack was compatible with the low temperatures required for polymer substrates. Optimisation of the electrode stack was achieved by modelling the optical and electrical properties of the device and a power conversion efficiency of 2.9% under AM1.5 illumination compared to 3.0% with an ITO-only anode and 3.5% for an ITO:PEDOT electrode. Dark I-V reverse bias characteristics indicate very low densities of occupied buffer states close to the HOMO level of the hole conductor, despite observed ionization potential being high enough. Their elimination should raise efficiency to that with ITO:PEDOT.

Room-temperature tilted-target sputtering deposition of highly transparent and low sheet resistance Al doped ZnO electrodes

Target-tilted room temperature sputtering of aluminium doped zinc oxide (AZO) provides transparent conducting electrodes with sheet resistances of <10 Ω □-1 and average transmittance in the visible region of up to 84%. The properties of the AZO electrode are found to be strongly dependent on the target-tilting angle and film thickness. The AZO electrodes showed comparable performance to commercial indium tin oxide (ITO) electrodes in organic photovoltaic (OPV) devices. OPV devices containing a bulk heterojunction active layer comprised of poly(3-n-hexylthiophene) (P3HT):phenyl-C61-butyric acid methyl ester (PCBM) and an AZO transparent conducting electrode had a power conversion efficiency (PCE) of up to 2.5% with those containing ITO giving a PCE of 2.6%. These results demonstrate that AZO films are a good alternative to ITO for transparent conducting electrodes.

An investigation of Nano-particle deposition in cylindrical tubes under Laminar condition using Lagrangian transport model

Aerosol deposition in cylindrical tubes is a subject of interest to researchers and engineers in many applications of aerosol physics and metrology. Investigation of nano-particles in different aspects such as lungs, upper airways, batteries and vehicle exhaust gases is vital due the smaller size, adverse health effect and higher trouble for trapping than the micro-particles. The Lagrangian particle tracking provides an effective method for simulating the deposition of nano-particles as well as micro-particles as it accounts for the particle inertia effect as well as the Brownian excitation. However, using the Lagrangian approach for simulating ultrafine particles has been limited due to computational cost and numerical difficulties. In this paper, the deposition of nano-particles in cylindrical tubes under laminar condition is studied using the Lagrangian particle tracking method. The commercial Fluent software is used to simulate the fluid flow in the pipes and to study the deposition and dispersion of nano-particles. Different particle diameters as well as different flow rates are examined. The point analysis in a uniform flow is performed for validating the Brownian motion. The results show good agreement between the calculated deposition efficiency and the analytic correlations in the literature. Furthermore, for the nano-particles with the diameter more than 40 nm, the calculated deposition efficiency by the Lagrangian method is less than the analytic correlations based on Eulerian method due to statistical error or the inertia effect.

Fast growth of polycrystalline graphene by chemical vapor deposition of ethanol on copper

High conductive graphene films can be grown on metal foils by chemical vapor deposition (CVD). We here analyzed the use of ethanol, an economic precursor, which results also safer than commonly-used methane. A comprehensive range of process parameters were explored in order to obtain graphene films with optimal characteristics in view of their use in optoelectronics and photovoltaics. Commercially-available and electro-polished copper foils were used as substrates. By finely tuning the CVD conditions, we obtained few-layer (2-4) graphene films with good conductivity (-500 Ohm/sq) and optical transmittance around 92-94% at 550 nm on unpolished copper foils. The growth on electro-polished copper provides instead predominantly mono-layer films with lower conductivity (>1000 Ohm/sq) and with a transmittance of 97.4% at 550 nm. As for the device properties, graphene with optimal properties as transparent conductive film were produced by CVD on standard copper with specific process conditions.

A novel experimental method to assess industrial aerosol deposition in idealized porous channels

A novel and economical experimental technique has been developed to assess industrial aerosol deposition in various idealized porous channel configurations. This judicious examination on aerosol penetration in porous channels will assist engineers to better optimize designs for various engineering applications. Deposition patterns differ with porosity due to geometric configurations of the channel and superficial inlet velocities. Interestingly, it is found that two configurations of similar porosity exhibit significantly higher deposition fractions. Inertial impaction is profound at the leading edge of all obstacles, whereas particle build-up is observed at the trailing edge of the obstructions. A qualitative analysis shows that the numerical results are in good agreement with experimental results.

Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein ANKH

Familial autosomal dominant calcium pyrophosphate dihydrate (CPPD) chondrocalcinosis has previously been mapped to chromosome 5pl5. We have identified a mutation in the ANKH gene that segregates with the disease in a family with this condition. ANKH encodes a putative transmembrane inorganic pyrophosphate (PPi) transport channel. We postulate that loss of function of ANKH causes elevated extracellular PPi levels, predisposing to CPPD crystal deposition.

Genetic factors in the pathogenesis of CPPD crystal deposition disease

Crystal deposition is a very complex process ruled by numerous factors. A small but important proportion of cases of chondrocalcinosis are monogenic, and many of the genes involved have been identified. These genetic findings strongly point to control of the level of extracellular inorganic pyrophosphate as the primary mechanism for their association with either calcium pyrophosphate dihydrate or hydroxyapatite deposition. However, effects on extracellular inorganic pyrophosphate levels do not explain the mechanism of association in all of these monogenic diseases. Further, there are likely to be several as yet unidentified genes that are important in this common condition. This review highlights what genetic studies have demonstrated about the processes involved in these diverse but related disorders.

Visible light-driven cross-coupling reactions at lower temperatures using a photocatalyst of palladium and gold alloy nanoparticles

Palladium (Pd)-catalyzed cross-coupling reactions are among the most important methods in organic synthesis. We report the discovery of highly efficient and green photocatalytic processes by which cross-coupling reactions, including Sonogashira, Stille, Hiyama, Ullmann, and Buchwald–Hartwig reactions, can be driven with visible light at temperatures slightly above room temperature using alloy nanoparticles of gold and Pd on zirconium oxide, thus achieving high yields. The alloy nanoparticles absorb visible light, and their conduction electrons gain energy, which is available at the surface Pd sites. Results of the density functional theory calculations indicate that transfer of the light excited electrons from the nanoparticle surface to the reactant molecules adsorbed on the nanoparticle surface activates the reactants. When the light intensity was increased, a higher reaction rate was observed, because of the increased population of photoexcited electrons. The irradiation wavelength also has an important impact on the reaction rates. Ultraviolet irradiation can drive some reactions with the chlorobenzene substrate, while visible light irradiation failed to, and substantially improve the yields of the reactions with the bromobenzene substrate. The discovery reveals the possibility of using low-energy and -density sources such as sunlight to drive chemical transformations.