One‐Step Formulation of Protein Microparticles with Tailored Properties: Hard Templating at Soft Conditions

Formulation of therapeutic proteins into particulate forms is a main strategy for site‐specific and prolonged protein delivery as well as for protection against degradation. Precise control over protein particle size, dispersity, purity, as well as mild preparation conditions and minimal processing steps are highly desirable. It is, however, hard to fit all these criteria with conventional preparation techniques. Here a one‐step hard‐templating synthesis of microparticles composed of functional, non‐denatured protein is reported. The method is based on filling porous CaCO₃ microtemplates with the protein near to its isoelectric point (pI) followed by pH‐ or EDTA‐mediated dissolution of the tempplates. In principle, a wide variety of proteins can be converted into microparticles using this approach. The main requirement is an overlap of the protein insolubility and a template solubility for a certain parameter (here pH or EDTA). Here the formulation of insulin particles is studied in detail and it is shown that particles consisting of high molecular weight protein (catalase) can also be prepared. In this context, the synthesis of CaCO₃ templates with controlled size, the mechanism of the protein microparticle formation and mechanical properties of the microparticles are discussed. For the first time, the fabrication of mesoporous monodispersed CaCO₃ microtemplates with identical porocity but tuned diameter from 3 to 20 μm is demonstrated. The protein particle diameter can be adjusted by choosing the appropriate template size that is critical for successful pulmonary delivery of insulin. As a first step towards insulin delivery, the in vitro release of insulin at physiological conditions is studied.     

Guidelines and recommendations for indoor use of fuel cells and hydrogen systems

Hydrogen energy applications often require that systems are used indoors (e.g., industrial trucks for materials handling in a warehouse facility, fuel cells located in a room, or hydrogen stored and distributed from a gas cabinet). It may also be necessary or desirable to locate some hydrogen system components/equipment inside indoor or outdoor enclosures for security or safety reasons, to isolate them from the end-user and the public, or from weather conditions.Using of hydrogen in confined environments requires detailed assessments of hazards and associated risks, including potential risk prevention and mitigation features. The release of hydrogen can potentially lead to the accumulation of hydrogen and the formation of a flammable hydrogen-air mixture, or can result in jet-fires. Within Hyindoor European Project, carried out for the EU Fuel Cells and Hydrogen Joint Undertaking safety design guidelines and engineering tools have been developed to prevent and mitigate hazardous consequences of hydrogen release in confined environments. Three main areas are considered: Hydrogen release conditions and accumulation, vented deflagrations, jet fires and including under-ventilated flame regimes (e.g., extinguishment or oscillating flames and steady burns). Potential RCS recommendations are also identified.     

Particulate inorganic carbon production within E. huxleyi blooms in subpolar and polar seas: a satellite time series study (1998–2013)

Making use of the OC CCI (Ocean Colour Climate Change Initiative) satellite data, and based on the developed both Emiliania huxleyi bloom contouring methodologies and binary masks, areas of coccolithophore growth were distinguished without supervision from locations of mass developments of other algae. On these grounds, and employing special processing algorithms, multi-year time series of variations in occurrence, surficial extent, and content of particulate inorganic carbon (PIC) within E. huxleyi blooming areas in the North, Norwegian, Greenland, Barents, and Bering Seas were obtained for the time period 1998–2013. Analysis of algorithmic processing of the OC CCI data permitted to reveal the spatio-temporal sequence of E. huxleyi blooming events in the above seas of the North Atlantic and Arctic Oceans. During the intra-annual cycle, E. huxleyi blooms advance from temperate to higher latitudes along the pathways of the Gulf Stream propagation to the north. Annually, the blooms arise in the vicinity of the Great Britain southern extremity, and further on move northward along the western coast of this Island Country, round it to eventually appear first in the North and Norwegian Seas (in early June), then in the Greenland Sea (in late June), and finally in the Barents Sea (in late July–early September). The regularities in dates of bloom outbreak and their duration are revealed. The bloom areas in the North Atlantic–Arctic water are the lowest in the Greenland Sea (10,000–30,000 km²) and by an order of magnitude higher in the Barents Sea. The same pattern holds for the total PIC content within E. huxleyi blooms: 400 t–14 kt in the Greenland Sea and about 0.35 Mt in the Barents Sea. In the Bering Sea, the temporal and spatial dynamics of E. huxleyi development proved to be highly irregular: before and after the 1997–2001 period of high intensity of this phenomenon, the blooms are sporadic, their extent and PIC production are either very low or insignificant. Regarding the range of E. huxleyi bloom areas in the Bering Sea during 1997–2001, it is rather similar to that of the Barents Sea. However, the PIC content in the Bering Sea, as compared to that in the Barents Sea, is higher by a factor of about two with maximum values reaching 0.4 Mt and, on one occasion (in 2001), even about 0.7 Mt.     

Photonic Microhand with Autonomous Action

Grabbing and holding objects at the microscale is a complex function, even for microscopic living animals. Inspired by the hominid‐type hand, a microscopic equivalent able to catch microelements is engineered. This microhand is light sensitive and can be either remotely controlled by optical illumination or can act autonomously and grab small particles on the basis of their optical properties. Since the energy is delivered optically, without the need for wires or batteries, the artificial hand can be shrunk down to the micrometer scale. Soft material is used, in particular, a custom‐made liquid‐crystal network that is patterned by a photolithographic technique. The elastic reshaping properties of this material allow finger movement, using environmental light as the only energy source. The hand can be either controlled externally (via the light field), or else the conditions in which it autonomously grabs a particle in its vicinity can be created. This microrobot has the unique feature that it can distinguish between particles of different colors and gray levels. The realization of this autonomous hand constitutes a crucial element in the development of microscopic creatures that can perform tasks without human intervention and self‐organized automation at the micrometer scale.     

Phase-locking of multicore fibre laser due to talbot self-reproduction

Abstract

The multicore fibre laser (MCFL), containing an array of single-mode microcores in a circle inside the pump core, is a promising compact laser source. The problem is to synchronize the radiation of microcores with different propagation constants at a given radiation frequency. The theory of phase-locking of an MCFL with an external mirror and an annular waveguide matched to the multicore fibre and having a length some fraction of the Talbot distance is developed. Collective mode selection appears to occur due to spatial filtering at fractional Talbot distances, while the radiation frequency self-adjusts within the spectral gain range to minimize losses. Parallel coupling between microcores is achieved in the limit of a small fill factor. The maximum number of microcores that can be coupled is found. Good agreement is achieved between the theory and previously published experimental results.     

DNA Antenna Tile‐Associated Deoxyribozyme Sensor with Improved Sensitivity

Some natural enzymes increase the rate of diffusion‐limited reactions by facilitating substrate flow to their active sites. Inspired by this natural phenomenon, we developed a strategy for efficient substrate delivery to a deoxyribozyme (DZ) catalytic sensor. This resulted in a three‐ to fourfold increase in sensitivity and up to a ninefold improvement in the detection limit. The reported strategy can be used to enhance catalytic efficiency of diffusion‐limited enzymes and to improve sensitivity of enzyme‐based biosensors.     

Kinetic modeling of hemicellulose hydrolysis in the presence of homogeneous and heterogeneous catalysts

Kinetic models were developed for the hydrolysis of O‐acetyl‐galactoglucomannan (GGM), a hemicellulose appearing in coniferous trees. Homogeneous and heterogeneous acid catalysts hydrolyze GGM at about 90°C to the monomeric sugars galactose, glucose, and mannose. In the presence of homogeneous catalysts, such as HCl, H₂SO₄, oxalic acid, and trifluoroacetic acid, the hydrolysis process shows a regular kinetic behavior, while a prominent autocatalytic effect was observed in the presence of heterogeneous cation‐exchange catalysts, Amberlyst 15 and Smopex 101. The kinetic models proposed were based on the reactivities of the nonhydrolyzed sugar units and the increase of the rate constant (for heterogeneous catalysts) as the reaction progresses and the degree of polymerization decreases. General kinetic models were derived and special cases of them were considered in detail, by deriving analytical solutions for product distributions. The kinetic parameters, describing the autocatalytic effect were determined by nonlinear regression analysis. The kinetic model described very well the overall kinetics, as well as the product distribution in the hydrolysis of water soluble GGM by homogeneous and heterogeneous catalysts. The modelling principles developed in the work can be in principle applied to hydrolysis of similar hemicelluloses as well as starch and cellulose. © 2014 American Institute of Chemical Engineers AIChE J, 60: 1066–1077, 2014     

Heat Treatment and Chemical Composition of Fatty Acids and Rosin Acids Mixtures: Effects on Their Thermal Properties and Morphology

Mixtures of fatty acids and rosin acids are industrially important products utilized as a raw material for several purposes. Their thermal properties, especially cold stability and crystallization behavior is also important. Several fatty acid and rosin acid mixtures both from industrial products and from commercially available fatty and rosin acids were prepared and treated for 30 min at 80 °C under an inert atmosphere. Thereafter, the mixture was cooled to the desired temperature. Determination of the cloud point, chemical analysis of liquid and solid phase, thermal analysis by differential scanning calorimetry as well as morphology analysis by scanning electron microscopy were performed. The results revealed that crystallization was more rapid when it occurred at 10 °C compared to 25 °C. The crystal sizes increased with decreasing the crystallization temperature. Furthermore, crystals were of irregular shape and agglomerated when rapid cooling of the mixture occurred. Chemical analysis revealed that liquid phase was enriched with stearic acid, whereas crystals contained large amounts of abietic, dehydroabietic and linoleic acids. The cloud point of the mixtures increased with increasing amount of stearic and rosin acids. Dehydroabietic acid addition improved the cold stability of the synthetic fatty acid–rosin acids mixture.     

Design of Porous Alginate Hydrogels by Sacrificial CaCO3 Templates: Pore Formation Mechanism

Fabrication of porous alginate hydrogels with a well‐controlled architecture useful for tissue engineering is still a challenge. Here, CaCO₃‐based templating is utilized to design stable alginate gels with controlled pore dimensions in the range of 5–50 μm. The mechanism of pore formation is studied considering two factors affecting the pore size: i) osmotic pressure generated during the dissolution of sacrificial CaCO₃ templates and ii) alginate gel network density. Osmotic pressure can achieve an upper limit of 100 MPa but does not affect the gel porosity. Additional osmotic pressure (range of kPa) induced by dextrans pre‐encapsulated into CaCO₃ vaterite is also insufficient for pore enlargement. Pore stability depends merely on the gel network density and on the number of crosslinking calcium ions provided locally per unit time; pores are collapsed when template dissolution is too slow or if there is insufficient alginate concentration (below 2%). Young's modulus indicates the soft nature of the prepared hydrogels (tens of kPa) applicable as soft porous scaffolds with a tuned internal structure.