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.     

Aqueous-Base-Developable Benzocyclobutene (BCB)-Based Material Curable in Air

A positive-tone and aqueous-base-developable benzocyclobutene (BCB)-based dielectric material curable in air is described in this paper. The prepolymer is made from divinylsiloxane bisbenzocyclobutene (DVS-bisBCB) and BCB-acrylic acid. The formulation contains antioxidants that allow the prepolymer to cure in air and a diazonaphthaquinone to make it photosensitive. Patterned films have high resolution, and via openings are scum-free without a descum operation. Whether cured in nitrogen or in air, the prepolymer produces a film with optical, electrical, thermal, and mechanical properties desirable for many microelectronic applications, such as packaging applications and as a planarization or insulation layer in display applications     

Information Capacity of Nonlinear Wavelength Division Multiplexing Fiber Optic Transmission Line

We report the first determination of the impact of optical nonlinearities on the information capacity of a fiber optic transmission channel. By modeling interchannel interference in a nonlinear wavelength division multiplexing transmission system as multiplicative Gaussian noise, we show that the information capacity is reduced below the Shannon capacity of the linear communications channel. For systems of practical interest, this imposes a fundamental limitation on the spectral efficiency of optical data transmission.     

Circuit techniques for large CSEA SRAMs

The CMOS-storage emitter-access (CSEA) memory cell offers faster access than the MOS cells used in conventional BiCMOS SRAMs but using it in large memory arrays poses several problems. Novel BiCMOS circuit approaches to address the problems of decoding power, electronic noise, level translation, and write disturbance are described. Results on a 64-kb CSEA SRAM using these techniques are reported. The device, fabricated in an 0.8-μm BiCMOS technology, achieves read access and write pulse time of less than 4 ns while dissipating 1.7 W at a case temperature of 70°C     

Neurophysiological Model of the Normal and Abnormal Human Pupil

A model of the pathways controlling the size of the human pupil is presented. Computer simulation of this model demonstrates the role played by each of the elements in the pupil pathways. Simulations of the effects of drugs and a few common abnormalities in the system also help to illustrate the workings of the internal processes. Computer models of this type can be used as teaching aids or as tools for testing of hypotheses regarding the system.     

A role of sea buckthorn on Alzheimer’s disease

Evidence suggests that diets rich in antioxidants reduce the risk factors of Alzheimer’s disease (AD). Hippophae rhamnoides, commonly known as sea buckthorn (SB), is rich in antioxidants which could have direct effects on amyloid-beta (Aβ) levels and consequently influence AD pathogenesis. In this study, sea buckthorn powder (SBP) was administered at varying concentrations (0.6, 0.9, 1.2, 1.5 and 1.8 µg mL⁻¹) to cell cultures (BE(2)-M17) with 20 mm Aβ for 72 h. MTS test indicated that SB significantly increased cell viability in Aβ-induced cells up to 95%. Results of Western blot showed maximum 38% inhibition of Aβ compared to the control (Aβ only). ELISA demonstrated significantly lower amyloid-β level (6672 pg mL⁻¹) than the control (10189 pg mL⁻¹). Images of AFM further confirmed the presence of low quantity of amyloid beta in SBP-treated cells. These findings suggest that SB warrants further investigation as potential therapeutic agent in the treatment of AD.     

Assessing Changes in Enriched Maize Flour Formulations After Extrusion by Means of FTIR,XRD, and Chemometric Analysis

Spectral analysis employing multivariate techniques was employed to differentiate plain maize flours from formulations containing maize with added milled chia or quinoa seeds for producing cereal breakfast extrudates. The physicochemical changes of the enriched formulations due to processing stages and formulation were evaluated by using FTIR and chemometric analysis, which allowed a rapid and non-destructive discrimination between sample processing and compositional aspects. Specific IR frequencies were selected which provided highest sample discrimination. Selected IR absorbance relationships at those specific wavenumbers were useful to track changes promoted by extrusion for carbohydrates, proteins, and lipids. The complexes between amylose and lipids, that takes place during extrusion, underwent distinctive changes as confirmed by XRD. The crystallinity loss, after extrusion (with an average value of 50%), shows evidence of amylose-lipid complexes formation of type E_h and V_h. Correlations between the textural behavior, composition, and selected FTIR indices were obtained.     

Temperatures and ages of boxed beef packed and distributed in Canada

Boxes of beef were examined when product was packed and when boxes were loaded out of five packing plants, when boxes were loaded into and loaded out of seven refrigerated warehouses, and when boxes were received and opened at 21 retail stores. At each stage of handling at each facility, the boxes to be examined were selected at random. For each selected box, the temperature of product at the centre of the box was measured, and the date of packing and the plant of origin were noted. When cuts were packed, the minimum, median and maximum temperatures were about 2, 6 and 18 °C, respectively. Temperatures were successively lower when boxes were loaded out of packing plants, into warehouses and out of warehouses. When loaded out of warehouses, the minimum, median and maximum temperatures were about −2, 1 and 8 °C, respectively. The ranges of temperatures were similar, but the median temperatures were about 2 or 1.5 °C, respectively, when boxes were received at or were opened at retail stores. At packing plants and warehouses, the temperatures of manufacturing and ground beef were lower than those of cuts, but at the retail store the temperatures of all types of product were similar. When boxes were opened at retail stores, the minimum, median and maximum ages of cuts were about 2, 20 and 130 days, respectively; and the corresponding ages for manufacturing and ground beef were 2, 7 and 56 days, respectively. The data indicate that boxed beef is generally cooled to and maintained at temperatures within the range sought by the meat industry. However, cooling to chiller temperatures of product that is packed while warm can take several days; and some product is held for times that are excessive in view of the temperatures of boxed beef.     

Toxikologie der synthetischen Antioxidantien BHA und BHT im Vergleich mit dem natürlichen Antioxidans Vitamin E

The toxicology of the food preservatives butylhydroxyanisole (BHA) and butylhydroxytoluene (BHT) as well as the naturally occurring vitamin E (α-tocopherol) is described. In high dosages all three compounds induce in animals impairment of blood clotting, which can be explained by an antagonism with vitamin K. Specific toxic effects to the lung have only been observed with BHT. The other described toxic effects of BHA and BHT are less characteristic and often occur only after high dosage and long-term treatment. However, BHA induces in animals tumours of the forestomach, which are dose dependent, whereas BHT induces liver tumours in long-term experiments. Because there is no indication of genotoxicity of BHA and BHT, all published findings agree with the fact that BHA and BHT are tumour promoters. In contrast to BHA and BHT, vitamin E is not carcinogenic. On the other hand, all three antioxidants have also anticarcinogenic properties. The intake of the necessary high doses as for these effects are, however, contraindicated with BHA and BHT because of their carcinogenic effects. The present overview concludes that the concentrations of BHA and BHT nowadays used in food, drugs and cosmetics are probably harmless. In addition, vitamin E can also be used in higher doses without the occurrence of adverse effects.