Scanning white-light interferometry as a novel technique to quantify the surface roughness of micron-sized particles for inhalation

A novel approach of measuring the surface roughness of spherical and flat micron-sized drug particles using scanning white-light interferometry was applied to investigate the surface morphology of micron-sized active pharmaceutical ingredients (APIs) and excipient particles used for inhalation aerosols. Bovine serum albumin (BSA) and alpha-lactose monohydrate particles were chosen as model API and excipient particles, respectively. Both BSA and lactose particles were prepared with different degrees of surface corrugation using either controlled spray drying (four samples of BSA) or decantation (two samples of lactose). Particle size distributions were characterized by laser diffraction, and particles were imaged by scanning electron microscopy (SEM). Surface roughness of the BSA and lactose particles was quantified by white-light optical profilometry using vertical scanning interferometry (VSI) at full resolution using a 50x objective lens with 2.0x and 0.5x fields of view for BSA and lactose, respectively. Data were analyzed using Vision software (version 32, WYKO), and surface roughness values are expressed as root-mean-square roughness ( Rrms). Furthermore, data were compared to topographical measurements made using conventional atomic force microscopy. Analysis of the optical profilometry data showed significant variation in BSA roughness ranging from 18.58 +/- 3.80 nm to 110.90 +/- 13.16 nm for the smoothest and roughest BSA particles, respectively, and from 81.20 +/- 15.90 nm to 229.20 +/- 68.20 nm for decanted and normal lactose, respectively. The Rrms values were in good agreement with the AFM-derived values. The particle morphology was similar to SEM and AFM images. In conclusion, scanning white-light interferometry provides a useful complementary tool for rapid evaluation of surface morphology and roughness in particles used for dry powder inhalation formulation.     

Characterizing Single‐Molecule FRET Dynamics with Probability Distribution Analysis

Probability distribution analysis (PDA) is a recently developed statistical tool for predicting the shapes of single‐molecule fluorescence resonance energy transfer (smFRET) histograms, which allows the identification of single or multiple static molecular species within a single histogram. We used a generalized PDA method to predict the shapes of FRET histograms for molecules interconverting dynamically between multiple states. This method is tested on a series of model systems, including both static DNA fragments and dynamic DNA hairpins. By fitting the shape of this expected distribution to experimental data, the timescale of hairpin conformational fluctuations can be recovered, in good agreement with earlier published results obtained using different techniques. This method is also applied to studying the conformational fluctuations in the unliganded Klenow fragment (KF) of Escherichia coli DNA polymerase I, which allows both confirmation of the consistency of a simple, two‐state kinetic model with the observed smFRET distribution of unliganded KF and extraction of a millisecond fluctuation timescale, in good agreement with rates reported elsewhere. We expect this method to be useful in extracting rates from processes exhibiting dynamic FRET, and in hypothesis‐testing models of conformational dynamics against experimental data.     

Biological monitoring of solar UV radiation at 17 sites in Asia, Europe and South America from 1999 to 2004

A small and robust dosimeter for determining the biologically effective dose of ambient UV radiation has been developed using UV-sensitive mutant spores of Bacillus subtilis strain TKJ6312. A membrane filter with four spots of the spores was snapped to a slide mount. The slide was wrapped and covered with two or more layers of polyethylene sheet to protect the sample from rain and snow and to reduce monthly-cumulative doses within the measurable range. From 1999, monthly data were collected at 17 sites for more than 1 year, and data for 4 to 6 consecutive years were obtained from 12 sites. Yearly total values of the spore inactivation dose (SID) ranged from 3200 at subarctic Oulu to 96000 at tropical Denpasar, and the mean yearly values of SID exhibited an exponential dependence on latitude in both hemispheres with a doubling for about every 14 degrees of change. During the observation period, increasing trends of UV doses have been observed at all sites with more than 5 years of data available. Year-to-year variations at high and middle latitude sites are considered due mostly to climatic variation. At three tropical sites, negative correlations between the yearly doses and the column ozone amounts were observed. The results verified the applicability of spore dosimetry for global and long-time monitoring of solar UV radiation, in particular at tropical sites where no monitoring is taking place.     

Determination of chemical elements in airborne particulate matter collected at Lembang, Indonesia by particle induced X-ray emission

Monitoring the air quality in ambient air is an important step for assessing the air pollution level in one region and its impact to the human health. In this study, the determination of chemical elements concentrations in airborne particulate matter collected in suburban area of Lembang, Indonesia was carried out. Samples were collected using a Gent stacked filter unit sampler in two size fractions of <2.5 μm (fine) and 2.5–10 μm (coarse). Sampling was conducted twice a week for 24 h from January 2008 to June 2009 and 123 pairs of samples were collected. Black carbon was determined by reflectance and chemical elements analysis were performed using particle induced X-ray emission (PIXE). PIXE as one of ion beam analysis techniques is suitable for analyzing particulate matter for its multielemental analysis with good limits of detection. Results showed that none of daily concentrations of PM_2.5 and PM₁₀ exceeded the 24 h Indonesian NAAQS for PM_2.5 and PM₁₀. Chemical elements such as Mg, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Hg and Pb were determined and the correlation between these elements was reported in order to understand the anthropogenic sources of particulate matter.     

Characterization of airborne particulate matter collected at Jakarta roadside of an arterial road

A total of 44 pairs of airborne particulate matter samples were collected in the intersection of Simprug, Pondok Indah, South Jakarta. Sampling of airborne particulate matter was conducted in July 2008–July 2009 using a Gent stacked filter unit sampler in two size fractions of <2.5 µm (fine) and 2.5–10 µm (coarse). Mass concentrations, black carbon as well as elemental concentrations were investigated as a pre-study in step to the evaluation of air quality in these roadside areas. Black carbon was determined by reflectance and elemental analysis was performed using proton induced X-ray emission, PIXE. The data set of fine particulate matters obtained from the characterization was then analyzed using receptor modeling EPA PMF3 for source apportionment. Source apportionment identified 5 factors, i.e. soil (9.2 %), construction mixed with road dust (20.9 %), motor vehicles (31.5 %), biomass burning mixed with seasalt (30.9 %), and industry (7.5 %). Motor vehicles is the dominant sources that contributes to the fine particulate matter in Jakarta.     

Total chemical synthesis of a biologically active and homogeneous analog of Human Growth Hormone [Nle14,125,170,Glu29,91,Gln74,Asn107,Asp109]hGH-NH2 by sequential native chemical ligation

We report herein, for the first time, a sequential total chemical synthesis of the Human Growth Hormone analog [Nle^14,125,170,Glu^29,91,Gln⁷⁴,Asn¹⁰⁷,Asp¹⁰⁹]hGH-NH₂, composed of a 191 amino acid residue polypeptide chain containing two disulfide bonds and nine modifications in the natural sequence. Sequential native chemical ligation of three discrete segments of 52, 52 and 87 amino acid residues gave the target full-length polypeptide chain. Subsequent folding with concomitant formation of the native disulfide bonds afforded a correctly folded homogeneous analog which is biologically active.     

Convexity of momentum maps: A topological analysis

The Local-to-Global-Principle used in the proof of convexity theorems for momentum maps has been extracted as a statement of pure topology enriched with a structure of convexity. We extend this principle to not necessarily closed maps f:X→Y where the convexity structure of the target space Y need not be based on a metric. Using a new factorization of f, convexity of the image is proved without local fiber connectedness, and for arbitrary connected spaces X.     

A review on synthesis of kaolin-based zeolite and the effect of impurities

Zeolite is extensively synthesized for the application in a large variety of catalysis processes such as ion exchange, hydrocarbon cracking, and organic synthesis. In order to satisfy the serious terms of sustainability that denotes to the reduction of costs and chemical waste, kaolinite-based zeolites were produced from cheap natural resources as against to the conventional process that employs pure sodium silicate and sodium aluminate. This review paper is to highlight the current trends in the synthesis of zeolite. Prior to previous reviews, great concern is focused on the impurities effect on the catalytic performance of kaolinite-based zeolites. This study reveals that the impact of impurities in a catalytic reaction was in fact, underestimated or neglected. For instance, it was found that Fe ion concentration as small as 60 ppm gives significant catalytic output. Hence, a new practice to report the concentration of impurities in the research publication is suggested. This undoubtedly will generate a better interpretation of the catalytic activity from the zeolite framework.     

A solver for the stochastic master equation applied to gene regulatory networks

An important driver of gene regulatory networks is noise arising from the stochastic nature of interactions of genes, their products and regulators. Thus, such systems are stochastic and can be modelled by the chemical master equations. A major challenge is the curse of dimensionality which occurs when one attempts to integrate these equations. While stochastic simulation techniques effectively address the curse, many repeated simulations are required to provide precise information about stationary points, bifurcation phenomena and other properties of the stochastic processes. An alternative way to address the curse of dimensionality is provided by sparse grid approximations. The sparse grid methodology is applied and the application demonstrated to work efficiently for up to 10 proteins. As sparse grid methods have been developed for the approximation of smooth functions, a variant for infinite sequences had to be developed together with a multiresolution analysis similar to Haar wavelets. Error bounds are provided which confirm the effectiveness of sparse grid approximations for smooth high-dimensional probability distributions.