Development of clinically relevant in vitro performance tests for powder inhalers

While realistic in vitro testing of dry powder inhalers (DPIs) can be used to establish in vitro–in vivo correlations (IVIVCs) and predict in vivo lung doses, the aerodynamic particle size distributions (APSDs) of those doses and their regional lung deposition remains unclear. Four studies were designed to improve testing centered on the behavior of Novolizer®. Different oropharyngeal geometries were assessed by testing different mouth-throat (MT) models across a realistic range of inhalation profiles (IPs) with Salbulin® Novolizer®. Small and large Virginia Commonwealth University (VCU) and Oropharyngeal Consortium (OPC) models produced similar ranges for total lung dose in vitro (TLDin vitro), while results for medium models differed significantly. While either group may be selected to represent variations in oropharyngeal geometry, OPC models were more difficult to use, indicating that VCU models were preferable. To facilitate simulation of human IPs through DPIs, inhalation profile data from a VCU clinical trial were analyzed. Equations were developed to represent the range of flow rate vs. time curves for use with DPIs of known airflow resistance. A new method was developed to couple testing using VCU MT models and simulated IPs with cascade impaction to assess the APSDs of TLDin vitro for Budelin® Novolizer®. This method produced IVIVCs for Budelin’s total lung dose, TLD, and was sufficiently precise to distinguish between values of TLDin vitro and their APSDs, resulting from tests using appropriately selected MT models and IPs. For example, for slow inhalation, TLD values were comparable in vivo and in vitro; TLDin vitro ranged from 12.2±2.9 to 66.8±1.7 mcg aerosolized budesonide while APSDs in vitro had mass median aerodynamic diameters of 3.26±0.27 and 2.17±0.03 µm, respectively. To explore the clinical importance of these variations, a published computational fluid dynamic (CFD) model was modified and coupled to accept the output of realistic in vitro tests as initial conditions at the tracheal inlet. While simplified aerosol size metrics and flow conditions used to shorten CFD simulations produced small differences in theoretical predictions of regional lung deposition, the results broadly agreed with the literature and were generally consistent with the median values reported clinically for Budelin

Tunable and absolute electromagnetic vacuum in two-dimensional photonic-band-gap Based on multiferroic materials

When multiferroic terbium manganite (TbMnO₃) crystal cylinders are periodically arranged in a square lattice, the resulting two-dimensional (2D) system exhibits photonic band gaps (PBGs). The absolute PBG originating from the Mie resonance is modulated from closed to open by applying an external static magnetic field, which is attributed to the electromagnon depression of the dielectric constant by the rearrangement of antiferromagnetic order. Tunable electromagnetic band structure may be realized by controlling the magnetic transition of manganese spins in TbMnO₃.The authors are grateful for financial support from the Outstanding Foundation of NJUST, the NJUST Research Funding (No. 2010ZDJH06), the National Natural Science Foundation of China (Grant Nos. 11004106, 50672034, 50832002, and 50901042), and the State Key Program for Basic Research of China (Grant Nos. 2009CB623303 and 2009CB929501)

Analysis and Prediction of the Metabolic Stability of Proteins Based on Their Sequential Features, Subcellular Locations and Interaction Networks

The metabolic stability is a very important idiosyncracy of proteins that is related to their global flexibility, intramolecular fluctuations, various internal dynamic processes, as well as many marvelous biological functions. Determination of protein's metabolic stability would provide us with useful information for in-depth understanding of the dynamic action mechanisms of proteins. Although several experimental methods have been developed to measure protein's metabolic stability, they are time-consuming and more expensive. Reported in this paper is a computational method, which is featured by (1) integrating various properties of proteins, such as biochemical and physicochemical properties, subcellular locations, network properties and protein complex property, (2) using the mRMR (Maximum Relevance & Minimum Redundancy) principle and the IFS (Incremental Feature Selection) procedure to optimize the prediction engine, and (3) being able to identify proteins among the four types: “short”, “medium”, “long”, and “extra-long” half-life spans. It was revealed through our analysis that the following seven characters played major roles in determining the stability of proteins: (1) KEGG enrichment scores of the protein and its neighbors in network, (2) subcellular locations, (3) polarity, (4) amino acids composition, (5) hydrophobicity, (6) secondary structure propensity, and (7) the number of protein complexes the protein involved. It was observed that there was an intriguing correlation between the predicted metabolic stability of some proteins and the real half-life of the drugs designed to target them. These findings might provide useful insights for designing protein-stability-relevant drugs. The computational method can also be used as a large-scale tool for annotating the metabolic stability for the avalanche of protein sequences generated in the post-genomic age

Changes in soil faunal density and microbial community under altered litter input in forests and grasslands

Root and foliar litter inputs are the primary sources of carbon and nutrients for soil fauna and microorganisms, yet we still lack a quantitative assessment to evaluate the effects of root and foliar litter on various groups of soil organisms across terrestrial ecosystems. Here, we compiled 978 paired observations from 68 experimental sites to assess the directions and magnitudes of adding and removing foliar and root litter on the soil faunal density and microbial biomass that was evaluated by phospholipid fatty acids (PLFAs) across forests and grasslands worldwide. We found that litter addition had only a marginal effect on soil faunal density but significantly increased the soil total microbial-, fungal- and bacterial-PLFAs by 13%, 14%, and 10%, respectively, across ecosystems, suggesting that the soil microbial community is more sensitive to carbon source addition than soil fauna, particularly in soils with low carbon to nitrogen ratios. In contrast, removing litter significantly decreased the soil faunal density by 17% but had few effects on soil microorganisms. Compared with foliar litter, root litter input had a more positive effect on the development of soil fungal taxa. The effect of both litter addition and removal on soil faunal density and microbial biomass did not differ between humid and arid regions, but a greater influence was observed in grasslands than in forests for soil microbial community. Our results highlight that the increasing litter production under a global greening scenario would stimulate microbial activity in grasslands more than in forests, and this stimulation would be greater for soil microbes than soil fauna

Short-Term Responses of Soil Respiration and C-Cycle Enzyme Activities to Additions of Biochar and Urea in a Calcareous Soil

<div><p>Biochar (BC) addition to soil is a proposed strategy to enhance soil fertility and crop productivity. However, there is limited knowledge regarding responses of soil respiration and C-cycle enzyme activities to BC and nitrogen (N) additions in a calcareous soil. A 56-day incubation experiment was conducted to investigate the combined effects of BC addition rates (0, 0.5, 1.0, 2.5 and 5.0% by mass) and urea (U) application on soil nutrients, soil respiration and C-cycle enzyme activities in a calcareous soil in the North China Plain. Our results showed soil pH values in both U-only and U plus BC treatments significantly decreased within the first 14 days and then stabilized, and CO₂emission rate in all U plus BC soils decreased exponentially, while there was no significant difference in the contents of soil total organic carbon (TOC), dissolved organic carbon (DOC), total nitrogen (TN), and C/N ratio in each treatment over time. At each incubation time, soil pH, electrical conductivity (EC), TOC, TN, C/N ratio, DOC and cumulative CO₂ emission significantly increased with increasing BC addition rate, while soil potential activities of the four hydrolytic enzymes increased first and then decreased with increasing BC addition rate, with the largest values in the U + 1.0%BC treatment. However, phenol oxidase activity in all U plus BC soils showed a decreasing trend with the increase of BC addition rate. Our results suggest that U plus BC application at a rate of 1% promotes increases in hydrolytic enzymes, does not highly increase C/N and C mineralization, and can improve in soil fertility.</p></div

Short-Term Responses of Soil Respiration and C-Cycle Enzyme Activities to Additions of Biochar and Urea in a Calcareous Soil - Fig 4

<p>Dynamic variation of soil pH (a) and electrical conductivity (b) in different treatments over a 56-day incubation. Vertical bars in the figures represent standard error of the means (<i>n</i> = 3).</p