Quality assurance in research: incorporating ISO9001:2000 into a GMP quality management system in a pharmaceutical R+D+I center

There is currently no universal or standardized quality system for the recognition of excellence of a research center. Knowledge and competence may not be enough in the current rapidly changing world in which high productivity and continuous improvement are essential. The purpose of this study was to assess the impacts of implementing the ISO9001:2000:2000 standard in an academic research center dedicated to R+D+I (research, development and innovation) in the pharmaceutical industry. The article describes the stages we followed to implement the ISO9001:2000 system, which was achieved by integrating it into the previous regulatory system of GMP (Good Manufacturing Practices). As a result of implementing ISO9001:2000, the center has seen distinct improvements, such as fewer errors in project documentation, improved assessment of customer satisfaction, and the effective implementation of periodic plans, e.g., in calibration, preventive maintenance, and investments. Overall, ISO9001:2000 implementation has been beneficial for the organization and could be applied to other research centers.     

Smart poly(2-hydroxyethyl methacrylate/itaconic acid) hydrogels for biomedical application

pH- and temperature-sensitive hydrogels, based on 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA) copolymers, were prepared by γ-irradiation and characterized in order to examine their potential use in biomedical applications. The influence of comonomer ratio in these smart copolymers on their morphology, mechanical and thermal properties, biocompatibility and microbe penetration capability was investigated. The mechanical properties of copolymers were investigated using the dynamic mechanical analysis (DMA), while their thermal properties and morphology were examined by thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The morphology, mechanical and thermal properties of these hydrogels were found to be suitable for most requirements of biomedical applications. The in vitro study of P(HEMA/IA) biocompatibility showed no evidence of cell toxicity nor any considerable hemolytic activity. Furthermore, the microbe penetration test showed that neither Staphylococcus aureus nor Escherichia coli passed through the hydogel dressing; thus the P(HEMA/IA) dressing could be considered a good barrier against microbes. All results indicate that stimuli-responsive P(HEMA/IA) hydrogels have great potential for biomedical applications, especially for skin treatment and wound dressings.     

Evaluation of dispersive liquid-liquid microextraction for the simultaneous determination of chlorophenols and haloanisoles in wines and cork stoppers using gas chromatography-mass spectrometry

Dispersive liquid-liquid microextraction (DLLME) coupled with gas chromatography-mass spectrometry (GC-MS) was evaluated for the simultaneous determination of five chlorophenols and seven haloanisoles in wines and cork stoppers. Parameters, such as the nature and volume of the extracting and disperser solvents, extraction time, salt addition, centrifugation time and sample volume or mass, affecting the DLLME were carefully optimized to extract and preconcentrate chlorophenols, in the form of their acetylated derivatives, and haloanisoles. In this extraction method, 1mL of acetone (disperser solvent) containing 30μL of carbon tetrachloride (extraction solvent) was rapidly injected by a syringe into 5mL of sample solution containing 200μL of acetic anhydride (derivatizing reagent) and 0.5mL of phosphate buffer solution, thereby forming a cloudy solution. After extraction, phase separation was performed by centrifugation, and a volume of 4μL of the sedimented phase was analyzed by GC-MS. The wine samples were directly used for the DLLME extraction (red wines required a 1:1 dilution with water). For cork samples, the target analytes were first extracted with pentane, the solvent was evaporated and the residue reconstituted with acetone before DLLME. The use of an internal standard (2,4-dibromoanisole) notably improved the repeatability of the procedure. Under the optimized conditions, detection limits ranged from 0.004 to 0.108ngmL(-1) in wine samples (24-220pgg(-1) in corks), depending on the compound and the sample analyzed. The enrichment factors for haloanisoles were in the 380-700-fold range.     

New features of the steady-state rate related with the initial concentration of substrate in the diphenolase and monophenolase activities of tyrosinase

Tyrosinase has two types of enzymatic activities: the hydroxylation of monophenols to o-diphenols (monophenolase activity) and oxidation of o-diphenols to o-quinones (diphenolase activity). The action on o-diphenols involves two substrates: oxygen and o-diphenol, while the mechanism proposed is a Uni Uni Bi Bi ping-pong. In this contribution, we demonstrate experimentally that there is a kinetically preferred pathway, which translates into the appearance of curves of initial velocity vs. initial diphenol concentration shows inhibition by an excess of substrate, while sigmoid curves are obtained when the initial velocity vs. initial oxygen concentration are graphed. However, the action mechanism of the enzyme on monophenols, which is more complex because it involves three substrates (monophenol, oxygen and o-diphenol), does behave differently from the hyperbolic behaviour as regards the initial velocity vs. initial monophenol concentration, results that can be explained if the limiting step in the action of tyrosinase is the hydroxylation of monophenol to o-diphenol.     

螺二芴基可溶性共聚物的合成及发光性能

以9,9'-螺二芴和不同链长的二烷氧基苯为单体, 以FeCl3为催化剂, 采用化学氧化法合成了一系列聚合物发光材料. 溶解度测试表明, 共聚物在二氯甲烷、四氢呋喃(THF)、氯仿等极性溶剂中具有良好的溶解性. 利用核磁共振氢谱(1H NMR)、傅里叶变换红外(FT-IR)光谱、紫外-可见(UV-Vis)光谱和荧光(PL)光谱研究了共聚物的化学结构和发光性能, 结果表明共聚物在二甲基亚砜(DMSO)中均发射蓝色荧光, 最大吸收和荧光发射峰分别为356和413 nm. 以硫酸奎宁溶液作为参比, 测得共聚物的荧光量子效率为0.69至0.77. 通过循环伏安法(CV)测得所合成的三种共聚物的最高占有分子轨道(HOMO)能级均位于-5.85至-5.69 eV之间.     

Observation and analysis of in vivo vocal fold tissue instabilities produced by nonlinear source-filter coupling: a case study

Different source-related factors can lead to vocal fold instabilities and bifurcations referred to as voice breaks. Nonlinear coupling in phonation suggests that changes in acoustic loading can also be responsible for this unstable behavior. However, no in vivo visualization of tissue motion during these acoustically induced instabilities has been reported. Simultaneous recordings of laryngeal high-speed videoendoscopy, acoustics, aerodynamics, electroglottography, and neck skin acceleration are obtained from a participant consistently exhibiting voice breaks during pitch glide maneuvers. Results suggest that acoustically induced and source-induced instabilities can be distinguished at the tissue level. Differences in vibratory patterns are described through kymography and phonovibrography; measures of glottal area, open/speed quotient, and amplitude/phase asymmetry; and empirical orthogonal function decomposition. Acoustically induced tissue instabilities appear abruptly and exhibit irregular vocal fold motion after the bifurcation point, whereas source-induced ones show a smoother transition. These observations are also reflected in the acoustic and acceleration signals. Added aperiodicity is observed after the acoustically induced break, and harmonic changes appear prior to the bifurcation for the source-induced break. Both types of breaks appear to be subcritical bifurcations due to the presence of hysteresis and amplitude changes after the frequency jumps. These results are consistent with previous studies and the nonlinear source-filter coupling theory.     

A Geometric Approach to Integrability of Abel Differential Equations

A geometric approach is used to study the Abel first-order differential equation of the first kind. The approach is based on the recently developed theory of quasi-Lie systems which allows us to characterise some particular examples of integrable Abel equations. Second order Abel equations will be discussed and the inverse problem of the Lagrangian dynamics is analysed: the existence of two alternative Lagrangian formulations is proved, both Lagrangians being of a non-natural class. The study is carried out by means of the Darboux polynomials and Jacobi multipliers.     

Detecting quantum states with a positive Wigner function beyond mixtures of Gaussian states

We propose a criterion giving a sufficient condition for quantum states of a harmonic oscillator not to be expressible as a convex mixture of Gaussian states. This nontrivial property is inherent to, e.g., a single-photon state and the criterion thus allows one to reveal a signature of the state even in quantum states with a positive Wigner function. The criterion relies on directly measurable photon number probabilities and enables detection of this manifestation of a single-photon state in quantum states produced by solid-state single-photon sources in a weak coupling regime.