超高反差体系的显影动力学研究

本文通过研究肼感染显影动力学,对肼感染显影的显影速度及其活化能进行测试和计算,籍以讨论有关肼感染显影过程的机理。实验结果表明:肼感染显影的早期是直接显影,活化能低;后期是灰化成核显影,活化能高;而低曝光量潜影核无灰化成核显影,活化能较高。高反差、短趾部的形成原因是由于显影加速和显影抑制的竞争结果。     

Computer-aided optimization of stepwise gradient and multiple-development thin-layer chromatography

Summary Equations for the final R_F values for mobile phase gradient development and gradient multiple development are presented. Computer simulations of gradient development for both modes of thin-layer chromatography are discussed for the preliminary optimization of gradient programs.     

Morphology development and phase inversion during dynamic vulcanisation of EPDM/PP blends

Morphology development and phase inversion were investigated during dynamic vulcanisation of ethylene–propylene–diene terpolymer (EPDM)/polypropylene (PP) blends. The effects of viscosity ratio and cross-linking reactions were also addressed. EPDM/PP blends were dynamically vulcanised in a Haake batch mixer using resole and SnCl₂ as cross-linking agents. The morphology development and cross-linking degree with reaction time were followed by morphology analysis (SEM and TEM) and measurement of EPDM gel content, respectively. For the same reaction time, it was found that the EPDM gel content decreased when the low-molecular-weight EPDM was used. As a result, the morphological development was delayed and the phase-inversion point was shifted to higher reaction times, allowing us to monitor morphological development during a thermoplastic vulcanisate (TPV) preparation. Using the low-molecular-weight EPDM and increasing the PP viscosity accelerated the morphological development, shifting phase-inversion to lower reaction times. While blend composition influenced final TPV morphology, it had a minor effect on the mechanism of morphological development. A correlation between cross-linking degree and morphology development was established. The results obtained allowed to propose a mechanism of morphology development during dynamic vulcanisation of the EPDM/PP blends, including phase inversion.     

Advanced ceramics and their basic products: A challenge to the analytical sciences

The analytical characterization required in the development and in the quality control of new ceramics is discussed. For the basic substances, the problems encountered in the development of routine techniques for a direct and reliable analysis of Al₂O₃, AlN, Si₃N₄, SiC, and ZrO₂ powders are reported. Among the atomic spectrometric methods, especially slurry atomization ICP-spectrometry is described. Also the problems encountered in the development of combined procedures as required for the characterization of reference samples are presented. Methods for the direct bulk analysis of ceramics and microdistributional analysis, as they are now under development with laser-based techniques and various probe techniques, are described as well.     

Purification and characterization of recombinant human renin for X-ray crystallization studies

Background  

The renin-angiotensin-aldosterone system (RAS) cascade is a major target for the clinical management of hypertension. Although inhibitors of various components of this cascade have been developed successfully, development of renin inhibitors has proven to be problematic. The development of these inhibitors has been hindered by poor bioavailability and complex synthesis. However, despite the challenges of designing renin inhibitors, the enzyme remains a promising target for the development of novel treatments for hypertension. X-ray crystallographic data could greatly assist the design and development of these inhibitors. Here we describe the purification and characterization of recombinant human renin for x-ray crystallization studies.     

Un siècle de Hautes Pressions : Développements technologiques et scientifiques

A century of high pressure: technological and scientific developments. This paper is devoted to the development of high pressures during approximately one century and the main scientific domains concerned by such a development.Roughly three main periods have been considered: (i) the early period at the beginning of XX^th century (1900 → 1970), the second period (1970 → 2005) taking into account some important technical developments (the high pressure vessels with a large volume, the diamond anvil cell associated with the laser heating…), and a prospective concerning, on the basis of recent results, the possible developments during the next 10 years.The early period was mainly characterized by some industrial problems: the improvement of the mechanical properties of alloys and consequently the requirement for performant cutting and machining tools (leading to the diamond synthesis), the synthesis of ammonia (initiated both by the development of explosives and the requirement of fertilisers), the preservation of foods (correlated to a new organization of the Society), the elaboration of single crystals characterized by specific physical properties with functional properties for the development of some industrial sectors (telecommunications, computer science…).The more recent period (1970–2005) has been characterized by the development of new performant tools able to improve the development of scientific domains (diamond-anvil-cell and Geosciences, Belt-type, multi-anvils and toroïd equipments and the Chemistry of Materials, high pressure vessels and Food-Science…).During these last years roughly three main tendances have been observed: (i) the investigation of researches at extreme (P, T) conditions, (ii) the improvement of researches involving mild (P, T) conditions mainly in liquid phase (hydrothermal and solvothermal synthesis), (iii) the development of high pressures in Biology and Biotechnology.During the next years the extension of high pressure level and also the development of the next scientific domains would improve research involving different planets. In parallel the development of chemical reactions in mild P, T conditions in a liquid phase would allow to prepare new hybrid nano-systems at the interface between inorganic and organic chemistry, inorganic and biological chemistry or new supramolecular systems. The applications of high pressures in Biotechnology – due in particular to the low energy conveyed by pressure – would lead to new research domains or industrial processes involving either the inactivation of pathogen microorganisms with the development of new vaccines or the domain of the proteins…     

Radioactivation analysis. Past achievements,present trends and perspective for the future

The development and applications of activation analysis in the period 1945–1980 are reviewed. In analysing the number of publications reported with time three periods can be distinguished: (a) A first period of slow development, up to 1960, in which the technique showed its very high sensitivity and demonstrated the importance of trace elements; (b) A second period of fast development (1960–1970) in which all aspects of the technique were developed; (c) A third period (after 1970) in which development occurred at a rate approximately equal to the average development rate of analytical chemistry, in terms of the number of publications reported. The present trends shows only minor developments in the methodology, while a good a potential for new and original applications is evident. The importance of a good scientific knowledge of the specific areas of applications is considered necessary to properly frame the analytical activities.     

Rapid high performance liquid chromatography method development with high prediction accuracy,using 5 cm long narrow bore columns packed with sub-2 μm particles and Design Space computer modeling

Many different strategies of reversed phase high performance liquid chromatographic (RP-HPLC) method development are used today. This paper describes a strategy for the systematic development of ultrahigh-pressure liquid chromatographic (UHPLC or UPLC) methods using 5 cm × 2.1 mm columns packed with sub-2 μm particles and computer simulation (DryLab^® package). Data for the accuracy of computer modeling in the Design Space under ultrahigh-pressure conditions are reported. An acceptable accuracy for these predictions of the computer models is presented. This work illustrates a method development strategy, focusing on time reduction up to a factor 3–5, compared to the conventional HPLC method development and exhibits parts of the Design Space elaboration as requested by the FDA and ICH Q8R1. Furthermore this paper demonstrates the accuracy of retention time prediction at elevated pressure (enhanced flow-rate) and shows that the computer-assisted simulation can be applied with sufficient precision for UHPLC applications (p > 400 bar). Examples of fast and effective method development in pharmaceutical analysis, both for gradient and isocratic separations are presented.     

Quality assurance in research and development: an insoluble dilemma?

The implementation of quality elements in research and development is a hot issue, still under discussion and development. In recent years much progress has been made in the development of effective proposals. However there are still problems and misunderstandings on how to apply quality assurance in research and development. This work clarifies these issues, mainly caused by the application of formal standards for quality assurance in R&D. It lists reasons for, and demonstrates benefits of, implementing quality elements in R&D and then offers detailed suggestions for addressing the most important issues without hampering the flexibility and creativity of R&D.     

Influence of development distance on resolution in thin-layer chromatography

Theoretical equations are given to relate resolution with development distance. Comparative experiments undertaken with quaternary ammonium compounds as test substances and using a selection of basic drugs are presented. As expected, resolution decreases with shorter development distance. However, this effect is less pronounced for compounds with small R_f values and when the spot size at the starting point is kept small. It was also shown that, for correctly assessing resolution in relation to development distance, the amounts of material spotted have to be decreased for shorter development distances.     

Advances in the First Total Synthesis of Natural Flavonoids

Flavonoids, composed of a C₆-C₃-C₆ backbone, are a kind of secondary metabolites of natural medicine, which widely exist in the higher plant. They have received extensive attention from all over the world and obtained rapid development owing to widespread distribution, structural complexity, active diversity, and molecular plasticity. Total synthesis of natural products is not only one of the most driving forces in organic chemistry but also the embodiment of the development level of organic synthesis chemistry. Total synthesis research possesses not only important theoretical significance to the development of organic chemistry but also potential marketing prospects to clinical medicine and significant practical value to the development of natural medicine. Flavonoids contain flavan, chalcone, flavone, biflavone, isoflavone, xanthone, pterocarpin, homoisoflavone, flavonol, favonolignan, and some other main structure types. This article summarizes the latest research on first total synthesis, including the plant sources and biological activities, of these main structure types, so as to provide some reference for both the research of first total synthesis of natural flavonoids and the development and utilization of their medicinal value.     

Visible-to-UV Photon Upconversion: Recent Progress in New Materials and Applications

Ultraviolet (UV, λ<400 nm) light is essential for various photochemical reactions, but its intensity in the solar spectrum is very low, and light sources that artificially generate high-energy UV light are inefficient and environmentally unfriendly. A solution to this problem is photon upconversion (UC) from visible (vis, λ>400 nm) light to UV light. Among several mechanisms, UC based on triplet-triplet annihilation (TTA-UC) in particular has made remarkable progress in recent years. The development of new chromophores has enabled highly efficient conversion of low-intensity visible light into UV light. In this review, we summarize the recent development of visible-to-UV TTA-UC, from the development of chromophores and their production into films to their application in various photochemical processes such as catalysis, bond activation and polymerization. Finally, challenges and opportunities in future material development and applications will be discussed.     

New technologies around biomarkers and their interplay with drug development

What conductors are to their orchestras, biomarkers are to their associated technologies. Building fundamental science, supporting early diagnosis of diseases and following their progression, improving efficacy and safety of treatments, optimizing patient selection and adapting dosing of drugs, helping decide which therapy is most appropriate; these are examples of a few contexts in which biomarkers are key players. Technology development can definitely not escape being associated with these steps. In other words, today’s biomarkers are the thermometers of tomorrow’s therapies. This review provides an overview of recently established platforms as well as new and upcoming technologies for biomarker development in the context of drug development. The roles as well as the pros and cons of different disciplines such as genetics, genomics, proteomics, metabonomics, and assay development will be discussed.     

Synthetic Enterobacterial Common Antigen (ECA) for the Development of a Universal Immunotherapy for Drug‐Resistant Enterobacteriaceae

All Enterobacteriaceae express a polysaccharide known as enterobacterial common antigen (ECA), which is an attractive target for the development of universally acting immunotherapies. The first chemical synthesis of ECA‐derived oligosaccharides for the development of such therapies is described. A number of synthetic challenges had to be addressed, including the development of concise synthetic procedures for unusual monosaccharides, the selection of appropriate orthogonal protecting groups, the development of stereoselective glycosylation methods, appropriate timing for the introduction of the carboxylic acid groups on the ManpNAcA moieties, and the selection of appropriate conditions for the reduction of multiple azido moieties. The synthetic compounds were employed to uncover immunodominant moieties of ECA. Furthermore, a monoclonal antibody (mAb) was developed that binds to ECA and can selectively recognize a wide range of Enterobacteriaceae species.     

Prediction of retention data when using incremental multiple development techniques

Summary The apparentRF value of a compound after successive development steps in incremental multiple development (IMD) is determined. The model developed enables prediction of the migration and the zone width of investigated compounds in IMD with linearly and quadratically increasing development distances. For the experimental investigations we examined naturally occurring compounds as model substances on different stationary phases. The coincidence of predicted and measured chromatographic data strongly support our formulas. Presented at the 21^st ISC held in Stuttgart, Germany, 15^th–20^th September, 1996     

Mass spectrometry imaging of latent fingerprints using titanium oxide development powder as an existing matrix

Recent research has focused on increasing the evidentiary value of latent fingerprints through chemical analysis. Although researchers have optimized the use of organic and metal matrices for matrix‐assisted laser desorption/ionization‐mass spectrometry imaging (MALDI‐MSI) of latent fingerprints, the use of development powders as matrices has not been fully investigated. Carbon forensic powder (CFP), a common nonporous development technique, was shown to be an efficient one‐step matrix; however, a high‐resolution mass spectrometer was required in the low mass range due to carbon clusters. Titanium oxide (TiO₂) is another commonly used development powder, especially for dark nonporous surfaces. Here, forensic TiO₂ powder is utilized as a single‐step development and matrix technique for chemical imaging of latent fingerprints without the requirement of a high‐resolution mass spectrometer. All studied compounds were successfully detected when TiO₂ was used as the matrix in positive mode, although, generally, the overall ion signals were lower than the previously studied CFP. TiO₂ provided quality mass spectrometry (MS) images of endogenous and exogenous latent fingerprint compounds. The subsequent addition of traditional matrices on top of the TiO₂ powder was ineffective for universal detection of latent fingerprint compounds. Forensic TiO₂ development powder works as an efficient single‐step development and matrix technique for MALDI‐MSI analysis of latent fingerprints in positive mode and does not require a high‐resolution mass spectrometer for analysis.     

Degradation products formed during UV exposure of polyethylene-ZnO nano-composites

Photodegradation of low density polyethylene (LDPE) containing nano-particulate ZnO has been studied using FTIR to follow the development of oxidation products in the polymer film and to monitor carbon dioxide evolved as a principal product of oxidation. The degradation behaviour of ZnO-free LDPE has been compared with that of compounds containing 0.25% and 0.75% ZnO and these results are compared with those obtained using similar films containing nano-particulate TiO₂. Under UV exposure, the presence of ZnO accelerated the development of carbonyl groups and CO₂ production. The carbonyl group development was more rapid when TiO₂ was used whereas ZnO caused greater CO₂ generation. Carbonyl group development seemed to correlate better with the reduction in mechanical properties whereas CO₂ generation correlated better with weight change measurements. The influence of ZnO on the oxidation pathways in LDPE is discussed; it is proposed that photo-oxidation is relatively much more likely to occur at terminal sites (rather than at pendent sites) when ZnO is present.     

A validation concept for purity determination and assay in the pharmaceutical industry using measurement uncertainty and statistical process control

 The analytical chemists in process development in the pharmaceutical industry have to solve the difficult problem of producing high quality methods for purity determination and assay within a short time without a clear definition of the substance to be analyzed. Therefore the quality management is very difficult. The ideal situation would be that every method is validated before use. This is not possible because this would delay the development process. A process-type quality development approach with an estimation type fast validation (measurement uncertainty) is therefore suggested. The quality management process consists of the estimation of measurement uncertainty for early project status. Statistical process control (SPC) is started directly after measurement uncertainty estimation and a classical validation for the end of the project. By this approach a process is defined that allows a fast and cost-efficient way of supporting the development process with the appropriate quality at the end of the process and provides the transparency needed in the development process. The procedure presented tries to solve the problem of the parallelism between the two development processes (chemical and analytical development) by speeding up the analytical development process initially. Received: 25 March 1997 · Accepted: 17 May 1997     

Present status and potential of group contribution methods for process development

The development of chemical processes can be performed with the help process simulators. However, for the simulation, besides kinetic data, a reliable knowledge of the pure component and mixture properties is required. Since often 60–80% of the total costs arise in the separation step, a reliable knowledge of the phase equilibrium behaviour of the system to be separated is of special importance.The models for excess Gibbs energy g^E and equations of state allow the calculation of the phase equilibrium behaviour of multicomponent systems using binary information alone. But often, the required binary experimental data are missing. For these systems, a reliable predictive thermodynamic model with a large range of applicabilities would be most desirable.With a view to the development of a powerful predictive method, work on the development of a group contribution method was started in Dortmund 1973. A prerequisite for this work is a large database. Therefore, all published pure component properties, phase equilibrium data, and excess properties were stored in a computerized form. At the same time, experimental techniques for the systematic measurements were built up to measure the missing values.The information stored was used for the development of the group contribution method UNIFAC. The weaknesses of this method were removed with the development of modified UNIFAC. With the introduction of g^E-mixing rules in equations of state, the usage of the “solution of groups”-concept lead to group contribution equations of state. In combination with electrolyte models, the influence of strong electrolytes on the phase equilibrium behaviour can be taken into account.In this paper, the continuous development, present status, and potential of group contribution methods for the development of chemical processes will be shown.