Biological methods for marine toxin detection

The presence of marine toxins in seafood poses a health risk to human consumers which has prompted the regulation of the maximum content of marine toxins in seafood in the legislations of many countries. Most marine toxin groups are detected by animal bioassays worldwide. Although this method has well known ethical and technical drawbacks, it is the official detection method for all regulated phycotoxins except domoic acid. Much effort by the scientific and regulatory communities has been focused on the development of alternative techniques that enable the substitution or reduction of bioassays; some of these have recently been included in the official detection method list. During the last two decades several biological methods including use of biosensors have been adapted for detection of marine toxins. The main advances in marine toxin detection using this kind of technique are reviewed. Biological methods offer interesting possibilities for reduction of the number of biosassays and a very promising future of new developments.     

Scientific fraud in corrosion science research: A review

This article examines the issue of scientific misconduct and its implications on corrosion science research through a decade (2001–2011). An analysis is presented of an increasing body of cases in which allegations have been made and violations of legal and ethical research standards have been substantiated. The frequencies with which scientists fabricate and falsify data, or commit other forms of scientific misconduct, are discussed. In this review, the image of scientists as objective seekers of truth is periodically jeopardized by the discovery of a major scientific fraud. This review shows how easy it can be for a scientist to publish fabricated data in the most prestigious journals, and how this can cause a waste of financial and human resources. Case examples illustrated and investigated in this review are related to corrosion science research. Recommendations toward the prevention and resolution of potential or actual instances of scientific misconduct in corrosion science research are proposed.     

EPA's approach to radon risk assessment

The Environmental Protection Agency has estimated that 20,000 lung cancer deaths per year may be related to radon exposure. This paper briefly describes the approach used to derive the Agency's central estimate of risk to the population. The weight-of-evidence for classifying radon as a known human carcinogen and the uncertainties associated with estimating risks from radon exposure provide an important context for these estimates and are briefly discussed.This paper has been reviewed in accordance with the U. S. Environmental Protection Agency's peer and administrative review policies and approved for presentation and publication.     

PPI Modulators of E6 as Potential Targeted Therapeutics for Cervical Cancer: Progress and Challenges in Targeting E6

Advanced cervical cancer is primarily managed using cytotoxic therapies, despite evidence of limited efficacy and known toxicity. There is a current lack of alternative therapeutics to treat the disease more effectively. As such, there have been more research endeavors to develop targeted therapies directed at oncogenic host cellular targets over the past 4 decades, but thus far, only marginal gains in survival have been realized. The E6 oncoprotein, a protein of human papillomavirus origin that functionally inactivates various cellular antitumor proteins through protein–protein interactions (PPIs), represents an alternative target and intriguing opportunity to identify novel and potentially effective therapies to treat cervical cancer. Published research has reported a number of peptide and small-molecule modulators targeting the PPIs of E6 in various cell-based models. However, the reported compounds have rarely been well characterized in animal or human subjects. This indicates that while notable progress has been made in targeting E6, more extensive research is needed to accelerate the optimization of leads. In this review, we summarize the current knowledge and understanding of specific E6 PPI inhibition, the progress and challenges being faced, and potential approaches that can be utilized to identify novel and potent PPI inhibitors for cervical cancer treatment.     

Collection and identification of human remains volatiles by non-contact,dynamic airflow sampling and SPME-GC/MS using various sorbent materials

Human remains detection canines are used in locating deceased humans in diverse scenarios and environments based on odor produced during the decay process of the human body. It has been established that human remains detection canines are capable of locating human remains specifically, as opposed to living humans or animal remains, thus suggesting a difference in odor between the different sources. This work explores the collection and determination of such odors using a dynamic headspace concentration device. The airflow rate and three sorbent materials—Dukal cotton gauze, Johnson & Johnson cotton-blend gauze, and polyester material—used for odor collection were evaluated using standard compounds. It was determined that higher airflow rates and openly woven material, e.g., Dukal cotton gauze, yielded significantly less total volatile compounds due to compound breakthrough through the sorbent material. Collection from polymer- and cellulose-based materials demonstrated that the molecular backbone of the material is a factor in compound collection as well. Volatiles, including cyclic and straight-chain hydrocarbons, organic acids, sulfides, aldehydes, ketones, and alcohols, were collected from a population of 27 deceased bodies from two collection locations. The common compounds between the subjects were compared and the odor profiles were determined. These odor profiles were compared with those of animal remains and living human subjects collected in the same manner. Principal component analysis showed that the odor profiles of the three sample types were distinct.     

多模式小动物活体成像系统在本科生创新实践中的使用与开发

多模式小动物活体成像系统广泛应用于高校科研实验室的活体动物检测研究,为癌症的发生及发展、基因治疗和免疫学及分子生物学等相关研究领域提供直观的活体侦测手段.结合多年的多模式小动物活体成像系统的使用,总结了多模式小动物活体成像系统的使用经验,并探讨了多模式小动物活体成像系统在大学生创新实践中的应用.旨在提高多模式小动物活体成像系统的使用效率,并拓宽多模式小动物活体成像系统的实验资源.     

The quality approach and fundamental research: Working towards a constructive alliance (Part I)

 The quality approach is being progressively used in scientific research and is likely to become a key point in the future. This article critically examines the applicability of the quality approach to fundamental research. A critical survey of the basic concepts of the quality approach is proposed (conformity to a reference, satisfaction of requirements and/or adaptation to use, planning and formalization). The need for quality in fundamental research is then discussed through a review of the scientific, economic and financial, human, social and environmental issues that research will face in the future. An attempt is made to demonstrate that the quality approach incorporates concerns and current practices of the scientific community which are not normally identified and labelled as pertaining to the field of Quality. Received: 8 March 1998 / Accepted: 8 December 1998     

Supramolecular Polymerization from Controllable Fabrication to Living Polymerization

Supramolecular polymers have attracted plenty of interest in the scientific community; however, developing controllable methods of supramolecular polymerization remains a serious challenge. This article reviews some recent developments of methods for supramolecular polymerization from controllable fabrication to living polymerization. Three facile methods with general applicability for controllable fabrication of supramolecular polymers have been established recently: the first method is a self‐sorting approach by manipulating ring–chain equilibrium based on noncovalent control over rigidity of monomers; the second is covalent polymerization from supramonomers formed by noncovalent interactions; and the third is supramolecular interfacial polymerization. More excitingly, living supramolecular polymerization has been achieved by two elegant strategies, including seeded supramolecular polymerization under pathway complexity control and chain‐growth supramolecular polymerization by metastable monomers. It is anticipated that this review may provide some guidance for precise fabrication of supramolecular polymers, leading to the construction of supramolecular polymeric materials with controllable architectures and functions.     

Occurrence patterns of pharmaceuticals in water and wastewater environments

The occurrence of pharmaceuticals and their metabolites and transformation products in the environment is becoming a matter of concern, because these compounds, which may have adverse effects on living organisms, are extensively and increasingly used in human and veterinary medicine and are released continuously into the environment. A variety of pharmaceuticals have been detected in many environmental samples worldwide. Their occurrence has been reported in sewage-treatment-plant effluents, surface water, seawater, groundwater, soil, sediment and fish. This paper provides an overview of recent scientific research on the sources, occurrence, and fate of pharmaceuticals in water and wastewater.     

Blood Coagulation and Living Tissue Sterilization by Floating-Electrode Dielectric Barrier Discharge in Air

Thermal plasma discharges have been widely used in the past for treatment of living human and animal tissue. However, extensive thermal damage and tissue desiccation occurs due to extreme temperatures. Some solutions have been offered where the temperature is lowered by short current pulses, addition of noble gases, or significant decrease in the size of treatment electrodes. We propose a method of direct treatment of living tissue that occurs at room temperature and pressure without visible or microscopic tissue damage. The presented Floating-Electrode Dielectric Barrier Discharge plasma is proven electrically safe to human subjects and our results show no gross (visual) or histological (microscopic) damage to skin samples in minutes, complete tissue sterilization from skin flora in seconds, and blood clot formation in seconds of electric plasma treatment. We also observe significant hastening of blood clot formation via electric plasma induced catalysis of “natural” processes occurring in human blood. A model describing these processes is offered.An erratum to this article can be found at     

Ménage À Trois: Activation, Analysis and Uncertainty, 10 Projections into the Impending Millenium

For more than half a century we have been using activation of stable isotopes to determine chemical elements, and significant contributions have been made to a variety of scientific subjects. Nevertheless, activation analysis has not yet become integrated in the field of chemical analysis, and therefore the special features characteristic of activation analysis have not been fully realised in analytical chemistry. At the same time basic chemical knowledge has only to a limited extent been utilised in the development of analytical methods based on activation. This situation has only now become painfully clear, when a world-wide requirement is being made to express the uncertainty of analytical results in accordance with the BIPM philosophy. The identification and estimation of all uncertainty components needed to produce a reliable uncertainty budget requires the combined efforts of all parties. An attempt is here made to extrapolate current trends for the expression of uncertainty in activation and analysis into the future and to show, how the implementation of the BIPM Guidelines with respect to correction for all known or suspected biases, achievement of statistical control, and full traceability, can help bringing analytical chemistry into its rightful position as a scientific discipline in the field of metrology.     

Fractional mass filtering as a means to assess circulating metabolites in early human clinical studies

Recent changes in the regulatory environment have led to a need for new methods to assess circulating human drug metabolites in early clinical studies with respect to their potential toxicological impact. The specific goals of such studies are to determine if the metabolites present in human plasma following administration of a drug candidate also are observed in plasma from the animal studies employed for preclinical toxicological evaluation, and to estimate corresponding exposure margins (animal:human) for the major metabolites. Until recently, the accepted best practice for the characterization of circulating drug metabolites utilized liquid chromatography/tandem mass spectrometry (LC/MS/MS)-based methodologies, in conjunction with authentic chemical standards, for the detection and quantitative analyses of metabolites predicted from both animal studies and experiments with human liver preparations in vitro. While this approach is satisfactory for anticipated biotransformation products, metabolites that were not expected to circulate in human plasma frequently escape detection. Current accurate mass instruments enable the use of the technique of fractional mass filtering to detect both expected and unexpected metabolites in a rapid, less resource-intensive and more robust manner. Application of this technology to several clinical development programs at Merck Research Laboratories has demonstrated the value of fractional mass filtering in the assessment of circulating drug metabolites in early clinical trials.     

浙江大学求是化学班人才培养的多层次科研实践体系

浙江大学化学系在求是化学班的培养过程中,以基础学科拔尖创新人才为培养目标,注重提升本科生科研能力,依托学科优势,从科研基础知识体系构建、科研思维模式拓展和科研创新实践能力强化等方面构筑分阶段、分层次、多平台、多模式的科研实践培养体系。该体系总体上以科研训练为主线,从广度科研认知到深度科研实践,融通校内第一、二课堂和校外第三、四课堂,贯穿整个拔尖人才培养过程。经过多年的探索与实践,该科研实践体系在培养学生的科研能力、创新思维和国际视野等方面已经初见成效。     

Isothermal microcalorimetry near ambient temperature: An overview and discussion

Isothermal microcalorimeters are employed both in thermodynamic work and as general analytical tools. Important application areas include ligand binding studies by use of titration techniques, sorption of solutes and vapours on solid materials, measurements of dissolution processes (particularly for slightly soluble compounds), assessment of physical and chemical stabilities and investigations of living systems: microorganisms, animal and human cells and tissues, small animals and plants tissues.During the past 30 years much development work has been conducted in these areas in relation to instrument design and experimental procedures. At present, an important trend involves the combination of microcalorimetry with different specific analytical methods.     

Chemistry for the Future—State of the Art and Perspectives

A particularly close relationship exists between chemistry, the science of the transformation of matter, and developments in human living conditions. Though little more than 150 years old, chemical technology has had a greater influence on our civilization than any other technological discipline. Its roots lie not in the crafts, but in scientific research. Relationships derived from the laws of nature were taken as a basis for the systematic solution of practical problems. It is to this strategy that chemistry owes its success. New opportunities arise from new discoveries. These result from basic research at universities, research institutes, and industrial laboratories. Applied research in turn transforms the discoveries into innovative solutions to problems on an industrial scale. The objectives of applied research are oriented toward the marketplace and to the needs of mankind. Our knowledge of scientific interrelationships has been growing with unabated vigor for decades, but so too has our insight into the enormous complexity of the material world. Many of the problems that civilization faces result from the fact that our knowledge is still inadequate. Intensive research and development offer the only hope for progress. Scientists must of course act responsibly with the knowledge they acquire, and they must provide the information necessary to establish public confidence in their methods and products. This is the prerequisite for broad acceptance of technological progress, and given the extent of the world's population no alternative to progress exists. The shape of that progress is also subject to influences outside the realm of science, however, including social norms and political activities. A country that is not rich in raw materials, like the Federal Republic of Germany, must pay particular attention to these factors as well if it is to maintain its innovative strength.     

MALDI-MS imaging of lipids in ex vivo human skin

Lipidomics is a rapidly expanding area of scientific research and there are a number of analytical techniques that are employed to facilitate investigations. One such technique is matrix-assisted laser desorption ionisation (MALDI) mass spectrometry (MS). Previous MALDI-MS studies involving lipidomic investigation have included the analysis of a number of different ex vivo tissues, most of which were obtained from animal models, with only a few being of human origin. In this study, we describe the use of MALDI-MS, MS/MS and MS imaging methods for analysing lipids within cross-sections of ex vivo human skin. It has been possible to tentatively identify lipid species via accurate mass measurement MALDI-MS and also to confirm the identity of a number of these species via MALDI-MS/MS, in experiments carried out directly on tissue. The main lipid species detected include glycerophospholipids and sphingolipids. MALDI images have been generated at a spatial resolution of 150 and 30 μm, using a MALDI quadrupole time-of-flight Q-Star Pulsar-i ^TM (Applied Biosystems/MDS Sciex, Concord, ON, Canada) and a MALDI high-definition MS (HDMS) SYNAPT G2-HDMS^TM system (Waters, Manchester, UK), respectively. These images show the normal distribution of lipids within human skin, which will provide the basis for assessing alterations in lipid profiles linked to specific skin conditions e.g. sensitisation, in future investigations.     

Phantoms for Noninvasive Blood Glucose Sensing with Near Infrared Transmission Spectroscopy

In vivo spectra from human subjects can be simulated with a phantom composed of different layers of water, fat and muscle tissue. All three components are necessary to simulate in vivo spectra collected over the combination spectral region (5000–4000 cm⁻¹). Muscle tissue is not required, however, to accurately simulate overtone spectra (6600–5400 cm⁻¹). The near-IR spectral characteristics of fat and muscle tissue from several animal sources are essentially identical to those found for human tissue, hence, the animal source for these phantom components is not critical. Thickness of each tissue layer can be determined by a regression analysis where the in vivo spectrum of interest is regressed against standard absorbance spectra of the necessary model components (water, fat and muscle). In general, in vivo overtone spectra collected across human webbing tissue with a thickness of 6.7 mm can be simulated with water layer thicknesses ranging from 5.0 to 6.4 mm combined with fat layer thicknesses from 1.4 to 4.2 mm.     

Development and Application of an LC-MS/MS Untargeted Exposomics Method with a Separated Pooled Quality Control Strategy

Pooled quality controls (QCs) are usually implemented within untargeted methods to improve the quality of datasets by removing features either not detected or not reproducible. However, this approach can be limiting in exposomics studies conducted on groups of exposed and nonexposed subjects, as compounds present at low levels only in exposed subjects can be diluted and thus not detected in the pooled QC. The aim of this work is to develop and apply an untargeted workflow for human biomonitoring in urine samples, implementing a novel separated approach for preparing pooled quality controls. An LC-MS/MS workflow was developed and applied to a case study of smoking and non-smoking subjects. Three different pooled quality controls were prepared: mixing an aliquot from every sample (QC-T), only from non-smokers (QC-NS), and only from smokers (QC-S). The feature tables were filtered using QC-T (T-feature list), QC-S, and QC-NS, separately. The last two feature lists were merged (SNS-feature list). A higher number of features was obtained with the SNS-feature list than the T-feature list, resulting in identification of a higher number of biologically significant compounds. The separated pooled QC strategy implemented can improve the nontargeted human biomonitoring for groups of exposed and nonexposed subjects.     

Human biomonitoring of emerging pollutants through non-invasive matrices: state of the art and future potential

Human biomonitoring (HBM) is a scientific technique that allows us to assess whether and to what extent environmental pollutants enter humans. We review here the current HBM efforts for organophosphate esters, emerging flame retardants, perfluoroalkyl substances, and phthalate esters. Use of some of these chemicals has already been banned or restricted; they are regularly detected in the environment, wildlife, and human matrices. Traditionally, blood and urine collection have been widely used as sampling methods. New non-invasive approaches (e.g., saliva, hair, nails) are emerging as valid alternatives since they offer advantages with respect to sampling, handling, and ethical aspects, while ensuring similar reliability and sensitivity. Nevertheless, the identification of biomarkers of exposure is often difficult because chemicals may be metabolized in the human body. For many of the above-mentioned compounds, the mechanisms of the favorable metabolization pathways have not been unraveled, but research on important metabolites that could be used as biomarkers of exposure is growing. This review summarizes the state of the art regarding human exposure to, (non-invasive) HBM of, and metabolism of major organophosphate esters, emerging flame retardants, perfluoroalkyl substances, and phthalate esters currently detected in the environment.