A new approach for environmental risk assessment

Environmental problems, such as global warming, the limited supply of sustainable energy, the depletion of natural resources, hazardous emissions released into the atmosphere and waste, are increasing global concerns. Therefore, individuals, communities, and businesses need to address environmental protection and sustainability. Environmental impact assessments are needed to identify, mitigate, and control aspects that affect the environment or a company's products, services, or activities. In this study, a general environmental aspect and impact assessment approach, which can be applied to any company that is involved in the production or service sector, is created. An environmental impact pattern that consists of 10 main and 32 sub-categories was formed based on the ISO 14001, environmental studies and field applications. The developed approach was applied to the dyeing units of a manufacturing firm. Sixteen environmental aspects were identified and assessed using the environmental impact template via the environmental failure mode and effect analysis (E-FMEA) method. The developed-approach can be applied to each sector, which will enable us to perform a detailed analysis of the environmental aspects in the environmental impact category. This approach provides a checklist for the environmental impact studies of businesses and has been pioneered as an effective method for company resources to improve their environmental performance.     

Contact sensitization: A new approach to risk assessment

The murine local lymph node assay is a novel predictive test for the identification of skin sensitizing chemicals. The method measures sensitization potential of a chemical in mice as a function of proliferative activity induced in lymph nodes draining the site of topical exposure to that test chemical. Here we describe the use of the local lymph node assay for evaluation of the relative potency of skin sensitizing chemicals via derivation of the concentration required to produce a threshold positive reaction. Subsequently, the development of risk assessments based on comparisons with index contact allergens is outlined.     

A simple solid phase mass tagging approach for quantitative proteomics

New mass-tagging reagents for quantitative proteomics measurements have been designed using solid phase peptide synthesis technology. The solid phase mass tags have been used to accurately measure the relative amounts of cysteine-containing peptides in model peptide mixtures as well as in mixtures of tryptic digests in the femtomol range. Measurements were made using both matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and online reversed-phase capillary liquid chromatography coupled through a nanoelectrospray interface to an ion trap mass spectrometer (capillary LC/ESI-MS). Results of mass-tagging experiments obtained from these two mass spectrometry techniques and their relative advantages and disadvantages for identification and quantitation of mass tagged peptides are compared. These reagents provide a simple, rapid and cost-effective alternative to currently available mass tagging technologies.     

Inflorescence architecture: A developmental genetics approach

We are characterizing a suiteof Pisum sativum mutants that alter inflorescence architecture to construct a model for the genetic regulation of inflorescence development in a plant with a compound raceme. Such a model, when compared with those created forAntirrhinum majus andArabidopsis thaliana, both of which have simple racemes, should provide insight into the evolution of the development of inflorescence architecture. The highly conserved nature of cloned genes that regulate reproductive development in plants and the morphological similarities among our mutants and those identified inA. majus andA. thaliana enhance the probability that a developmental genetics approach will be fruitful. Here we describe sixP. sativum mutants that affect morphologically and architecturally distinct aspects of the inflorescence, and we analyze interactions among these genes. Both vegetative and inflorescence growth of the primary axis is affected byUNIFOLIA TA, which is necessary for the function ofDETERMINATE (DET).DET maintains indeterminacy in the first-order axis. In its absence, the meristem differentiates as a stub covered with epidermal hairs.DET interacts withVEGETATIVE1 (VEG1).VEG1 appears essential for second-order inflorescence (I₂) development.veg1 mutants fail to flower or differentiate the I₂ meristem into a rudimentary stub,det veg1 double mutants produce true terminal flowers with no stubs, indicating that two genes must be eliminated for terminal flower formation inP. sativum, whereas elimination of a single gene accomplishes this inA. thaliana andA. majus. NEPTUNE also affects I₂ development by limiting to two the number of flowers produced prior to stub formation. Its role is independent ofDET, as indicated by the additive nature of the double mutantdet nep. UNI, BROC, and PIM all play roles in assigning floral meristem identity to the third-order branch.pim mutants continue to produce inflorescence branches, resulting in a highly complex architecture and aberrant flowers.uni mutants initiate a whorl of sepals, but floral organogenesis is aberrant beyond that developmental point, and the double mutantuni pim lacks identifiable floral organs. A wild-type phenotype is observed inbroc plants, butbroc enhancesthe pim phenotype in the double mutant, producing inflorescences that resemble broccoli. Collectively these genes ensure that only the third-order meristem, not higher- or lower-order meristems, generates floral organs, thus precisely regulating the overall architecture of the plant. Gene symbols used in this article: For clarity a common symbolization is used for genes of all species discussed in this article. Genes are symbolized with italicized capital letters. Mutant alleles are represented by lowercase, italicized letters. In both cases, the number immediately following the gene symbol differentiates among genes with the same symbol. If there are multiple alleles, a hyphen followed by a number is used to distinguish alleles. Protein products are represented by capital letters without italics.     

Mass tagging approach for mitochondrial thiol proteins

A mass tagging approach is described for mitochondrial thiol proteins under nondenaturing conditions. This approach utilizes stable isotope-coded, thiol-reactive (4-iodobutyl)triphenylphosphonium (IBTP) reagents, i.e., the isotopomers IBTP-d(0) and IBTP-d(15). The mass spectrometric properties of IBTP-labeled peptides were evaluated using an ESI-q-TOF and a MALDI-TOF/TOF instrument. High energy collision induced dissociation (CID) in the TOF/TOF instrument caused side-chain fragmentation in the butyltriphenylphosphonium moiety-containing Cys-residue. By contrast, low energy CID in the qTOF instrument yielded sequence tags of IBTP-labeled peptides that were suitable for automated database searching. The IBTP labeling strategy was then applied to the analysis of a protein extract obtained from cardiac mitochondria. The relative abundance measurements for identified IBTP-labeled peptides showed an average variability for peptide quantitation of approximately 10% based on peak area ratios of ion signals for the d(0)/d(15)-tagged peptide pairs. The reactivity of the IBTP reagents was further studied by molecular modeling and visualization. The present study suggests that the IBTP reagent seems to show a bias toward highly surface-exposed protein thiols. Hence, the described mass tagging approach might become potentially useful in redox proteomics studies designed to identify protein thiols that are particularly prone to oxidative modifications.     

A new approach for optical assessment of directional anisotropy in turbid media

A study of polarized light transport in scattering media exhibiting directional anisotropy or linear birefringence is presented in this paper. Novel theoretical and experimental methodologies for the quantification of birefringent alignment based on out‐of‐plane polarized light transport are presented here. A polarized Monte Carlo model and a polarimetric imaging system were devised to predict and measure the impact of birefringence on an impinging linearly polarized light beam. Ex‐vivo experiments conducted on bovine tendon, a biological sample consisting of highly packed type I collagen fibers with birefringent property, showed good agreement with the analytical results.

Top view geometry of the in‐plane ( a ) and the out‐of‐plane ( b ) detection. Letter C indicates the location of the detection arm.     

Three-dimensional endocardial impedance mapping: a new approach for myocardial infarction assessment

Precise identification of infarcted myocardial tissue is of importance in diagnostic and interventional cardiology. A three-dimensional, catheter-based endocardial electromechanical mapping technique was used to assess the ability of local endocardial impedance in delineating the exact location, size, and border of canine myocardial infarction. Electromechanical mapping of the left ventricle was performed in a control group (n = 10) and 4 wk after left anterior descending coronary artery ligation (n = 10). Impedance, bipolar electrogram amplitude, and endocardial local shortening (LS) were quantified. The infarcted area was compared with the corresponding regions in controls, revealing a significant reduction in impedance values [infarcted vs. controls: 168.8 +/- 11. 7 and 240.7 +/- 22.3 Omega, respectively (means +/- SE), P < 0.05] bipolar electrogram amplitude (1.8 +/- 0.2 mV, 4.4 +/- 0.7 mV, P < 0. 05), and LS (-2.36 +/- 1.6%, 11.9 +/- 0.9%, P < 0.05). The accuracy of the impedance maps in delineating the location and extent of the infarcted region was demonstrated by the high correlation with the infarct area (Pearson's correlation coefficient = 0.942) and the accurate identification of the infarct borders in pathology. By accurately defining myocardial infarction and its borders, endocardial impedance mapping may become a clinically useful tool in differentiating healthy from necrotic myocardial tissue.     

ScanRanker: Quality assessment of tandem mass spectra via sequence tagging

In shotgun proteomics, protein identification by tandem mass spectrometry relies on bioinformatics tools. Despite recent improvements in identification algorithms, a significant number of high quality spectra remain unidentified for various reasons. Here we present ScanRanker, an open-source tool that evaluates the quality of tandem mass spectra via sequence tagging with reliable performance in data from different instruments. The superior performance of ScanRanker enables it not only to find unassigned high quality spectra that evade identification through database search but also to select spectra for de novo sequencing and cross-linking analysis. In addition, we demonstrate that the distribution of ScanRanker scores predicts the richness of identifiable spectra among multiple LC-MS/MS runs in an experiment, and ScanRanker scores assist the process of peptide assignment validation to increase confident spectrum identifications. The source code and executable versions of ScanRanker are available from http://fenchurch.mc.vanderbilt.edu.     

Cyalume tagging: a new method for tracking reef fishes at night

A new method for tracking nocturnal reef fishes using a Cyalume light stick is described. The Cyalume is attached to the dorsal musculature using dissolvable sutures. The tagged fish can then be monitored throughout the night. Potential uses and problems are discussed. Key words: tagging; nocturnal fishes; tracking; Cyalumes.     

A risk assessment approach for fresh fruits

Aims:  To describe the approach used in conducting a fit‐for‐purpose risk assessment of microbiological human pathogens associated with fresh fruit and the risk management recommendations made. Methods and Results:  A qualitative risk assessment for microbiological hazards in fresh fruit was carried out based on the Codex Alimentarius (Codex) framework, modified to consider multiple hazards and all fresh (whole) fruits. The assessment determines 14 significant bacterial, viral, protozoal and nematodal hazards associated with fresh produce, assesses the probable level of exposure from fresh fruit, concludes on the risk from each hazard, and considers and recommends risk management actions. A review of potential risk management options allowed the comparison of effectiveness with the potential exposure to each hazard. Conclusions:  Washing to a recommended protocol is an appropriate risk management action for the vast majority of consumption events, particularly when good agricultural and hygienic practices are followed and with the addition of refrigerated storage for low acid fruit. Additional safeguards are recommended for aggregate fruits with respect to the risk from protozoa. Significance and Impact of the Study:  The potentially complex process of assessing the risks of multiple hazards in multiple but similar commodities can be simplified in a qualitative assessment approach that employs the Codex methodology.     

A comprehensive approach for drug safety assessment

A comprehensive, multidisciplinary approach is proposed here for the development of a drug with an acceptable safety profile. Key parameters to be considered for drug safety evaluation based on this comprehensive approach include the following: (1) Pharmacology: Possible toxicity due to drug-target interactions, including interactions with unintended molecular targets, or with molecular targets in unintended organs. (2) Chemistry: Chemical scaffolding and side-chains with safety concerns. (3) Toxicology: Toxicity in animals in vivo, and in relevant animal and human cells in culture. (4) Drug metabolism and pharmacokinetics: Safety concerns due to toxification or detoxification, organ distribution, clearance and pharmacokinetic drug-drug interactions. (5) Risk factors: Physiological, environmental and genetic factors that may enhance a patient's susceptibility. It is proposed that this integrated, multidisciplinary approach to safety evaluation may enhance the accuracy of the prediction of drug safety and thereby the efficiency of drug development.     

干细胞研究的新途径:miRNAs

微小RNA(microRNAs,miRNAs)是一类内源性的非编码单链RNA,能够通过与靶mRNA特异性的碱基配对而导致靶mRNA降解或抑制其翻译,从而对基因进行转录后调控。干细胞的自我更新和多向分化过程依赖于广泛而多样的调控机制,miRNAs正是这些调控机制中非常重要的一类分子。研究发现,干细胞的自我更新功能需要多种miRNAs的参与来维持;干细胞的分化也是多种miRNAs参与调控的结果。miRNAs可以作为干细胞研究的一个新的切入点。     

生态系统途径——生态系统管理的一种新理念

介绍了生态系统途径的概念和内涵．生态系统途径最早由西方生态学家提出。随后得到一系列国际学术组织和国家的认同和支持,其中《生物多样性公约》、世界自然保护联盟和世界野生动物基金发挥了重要作用,．生态系统途径的实质是对土地、水和生物资源进行综合管理,旨在生态系统保护、生物资源可持续利用和共享生物资源三者之间达到平衡．作为生态系统管理的一种方法论,它以生物为核心。将人类及文化的多样性视为生态系统的一个组成部分,2000年《生物多样性公约》缔约国会议上制定的生态系统管理的12条基本原则和5项行动指南,丰富了生态系统途径的内涵,明确了实施的办法,我国在生态系统管理方面有着丰富的学术储备和经验总结。但也存在一定问题。

     

Protein architecture: new superfamilies

Protein families whose members have evolved beyond any statistically significant similarities in sequence are sometimes called superfamilies. Structural and functional characteristics are conserved within such families and can be revealed by an analysis of protein architecture. We describe ten superfamilies that have resulted from recently determined structures; four of these are described here for the first time.     

SHORT COMMUNICATION: A rapid method for the assessment of bone architecture by confocal microscopy

Conventional ways of demonstrating and analysing the components of osseous tissue have always been hampered by the difficulty of physically sectioning bone. In this study, we have used Acridine Orange staining of 100-mu m-thick unembedded bone slices and then assessed the cellular and tissue architecture by confocal microscopy. The result showed the Acridine Orange, by differential staining of the cellular nucleic acids, permits ready assessment of cell shape and cell organization as well as variations in growth patterns. Our studies have provided a new and relatively easy way of assessing the morphology of bone specimens by rendering unnecessary the need for embedding, decalcification and thin sectioning of the osseous tissue. This revised version was published online in November 2006 with corrections to the Cover Date.     

A novel approach to pharmacodynamic assessment of antimicrobial agents: new insights to dosing regimen design

Pharmacodynamic modeling has been increasingly used as a decision support tool to guide dosing regimen selection, both in the drug development and clinical settings. Killing by antimicrobial agents has been traditionally classified categorically as concentration-dependent (which would favor less fractionating regimens) or time-dependent (for which more frequent dosing is preferred). While intuitive and useful to explain empiric data, a more informative approach is necessary to provide a robust assessment of pharmacodynamic profiles in situations other than the extremes of the spectrum (e.g., agents which exhibit partial concentration-dependent killing). A quantitative approach to describe the interaction of an antimicrobial agent and a pathogen is proposed to fill this unmet need. A hypothetic antimicrobial agent with linear pharmacokinetics is used for illustrative purposes. A non-linear functional form (sigmoid Emax) of killing consisted of 3 parameters is used. Using different parameter values in conjunction with the relative growth rate of the pathogen and antimicrobial agent concentration ranges, various conventional pharmacodynamic surrogate indices (e.g., AUC/MIC, Cmax/MIC, %T>MIC) could be satisfactorily linked to outcomes. In addition, the dosing intensity represented by the average kill rate of a dosing regimen can be derived, which could be used for quantitative comparison. The relevance of our approach is further supported by experimental data from our previous investigations using a variety of gram-negative bacteria and antimicrobial agents (moxifloxacin, levofloxacin, gentamicin, amikacin and meropenem). The pharmacodynamic profiles of a wide range of antimicrobial agents can be assessed by a more flexible computational tool to support dosing selection.