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Examines the growing use of "work transformation" or process re-engineering techniques in health-care organizations. Identifies how pressures on funding and increased expectations are forcing health-care organizations to adopt radical solutions in their search for lower costs and improved quality of care. Also examines the experience of a number of organizations, and highlights some of the risks involved in taking these approaches.
OBJECTIVES: To review the advances in clinically useful molecular biological techniques and to identify their applications in clinical practice, as presented at the Tenth Annual William Beaumont Hospital DNA Symposium. DATA SOURCES: The 11 manuscripts submitted were reviewed and their major findings were compared with literature on the same topic. STUDY SELECTION: Manuscripts address creative thinking techniques applied to DNA discovery, extraction of DNA from clotted blood, the relationship of mitochondrial dysfunction in neurodegenerative disorders, and molecular methods to identify human lymphocyte antigen class I and class II loci. Two other manuscripts review current issues in molecular microbiology, including detection of hepatitis C virus and biological warfare. The last 5 manuscripts describe current issues in molecular cardiovascular disease, including assessing thrombotic risk, genomic analysis, gene therapy, and a device for aiding in cardiac angiogenesis. DATA SYNTHESIS: Novel problem-solving techniques have been used in the past and will be required in the future in DNA discovery. The extraction of DNA from clotted blood demonstrates a potential cost-effective strategy. Cybrids created from mitochondrial DNA-depleted cells and mitochondrial DNA from a platelet donor have been useful in defining the role mitochondria play in neurodegeneration. Mitochondrial depletion has been reported as a genetically inherited disorder or after human immunodeficiency virus therapy. Hepatitis C viral detection by qualitative, quantitative, or genotyping techniques is useful clinically. Preparedness for potential biological warfare is a responsibility of all clinical laboratorians. Thrombotic risk in cardiovascular disorders may be assessed by coagulation screening assays and further defined by mutation analysis for specific genes for prothrombin and factor V Leiden. Gene therapy for reducing arteriosclerotic risk has been hindered primarily by complications introduced by the vectors used to introduce the therapeutic genes. Neovascularization in cardiac muscle with occluded vessels represents a promising method for recovery of viable tissue following ischemia. CONCLUSIONS: The sequence of the human genome was reported by 2 groups in February 2001. The postgenomic era will emphasize the use of microarrays and database software for genomic and proteomic screening in the search for useful clinical assays. The number of molecular pathologic techniques and assays will expand as additional disease-associated mutations are defined. Gene therapy and tissue engineering will represent successful therapeutic adjuncts.
Regulations, accreditation, economics and public outcry are just some of the reasons hospitals are becoming more environmentally conscious. Others just want to do their part to help the environment. Whatever the reason, healthcare organizations seem to be searching for ways to mitigate their effect on the environment.
The rules to cost benefits realization are simple. System must be designed and built to replace functions. Those that are built this way, need the added management engineering benefit to realize the potential savings. Other industries have stepped up to this challenge. If your system does not replace functions, perhaps it's time to search for one that does.
Although heuristic optimization techniques are increasingly applied in environmental engineering applications, algorithm selection and configuration are often approached in an ad hoc fashion. In this study, the design of a multilayer sorptive barrier system served as a benchmark problem for evaluating several algorithm-tuning procedures, as applied to three global optimization techniques (genetic algorithms, simulated annealing, and particle swarm optimization). Each design problem was configured as a combinatorial optimization in which sorptive materials were selected for inclusion in a landfill liner to minimize the transport of three common organic contaminants. Relative to multilayer sorptive barrier design, study results indicate (i) the binary-coded genetic algorithm is highly efficient and requires minimal tuning, (ii) constraint violations must be carefully integrated to avoid poor algorithm convergence, and (iii) search algorithm performance is strongly influenced by the physical-chemical properties of the organic contaminants of concern. More generally, the results suggest that formal algorithm tuning, which has not been widely applied to environmental engineering optimization, can significantly improve algorithm performance and provide insight into the physical processes that control environmental systems.
We introduce PHASE, a highly flexible system for common pharmacophore identification and assessment, 3D QSAR model development, and 3D database creation and searching. The primary workflows and tasks supported by PHASE are described, and details of the underlying scientific methodologies are provided. Using results from previously published investigations, PHASE is compared directly to other ligand-based software for its ability to identify target pharmacophores, rationalize structure-activity data, and predict activities of external compounds.
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Environmental protection and green science have an integral association and yet both terms can mean different things to different people and both refer to methods of preventing or removing pollution. The former includes such things as the development of low pollution fuels (including the use of biodiesel and fuel cells for vehicles) and the search for cleaner synthetic routes in the chemical industry. The latter tends to be more closely associated with the clean-up of the environment e.g. the purification of water (chemical and biological), the decontamination of the atmosphere and soil. In this article recent developments in the application of ultrasound in both environmental protection and remediation will be considered.
Cholinesterases are targets for organophosphorus compounds which are used as insecticides, chemical warfare agents and drugs for the treatment of disease such as glaucoma, or parasitic infections. The widespread use of these chemicals explains the growing of this area of research and the ever increasing number of sequences, structures, or biochemical data available. Future advances will depend upon effective management of existing information as well as upon creation of new knowledge. The ESTHER database goal is to facilitate retrieval and comparison of data about structure and function of proteins presenting the alpha/beta hydrolase fold. Protein engineering and in vitro production of enzymes allow direct comparison of biochemical parameters. Kinetic parameters of enzymatic reactions are now included in the database. These parameters can be searched and compared with a table construction tool. ESTHER can be reached through internet (http://www.ensam.inra.fr/cholinesterase). The full database or the specialised X-window Client-server system can be downloaded from our ftp server (ftp://ftp.toulouse.inra.fr./pub/esther). Forms can be used to send updates or corrections directly from the web.
A strategy for rational enzyme design is reported and illustrated by the engineering of a protein catalyst for thiol-ester hydrolysis. Five mutants of human glutathione (GSH; gamma-Glu-Cys-Gly) transferase A1-1 were designed in the search for a catalyst and to provide a set of proteins from which the reaction mechanism could be elucidated. The single mutant A216H catalyzed the hydrolysis of the S-benzoyl ester of GSH under turnover conditions with a k(cat)/K(M) of 156 M(-1) x min(-1), and a catalytic proficiency of >10(7) M(-1) when compared with the first-order rate constant of the uncatalyzed reaction. The wild-type enzyme did not hydrolyze the substrate, and thus, the introduction of a single histidine residue transformed the wild-type enzyme into a turnover system for thiol-ester hydrolysis. By kinetic analysis of single, double, and triple mutants, as well as from studies of reaction products, it was established that the enzyme A216H catalyzes the hydrolysis of the thiol-ester substrate by a mechanism that includes an acyl intermediate at the side chain of Y9. Kinetic measurements and the crystal structure of the A216H GSH complex provided compelling evidence that H216 acts as a general-base catalyst. The introduction of a single His residue into human GSH transferase A1-1 created an unprecedented enzymatic function, suggesting a strategy that may be of broad applicability in the design of new enzymes. The protein catalyst has the hallmarks of a native enzyme and is expected to catalyze various hydrolytic, as well as transesterification, reactions.
UNLABELLED: The presence of a used filter in a ventilation system can have an adverse impact on perceived air quality, SBS symptoms, and performance of office work. The present paper reviews the studies leading to this conclusion and discusses recent work that has been performed in a search for the mechanisms involved. One promising hypothesis involves chemical reactions on the surface of the collected particles in the formation of noxious compounds. Finally, a discussion on engineering solutions is presented. PRACTICAL IMPLICATIONS: Loaded particle filters provide a significant source of air pollution. To counteract this, filters should be changed frequently or an alternative method of removing particles from the air should be applied.
The NeuroHomology Database system (NHDB) combines databases related to brain structures from different species with different knowledge management systems (KMSs) for systematization, evaluation and processing neurobiological data. Special attention is assessment of similarity of data from different species as a basis for exploring neural homologies. NHDB includes modules that handle brain structure and connectivity data, as well as inference engines for evaluation of the stored neurobiological information. The spatial inference engine evaluates the possible topological relations between cortical structures in different neuroanatomical atlases. The connectivity inference engine evaluates the reliability of information pertaining to fiber tracts as those are reflected in the literature. The inference engine for translation of neuroanatomical connections in different atlases evaluates the probability of existence of connections of interest in different parcellation schemes. Finally, the similarity inference engine calculates the overall degree of similarity of pairs of brain structures from different species by taking into account a set of eight criteria. We present examples of search for information in NHDB system, inferences of relations between cortical structures from equivalent neuroanatomical atlases, reconstruction of functional networks of brain structures from data collated from the literature, translation of connectivity matrices in equivalent parcellation schemes, and evaluations of similarities of brain structures from humans, macaques and rats.
The present study describes cause-specific mortality among dentists living in the city of São Paulo, Brazil, from 1980 to 2000, in search of possible indications of work-attributable risk. Official mortality information was supplied by the State Data Analysis System. Comparative analysis used analogous information for physicians and engineers. Analysis of death distribution according to underlying causes indicated the absence of significant differences that might suggest increased risk of death for dentists as compared to physicians and engineers. Dentists' deaths did not present worse indications for global and specific categories of infectious diseases, neoplasms, suicide, or central nervous system or circulatory diseases. A systematic excess mortality caused by injuries was observed for engineers, especially in traffic-related accidents, accidental falls, and other accidents. We observed the absence of significant discrepancies indicating work-attributable risk for dentists. This observation suggests that dentistry can be considered a safe profession, at least regarding exposure to systematic risk of death.
Computational methods play a central role in the rational design of novel proteins. The present work describes a new hybrid exact rotamer optimization (HERO) method that builds on previous dead-end elimination algorithms to yield dramatic performance enhancements. Measured on experimentally validated physical models, these improvements make it possible to perform previously intractable designs of entire protein core, surface, or boundary regions. Computational demonstrations include a full core design of the variable domains of the light and heavy chains of catalytic antibody 48G7 FAB with 74 residues and 10(128) conformations, a full core/boundary design of the beta1 domain of protein G with 25 residues and 10(53) conformations, and a full surface design of the beta1 domain of protein G with 27 residues and 10(60) conformations. In addition, a full sequence design of the beta1 domain of protein G is used to demonstrate the strong dependence of algorithm performance on the exact form of the potential function and the fidelity of the rotamer library. These results emphasize that search algorithm performance for protein design can only be meaningfully evaluated on physical models that have been subjected to experimental scrutiny. The new algorithm greatly facilitates ongoing efforts to engineer increasingly complex protein features.
The high computational cost of complex engineering optimization problems has motivated the development of parallel optimization algorithms. A recent example is the parallel particle swarm optimization (PSO) algorithm, which is valuable due to its global search capabilities. Unfortunately, because existing parallel implementations are synchronous (PSPSO), they do not make efficient use of computational resources when a load imbalance exists. In this study, we introduce a parallel asynchronous PSO (PAPSO) algorithm to enhance computational efficiency. The performance of the PAPSO algorithm was compared to that of a PSPSO algorithm in homogeneous and heterogeneous computing environments for small- to medium-scale analytical test problems and a medium-scale biomechanical test problem. For all problems, the robustness and convergence rate of PAPSO were comparable to those of PSPSO. However, the parallel performance of PAPSO was significantly better than that of PSPSO for heterogeneous computing environments or heterogeneous computational tasks. For example, PAPSO was 3.5 times faster than was PSPSO for the biomechanical test problem executed on a heterogeneous cluster with 20 processors. Overall, PAPSO exhibits excellent parallel performance when a large number of processors (more than about 15) is utilized and either (1) heterogeneity exists in the computational task or environment, or (2) the computation-to-communication time ratio is relatively small.
There have been reports in the media and claims in the courts that radiofrequency (RF) emissions from mobile phones are a cause of cancer, and there have been numerous public objections to the siting of mobile phone base antennas because of a fear of cancer. This review summarizes the current state of evidence concerning whether the RF energy used for wireless communication might be carcinogenic. Relevant studies were identified by searching MedLine with a combination of exposure and endpoint terms. This was supplemented by a review of the over 1700 citations assembled by the Institute of Electrical and Electronics Engineers (IEEE) International Committee on Electromagnetic Safety as part of their updating of the IEEE C95.1 RF energy safety guidelines. Where there were multiple studies, preference was given to recent reports, to positive reports of effects and to attempts to confirm such positive reports. Biophysical considerations indicate that there is little theoretical basis for anticipating that RF energy would have significant biological effects at the power levels used by modern mobile phones and their base station antennas. The epidemiological evidence for a causal association between cancer and RF energy is weak and limited. Animal studies have provided no consistent evidence that exposure to RF energy at non-thermal intensities causes or promotes cancer. Extensive in vitro studies have found no consistent evidence of genotoxic potential, but in vitro studies assessing the epigenetic potential of RF energy are limited. Overall, a weight-of-evidence evaluation shows that the current evidence for a causal association between cancer and exposure to RF energy is weak and unconvincing. However, the existing epidemiology is limited and the possibility of epigenetic effects has not been thoroughly evaluated, so that additional research in those areas will be required for a more thorough assessment of the possibility of a causal connection between cancer and the RF energy from mobile telecommunications.
Recent computational and experimental work suggests that functional modules underlie much of cellular physiology and are a useful unit of cellular organization from the perspective of systems biology. Because interactions among modules can give rise to higher-level properties that are essential to cellular function, a complete knowledge of these interactions is necessary for future work in systems biology, including in silico modeling and metabolic engineering. Here we present a computational method for the systematic identification and analysis of functional modules whose activity is coordinated at the level of transcription. We applied this method, Search for Pairwise Interactions (SPIN), to obtain a global view of functional module connectivity in Saccharomyces cerevisiae and to provide insight into the biological mechanisms underlying this coordination. We also examined this global network at higher resolution to obtain detailed information about the interactions of particular module pairs. For instance, our results reveal possible transcriptional coordination of glycolysis and lipid metabolism by the transcription factor Gcr1p, and further suggest that glycolysis and phosphoinositide signaling may regulate each other reciprocally.
This paper presents a work on the retrieval of artworks for color artistry concepts. First we affirm the view that the Query-by-Example paradigm fundamental to the current content-based retrieval systems is able to extend only limited usefulness. We then propose a concept-based retrieval engine based on the generative grammar of elemental concepts methodology. In the latter, the language by which color artistry concepts are communicated in artworks is used to operate semantic searches. The color artistry language is explicated into elemental concepts and the associated generative grammar. The elemental concepts are used to index the artworks, while the generative grammar is used to facilitate post-coordinate expression of color artistry concept queries by using the elemental concepts.