bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model of the early development of diffuse gastric cancer in E‐cadherin mutation carriers and its implications for patient screening
Authors: Carneiro Fátima , Huntsman David G , Smyrk Thomas C , Owen David A , Seruca Raquel , Pharoah Paul , Caldas Carlos , Sobrinho‐Simões Manuel 
Published: April 2004

AbstractHereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome caused, in 30–40% of cases, by germline mutations of the E‐cadherin/CDH1 gene. The presence of clinically undetectable early gastric cancers has been previously reported in ten of ten prophylactic gastrectomies from germline E‐cadherin mutation carriers. In the present study, detailed maps of the distribution of invasive cancers in nine of these ten stomachs were produced and precursor lesions of HDGC searched for. The nine gastrectomy specimens contained from 1 to 161 foci of early diffuse gastric cancer, occupying 0.005–2.96% of the gastric mucosa. Seven specimens contained focal in situ signet ring carcinoma. Pagetoid spread of signet ring cells was observed beneath the epithelial lining of gastric foveolae/glands. Helicobacter pylori organisms and associated pathology were absent from all cases. Two‐dimensional maps of the gastrectomy specimens revealed lesions throughout the gastric mucosa without evidence of antral clustering. The distribution and size of the cancers in the gastrectomy specimens indicate that standard endoscopic screening with random or geographically targeted biopsies is unlikely to provide sufficiently sensitive clinical screening for at‐risk individuals. An in situ precursor of signet ring carcinoma was identified and a model for neoplastic progression in the setting of HDGC is proposed. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A physical reference state unifies the structure‐derived potential of mean force for protein folding and binding
Authors: Liu Song , Zhang Chi , Zhou Hongyi , Zhou Yaoqi 
Published: April 2004

AbstractExtracting knowledge‐based statistical potential from known structures of proteins is proved to be a simple, effective method to obtain an approximate free‐energy function. However, the different compositions of amino acid residues at the core, the surface, and the binding interface of proteins prohibited the establishment of a unified statistical potential for folding and binding despite the fact that the physical basis of the interaction (water‐mediated interaction between amino acids) is the same. Recently, a physical state of ideal gas, rather than a statistically averaged state, has been used as the reference state for extracting the net interaction energy between amino acid residues of monomeric proteins. Here, we find that this monomer‐based potential is more accurate than an existing all‐atom knowledge‐based potential trained with interfacial structures of dimers in distinguishing native complex structures from docking decoys (100% success rate vs. 52% in 21 dimer/trimer decoy sets). It is also more accurate than a recently developed semiphysical empirical free‐energy functional enhanced by an orientation‐dependent hydrogen‐bonding potential in distinguishing native state from Rosetta docking decoys (94% success rate vs. 74% in 31 antibody–antigen and other complexes based on Z score). In addition, the monomer potential achieved a 93% success rate in distinguishing true dimeric interfaces from artificial crystal interfaces. More importantly, without additional parameters, the potential provides an accurate prediction of binding free energy of protein–peptide and protein–protein complexes (a correlation coefficient of 0.87 and a root‐mean‐square deviation of 1.76 kcal/mol with 69 experimental data points). This work marks a significant step toward a unified knowledge‐based potential that quantitatively captures the common physical principle underlying folding and binding. A Web server for academic users, established for the prediction of binding free energy and the energy evaluation of the protein–protein complexes, may be found at http://theory.med.buffalo.edu. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Virtual screening for inhibitors of human aldose reductase
Authors: Kraemer Oliver , Hazemann Isabelle , Podjarny Alberto D. , Klebe Gerhard 
Published: April 2004

AbstractThe inhibition of aldose reductase (AR) provides an interesting strategy to prevent the complications of chronic diabetes. Although a large number of different AR inhibitors are known, very few of these compounds exhibit sufficient efficacy in clinical trials. We performed a virtual screening based on the ultrahigh resolution crystal structure of the inhibitor IDD594 in complex with human AR. AR operates on a large scale of structurally different substrates. To achieve this pronounced promiscuity, the enzyme can adapt rather flexibly to its substrates. Likewise, it has a similar adaptability for the binding of inhibitors. We applied a protocol of consecutive hierarchical filters to search the Available Chemicals Directory. In the first selection step, putative ligands were chosen that exhibit functional groups to anchor the anion‐binding pocket of AR. Subsequently, a pharmacophore model based on the binding geometry of IDD594 and the mapping of the binding pocket in terms of putative “hot spots” of binding was applied as a second consecutive filter. In a third and final filtering step, the remaining candidate molecules were flexibly docked into the binding pocket of IDD594 with FlexX and ranked according to their estimated DrugScore values. Out of 206 compounds selected by this search and complemented by a cluster analysis and visual inspection, 9 compounds were selected and subjected to biological testing. Of these, 6 compounds showed IC50 values in the micromolar range. According to the proposed binding mode, the two inhibitors BTB02809 (IC50 = 2.4 ± 0.5 μM) and JFD00882 (IC50 = 4.1 ± 1.0 μM) both place a nitro group into the hydrophobic specificity pocket of human AR in an orientation coinciding with the position of the bromine atom of IDD594. The interaction of this Br with Thr113 has been identified as a key feature that is responsible for selectivity enhancement. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Probabilistic description of protein alignments for sequences and structures
Authors: Koike Ryotaro , Kinoshita Kengo , Kidera Akinori 
Published: April 2004

AbstractA number of equally optimal alignments inherently exist in the sequence and structure comparisons among proteins. To represent the sub‐optimal alignments systematically, we have developed a method of generating probabilistic alignments for sequences and structures, by which the correspondence between pairs of residues is evaluated in a probabilistic manner. Our method uses the periodic boundary condition to avoid the entropy artifact favoring full‐length matches. In the structure comparison, the environmental effects are incorporated by the mean‐field approximation. We applied this method in comparisons of two pairs of proteins with internal symmetry; the first set were proteins of TIM‐barrel fold and the second were β‐trefoil fold. These pairs are expected to have distinct sub‐optimal alignments suitable for probabilistic description with the periodic boundary. It was shown that the sequence and structure alignments are consistent with each other and that the alignments with the highest probability represent circular permutation. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Prediction of the bonding states of cysteines Using the support vector machines based on multiple feature vectors and cysteine state sequences
Authors: Chen Yu‐Ching , Lin Yeong‐Shin , Lin Chih‐Jen , Hwang Jenn‐Kang 
Published: April 2004

AbstractThe support vector machine (SVM) method is used to predict the bonding states of cysteines. Besides using local descriptors such as the local sequences, we include global information, such as amino acid compositions and the patterns of the states of cysteines (bonded or nonbonded), or cysteine state sequences, of the proteins. We found that SVM based on local sequences or global amino acid compositions yielded similar prediction accuracies for the data set comprising 4136 cysteine‐containing segments extracted from 969 nonhomologous proteins. However, the SVM method based on multiple feature vectors (combining local sequences and global amino acid compositions) significantly improves the prediction accuracy, from 80% to 86%. If coupled with cysteine state sequences, SVM based on multiple feature vectors yields 90% in overall prediction accuracy and a 0.77 Matthews correlation coefficient, around 10% and 22% higher than the corresponding values obtained by SVM based on local sequence information. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Toward the active conformations of rhodopsin and the β2‐adrenergic receptor
Authors: Gouldson Paul R. , Kidley Nathan J. , Bywater Robert P. , Psaroudakis Georgios , Brooks Harry D. , Diaz Constantino , Shire David , Reynolds Christopher A. 
Published: April 2004

AbstractUsing sets of experimental distance restraints, which characterize active or inactive receptor conformations, and the X‐ray crystal structure of the inactive form of bovine rhodopsin as a starting point, we have constructed models of both the active and inactive forms of rhodopsin and the β2‐adrenergic G‐protein coupled receptors (GPCRs). The distance restraints were obtained from published data for site‐directed crosslinking, engineered zinc binding, site‐directed spin‐labeling, IR spectroscopy, and cysteine accessibility studies conducted on class A GPCRs. Molecular dynamics simulations in the presence of either “active” or “inactive” restraints were used to generate two distinguishable receptor models. The process for generating the inactive and active models was validated by the hit rates, yields, and enrichment factors determined for the selection of antagonists in the inactive model and for the selection of agonists in the active model from a set of nonadrenergic GPCR drug‐like ligands in a virtual screen using ligand docking software. The simulation results provide new insights into the relationships observed between selected biochemical data, the crystal structure of rhodopsin, and the structural rearrangements that occur during activation. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Classification of common functional loops of kinase super‐families
Authors: Fernandez‐Fuentes Narcis , Hermoso Antoni , Espadaler Jordi , Querol Enrique , Aviles Francesc X. , Oliva Baldomero 
Published: April 2004

AbstractA structural classification of loops has been obtained from a set of 141 protein structures classified as kinases. A total of 1813 loops was classified into 133 subclasses (9 ββlinks, 15 ββhairpins, 31 α–α, 46 α–β and 32 β–α). Functional information and specific features relating subclasses and function were included in the classification. Functional loops such as the P‐loop (shared by different folds) or the Gly‐rich‐loop, among others, were classified into structural motifs. As a result, a common mechanism of catalysis and substrate binding was proved for most kinases. Additionally, the multiple‐alignment of loop sequences made within each subclass was shown to be useful for comparative modeling of kinase loops. The classification is summarized in a kinase loop database located at http://sbi.imim.es/archki. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Predicting blast overpressures caused by vapor cloud explosions in the vicinity of control rooms
Authors: Van Wingerden Kees , Hansen Olav Roald , Foisselon Pierre 
Published: April 2004

AbstractWhen considering the consequences of gas explosions in petro‐chemical installutions simple methods are used such as TNT‐equivalenc methods and the Multi‐Energy method. These methods howewr, do not take into account directional effects, focusing effects, factors related to the source of the explosion (initial strength, shape) and reflections. FLACS, a 3‐D CFD tool, allows for all factors mentioned including focusing on effects and reflections near buildings.A comparison of the CFD‐method including the two traditional prediction methods for a practical case demonstrates the application areas of the FLACS method as well as the limitations of the traditional methods.
Developing screening risk evalution criteria for facility siting vapor cloud explosion hazards
Authors: Hobbs Douglas H. 
Published: April 2004

AbstractThe building location evaluation methodologies published in API RP 752, Management of Hazards Associated with Location of Process Plant Buildings/CMA Manager's Guide [1] and Guidelines for Evaluating Process Plant Buildings for External Explosions and Fires [2], provide the option of performing a “screening risk analysis”.As with any risk evaluation the results should be judged against a “level of goodness” or evaluation criteria so that meaningful conclusions can be made from the evaluation. These evaluation criteria must be developed in consideration of the hazards evaluated, the extent and purpose of screening risk analysis, and the possible scrutiny the study may receive as part of compliance audits or post‐accident investigations.This paper addresses underlying conceptual issues associated with developing company‐specific evaluation criteria for facility siting risk screening evaluations with regards to vapor cloud explosion (VCE) hazards. The CCPS publication suggests a range of values for individual screening risk evaluation criteria, which companies might consider using as a starting point. The CCPS publication offers, for the first time, a risk measure called “Aggregate Risk” as a tool to distinguish between risks to workers and risks to the public.Despite this guidance, the development and application of risk evaluation criteria remains an emerging science and practice. While risk issues extend well beyond facility siting problems, many companies are currently faced with spending millions of dollars to implement risk reduction measures for process plant buildings. Since all risk cannot be eliminated, a residual risk for individuals and the company, associated with occupying a building, must be identifed to evaluate the appropriateness of building location. To make reasonable and defensible decisions about their buildings, companies are developing and applying risk evaluation criteria.
Emergency relief adequacy for acrylic polymerization processes
Authors: Balchan A. S. , Paquet D. A. , Klein J. A. 
Published: April 2004

AbstractAcrylic polymerizations are highly exothermic processes which must be carefully evaluated to ensure safe manufacture. In particular, failure to remove the heat of reaction can lead to runaway polymerizations, characterized by sudden and rapid increases in reaction rate, temperature, and pressure. If not adequately vented, runaway polymerizations can quickly lead to reactor overpressure, possible vessel rupture, and release of flammable or toxic materials.Because of complex polymerization kinetics and the large number of industrial acrylic polymer processes, practical application of DIERS two‐phase flow methodology for sizing reactor emergency vents required development of a computer model to simulate specific commercial polymerizations. This model is currently used to determine the emergency vent adequacy of reactors prior to manufacture of new resins in existing equipment, as well as to assist in design of new reactor systems. The purpose of this paper is to discuss practical application of DIERS technology for ensuring safe acrylic resin manufacture through use of computer simulation.
Experiments on the propagation of vented dust explosions to connected equipment
Authors: Valiulis John V. , Tamanini Francesco , Zalosh Robert G. 
Published: April 2004

AbstractSome air streams within closed, pneumatic dust handling systems are essentially free of dust. Such is the case within the clean air duct downstream of dust collectors. In the event of a dust explosion in the equipment connected to the dust‐free air ducts, some of the explosion products (dust and flame) will be ejected into the duct. However, because the interior of the duct has no dust to act as fuel prior to the explosion, the distance of explosion propagation (as defined by a flame front) will necessarily be limited.An experimental project is being conducted to study the distance of flame front propagation into a clean duct for dust explosions occurring in a primary volume which is provided with explosion venting. A near‐cubical primary explosion chamber measuring 23 ft3 (0.64 m3) is used. The effect of the most significant process variables on propagation distance is being studied. The process parameters whose effects are being studied are: dust reactivity, vented explosion pressure, explosion vent relief pressure, in‐duct air velocity, and dust concentration. Tests conducted to date in an 8 in. (200 mm) diameter, 89 ft (27 m) long duct have resulted in flame propagation distances in the range of 22‐89ft (7‐27 m).
Pressure refief valve piping failures and fire: Ammonia synthesis loop
Authors: Sutherland Lester E. , Holman Michael , Hansen Don 
Published: April 2004

AbstractThis paper describes a piping failure and fire resulting from inadequate support of an ammonia synthesis loop pressure relief valve, the non‐destructive testing and evaluation of fire‐impinged equipment, and the pipe failure mode. It also addresses support criteria for relief valves and other piping systems illustrating the importance of evaluating both static and dynamic loads.
Safety instrumented system design: Lessons learned
Authors: Gruhn Paul 
Published: April 2004

AbstractEngineering is a bold discipline. Engineers are constantly reaching for new heights, searching for new materials and greater efficiency. Unfortunately, part of that process means we occasionally exceed known boundaries. It is regrettable, but it would appear that human nature requires that we learn the hard way. While this is an obviously painful process, we can learn more from our few mistakes than from our many successes. Our many successes may contain flaws that are never revealed under normal conditions, and we may go on repeating them over and over. It is only when expected conditions are exceeded, and failure is the result, that we learn where we went wrong [12].Valuable lessons can be learned from failures, and there are plenty of examples from industry in general as well as specific details regarding failures of safety control system. For example, the UKHSE (Health and safety Executive) issued a publication in 1995 [2] that reviewed 34 accidents that were directly caused by control and safety system failures. The HSE published the reviews so that engineers could learn from and hopefully not repeat the mistakes discussed in the book. The IEC and ISA standards on this subject, as well as the CCPS Guidelines, are based upon a “Safety Life Cycle” which is a set of steps one should go through in the overall design process in an effort to ensure that nothing falls through the cracks.As responsible engineers, we should not have to learn the hard way. Plants have become too large and the risks have become too great for us to learn by mere trial and error. Because we cannot do a recall on all refineries we need to get things right the first time. We can, however, learn from the mistakes of otherts without re‐inventing the wheel or operating in isolation.
Hazard identification analysis of a hydrogen plant
Authors: Brown A. E. P. , Buchier P. M. 
Published: April 2004

AbstractProcess risk analysis is used in industrial activities to diminish accident potential by the application of prevention or protection techniques to improve process safety. For this purpose, Preliminary Hazard Analysis and HAZOP have been applied to a hydrogen gaseous effluent treatment and purification plant. This plant recovers contaminated gaseous effluent hydrogen from a metallurgical iron powder reduction furnace. Purified hydrogen is recycled to the process. The process safety studies included hazard identification and consequences to materials, equipment and people. The study proposed specific process safety measures and future additional process safety studies.
Explosion hazard analysis for an enclosure partially filled with a flammable gas
Authors: Ogle Russell A. 
Published: April 2004

AbstractThe constant volume explosion of a flammable gas is one of the more common accidental explosions. The explosion pressure at the stoichiometric condition is approximately 50 times greater than the failure pressure of most industrial structures. Observations from accident scenes suggest that some explosions are caused by a quantity of fuel significantly less than the stoichiometric amount required to fill an enclosure.This paper presents a method for analyzing the explosion hazard in an enclosure which is only partially filled with a flammable gas. The method, called the adiabatic mixing model, is based on thermodynamics and can be used to calculate the minimum fuel quantity which will yield a specified explosion pressure. Results are presented for a set of representative fuels and are compared with alternative explosion models.The results demonstrate that catastrophic structural damage can be achieved with a volume of flammable gas which is less than one percent of the enclosure volume. The method can be a useful tool for both hazard analysis and accident investigations.
Avoiding exposure to mercury during inspection and maintenance operations in oil and gas processing
Authors: Mark Wilhelm S. 
Published: April 2004

AbstractExposure to mercury and its compounds poses a potential health risk to workers involved with inspection and maintenance activities in facilities that process hydrocarbons containing significant amounts. The risks of exposure to mercury are often underestimated for a variety of reasons. Foremost is the fact that the exact amount of mercury present in processed petroleum often is not known with certainty. Secondly, the specific quantities of mercury compounds that may be present in hydrocarbon liquids seldom are known at all. Thirdly, monitoring for mercury vapor in work environments is not a routine procedure for many processing facilities. Lastly, mercury toxicity is gradual and produces no immediately apparent impairment that can easily be associated with occupational exposure. Superimposed on the risk issues are several aspects of the chemistry of mercury that make it illusive both to quantitative analysis and to detection in work environments. Tbe combination of the cited factors increases the likelihood that workers who are inadvertently exposed to occupational environments that contain mercury will be adversely affected.