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PubMed2005

In situ exposures using caged organisms: a multi-compartment approach to detect aquatic toxicity and bioaccumulation.

An in situ toxicity and bioaccumulation assessment approach is described to assess stressor exposure and effects in surface waters (low and high flow), the sediment-water interface, surficial sediments and pore waters (including groundwater upwellings). This approach can be used for exposing species, representing major functional and taxonomic groups. Pimephales promelas, Daphnia magna, Ceriodaphnia dubia, Hyalella azteca, Hyalella sp., Chironomus tentans, Lumbriculus variegatus, Hydra attenuatta, Hexagenia sp. and Baetis tibialis were successfully used to measure effects on survival, growth, feeding, and/or uptake. Stressors identified included chemical toxicants, suspended solids, photo-induced toxicity, indigenous predators, and flow. Responses varied between laboratory and in situ exposures in many cases and were attributed to differing exposure dynamics and sample-processing artifacts. These in situ exposure approaches provide unique assessment information that is complementary to traditional laboratory-based toxicity and bioaccumulation testing and reduce the uncertainties of extrapolating from the laboratory to field responses.

Animals↗

PubMed2006

Structure of a hyper-cleavable monomeric fragment of phage lambda repressor containing the cleavage site region.

The key event in the switch from lysogenic to lytic growth of phage lambda is the self-cleavage of lambda repressor, which is induced by the formation of a RecA-ssDNA-ATP filament at a site of DNA damage. Lambda repressor cleaves itself at the peptide bond between Ala111 and Gly112, but only when bound as a monomer to the RecA-ssDNA-ATP filament. Here we have designed a hyper-cleavable fragment of lambda repressor containing the hinge and C-terminal domain (residues 101-229), in which the monomer-monomer interface is disrupted by two point mutations and a deletion of seven residues at the C terminus. This fragment crystallizes as a monomer and its structure has been determined to 1.8 A resolution. The hinge region, which bears the cleavage site, is folded over the active site of the C-terminal oligomerization domain (CTD) but with the cleavage site flipped out and exposed to solvent. Thus, the structure represents a non-cleavable conformation of the repressor, but one that is poised for cleavage after modest rearrangements that are presumably stabilized by binding to RecA. The structure provides a unique snapshot of lambda repressor in a conformation that sheds light on how its self-cleavage is tempered in the absence of RecA, as well as a framework for interpreting previous genetic and biochemical data concerning the RecA-mediated cleavage reaction.

Bacteriophage lambda↗

PubMed2006

Structural basis of Src tyrosine kinase inhibition with a new class of potent and selective trisubstituted purine-based compounds.

The tyrosine kinase pp60src (Src) is the prototypical member of a family of proteins that participate in a broad array of cellular signal transduction processes, including cell growth, differentiation, survival, adhesion, and migration. Abnormal Src family kinase (SFK) signaling has been linked to several disease states, including osteoporosis and cancer metastases. Src has thus emerged as a molecular target for the discovery of small-molecule inhibitors that regulate Src kinase activity by binding to the ATP pocket within the catalytic domain. Here, we present crystal structures of the kinase domain of Src in complex with two purine-based inhibitors: AP23451, a small-molecule inhibitor designed to inhibit Src-dependent bone resorption, and AP23464, a small-molecule inhibitor designed to inhibit the Src-dependent metastatic spread of cancer. In each case, a trisubstituted purine template core was elaborated using structure-based drug design to yield a potent Src kinase inhibitor. These structures represent early examples of high affinity purine-based Src family kinase-inhibitor complexes, and they provide a detailed view of the specific protein-ligand interactions that lead to potent inhibition of Src. In particular, the 3-hydroxyphenethyl N9 substituent of AP23464 forms unique interactions with the protein that are critical to the picomolar affinity of this compound for Src. The comparison of these new structures with two relevant kinase-inhibitor complexes provides a structural basis for the observed kinase inhibitory selectivity. Further comparisons reveal a concerted induced-fit movement between the N- and C-terminal lobes of the kinase that correlates with the affinity of the ligand. Binding of the most potent inhibitor, AP23464, results in the largest induced-fit movement, which can be directly linked to interactions of the hydrophenethyl N9 substituent with a region at the interface between the two lobes. A less pronounced induced-fit movement is also observed in the Src-AP23451 complex. These new structures illustrate how the combination of structural, computational, and medicinal chemistry can be used to rationalize the process of developing high affinity, selective tyrosine kinase inhibitors as potential therapeutic agents.

Adenine↗

PubMed2003

Soluble extracts from Helicobacter pylori induce dome formation in polarized intestinal epithelial monolayers in a laminin-dependent manner.

Helicobacter pylori colonizes the stomach at the interface between the mucus layer and the apical pole of gastric epithelial cells. A number of secreted and shed products from the bacteria, such as proteins and lipopolysaccharide, are likely to have a role in the pathogenesis at the epithelial level. To determine the physiological response of transporting polarized epithelia to released soluble factors from the bacterium, we used the T84 cell line. Monolayers of T84 cells were exposed to soluble extracts from H. pylori. The extracts induced rapid "dome" formation as well as an immediate decrease in transepithelial electrical resistance. Domes are fluid-filled blister-like structures unique to polarized epithelia. Their formation has been linked to sodium-transporting events as well as to diminished adherence of the cells to the substrate. H. pylori-induced dome formation in T84 monolayers was exacerbated by amiloride and inhibited by ouabain. Furthermore, it was associated with changes in the expression of the laminin binding alpha 6 beta 4 integrin and the 67-kDa laminin receptor. Domes formed primarily on laminin-coated filters, rather than on fibronectin or collagen matrices, and their formation was inhibited by preincubating the bacterial extract with soluble laminin. This effect was specific to H. pylori and independent of the urease, vacA, cagA, and Lewis phenotype of the strains. These data indicate that released elements from H. pylori can alter the physiological balance and integrity of the epithelium in the absence of an underlying immune response.

Animals↗

PubMed1994

A monocysteine approach for probing the structure and interactions of the UmuD protein.

UmuD participates in a variety of protein-protein interactions that appear to be essential for its role in UV mutagenesis. To learn about these interactions, we have initiated an approach based on the construction of a series of monocysteine derivatives of UmuD and have carried out experiments exploring the chemistry of the unique thiol group in each derivative. In vivo and in vitro characterizations indicate that these proteins have an essentially native structure. In proposing a model for the interactions of UmuD in the homodimer, we have made the following assumptions: (i) the conformations of the mutant proteins are similar to that of the wild type, and (ii) the differences in reactivity of the mutant proteins are predominantly due to the positional effects of the single cysteine substitutions. The model proposes the following. The region including the Cys-24-Gly-25 cleavage site, Val-34, and Leu-44 are closer to the interface than the other positions tested as suggested by the relative ease of dimer cross-linking of the monocysteine derivatives at these positions by oxidation with iodine (I2) and by reaction with bis-maleimidohexane. The mutant with a Ser-to-Cys change at position 60 (SC60) is similar in iodoacetate reactivity to the preceding derivatives but cross-links less efficiently by I2 oxidation. This suggests that Ser-60, the site of the putative nucleophile in the cleavage reaction, is located further from the dimer interface or in a cleft region. Both Ser-19, located in the N-terminal fragment of UmuD that is removed by RecA-mediated cleavage, and Ser-67 are probably not as close to the dimer interface, since they are cross-linked more easily with bis-maleimidohexane than with I2. The SC67 mutant phenotype also suggests that this position is less important in RecA-mediated cleavage but more important in a subsequent role for UmuD in mutagenesis. Ala-89, Gln-100, and Asp-126 are probably not particularly solvent accessible and may play important roles in protein architecture.

Bacterial Proteins↗

PubMed1983

Neonatal kidneys: sonographic anatomic correlation.

The ultrasound appearances of the neonatal and adult kidney contrast dramatically. In the normal kidney of a newborn infant, the echogenicity of the renal cortex equals that of the liver. To determine the morphological reasons for the unique and specific sonographic findings, we performed a quantitative anatomic analysis of the components of the kidney on autopsy specimens from four neonates. Our analysis reveals that the glomeruli occupy proportionally a much greater volume of the renal cortex during the first two months of life (18% as compared with 8.6% in the adult). Other anatomic differences include the greater proportional volume of the cellular component of the glomerular tuft in the neonate, and the location of 20% of the loops of Henle within the neonatal cortex rather than in the medulla. The increased number of anatomical structures, and thus interfaces, undoubtedly accounts for the increased echogenicity. The neonatal kidney often demonstrates prominent and hypoechoic renal pyramids. This may be explained by the larger volume of medulla in the neonatal kidney, which results in a ratio of cortex to medulla of 1.64:1 in the neonate as compared with a ratio of 2.59:1 in the adult. There is also a noted lack of echogenicity in the renal sinus region in neonates. Anatomically this is secondary to the absence of renal sinus adipose tissue in the kidney of the neonate.

Adult↗

PubMedDate not supplied

Designing an information technology application for use in community-focused nursing education. Nightingale Tracker Field Test Nurse Team.

Changes in healthcare are highlighting the need for nurse educators to include more community-focused clinical experiences in the nursing curriculum. Because community experiences often require students to travel to clinics and patients' homes at multiple distant sites, nurse educators are concerned about how to best supervise their students and maintain reliable communication links. In light of these needs, FITNE (formerly the Fuld Institute for Technology in Nursing Education) undertook a 3-year information technology research and development project known as the Nightingale Tracker. The design for the Nightingale Tracker included activities aimed toward analyzing the unique communication needs faced by practitioners in community settings. It incorporated multiple forms of user input, including requirements-gathering focus groups, nurse educator surveys, and feedback from two user tests. Subject feedback from using Tracker prototypes in the field was invaluable in the design of the final product.

Community Health Nursing↗

PubMed2003

Cytochemical studies of the neuromuscular systems of the diporpa and juvenile stages of Eudiplozoon nipponicum (Monogenea: diplozoidae).

Using indirect immuno- and enzyme-cytochemical techniques, interfaced with confocal scanning laser microscopy and standard optical microscopy, neuronal pathways have been demonstrated in whole-mount preparations of the unpaired diporpae and freshly paired juvenile stages of Eudiplozoon nipponicum (Monogenea: Diplozoidae). All 3 main classes of neuronal mediators, cholinergic, aminergic and peptidergic, were identified throughout both central and peripheral elements of a well-differentiated orthogonal nervous system. Neural mapping revealed considerable overlap and similarity in staining of the nervous systems of the diporpa and adult worm. The main differences in the diporpa relate to the innervation of the temporary ventral sucker and dorsal papilla, structures which are unique to the larva and which enable fusion between worms but then disappear. Branches from the longitudinal nerve cords innervate these structures and appear to be involved in the process of somatic fusion, probably giving rise to the inter-specimen connections that later link the 2 central nervous systems in paired adult parasites. In the hindbody, there is extensive haptoral innervation associated with the developing clamps and small central hooks. Reactive neuronal components were found associated with the early stages of clamp development prior to connections being made with the extrinsic adductor muscle bundles. The muscle systems of the diporpa and juvenile stages comprise a lattice-like arrangement of circular, longitudinal and diagonal fibres that make up the body wall, together with buccal suckers, haptoral clamps and associated adductor muscles, and the transient ventral sucker. All have obvious importance to diporpae when they migrate over the gill and undertake body contact, torsion and fusion during the process of pairing. Behaviour during the pairing of diporpae is described.

Acetylcholine↗

PubMed1993

Spatial and temporal changes in the expression of fibroglycan (syndecan-2) during mouse embryonic development.

Fibroglycan (syndecan-2) is a member of a family of cell surface heparan sulfate proteoglycans that interact with adhesion molecules, growth factors and a variety of other effector systems that support the shaping, maintenance and repair of an organism. To investigate this apparent redundancy of proteoglycans at the cell surface, we have studied the expression of fibroglycan in the mouse embryo and compared this expression with that of syndecan-1. The characterisation of mouse embryo cDNA clones that crosshybridized to human fibroglycan-cDNA predicted that murine and human fibroglycan were highly similar in structure. Consistently, the analysis of transfectant cells, murine cell lines and embryo extracts indicated that the murine proteoglycan reacted specifically with monoclonal antibody 10H4 developed against the human protein. Fibroglycan, as detected by monoclonal antibody 10H4 in sections of embryonic tissues, occurred exclusively on mesenchymal cells that represented the putative precursors of the hard and connective tissue cells. No fibroglycan was detected in epithelia or in muscle cells. Areas where fibroglycan was particularly abundant were sites of high morphogenetic activity where intense cell-cell and cell-matrix interactions are known to occur (e.g. the epithelial-mesenchymal interfaces, the prechondrogenic and preosteogenic mesenchymal condensations). The expression of fibroglycan was weak in the early embryo, culminated during the morphogenetic phase and at the moment of cell lineage differentiation, and persisted in the perichondrium, periosteum and connective tissue cells. Syndecan-1, in contrast, was primarily detected in epithelia, and transiently in some mesenchymal cells, with mesenchymal localisations that did not or only partially overlap with those of fibroglycan. In situ hybridization analyses confirmed these expression patterns at the transcriptional level, identifying mesenchymal cells as the major source of fibroglycan production. These data indicate that the expression of fibroglycan occurs along unique and developmentally regulated patterns, and suggest that fibroglycan and syndecan-1 may have distinctive functions during tissue morphogenesis and differentiation.

Amino Acid Sequence↗

PubMed1999

Structural and functional basis of plasminogen activation by staphylokinase.

Staphylokinase (Sak), a 15.5-kDa bacterial protein, forms a complex with human plasmin, which in turn activates other plasminogen molecules to plasmin. Three recombinant DNA-based approaches, (i) site directed substitution with alanine, (ii) search for proximity relationships at the complex interface, and (iii) active-site accessibility to protease inhibitors have been used to deduce a coherent docking model of the crystal structure of Sak on the homology-based model of microplasmin (microPli), the serine protease domain of plasmin. Sak binding on microPli is primarily mediated by two surface-exposed loops, loops 174 and 215, at the rim of the active-site cleft, while the binding epitope of Sak on microPli involves several residues located in the flexible NH2-terminal arm and in the five-stranded mixed beta-sheet. Several Sak residues located within the unique alpha-helix and the beta2 strand do not contribute to the binding epitope but are essential to induce plasminogen activating potential in the Sak:microPli complex. These residues form a topologically distinct activation epitope, which, upon binding of Sak to the catalytic domain of microPli, protrudes into a broad groove near the catalytic triad of microPli, thereby generating a competent binding pocket for micro-plasminogen (microPlg), which buries approximately 2500 A of the Sak:microPli complex upon binding. This structural and functional model may serve as a template for the design of improved Sak-derived thrombolytic agents. Following the completion and presentation of the present study, the deduced Sak:microPli:microPlg complex was fully confirmed by X-ray crystallography, which further illustrates the power and potential of the present approach.

Bacteriophages↗

PubMed1987

Codification and evolution of experimentally observed specific recognition sites for restriction enzymes on DNA.

The list of published restriction endonucleases along with their substrates provides an excellent data base for the evaluation of the evolution and codification of the key elements for specific recognition sites on the DNA. In this paper the considerations will be limited to palindromic tetramer-, pentamer-, and hexamer-sequences. It is basically assumed that each base pair within these sequences has to be recognized by directionally unique bidentate hydrogen bonds either within the plane of the base pair or by bridging the appropriate H-bond donor/acceptor groups of the neighbouring bases of the same strand. Thus sequence specificity is mediated by twelve (eight) H-bonds, originating from the protein recognition modules. Besides a pronounced preference for GC base pairs expressed by their high frequency in the most abundant sequences, serving the need of maximal thermodynamic stability of the double helical substrates, it can also be shown that the stacking of consecutive bases within the recognition site sequences plays a major role in shaping the particular DNA/protein interface. Finally it will be demonstrated that the full set of sequences discussed in this paper can readily be derived by stepwise expanding the vocabulary of three simple tetrameric sequences by inserting single base pairs into the centre of a minimal sequence, thus creating all the published pentameric restriction sites, or by inserting/adding two GC base pairs in a palindromic way, thus creating the known multiplicity of hexameric sites.

Base Sequence↗

PubMed2005

Practical applications of usability theory to electronic data collection for clinical trials.

Pharmaceutical and device companies are more frequently considering and using electronic data collection (EDC) to collect patient-reported outcomes such as satisfaction and quality of life for clinical trials. The transition from paper-and-pencil data collection to EDC is not without risks. The unique context of clinical trials presents challenges that, if not addressed, can lead to expensive mistakes. The advantages inherent to EDC can easily be cancelled out without careful attention to the characteristics of the clinical setting. This paper provides an overview of EDC issues specific to clinical trials and health care settings. In particular, it evaluates usability issues associated with methods of EDC and suggests strategies to minimize potential problems. Lessons learned from usability testing in the unique setting of the clinical trial can be applied to other projects to decrease costs, enhance the quality of the data, and minimize time to analysis.

Clinical Trials as Topic↗

PubMed2001

Functional proteomics: examining the effects of hypoxia on the cytotrophoblast protein repertoire.

The outcome of human pregnancy depends on the differentiation of cytotrophoblasts, specialized placental cells that physically connect the embryo/fetus to the mother. As cytotrophoblasts differentiate, they acquire tumor-like characteristics that enable them to invade the uterus. In a novel feedback loop, the increasingly higher levels of oxygen they encounter within the uterine wall influence their differentiation into vascular-like cells. Together, the invasive and cell surface properties of cytotrophoblasts enable them to form vascular connections with uterine blood vessels that divert maternal blood flow to the placenta, a critical hurdle in pregnancy. It is therefore important to understand how cytotrophoblasts respond to changes in oxygen tension. Here we used a proteomics approach, two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) combined with mass spectrometry, to characterize the protein repertoire of first trimester human cytotrophoblasts that were maintained under standard tissue culture conditions (20% O(2)). 2-D PAGE showed a unique protein map as compared to placental fibroblasts and human JEG-3 choriocarcinoma cells. Mass spectrometry allowed the identification of 43 spots on the cytotrophoblast map. Enzymes involved in glycolysis and responses to oxidative stress, as well as the 14-3-3 signaling/adapter proteins, were particularly abundant. Hypoxia in vitro (2% O(2)) produced discrete changes in the expression of a subset of proteins in all the aforementioned functional categories. Together, these data offer new information about the early gestation cytotrophoblast protein repertoire and the generalized mechanisms the cells use to respond to changes in oxygen tension at the maternal-fetal interface.

14-3-3 Proteins↗

PubMed2003

A structural state of the myosin V motor without bound nucleotide.

The myosin superfamily of molecular motors use ATP hydrolysis and actin-activated product release to produce directed movement and force. Although this is generally thought to involve movement of a mechanical lever arm attached to a motor core, the structural details of the rearrangement in myosin that drive the lever arm motion on actin attachment are unknown. Motivated by kinetic evidence that the processive unconventional myosin, myosin V, populates a unique state in the absence of nucleotide and actin, we obtained a 2.0 A structure of a myosin V fragment. Here we reveal a conformation of myosin without bound nucleotide. The nucleotide-binding site has adopted new conformations of the nucleotide-binding elements that reduce the affinity for the nucleotide. The major cleft in the molecule has closed, and the lever arm has assumed a position consistent with that in an actomyosin rigor complex. These changes have been accomplished by relative movements of the subdomains of the molecule, and reveal elements of the structural communication between the actin-binding interface and nucleotide-binding site of myosin that underlie the mechanism of chemo-mechanical transduction.

Actins↗

PubMed2005

Identification of novel prognostic markers in cervical intraepithelial neoplasia using LDMAS (LOH Data Management and Analysis Software).

BACKGROUND: Detection of Loss of Heterozygosity (LOH) is one of the most common molecular applications in the study of human diseases, in particular cancer. The technique is commonly used to examine whether a known tumour suppressor gene is inactivated or to map unknown tumour suppressor gene(s). However, with the increasing number of samples analysed using different software, no tool is currently available to integrate and facilitate the extensive and efficient data retrieval and analyses, such as correlation of LOH data with various clinical data sets. RESULTS: An algorithm to identify prognostic disease markers is devised and implemented as novel software called LDMAS. LDMAS is a software suite designed for data retrieval, management and integrated analysis of the clinico-pathological data and molecular results from independent databases. LDMAS is used in stratification of disease stages according to clinical stage or histological features and correlation of various clinico-pathological features with molecular findings to obtain relevant prognostic markers such as those used in predicting the outcome of cervical intraepithelial neoplasia (CIN). This approach lead to the identification of novel prognostic cervical cancer markers and extraction of useful clinical information such as correlation of Human Papilloma Virus (HPV) status with CIN lesions. CONCLUSIONS: A novel software called LDMAS is implemented and used to extract and identify prognostic disease markers. The software is used to successfully identify 4 novel prognostic markers that can be used to predict the outcome of CIN. LDMAS provides an essential platform for the extraction of useful information from large amount of data generated by LOH studies. LDMAS provides three unique and novel features for LOH analysis: (1) automatic extraction of relevant data from patient records and reports (2) correlation of LOH data with clinico-pathological data and (3) storage of complex data in flexible format. The first feature automates the creation of database of clinically relevant information from huge amount of data, the second feature extracts useful biomedical information such as prognostic markers in CIN and the third feature simplifies the statistical analyses of the data and allows non-statisticians to carry out the analysis. Additionally, LDMAS can be used to extract clinically useful markers from other diseases and interface to high throughput genotyping analysis software such as GDAS used to generate LOH data from Affymetrix GeneChip Mapping arrays.

Algorithms↗

PubMedDate not supplied

Management of prenatal care information: integration of the problem list and clinical comments.

To improve the functionality of our MAternal Record System (MARS), we reviewed the clinical problems entered into the MARS database from approximately 2800 patient records and interviewed representative clinicians about their use of the Clinical Comments and Problem List sections of MARS. Problems were assigned a unique term that corrected for spelling, spacing, synonyms, and abbreviation variations. Analysis of these terms suggested design changes that would increase the number of unique entries into the Problem List, including (1) modifications in the automated problem entry functions within MARS and (2) integration of the Problem List and Clinical Comments sections.

Attitude of Health Personnel↗

PubMed2000

Artificial Molecular Machines.

The miniaturization of components used in the construction of working devices is being pursued currently by the large-downward (top-down) fabrication. This approach, however, which obliges solid-state physicists and electronic engineers to manipulate progressively smaller and smaller pieces of matter, has its intrinsic limitations. An alternative approach is a small-upward (bottom-up) one, starting from the smallest compositions of matter that have distinct shapes and unique properties-namely molecules. In the context of this particular challenge, chemists have been extending the concept of a macroscopic machine to the molecular level. A molecular-level machine can be defined as an assembly of a distinct number of molecular components that are designed to perform machinelike movements (output) as a result of an appropriate external stimulation (input). In common with their macroscopic counterparts, a molecular machine is characterized by 1) the kind of energy input supplied to make it work, 2) the nature of the movements of its component parts, 3) the way in which its operation can be monitored and controlled, 4) the ability to make it repeat its operation in a cyclic fashion, 5) the timescale needed to complete a full cycle of movements, and 6) the purpose of its operation. Undoubtedly, the best energy inputs to make molecular machines work are photons or electrons. Indeed, with appropriately chosen photochemically and electrochemically driven reactions, it is possible to design and synthesize molecular machines that do work. Moreover, the dramatic increase in our fundamental understanding of self-assembly and self-organizational processes in chemical synthesis has aided and abetted the construction of artificial molecular machines through the development of new methods of noncovalent synthesis and the emergence of supramolecular assistance to covalent synthesis as a uniquely powerful synthetic tool. The aim of this review is to present a unified view of the field of molecular machines by focusing on past achievements, present limitations, and future perspectives. After analyzing a few important examples of natural molecular machines, the most significant developments in the field of artificial molecular machines are highlighted. The systems reviewed include 1) chemical rotors, 2) photochemically and electrochemically induced molecular (conformational) rearrangements, and 3) chemically, photochemically, and electrochemically controllable (co-conformational) motions in interlocked molecules (catenanes and rotaxanes), as well as in coordination and supramolecular complexes, including pseudorotaxanes. Artificial molecular machines based on biomolecules and interfacing artificial molecular machines with surfaces and solid supports are amongst some of the cutting-edge topics featured in this review. The extension of the concept of a machine to the molecular level is of interest not only for the sake of basic research, but also for the growth of nanoscience and the subsequent development of nanotechnology.

Journal Article↗

PubMed2001

Assessing portal design skills in the radiation oncology interactive case management examination.

The American Board of Radiology is developing a computerized interactive case management examination to be used to evaluate the clinical skills of radiation oncologists. In the past, these skills have been evaluated by a pencil and paper written examination and an oral examination. With the increasing capabilities of computers, these skills can be easily, and perhaps even better, evaluated digitally. The aim is to develop an examination, which will be based on actual clinical cases, and be interactive so that it better mimics the clinical practice of a radiation oncologist than a written examination. It will also be less labor-intensive and less expensive than an oral examination. One of the most important skills of a radiation oncologist is the ability to design treatment portals that will encompass the entire cancer and yet minimize the irradiation of critical tissues and normal organs. Important parameters for radiation oncologists include the direction of the treatment beam, the size and shape of the portals, and the location of the margins of the field relative to patient anatomy and tumor location. In order to evaluate a physician's ability to design treatment portals, the computer-based examination has the capability to interactively construct field lines. The computer interface allows the candidate to draw field lines on a digitized x-ray image in a manner similar to practice. After the candidate illustrates the field lines, the evaluation of the response must be performed quickly to avoid interrupting the flow of the examination. The answer key is stored as a lossless compressed image. The key contains three regions consisting of (1) the must include region, which contains the tumor; (2) the must-exclude region, which contains tissues that if damaged would affect patient vitality and quality of life; and (3) the envelope of acceptable curves. Each region is assigned a unique byte code. The candidate's response is assigned a fourth byte code. Using basic logic operations, the response is swiftly evaluated. The scoring algorithm scores a candidate's action as correct if his/her drawn area encompasses all of the "must-include region" and is within the "envelope of acceptable curves." It scores a candidate's action as incorrect if his/her drawn area overlaps any part of the "exclude region" and/or exceeds at any point the "envelope of acceptable curves."

Algorithms↗