Biomedical subjects

L Chen

Publications and source records attributed to L Chen.

At least 73 records · Page 4Linked to original sources

PubMed2004

Dosimetric evaluation of MRI-based treatment planning for prostate cancer.

The purpose of this study is to evaluate the dosimetric accuracy of MRI-based treatment planning for prostate cancer using a commercial radiotherapy treatment planning system. Three-dimensional conformal plans for 15 prostate patients were generated using the AcQPlan system. For each patient, dose distributions were calculated using patient CT data with and without heterogeneity correction, and using patient MRI data without heterogeneity correction. MR images were post-processed using the gradient distortion correction (GDC) software. The distortion corrected MR images were fused to the corresponding CT for each patient for target and structure delineation. The femoral heads were delineated based on CT. Other anatomic structures relevant to the treatment (i.e., prostate, seminal vesicles, lymph notes, rectum and bladder) were delineated based on MRI. The external contours were drawn separately on CT and MRI. The same internal contours were used in the dose calculation using CT- and MRI-based geometries by directly transferring them between MRI and CT as needed. Treatment plans were evaluated based on maximum dose, isodose distributions and dose-volume histograms. The results confirm previous investigations that there is no clinically significant dose difference between CT-based prostate plans with and without heterogeneity correction. The difference in the target dose between CT- and MRI-based plans using homogeneous geometry was within 2.5%. Our results suggest that MRI-based treatment planning is suitable for radiotherapy of prostate cancer.

Humans↗

PubMed2004

Optimization of combined electron and photon beams for breast cancer.

Recently, intensity-modulated radiation therapy and modulated electron radiotherapy have gathered a growing interest for the treatment of breast and head and neck tumours. In this work, we carried out a study to combine electron and photon beams to achieve differential dose distributions for multiple target volumes simultaneously. A Monte Carlo based treatment planning system was investigated, which consists of a set of software tools to perform accurate dose calculation, treatment optimization, leaf sequencing and plan analysis. We compared breast treatment plans generated using this home-grown optimization and dose calculation software for different treatment techniques. Five different planning techniques have been developed for this study based on a standard photon beam whole breast treatment and an electron beam tumour bed cone down. Technique 1 includes two 6 MV tangential wedged photon beams followed by an anterior boost electron field. Technique 2 includes two 6 MV tangential intensity-modulated photon beams and the same boost electron field. Technique 3 optimizes two intensity-modulated photon beams based on a boost electron field. Technique 4 optimizes two intensity-modulated photon beams and the weight of the boost electron field. Technique 5 combines two intensity-modulated photon beams with an intensity-modulated electron field. Our results show that technique 2 can reduce hot spots both in the breast and the tumour bed compared to technique 1 (dose inhomogeneity is reduced from 34% to 28% for the target). Techniques 3, 4 and 5 can deliver a more homogeneous dose distribution to the target (with dose inhomogeneities for the target of 22%, 20% and 9%, respectively). In many cases techniques 3, 4 and 5 can reduce the dose to the lung and heart. It is concluded that combined photon and electron beam therapy may be advantageous for treating breast cancer compared to conventional treatment techniques using tangential wedged photon beams followed by a boost electron field.

Breast↗

PubMed2004

Monitor unit calculation for Monte Carlo treatment planning.

In this work, we investigate a formalism for monitor unit (MU) calculation in Monte Carlo based treatment planning. By relating MU to dose measured under reference calibration conditions (central axis, depth of dose maximum in water, 10 cm x 10 cm field defined at 100 cm source-to-surface distance) our formalism determines the MU required for a treatment plan based on the prescription dose and Monte Carlo calculated dose distribution. Detailed descriptions and formulae are given for various clinical situations including conventional treatments and advanced techniques such as intensity-modulated radiotherapy (IMRT) and modulated electron radiotherapy (MERT). Analysis is made of the effects of source modelling, beam modifier simulation and patient dose calculation accuracy, all of which are important factors for absolute dose calculations using Monte Carlo simulations. We have tested the formalism through phantom measurements and the predicted MU values were consistent with measured values to within 2%. The formalism has been used for MU calculation and plan comparison for advanced treatment techniques such as MERT, extracranial stereotactic IMRT, MRI-based treatment planning and intensity-modulated laser-proton therapy studies. It is also used for absolute dose calculations using Monte Carlo simulations for treatment verification, which has become part of our comprehensive IMRT quality assurance programme.

Dose-Response Relationship, Radiation↗

PubMed2004

Stereotactic IMRT for prostate cancer: dosimetric impact of multileaf collimator leaf width in the treatment of prostate cancer with IMRT.

The focus of this work is the dosimetric impact of multileaf collimator (MLC) leaf width on the treatment of prostate cancer with intensity-modulated radiation therapy (IMRT). Ten patients with prostate cancer were planned for IMRT delivery using two different MLC leaf widths--4mm and 10mm--representing the Radionics micro-multileaf collimator (mMLC) and Siemens MLC, respectively. Treatment planning was performed on the XKnifeRT2 treatment-planning system (Radionics, Burlington, MA). All beams and optimization parameters were identical for the mMLC and MLC plans. All the plans were normalized to ensure that 95% of the planning target volume (PTV) received 100% of the prescribed dose. The differences in dose distribution between the two different plans were assessed by dose-volume histogram (DVH) analysis of the target and critical organs. We specifically compared the volume of rectum receiving 40 Gy (V40), 50 Gy (V50), 60 Gy (V60), the dose received by 17% and 35% of rectum (D17 and D35), and the maximum dose to 1 cm3 of the rectum for a prescription dose of 74 Gy. For the urinary bladder, the dose received by 25% of bladder (D25), V40, and the maximum dose to 1 cm3 of the organ were recorded. For PTV we compared the maximum dose to the "hottest" 1 cm3 (Dmax1 cm3) and the dose to 99% of the PTV (D99). The dose inhomogeneity in the target, defined as the ratio of the difference in Dmax1 cm3 and D99 to the prescribed dose, was also compared between the two plans. In all cases studied, significant reductions in the volume of rectum receiving doses less than 65 Gy were seen using the mMLC. The average decrease in the volume of the rectum receiving 40 Gy, 50 Gy, and 60 Gy using the mMLC plans was 40.2%, 33.4%, and 17.7%, respectively, with p < 0.0001 for V40 and V50 and p < 0.012 for V60. The mean dose reductions for D17 and D35 for the rectum using the mMLC were 20.4% (p < 0.0001) and 18.3% (p < 0.0002), respectively. There were consistent reductions in all dose indices studied for the bladder. The target dose inhomogeneity was improved in the mMLC plans by an average of 29%. In the high-dose range, there was no significant difference in the dose deposited in the "hottest" 1 cm3 of the rectum between the two plans for all cases (p > 0.78). In conclusion, the use of the mMLC for IMRT of the prostate resulted in significant improvement in the DVH parameters of the prostate and critical organs, which may improve the therapeutic ratio.

Equipment Design↗

PubMed2004

Vasodilator-stimulated phosphoprotein is a substrate for protein kinase C.

Vasodilator-stimulated phosphoprotein (VASP), an actin binding protein localized to areas of focal contacts, is a substrate for the cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP)-dependent protein kinases (PKA, PKG). In this study, we show that serum stimulation of vascular smooth muscle cells (SMCs) induces VASP phosphorylation on Ser157, in a mechanism not dependent on PKA or PKG. We tested the possibility that protein kinase C (PKC), a regulator of cytoskeletal function, is involved. PKC inhibition or down-regulation prevented serum-induced phosphorylation of VASP at Ser157 in rat vascular SMCs. Additionally, recombinant PKCalpha directly phosphorylated Ser157 on VASP. In summary, our data support the hypothesis that PKC phosphorylates VASP and mediates serum-induced VASP regulation.

Animals↗

PubMed2004

Coimmunization of Agaricus blazei Murill extract with hepatitis B virus core protein through DNA vaccine enhances cellular and humoral immune responses.

DNA vaccines induce protective humoral and cell-mediated immune responses in several animal models. Agaricus blazei Murill (ABM) is particularly rich in polysaccharides, and has shown particularly strong results in treating and preventing cancers. The goal of this study was to investigate whether co-immunization of the fungus ABM with hepatitis B virus (HBV) core DNA vaccine could increase the immune responses. Compared with the control mice which received hepatitis B virus core antigen (HBcAg) alone, significant increase in not only the HBcAg-specific antibody response but also T cell proliferation was observed in mice which received HBcAg DNA vaccine plus ABM extract. These results suggest that ABM extract might represent an adjuvant to improve the efficacy of DNA vaccines in vivo.

Adjuvants, Immunologic↗

PubMed2004

Neurotensin depolarizes globus pallidus neurons in rats via neurotensin type-1 receptor.

The globus pallidus is a major component in the indirect pathway of the basal ganglia. There is evidence that neurotensin receptors exist in this nucleus. To determine the electrophysiological effects of neurotensin on pallidal neurons, whole-cell patch-clamp recordings were performed in the acutely prepared brain slices. Under current-clamp recordings, neurotensin at 1 microM depolarized pallidal neurons. Voltage-clamp recordings also showed an inward current induced by neurotensin. The depolarizing effect of neurotensin could be mimicked by the C-terminal fragment, neurotensin (8-13), but not by the N-terminal fragment, neurotensin (1-8). Both SR 142948A, a non-selective neurotensin receptor type-1 and type-2 antagonist, and SR 48692, a selective type-1 receptor antagonist, blocked the depolarizing effect of neurotensin, and which themselves had no effect on membrane potential. Thus, neurotensin type-1 receptors appear to mediate the effect of neurotensin. The depolarization evoked by neurotensin persisted in the presence of tetrodotoxin, ionotropic and metabotropic glutamate and GABA receptor antagonists, indicating that neurotensin excited the pallidal neurons by activating the receptor expressed on the neurons recorded. Current-voltage relationship revealed that both the suppression of a potassium conductance and the activation of a cationic conductance are involved in the neurotensin-induced depolarization. Based on the action of neurotensin in the globus pallidus we hypothesize that alterations of the striatopallidal neurotensin system contribute to symptoms of basal ganglia motor disorders.

Action Potentials↗

PubMed2004

Assessment of liver function during extracorporeal membrane oxygenation in the non-heart beating donor swine.

INTRODUCTION: Although the use of non-heart beating donors (NHBD) could bridge the widening gap between organ demand and supply, its application to liver transplantation is limited due to warm ischemia (WI), biliary tree injury, and inadequate organ assessment. Warm blood reperfusion using extracorporeal membrane oxygenation (ECMO) can be a suitable option to reduce WI in organs from NHBD, allowing one to determine hepatic flow characteristics and bile production and facilitating assessment of organ viability. METHODS: This work evaluates the use of warm blood veno-arterial ECMO reperfusion in NHBD swine. Systemic and hepatic hemodynamics, bile, urine, and mixed venous blood were measured. After baseline data collection, 10 kU heparin was given intravenously followed by 1 g KCl to elicit cardiac arrest (CA). ECMO was started after 30 or 60 minutes of CA and kept running for 120 minutes. RESULTS: One-way repeated measures analysis of variance (ANOVA) with Tukey test analysis was used within a group. Two-way ANOVA was used between groups. ECMO can restore venous SO2 and pH in both groups; the values were close to baseline in the 30-minute CA group. Also, in this group, bile production was > 65% from baseline early during reperfusion and its value was lower in the longer CA group < 55% (P < .001). Aspartate aminotransferase (AST) was doubled at the end of ECMO support in the 60-minute CA group (P < .05). CONCLUSION: In this preheparinized NHBD swine model, ECMO support restores liver perfusion, oxygenation, and bile production after 60 minutes of CA. Quantification and analysis of bile production could be a determinant of liver function during ECMO resuscitation, and it may be a predictor of graft viability before transplantation.

Animals↗

PubMed2004

Improved transduction of primary murine hepatocytes by recombinant adeno-associated virus 2 vectors in vivo.

Adeno-associated virus 2 (AAV) vectors are currently in use in Phase I/II clinical trials for gene therapy of cystic fibrosis and hemophilia B. Although 100% of murine hepatocytes can be targeted by AAV vectors, the transgene expression is limited to approximately 5% of hepatocytes. Since the viral genome is a single-stranded DNA, and single strands of both polarities are encapsidated with equal frequency, it has been suggested that failure to undergo DNA strand-annealing accounts for the lack of efficient transgene expression. We and others, on the other hand, have proposed that failure to undergo viral second-strand DNA synthesis attributes to the observed low efficiency of transgene expression. We have previously documented that a cellular protein, designated FKBP52, when present in phosphorylated forms, inhibits the viral second-strand DNA synthesis, and consequently, limits transgene expression in nonhepatic cells, whereas unphosphorylated forms of FKBP52 have no effect. To further evaluate whether phosphorylated FKBP52 is also involved in regulating AAV-mediated transgene expression in murine hepatocytes, we generated transgenic mice overexpressing the cellular T-cell protein tyrosine phosphatase (TC-PTP) protein, known to catalyze dephosphorylation of FKBP52, as well as mice deficient in FKBP52. We demonstrate here that dephosphorylation of FKBP52 in TC-PTP transgenic (TC-PTP-TG) mice, and removal of FKBP52 in FKBP52-knockout (FKBP52-KO) mice results in efficient transduction of murine hepatocytes following tail-vein injection of recombinant AAV vectors. We also document efficient viral second-strand DNA synthesis in hepatocytes from both TC-PTP-TG and FKBP52-KO mice. Thus, our data strongly support the contention that the viral second-strand DNA synthesis, rather than DNA strand-annealing, is the rate-limiting step in the efficient transduction of hepatocytes, which should have implications in the optimal use of recombinant AAV vectors in human gene therapy.

Animals↗

PubMed2004

Shuffling of Sulfolobus genomes by autonomous and non-autonomous mobile elements.

Each of the sequenced Sulfolobus genomes contains large numbers of putatively mobile elements, both IS elements (insertion sequence elements) and MITEs (miniature inverted-repeat transposable elements). There are 344 in the 3.0 Mb genome of Sulfolobus solfataricus P2 and 95 in the 2.7 Mb genome of Sulfolobus tokodaii. In the former they constitute more than 10% of the genome. Experimental data suggest that transposition of IS elements occurs frequently. Moreover, the gene order between the two organisms differs greatly, indicating that multiple rearrangements have occurred. This has also led to considerable speculation as to how the cells are viable. Recently, a third Sulfolobus genome was completed which contains no IS elements or MITEs. This enabled us to compare the gene orders of the three genomes and provide evidence for mobile element-induced rearrangements of sections of the genomes.

DNA Transposable Elements↗

PubMed2004

Archaeal integrases and mechanisms of gene capture.

Archaeal integrases facilitate the formation of two distinctive types of integrated element within archaeal chromosomes: the SSV type and pNOB8 type. The former carries a smaller N-terminal and a larger C-terminal integrase gene fragment, and the latter an intact integrase gene. All integrated elements overlap tRNA genes that were target sites for integration. It has been demonstrated that SSV (Sulfolobus spindle virus) viruses, carrying an SSV-type integrase gene, and conjugative plasmids, carrying a pNOB8-type integrase, are integrative elements. Two mechanisms have been proposed for stably maintaining an integrated element within archaeal chromosomes. There is also evidence for changes having occurred in the captured integrated elements present in archaeal genomes. Thus we infer that site-specific integration constitutes an important mechanism for horizontal gene transfer and genome evolution.

Archaea↗

PubMed2004

Modelling periodic oscillation of biological systems with multiple timescale networks.

In this paper, we aim to develop a new methodology to model and design periodic oscillators of biological networks, in particular gene regulatory networks with multiple genes, proteins and time delays, by using multiple timescale networks (MTN). Fast reactions constitute a positive feedback-loop network (PFN), while slow reactions consist of a cyclic feedback-loop network (CFN), in MTN. Multiple timescales are exploited to simplify models according to singular perturbation theory. We show that a MTN has no stable equilibrium but stable periodic orbits when certain conditions are satisfied. Specifically, we first prove the basic properties of MTNs with only one PFN, and then generalise the result to MTNs with multiple PFNs. Finally, we design a biologically plausible gene regulatory network by the cI and Lac genes, to demonstrate the theoretical results. Since there is less restriction on the network structure of a MTN, it can be expected to apply to a wide variety of areas on the modelling, analysing and designing of biological systems.

Biological Clocks↗

PubMed2004

Study on the haplotypes of MICA and MICB microsatellite and HLA-B locus in the Guangzhou Han population.

The purpose of this study was to investigate the genetic polymorphisms and haplotypes of microsatellite locus in exon 5 of the MICA gene and intron 1 of the MICB gene and human leukocyte antigen-B (HLA-B) gene based on 106 samples of the Guangzhou Han population through means of polymerase chain reaction and the fluorescent technique (6-FAM). The corresponding haplotype frequencies, linkage disequilibrium values and relative linkage disequilibrium values were estimated based on population data. The results show that the genotype distributions of MICA and MICB microsatellite and HLA-B satisfy the Hardy-Weinberg equilibrium. In total, five alleles of MICA microsatellite locus and 14 alleles of MICB microsatellite locus were observed. MICA A5 was the most common allele (0.2877), whereas A4 was the least common (0.1321). MICB CA14 was the most common allele (0.3255), and CA19 and CA28 were the two least common (0.0047). CA27 was not observed at all. Five kinds of MICA-MICB haplotypes, 18 kinds of MICA-HLA-B haplotypes and 12 kinds of MICB-HLA-B haplotypes occurred at frequencies of more than 1%. The common haplotypes of MICA-MICB, MICA-HLA-B and MICB-HLA-B were A5-CA14, A5.1-CA18, A4-CA26, A9-CA15, A5-B*15(62), A5.1-B*1301/1302, A4-B*1301/1302, A6-B*51, A6-B*4403, A9-B*3802, CA14-B*4601, CA18-B*1301/1302 and CA26-B*1301/1302, and these haplotypes showed strong linkage disequilibrium. The polymorphisms and haplotype distributions of MICA and MICB microsatellite and HLA-B locus in the Guangzhou Han population have their own distinct genetic characteristics. The microsatellite locus of exon 5 of the MICA gene and intron 1 of the MICB gene could therefore be used as genetic markers in the studies of anthropology, gene linkage analysis in genetic diseases, individual identification and paternity testing in forensic medicine.

Asian People↗

PubMed2004

Early up-regulation of Th2 cytokines and late surge of Th1 cytokines in an atopic dermatitis model.

We investigated cytokine profiles in interleukin (IL)-4 transgenic (Tg) mice with a skin inflammatory disease resembling human atopic dermatitis. cDNA microarray revealed that the mRNAs encoding IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-13, tumour necrosis factor (TNF)-alpha, TNF-beta and interferon (IFN)-gamma were up-regulated in the skin of late lesion Tg mice and to a lesser degree in non-lesion Tg mice when compared to those of non-Tg mice. Real time reverse transcription-polymerase chain reaction (RT-PCR) analyses indicated that the cDNA copy numbers of IL-1beta, IL-4, IL-6, IL-10, TNF-alpha and IFN-gamma from the skin of late, early and non-lesions increased significantly compared to non-Tg mice. IL-2 and IL-12p40 cDNA copy numbers were increased significantly in early, but not late, lesions. Interestingly, IL-1beta, IL-3, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-alpha, and IFN-gamma cDNAs were increased significantly the skin of before-onset and/or non-lesion mice. Flow cytometry analyses demonstrated an increased percentage of keratinocytes producing IL-4 as the disease progressed. The percentage of IL-2, IL-4, IL-10 and IFN-gamma-producing T cells and IL-12-producing antigen-presenting cells in skin-draining lymph nodes and inflammatory skin also increased, particularly in mice with late lesion. These results suggest that disease induction is primarily triggered by Th2 cytokines and that Th1, Th2 and non-Th proinflammatory cytokines are all involved in the disease process.

Animals↗

PubMed2004

Endolysosomal processing of exogenous antigen into major histocompatibility complex class I-binding peptides.

An alternative endolysosomal pathway has recently been suggested for the processing of MHC-I-binding peptides, and peptide/MHC-I complexes have been demonstrated in this compartment. However, it remains unclear where in the antigen-presenting cells such peptides are processed, in the endolysosomes themselves or in the proteasomal complex. Here, we have investigated this using monoclonal antibodies specific for the immunodominant SIINFEKL/Kb complex (25-D1) or for the carbohydrate part of Db- or Kb-binding glycopeptides in combination with inhibitors for classical and endolysosomal MHC-I-processing pathways. Alternative processing was detected in both wt and TAP1(-/-) immature DC (iDC) as the expression of SIINFEKL/Kb complexes on the surface of OVA-treated cells in the presence of Brefeldin A (BFA) or lactacystin and their absence in the presence of the lysosomotropic amines ammonium chloride, chloroquine and methylamine. Internalized Db- and Kb-binding glycopeptides, detected with high specificity using an anti-galabiose (Gal2) monoclonal antibody, were found to appear on the cell surface of BFA-treated cells after intracellular MHC-I-binding. Peptide exchange in Kb was demonstrated as the gradual appearance of SIINFEKL/Kb complexes on BFA-treated cells which earlier had been saturated with another Kb-binding peptide. Our data support the presence of a fully functional endolysosomal processing pathway in iDC guided by the chaperone function of MHC-I molecules.

Animals↗

PubMed2004

Clinical implementation of intensity-modulated tangential beam irradiation for breast cancer.

A Monte Carlo based intensity-modulated radiation therapy (IMRT) treatment planning system has been developed and used for breast treatment. An iterative method was used for optimization to generate IMRT plans and a step-and-shoot technique was used for beam delivery. The patient setup and incident beam directions were the same as those for conventional tangential photon treatment. The weights for the opposed beamlets in the two tangential beams were determined first by the doses at the depths of the maximum dose at both sides to minimize hot spots. The intensity of an individual beamlet pair was then optimized based on the dose at the midplane. Fine tuning was made to achieve optimal target dose uniformity and to reduce the dose to the heart when necessary. The final dose calculations were performed using the Monte Carlo method and the plans were verified by phantom measurements. The dose distributions and dose-volume-histograms of IMRT plans were compared with those of conventional plans that were generated using a commercial treatment planning system and recalculated using an in-house Monte Carlo system for the first 25 patients. The dose comparisons showed that the percentage volume receiving more than 95% of the prescription dose (V95) and the percentage volume receiving more than 100% of the prescription dose (V100) for the clinical target volume (CTV) of IMRT plans were about the same as those of conventional plans. The percentage volume receiving more than 105% of the prescription dose (V105) for the CTV was reduced from 23.1% to 7.9% on average. The percentage volume of the lung receiving more than 20 Gy dose (V20 Gy) during the entire treatment was reduced by about 10%. The percentage volume of the heart receiving more than 30 Gy dose (V30 Gy) is reduced from 3.3% to 0.3%. Further studies revealed that a less than 5 degrees change in couch angle and collimator angle at patient setup had no significant effect on the dose coverage of CTV but had significant effect on the dose to the lung and heart. The study on the effect of beam spoiler showed that it increased the dose at the buildup region by 0- 13% that varies with location. The machine output linearity and stability for small monitor unit delivery of Siemens accelerators used for this study was checked and found to be suitable for breast IMRT. The total effect of variations was calculated to be less than 1% for typical breast treatments. The beam delivery time was increased by about 2 min compared with conventional tangential treatments. The whole treatment including patient setup and beam delivery can be completed in a 15 min slot. The IMRT technique has been proven practical for breast treatment clinically. The results showed that tangential IMRT improved the dose homogeneity in the breast and reduced the dose to the lung and heart.

Algorithms↗

PubMed2004

Biological nomenclatures: a source of lexical knowledge and ambiguity.

There has been increased work in developing automated systems that involve natural language processing (NLP) to recognize and extract genomic information from the literature. Recognition and identification of biological entities is a critical step in this process. NLP systems generally rely on nomenclatures and ontological specifications as resources for determining the names of the entities, assigning semantic categories that are consistent with the corresponding ontology, and assignment of identifiers that map to well-defined entities within a particular nomenclature. Although nomenclatures and ontologies are valuable for text processing systems, they were developed to aid researchers and are heterogeneous in structure and semantics. A uniform resource that is automatically generated from diverse resources, and that is designed for NLP purposes would be a useful tool for the field, and would further database interoperability. This paper presents work towards this goal. We have automatically created lexical resources from four model organism nomenclature systems (mouse, fly, worm, and yeast), and have studied performance of the resources within an existing NLP system, GENIES. Using nomenclatures is not straightforward because issues concerning ambiguity, synonymy, and name variations are quite challenging. In this paper we focus mainly on ambiguity. We determined that the number of ambiguous gene names within the individual nomenclatures, across the four nomenclatures, and with general English ranged from 0%-10.18%, 1.187%-20.30%, and 0%-2.49% respectively. When actually processing text, we found the rate of ambiguous occurrences (not counting ambiguities stemming from English words) to range from 2.4%-32.9% depending on the organisms considered.

Artificial Intelligence↗

PubMed2004

The status of structural genomics defined through the analysis of current targets and structures.

Structural genomics--large-scale macromolecular 3-dimenional structure determination--is unique in that major participants report scientific progress on a weekly basis. The target database (TargetDB) maintained by the Protein Data Bank (http://targetdb.pdb.org) reports this progress through the status of each protein sequence (target) under consideration by the major structural genomics centers worldwide. Hence, TargetDB provides a unique opportunity to analyze the potential impact that this major initiative provides to scientists interested in the sequence-structure-function-disease paradigm. Here we report such an analysis with a focus on: (i) temporal characteristics--how is the project doing and what can we expect in the future? (ii) target characteristics--what are the predicted functions of the proteins targeted by structural genomics and how biased is the target set when compared to the PDB and to predictions across complete genomes? (iii) structures solved--what are the characteristics of structures solved thus far and what do they contribute? The analysis required a more extensive database of structure predictions using different methods integrated with data from other sources. This database, associated tools and related data sources are available from http://spam.sdsc.edu.

Computational Biology↗