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1.
Waste Manag Res ; 32(4): 270-96, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24626794

ABSTRACT

Multicriteria spatial decision support systems (MC-SDSS) have emerged as an integration of the geographical information systems (GIS) and multiple criteria decision analysis (MCDA) methods. GIS-based MCDA allows the incorporation of conflicting objectives and decision maker (DM) preferences into spatial decision models. During recent decades, a variety of research articles have been published regarding the implementation of methods and/or tools in a variety of real-world case studies. The article discusses, in detail, the criteria and methods that are implemented in GIS-based landfill siting suitability analysis and especially the exclusionary and non-exclusionary criteria that can be considered when selecting sites for municipal solid waste (MSW) landfills. This paper reviews 36 seminal articles in which the evaluation of candidate landfill sites is conducted using MCDA methods. After a brief description of the main components of a MC-SDSS and the applied decision rules, the review focuses on the criteria incorporated into the decision models. The review provides a comprehensive guide to the landfill siting analysis criteria, providing details regarding the utilization methods, their decision or exclusionary nature and their monotonicity.


Subject(s)
Geographic Information Systems , Refuse Disposal/methods , Solid Waste/analysis , Waste Disposal Facilities , Decision Making , Decision Support Techniques
2.
Neoplasma ; 61(2): 205-12, 2014.
Article in English | MEDLINE | ID: mdl-24299316

ABSTRACT

Presented study was conducted to investigate the prognostic significance of the coexpression of serum interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in breast cancer, by correlating their presence with clinicopathological characteristics indicative of tumor progression and the overall survival of breast cancer patients. One hundred twelve consecutive patients with primary breast cancer were prospectively included and evaluated. Serum concentrations of IL-6 and TNF-a were measured by quantitative sandwich enzyme immunoassay (ELISA). Median split was used to subdivide patients with low or high IL-6 and TNF-a levels. A positive association between the expression of the two cytokines was found. The coexpression of high IL-6 and TNF-α was independently associated with extended lymph node (>3) involvement (aOR, 7.8) and lymphovascular invasion (aOR, 14.1), increasing the prognostic significance of each cytokine separately; it also provided additional prognostic information regarding survival, defining a high-risk subgroup of patients with significantly shorter survival and higher risk of death compared to patients with both cytokines low (aHR, 4.45) and patients with only one cytokine high (aHR, 3.63). Our findings suggest that the coexpression of these two cytokines could be used clinically as a useful tumor marker for the extension and the outcome of the disease.


Subject(s)
Breast Neoplasms/genetics , Interleukin-6/biosynthesis , Survival Analysis , Tumor Necrosis Factor-alpha/biosynthesis , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor , Breast Neoplasms/blood , Breast Neoplasms/pathology , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Interleukin-6/blood , Middle Aged , Neoplasm Staging , Prognosis , Treatment Outcome , Tumor Necrosis Factor-alpha/blood
3.
J Environ Manage ; 125: 41-54, 2013 Aug 15.
Article in English | MEDLINE | ID: mdl-23644589

ABSTRACT

The identification of sites for locating new natural systems for wastewater treatment (NSWT), such as stabilization ponds and constructed wetlands, should combine multiple crucial factors (environmental, design, social and economic), and thus the implementation of multicriteria decision-making (MCDM) methods is required. In addition, the spatial nature of the site selection process necessitates the use of geographic information systems (GISs) because they are unanimously recognized as the most appropriate tool capable of supporting sophisticated spatial decision making. The resulting multicriteria spatial decision support systems (MC-SDSSs) provide a consistent framework for dealing with conflicting objectives while integrating the decision makers' (DMs') preferences in spatially related patterns/problems. A map-based, interactive UTAII implementation is presented, which provides a link between a well-understood decision support method and exploratory geographic visualization. Spatial UTA (S-UTA) is applied in a real case study concerning the ranking of candidate sites for implementing natural systems for wastewater treatment in the Evros-Rodopi prefectures of northeastern Greece. Finally, the obtained results are compared with those derived using other MCDM approaches to evaluate the performance of S-UTA in GIS-based land use suitability analyses.


Subject(s)
Geographic Information Systems , Water Purification/methods , Decision Making
4.
Waste Manag ; 33(5): 1190-206, 2013 May.
Article in English | MEDLINE | ID: mdl-23453354

ABSTRACT

Multicriteria spatial decision support systems (MC-SDSS) have emerged as an integration of geographical information systems (GIS) and multiple criteria decision analysis (MCDA) methods for incorporating conflicting objectives and decision makers' (DMs') preferences into spatial decision models. This article presents a raster-based MC-SDSS that combines the analytic hierarchy process (AHP) and compromise programming methods, such as TOPSIS (technique for order preference by similarity to the ideal solution) and Ideal Point Methods. To the best of our knowledge it is the first time that a synergy of AHP and compromise programming methods is implemented in raster-driven GIS-based landfill suitability analysis. This procedure is supported by a spatial decision support system (SDSS) that was developed within a widely used commercial GIS software package. A real case study in the Thrace region in northeast Greece serves as a guide on how to conduct a suitability analysis for a MSW landfill site with the proposed MC-SDSS. Moreover, the procedure for identifying MSW disposal sites is accomplished by performing four computational models for synthesizing the DMs per criterion preferential system. Based on the case study results, a comparison analysis is performed according to suitability index estimations. According to them Euclidean distance metric and TOPSIS present strong similarities. When compared with Euclidean distance metric, TOPSIS seems to generate results closer to that derived by Manhattan distance metric. The comparison of Chebychev distance metric with all the other approaches revealed the greatest deviations.


Subject(s)
Decision Support Systems, Management , Geographic Information Systems , Refuse Disposal/methods , Expert Systems , Greece , Solid Waste
5.
Acta Haematol ; 126(1): 54-62, 2011.
Article in English | MEDLINE | ID: mdl-21474922

ABSTRACT

BACKGROUND/AIMS: Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) share the same acquired lesion JAK2(V617F) and may exhibit substantial overlap. Variability in JAK activation and allele burden, complemented by host, genetic and non-genetic modifiers, determine the phenotype. The aim of this study was to investigate the presence of the JAK2 mutation in association with the ratio of metallopeptidases inhibitors (TIMPs) to tissue metallopeptidases (MMPs) in MPNs, where inhibitory rather than proteolytic activity in marrow microenvironment appears to predominate. METHODS: 94 patients with polycythemia vera, essential thrombocythemia and primary myelofibrosis, and 102 healthy individuals were evaluated. Allele-specific PCR and RFLP were used to detect JAK2 and genomic status. Serum concentrations of MMP and TIMP were measured by ELISA. The parameters were assessed with covariance analysis, and adjusted for gender, age and co-morbidity. RESULTS: Mutation frequency was 81.91%. Abnormal TIMP/MMP ratios were identified in all three diseases. JAK2 mutation was correlated with significant changes in TIMP concentrations. CONCLUSIONS: Identification of an abnormal TIMP/MMP ratio in all three diseases, regardless of the JAK2 status, indicates invariable marrow remodeling. In this particular group of patients, presence of a JAK2(V617F) mutation, being associated with even higher ratios, appears to be a concurring participant in bone marrow-reforming processes. Additional research may delineate correlates with the JAK2 allelic burden.


Subject(s)
Genes, abl , Janus Kinase 2/genetics , Matrix Metalloproteinases/metabolism , Mutation , Myeloproliferative Disorders/metabolism , Protease Inhibitors/pharmacology , Aged , Female , Humans , Hydrolysis , Male , Matrix Metalloproteinase Inhibitors , Middle Aged , Myeloproliferative Disorders/enzymology , Myeloproliferative Disorders/genetics
6.
Int J Lab Hematol ; 31(6): 665-72, 2009 Dec.
Article in English | MEDLINE | ID: mdl-18691341

ABSTRACT

It is known that the presence of hemoglobin S (HbS) affects the determination of hemoglobin A(2) (HbA(2)) levels in clinical samples. We quantitated this effect using the Menarini HA-8160 analyzer and compared with other instruments (HELENA beta-thal quik column, TOSOH HLC-723G7 and BIORAD Variant II) using the HELENA SAS-MX alkaline gel electrophoresis kit as the reference method. The %HbA(2) values from the HA-8160 analyzer and the alkaline gel electrophoresis show a good linear correlation in the absence of HbS. A strong positive bias in the %HbA(2) values from the HA-8160 is apparent in the presence of HbS in the samples, when compared with the alkaline electrophoresis. The analytical imprecision and bias of the three HPLC instruments are comparable both in the presence and absence of HbS. The manual column method shows a lower bias in the absence of HbS but is more affected when HbS is present in the samples.


Subject(s)
Hemoglobin A2/analysis , Hemoglobin, Sickle/analysis , Automation, Laboratory , Chromatography, High Pressure Liquid , Chromatography, Ion Exchange , Electrophoresis, Capillary , False Positive Reactions , Hemoglobin A2/isolation & purification , Humans , Reagent Kits, Diagnostic , Reproducibility of Results
7.
J BUON ; 13(1): 17-22, 2008.
Article in English | MEDLINE | ID: mdl-18404781

ABSTRACT

The pathways that control cell differentiation and growth are almost always compromised in cancer. Although in the last years there have been major advances in understanding these changes and how they contribute to tumor initiation and growth, the task is far from complete. In this review we discuss some of the factors that are found in major key nodes of the signaling pathways. Included among them are the nuclear factor kappaB (NF-kappaB) that has a quite central role in inflammation, and the mammalian target of rapamycin (mTOR) kinase. Also an eminent role is played by the EGF (epidermal growth factor) and the Snail/Slug family of repressors. Since the expansion of tumor cells depends heavily on nutrient and oxygen supply, it requires the growth of new blood vasculature which is directed by the hypoxia inducible factor (HIF).


Subject(s)
Neoplasms/etiology , Signal Transduction/physiology , Animals , Cell Hypoxia , Epidermal Growth Factor/physiology , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/physiology , Inflammation/complications , NF-kappa B/physiology , Neoplasms/blood supply , Neoplasms/pathology , Protein Kinases/physiology , TOR Serine-Threonine Kinases
8.
Neoplasma ; 55(3): 229-38, 2008.
Article in English | MEDLINE | ID: mdl-18348656

ABSTRACT

The present study was conducted to clarify the predictive and prognostic significance of serum TGF-I(2)1 in breast cancer in relation to Ile655Val single nucleotide polymorphism (SNP) of human epidermal growth factor receptor-2 (HER-2). In a case-control study, 56 consecutive patients with primary breast cancer were prospectively included and evaluated. The control group consisted of 45 healthy women. Serum concentrations of TGF-I(2)1 were measured by quantitative sandwich enzyme immunoassay (ELISA). HER-2 SNP was genotyped using PCR-RFLP method. Serum levels of TGF-I(2)1 were significantly increased in breast cancer patients compared to healthy controls (p<0.001). For the evaluation of the diagnostic significance of serum TGF-I(2)1 the area under the receiver operating characteristic (ROC) curve (AUC) was 0.804, while the optimal cut-off point of 30.86 ng/ml was determined to classify breast cancer patients, which yielded sensitivity of 77%, specificity of 78% and accuracy of 77%. Significantly elevated serum TGF-I(2)1 levels were associated with advanced stages (p=0.023), positive lymph nodes (p=0.019) and postmenopausal status (p=0.031). A marginal trend towards higher TGF-I(2)1 levels was found among patients with Val-containing genotypes compared to homozygous Ile-Ile (p=0.094). In multivariate analysis lymph node metastases (p=0.009) remained the only significant independent determinant of high TGF-I(2)1 levels. With regard to prognostic significance for advanced stages (AUC, 0.704) and lymph node metastasis (AUC, 0.683), when the optimal cut-off value was set at 65.15 pg/ml, the sensitivity was 86% and 67%, the specificity was 60% and 62% and accuracy was 66% and 64%, respectively. Survival was shorter in patients with increased serum TGF-I(2)1 (36 months vs 46 months, p=0.022). Multivariate analysis demonstrated a marginal prognostic significance of serum TGF-I(2)1 for survival (p=0.072). The combination of high TGF-I(2)1 and Val-Val genotype predicts a worse prognosis than high serum TGF-I(2)1 alone. Our findings suggest that serum TGF-I(2)1 is involved in tumor malignancy and lymph node metastasis and could be used clinically as a useful tumor marker for evaluation, the extension and the outcome of the disease. They also provide clinical evidence for a significant association between HER-2 Ile655Val SNP and serum TGF-I(2)1, resulting to more aggressive phenotype of the tumor and poor prognosis.


Subject(s)
Breast Neoplasms/blood , Breast Neoplasms/genetics , Polymorphism, Genetic , Receptor, ErbB-2/genetics , Transforming Growth Factor beta1/blood , Aged , Biomarkers, Tumor/analysis , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Codon , Female , Humans , Lymphatic Metastasis , Middle Aged , Predictive Value of Tests , Prognosis , Survival Rate
9.
Neoplasma ; 55(2): 113-21, 2008.
Article in English | MEDLINE | ID: mdl-18237248

ABSTRACT

HER-2 (human epidermal growth factor receptor-2) proto-oncogene is a member of the EGFR family and plays an important role in the regulation of cell growth, differentiation and survival and is involved in the regulation of normal breast growth and development. Alterations of HER-2 have been associated with carcinogenesis and poor prognosis of breast cancer. The present case-control study was conducted to clarify the predictive and prognostic significance of serum HER-2 protein in breast cancer patients in relation to Ile655Val single nucleotide polymorphism (SNP) of this gene. Fifty-six consecutive patients with primary breast cancer and 45 healthy women were prospectively included and evaluated. Serum levels of HER-2 were significantly increased in breast cancer patients compared to healthy controls (p=0.035). The optimal cut-off point of 1.98 ng/ml, which was determined to classify breast cancer patients, yielded sensitivity of 54%, specificity of 73% and accuracy of 62%. Significantly elevated serum HER-2 levels were associated with lymphovascular invasion (p=0.022), poor differentiation (p=0.011), advanced clinical stages (p=0.001), lymph node metastasis (p=0.011), higher number of positive lymph nodes (p=0.007) and the immunohistochemical overexpression of HER-2 protein (p=0.016). Regarding to HER-2 Ile655Val SNP, Ile-Val and Val-Val genotypes exhibited highly significant serum HER-2 elevation compared to homozygous Ile-Ile (both p<0.001). In multivariate analysis advanced stages (p=0.003) and Val-containing genotypes (p=0.009) remained the two significant independent determinants of high HER-2 levels. Survival analysis demonstrated an independent prognostic significance of homozygous Val-Val genotype for reduced survival (p=0.045), but not of serum HER-2 (p=0.181). Our findings confirm that serum HER-2 could be used clinically as a useful tumor marker for the diagnosis and the progression of breast cancer. Furthermore, they provide clinical evidence that HER-2 Ile655Val SNP does affect serum HER-2 levels and it can be regarded as a predictive biomarker for breast cancer patients with poor prognosis.


Subject(s)
Breast Neoplasms/blood , Breast Neoplasms/genetics , Codon , Polymorphism, Single Nucleotide , Receptor, ErbB-2/blood , Receptor, ErbB-2/genetics , Adult , Aged , Biomarkers, Tumor/blood , Breast Neoplasms/mortality , Female , Humans , Middle Aged , Proto-Oncogene Mas
10.
Neoplasma ; 54(5): 365-73, 2007.
Article in English | MEDLINE | ID: mdl-17918664

ABSTRACT

Alterations of c-erbB-2 (neu or HER-2) proto-oncogene have been associated with carcinogenesis and poor prognosis of breast cancer. A single nucleotide polymorphism (SNP) at codon 655 resulting in a G to A transition (Ile655Val) in the transmembrane domain-coding region of this gene has been associated with an increased risk of breast cancer. This study aims to determine the prevalence of the HER-2 genotype and its association with breast cancer in the Greek Christian and Greek Muslim population of Thrace, Greece. In this case-control study, we genotyped 56 patients (43 Christians and 13 Muslims) with primary breast cancer and 45 healthy women (32 Christians and 13 Muslims) for the Ile655Val polymorphism, with the PCR-RFLP method. The Val allele and the Val-containing genotypes were significantly more frequent in Muslims than in Christians (p=0.020 and p=0.008, respectively). Among the Greek Christian population, a 5-fold and a 3.1-fold increase in risk of breast cancer was associated with the Val-Val genotype and the Ile-Val or Val-Val genotypes (95% CI, 1.3-18.4; p=0.017 and aOR, 3.1; 95% CI, 1.2-8.3; p=0.025; respectively) compared to homozygous Ile-Ile. No significant association was found in the Muslim population. Among the entire cohort, the Val allele confers a modest increase in breast cancer risk (OR, 2.6; 95% CI, 0.9-7.6; p=0.076, for Val-Val and OR, 2.2; 95% CI, 0.9-5.2; p=0.079 for Ile-Val or Val-Val). This effect was even more pronounced in younger women. Among breast cancer patients, invasive carcinomas, low differentiation tumors, advanced stages, positive lymph nodes, high number of lymph nodes and HER-2 overexpression were more frequent in patients with allele Val than those with allele Ile. Our study proposes the allelic imbalance of Ile655Val polymorphism between Greek Christian and Greek Muslim populations of Thrace contributes to the inconsistent association between this SNP and breast cancer risk across these two different ethnic groups. The association of the HER-2 genotype with clinicopathologic characteristics and HER-2 expression may indicate its possible implication on the more aggressive phenotype.


Subject(s)
Allelic Imbalance , Breast Neoplasms/genetics , Codon , Polymorphism, Single Nucleotide , Receptor, ErbB-2/genetics , Adult , Aged , Breast Neoplasms/pathology , Christianity , Ethnicity/genetics , Female , Greece , Humans , Islam , Menopause , Middle Aged , Phenotype , Proto-Oncogene Mas
11.
Presse Med ; 30(21): 1044-8, 2001.
Article in French | MEDLINE | ID: mdl-11471275

ABSTRACT

OBJECTIVE: The most practical method of assessing medication compliance is to ask the patient for a self-report; but the interview question has to be selected and validated. The aim of this work was to select and validate interview questions to be used in a self-administered questionnaire for measurement of medication compliance in hypertensive patients. PATIENTS AND METHODS: In 117 treated hypertensive patients, we compared an interview question to a clinical evaluation of medication compliance. Kappa indices were calculated to test the concordance between interview question and medication compliance. In 184 patients treated for hypertension since at least a year, the validated self-report was compared to a clinical evaluation of medication compliance. RESULTS: Interview questions were not equally sensitive for detection of medication compliance and 6 questions were included in the Compliance Evaluation Test (CET). In 184 patients, we compared the results obtained with CET to clinical evaluation of medication compliance. Values of kappa indices were above 0.5 in "good compliance" when "No" was answered to the 6 items, in "minor noncompliance" when 1 or 2 "Yes" were given, in "noncompliance" when 3 or more "Yes" were given. In this population of hypertensive patients followed in a hypertension clinic, we observed 10% "noncompliance", 24% "minor noncompliance", and 66% "good compliance". CONCLUSION: In clinical practice, interview may be the most useful method of measuring medication compliance. We demonstrated that the compliance evaluation test is validated and may help physicians to face the problem of nonadherence among their hypertensive patients.


Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Patient Compliance , Community Health Centers , Humans , Interviews as Topic , Surveys and Questionnaires
12.
Arch Mal Coeur Vaiss ; 93(8): 953-7, 2000 Aug.
Article in French | MEDLINE | ID: mdl-10989736

ABSTRACT

UNLABELLED: The aim of the 1999 WHO-ISH guidelines is to help the physicians in the management of hypertensive patients. The institution of antihypertensive treatment represents an important stage of this management sometimes at the detriment of lifestyle measures (non pharmacological treatments). OBJECTIVES: To evaluate if the 1999 WHO-ISH guidelines concerning the initiation of antihypertensive treatment are applied in a hypertension clinic. METHODS: Seventy hypertensive subjects never treated by antihypertensive drugs, aged 51 +/- 13 years, managed in daily hospitalization, were included in the study. According to their level of cardiovascular risk, we evaluated the concordance between the 1999 WHO-ISH guidelines and the clinical practice in term of institution of treatment. RESULTS: A concordance of 70% between the 1999 WHO-ISH guidelines and the clinical practice was observed (50/70 subjects) and a discordance in 30% of cases (20/70). Among the discordant subjects, the treatment was instituted in 65% of cases although it was not recommended. In contrast, in the remaining 35% of cases, lifestyle measures have been proposed although an antihypertensive treatment was recommended. The principal determinants of the discordance were the grade 2 of hypertension, the presence of 1 or 2 risk factors and an enhanced cardiovascular risk (> or = 3 risk factors). Neither age, nor gender were an explicative parameter of the observed discordance. CONCLUSIONS: The 1999 WHO-ISH guidelines concerning the initiation of antihypertensive treatment are more often applied in clinical practice. However, in some cases of grade 2 hypertension drug treatment is more often prescribed than recommended by guidelines, and not enough in the presence of numerous cardiovascular risk factors.


Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Practice Guidelines as Topic , Societies, Medical , World Health Organization , Age Factors , Ambulatory Care , Antihypertensive Agents/administration & dosage , Blood Pressure/physiology , Chi-Square Distribution , Decision Making , Female , Health Behavior , Heart Diseases/etiology , Humans , Hypertension/classification , Hypertension/therapy , Life Style , Male , Middle Aged , Risk Factors , Sex Factors
13.
J Biomol Struct Dyn ; 17(4): 617-28, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10698100

ABSTRACT

Crystals of the small ribosomal subunit from Thermus thermophilus diffract to 3A and exhibit reasonable isomorphism and moderate resistance to irradiation. A 5A MIR map of this particle shows a similar shape to the part assigned to this particle within the cryo-EM reconstructions of the whole ribosome and contains regions interpretable either as RNA chains or as protein motifs. To assist phasing at higher resolution we introduced recombinant methods aimed at extensive selenation for MAD phasing. We are focusing on several ribosomal proteins that can be quantitatively detached by chemical means. These proteins can be modified and subsequently reconstituted into depleted ribosomal cores. They also can be used for binding heavy atoms, by incorporating chemically reactive binding sites, such as -SH groups, into them. In parallel we are co-crystallizing the ribosomal particles with tailor made ligands, such as antibiotics or cDNA to which heavy-atoms have been attached or diffuse the latter compounds into already formed crystals.


Subject(s)
Bacterial Proteins/chemistry , Ribosomal Proteins/chemistry , Thermus thermophilus/chemistry , Thermus thermophilus/genetics , Bacterial Proteins/isolation & purification , Binding Sites , Cloning, Molecular , Crystallography, X-Ray , DNA, Complementary/metabolism , Models, Molecular , Nucleic Acid Hybridization , Ribosomal Proteins/isolation & purification
14.
Biol Chem ; 381(11): 1079-87, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11154066

ABSTRACT

The total protein mixture from the 50S subunit (TP-50) of the eubacterium Thermus thermophilus was characterized after blotting onto PVDF membranes from two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and sequencing. The proteins were numbered according to their primary structure similarity with their counterparts from other species. One of them has been marked with an asterisk, namely L*23, because unlike the other known ribosomal proteins it shows a very low degree of homology. A highly acidic 5S rRNA binding protein, TL5, was characterized and compared with the available primary structure information. Proteins L1 and L4 migrate similarly on 2D-PAGE. Protein L4, essential for protein biosynthesis, is N-terminally blocked and shows a strikingly low homology to other L4 proteins. In addition to L4, two other proteins, namely L10 and L11, were found to be N-terminally blocked. In conclusion, 33 proteins from the large subunit were identified, including TL5. Homologs to rpL25 and rpL26 were not found.


Subject(s)
Bacterial Proteins/analysis , Ribosomal Proteins/analysis , Thermus thermophilus/chemistry , Amino Acid Sequence , Animals , Bacterial Proteins/isolation & purification , Molecular Sequence Data , Ribosomal Proteins/isolation & purification , Ribosomes/chemistry
15.
J Struct Biol ; 127(2): 141-51, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10527903

ABSTRACT

Procedures were developed exploiting organometallic clusters and coordination compounds in combination with heavy metal salts for derivatization of ribosomal crystals. These enabled the construction of multiple isomorphous replacement (MIR) and multiple isomorphous replacement combined with anomalous scattering medium-resolution electron density maps for the ribosomal particles that yield the crystals diffracting to the highest resolution, 3 A, of the large subunit from Haloarcula marismortui and the small subunit from Thermus thermophilus. The first steps in the interpretation of the 7. 3-A MIR map of the small subunit were made with the aid of a tetrairidium cluster that was covalently attached to exposed sulfhydryls on the particle's surface prior to crystallization. The positions of these sulfhydryls were localized in difference Fourier maps that were constructed with the MIR phases.


Subject(s)
Microscopy, Electron/methods , Organometallic Compounds/chemistry , Ribosomes/chemistry , Ribosomes/ultrastructure , Animals , Crystallography/methods , Image Processing, Computer-Assisted , Metals, Heavy/chemistry , Molecular Conformation , RNA, Ribosomal/chemistry , RNA, Ribosomal/ultrastructure , Ribosomal Proteins/chemistry , Ribosomal Proteins/ultrastructure
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