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Cleft cluster: a strategy for concurrent correction of multiple secondary clefting deformities.

We have developed a strategy for concurrent correction of multiple secondary clefting deformities based on the model proposed by Henderson and Jackson [1] which combines several cleft-related procedures. We have expanded this concept significantly to include as many as eleven procedures. The selected procedures are dictated individually by patients' needs. The constellation of corrective cleft-related surgeries has been given the name "cleft cluster" in the interest of simplicity. We are reporting on our experience with 85 consecutive patients using this approach. All patients in this series received bone grafting of the alveolar cleft as the primary procedure, plus multiple additional procedures as necessary. None of the patients reported received primary lip or palate surgery by the authors. The average number of procedures performed was 7.2. The average hospitalization was 4.1 days. The patients have been followed from 1 to 7 yrs. The fistula recurrence rate was 8%. Average patient age was 16.8 yrs with a range of 8 to 54 yrs. This approach eliminates multiple hospitalizations and outpatient procedures, allows flexibility to individualize patient care, provides consistent results, and is cost-effective.

Adolescent↗

[The users of centers for AIDS information and prevention in the Comunidad Valenciana, Spain: a study based on cluster analysis].

OBJECTIVE: To measure the usefulness of multiple correspondence analysis (MCA) and cluster analysis applied to the epidemiological research of HIV infection. The specific are to explore the relationships between the different variables that characterize the users of the AIDS Information and Prevention Center (CIPS) and to identify clusters of characteristics which in terms of the attendance to these centers, could be considered similar. METHODS: The clinical history the CIPS in the Valencian region in Spain was used as data source. The target population target were intravenous drug users (IDUSs) attending these centers between 1987 and 1994 (n = 6211). Information about socio-demographic and HIV type I infection-related variables (drug use and sexual behaviour) was collected by means of a semistructured questionnaire. A MCA was carried out to obtain a group of quantitative factors that were used in a cluster analysis. RESULTS: A 44.8% HIV type I prevalence was found. Five factors were detected by MCA that explain 51.14% of the total variability, of which sex, age and the usual sexual partner were the variables best explained. Cluster analysis allowed to describe 5 different subgroups of CIPS users according to their socio-demographics characteristics, risk behaviours and serologic status. It is necessary to highlight the categories 1 and 2, which collect the serologic status and the most relevant characteristics of HIV infection. Category I contains users with a negative serology and characterized by being mainly single adolescent men, with a low educational level; they stated that they have no steady sexual partner, do not share syringes and have been intravenous drug users between 3 and 10 years. They mainly come from the city of Alicante. Category 2 contains mainly people that are HIV positive and older. They also share syringes and have been intravenous drug users for a longer time; they have a higher education level and most of them come from the city of Valencia. CONCLUSIONS: The proposed method of analysis was able to characterise the CIPS users, identifying those socio-demographic variables and risk behaviours that are more related to the serologic status. The applicability of these techniques to epidemiologic studies of HIV type I infection is discussed.

Acquired Immunodeficiency Syndrome↗

Gene teams with relaxed proximity constraint.

Functionally related genes co-evolve, probably due to the strong selection pressure in evolution. Thus we expect that they are present in multiple genomes. Physical proximity among genes, known as gene team, is a very useful concept to discover functionally related genes in multiple genomes. However, there are also many gene sets that do not preserve physical proximity. In this paper, we generalized the gene team model, that looks for gene clusters in a physically clustered form, to multiple genome cases with relaxed constraint. We propose a novel hybrid pattern model that combines the set and the sequential pattern models. Our model searches for gene clusters with and/or without physical proximity constraint. This model is implemented and tested with 97 genomes (120 replicons). The result was analyzed to show the usefulness of our model. Especially, analysis of gene clusters that belong to B. subtilis and E. coli demonstrated that our model predicted many experimentally verified operons and functionally related clusters. Our program is fast enough to provide a sevice on the web at http://platcom. informatics.indiana.edu/platcom/. Users can select any combination of 97 genomes to predict gene teams.

Algorithms↗

Single-particle selection and alignment with heavy atom cluster-antibody conjugates.

A method is proposed for selecting and aligning images of single biological particles to obtain high-resolution structural information by cryoelectron microscopy. The particles will be labeled with multiple heavy atom clusters to permit the precise determination of particle locations and relative orientations even when imaged close to focus with a low electron dose, conditions optimal for recording high-resolution detail. Heavy atom clusters should also allow selection of images free from many kinds of defects, including specimen movement and particle inhomogeneity. Heavy atom clusters may be introduced in a general way by the construction of "adaptor" molecules based on single-chain Fv antibody fragments, consisting of a constant framework region engineered for optimal cluster binding and a variable antigen binding region selected for a specific target. The success of the method depends on the mobility of the heavy atom cluster on the particle, on the precision to which clusters can be located in an image, and on the sufficiency of cluster projections alone to orient and select particles for averaging. The necessary computational algorithms were developed and implemented in simulations that address the feasibility of the method.

Antibodies↗

Discovery of young, isolated planetary mass objects in the final sigma Orionis star cluster.

We present the discovery by optical and near-infrared imaging of an extremely red, low-luminosity population of isolated objects in the young, nearby stellar cluster around the multiple, massive star final sigma Orionis. The proximity (352 parsecs), youth (1 million to 5 million years), and low internal extinction make this cluster an ideal site to explore the substellar domain from the hydrogen mass limit down to a few Jupiter masses. Optical and near-infrared low-resolution spectroscopy of three of these objects confirms the very cool spectral energy distribution (atmospheric effective temperatures of 1700 to 2200 kelvin) expected for cluster members with masses in the range 5 to 15 times that of Jupiter. Like the planets of the solar system, these objects are unable to sustain stable nuclear burning in their interiors, but in contrast they are not bound to stars. This new kind of isolated giant planet, which apparently forms on time scales of less than a few million years, offers a challenge to our understanding of the formation processes of planetary mass objects.

Journal Article↗

Ultrastructure of multiple microtubule initiation sites in mouse neuroblastoma cells.

Morphologically undifferentiated and differentiated mouse neuroblastoma N115 and N18 cells were examined after serial sectioning by electron microscopy. A sizeable percentage of the cells revealed multiple centrioles, usually clustered together in the perinuclear area with 2 preferential locations, i.e. above and below the largest nuclear diameter. These results indicate that the multiple microtubule-organizing centres previously visualized by immunofluorescence microscopy with tubulin antibody in neuroblastoma cells recovering from Colcemid poisoning are most likely in majority related to multiple centrioles. This interpretation is further strengthened by experiments in which cells are first recorded in the fluorescence microscope and then after serial sectioning in the electron microscope. The results show that under optimal conditions immunofluorescence microscopy is able to visualize single centrioles. The possible biological significance of the combined electron and immunofluorescence microscopical results is discussed.

Animals↗

Immune-type diversity in the absence of somatic rearrangement.

Immunoglobulin gene diversity has been characterized to varying degrees in modern representatives of all of the major radiations of cartilaginous fish. A pattern of overall chromosomal relationships of the various types of joined and unjoined Ig gene clusters is suggested in which the essential features are: (a) both Ig heavy and light-chain gene clusters occur on multiple chromosomes, (b) various classes of Ig are interspersed, (c) not all individual gene loci appear to be closely linked (Fig. 2). The cluster-type Ig gene system appears to be a series of (potentially) individually regulated loci analogous in part to the olfactory receptor gene system (BUCK and AXEL 1991) and markedly distinct from Ig loci in other vertebrate groups and TCR genes. Such a system would be ideal for the creation of variation in both form and function in a large number of clusters while preserving or partially preserving specificity in a number of other gene clusters. The full range of joined genes and the relative number of joined genes (as relates to unjoined genes), have yet to be determined. Nevertheless, a number of conclusions can be drawn: (a) four distinct forms of heavy-chain joining have been identified (VDD-J, VD-DJ, V-D-DJ, and VDJ; Fig. 1); (b) light-chain genes, which possess only two recombining elements, can be found in either unjoined (V-J) or joined (VJ) forms (Fig. 1); (c) physical linkage between individual joined and unjoined genes has not been established, although such investigations have not been pursued in a significantly rigorous manner as to rule out this possibility; (d) joined light-chain genes are expressed and can be somatically mutated. Can germline joining be viewed as an ancestral character? The answer to this needs to be considered in the context of an overall system in which the level of structural and functional redundancy is extremely high. Joining is an adaptation that is unique to multicluster gene families. The phenomenon overcomes the possibility of not generating a specific form of a receptor, a major shortcoming of conventional rearranging Ig and TCR gene systems. The limitation of encoding specific receptors is compensated through large numbers of additional gene clusters that retain the capacity to rearrange and generate new specificities. Commitment of a V region to diverse, fixed specificity also is a property of the NITR genes, which although not related closely to Ig in a structural sense, may reflect an analogous phenomena. The possibility that immune-type diversity is achieved in the absence of somatic rearrangement and that remnants of such systems could be operative in immune recognition in contemporary vertebrates is of extraordinary significance in terms of our overall understanding of the relationships between adaptive and innate immune recognition.

Animals↗

An unusual bronchial carcinoid tumor: light and electron microscopy.

An unusual bronchial carcinoid tumor was studied by light and electron microscopy. The tumor cells, which appeared to be monotonously uniform in hematoxylin and eosin stained sections, were found to be morphologically heterogeneous at the ultrastructural level with regard to the size, number, and morphology of the endocrine granules. Presumptive endocrine granules were seen in all tumor cells, but some cells contained only small round granules (2000 A largest diameter), other cells contained large round granules (some with as large a diameter as 1.0 mu), and some cells contained large polymorphic granules. Many of the cells stained positively at the light microscopic level when selective stains for endocrine cells were applied. All types of granules showed argyrophilia at the ultrastructural level. Numerous clusters of endocrine cells were observed in the otherwise normal bronchial and bronchial glandular epithelium. The spectrum of granule morphologies, as seen in the tumor cells, was displayed in cells of the intraepithelial clusters. Some mucous cells and sparsely ciliated cells within these clusters contained argyrophilic granules. Multiple continuities existed between the epithelial endocrine cell clusters and the underlying tumor mass. The intraepithelial clusters represent foci of carcinoma in situ, the genesis of which is discussed.

Bronchi↗

Function of the central domain of streptokinase in substrate plasminogen docking and processing revealed by site-directed mutagenesis.

The possible role of the central beta-domain (residues 151-287) of streptokinase (SK) was probed by site-specifically altering two charged residues at a time to alanines in a region (residues 230-290) previously identified by Peptide Walking to play a key role in plasminogen (PG) activation. These mutants were then screened for altered ability to activate equimolar "partner" human PG, or altered interaction with substrate PG resulting in an overall compromised capability for substrate PG processing. Of the eight initial alanine-linker mutants of SK, one mutant, viz. SK(KK256.257AA) (SK-D1), showed a roughly 20-fold reduction in PG activator activity in comparison to wild-type SK expressed in Escherichia coli (nSK). Five other mutants were as active as nSK, with two [SK(RE248.249AA) and SK(EK281.282AA), referred to as SK(C) and SK(H), respectively] showing specific activities approximately one-half and two-thirds, respectively, that of nSK. Unlike SK(C) and SK(H), however, SK(D1) showed an extended initial delay in the kinetics of PG activation. These features were drastically accentuated when the charges on the two Lys residues at positions 256 and 257 of nSK were reversed, to obtain SK(KK256.257EE) [SK(D2)]. This mutant showed a PG activator activity approximately 10-fold less than that of SK(D1). Remarkably, inclusion of small amounts of human plasmin (PN) in the PG activation reactions of SK(D2) resulted in a dramatic, PN dose-dependent rejuvenation of its PG activation capability, indicating that it required pre-existing PN to form a functional activator since it could not effect active site exposure in partner PG on its own, a conclusion further confirmed by its inability to show a "burst" of p-nitrophenol release in the presence of equimolar human PG and p-nitrophenyl guanidino benzoate. The steady-state kinetic parameters for HPG activation of its 1:1 complex with human PN revealed that although it could form a highly functional activator once "supplied" with a mature active site, the Km for PG was increased nearly eightfold in comparison to that of nSK-PN. SK mutants carrying simultaneous two- and three-site charge-cluster alterations, viz., SK(RE24249AA:EK281.282AA) [SK(CH)], SK(EK272.273AA;EK281.282AA) [SK(FH)], and SK(RE248.249AA;EK272.273AA:EK281.282AA+ ++) [SK(CFH)], showed additive/synergistic influence of multiple charge-cluster mutations on HPG activation when compared to the respective "single-site" mutants, with the "triple-site" mutant [SK(CFH)] showing absolutely no detectable HPG activation ability. Nevertheless, like the other constructs, the double- and triple-charge cluster mutants retained a native like affinity for complexation with partner PG. Their overall structure also, as judged by far-ultraviolet circular dichroism, was closely similar to that of nSK. These results provide the first experimental evidence for a direct assistance by the SK beta-domain in the docking and processing of substrate PG by the activator complex, a facet not readily evident probably because of the flexibility of this domain in the recent X-ray crystal structure of the SK-plasmin light chain complex.

Amino Acid Sequence↗

Prior distributions for the intracluster correlation coefficient, based on multiple previous estimates, and their application in cluster randomized trials.

Numerous estimates for the intracluster correlation coefficient (ICC) are available in research databases and publications. When planning a cluster randomized trial, an anticipated value for the ICC is required; currently, researchers base their choice informally on the magnitude of previous ICC estimates. In this paper, we make use of the wealth of ICC information by formally constructing informative prior distributions, while acknowledging the varying relevance and precision of the estimates available. Typically, for a planned trial in a given clinical setting, multiple relevant ICC estimates are available from each of several completed studies. Our preferred model allows for the imprecision in each ICC estimate around its underlying true value and, separately, allows for the similarity of ICC values from the same study. The relevance of each previous estimate to the planned clinical setting is considered, and estimates corresponding to less relevant outcomes or population types are given less influence. We find that such downweighting can increase the precision of the anticipated ICC. In trial design, the prior distribution constructed allows uncertainty about the ICC to be acknowledged, and we describe how to choose a design that provides adequate power across the range of likely ICC values. Prior information on the ICC can also be incorporated in analysis of the trial data, when taking a Bayesian approach. The methods proposed enable available ICC information to be summarised appropriately by an informative prior distribution, which is of direct practical use in cluster randomized trials.

Bayes Theorem↗

Regulatory analysis of the mouse Hoxb3 gene: multiple elements work in concert to direct temporal and spatial patterns of expression.

The expression pattern of the mouse Hoxb3 gene is exceptionally complex and dynamic compared with that of other members of the Hoxb cluster. There are multiple types of transcripts for Hoxb3 gene, and the anterior boundaries of its expression vary at different stages of development. Two enhancers flanking Hoxb3 on the 3' and 5' sides regulate Hoxb2 and Hoxb4, respectively, and these control regions define the two ends of a 28-kb interval in and around the Hoxb3 locus. To assay the regulatory potential of DNA fragments in this interval we have used transgenic analysis with a lacZ reporter gene to locate cis-elements for directing the dynamic patterns of Hoxb3 expression. Our detailed analysis has identified four new and widely spaced cis-acting regulatory regions that can together account for major aspects of the Hoxb3 expression pattern. Elements Ib, IIIa, and IVb control gene expression in neural and mesodermal tissues; element Va controls mesoderm-specific gene expression. The most anterior neural expression domain of Hoxb3 is controlled by an r5 enhancer (element IVa); element IIIa directs reporter expression in the anterior spinal cord and hindbrain up to r6, and the region A enhancer (in element I) mediates posterior neural expression. Hence, the regulation of segmental expression of Hoxb3 in the hindbrain is different from that of Hoxa3, as two separate enhancer elements contribute to expression in r5 and r6. The mesoderm-specific element (Va) directs reporter expression to prevertebra C1 at 12.5 dpc, which is the anterior limit of paraxial mesoderm expression for Hoxb3. When tested in combinations, these cis-elements appear to work as modules in an additive manner to recapitulate the major endogenous expression patterns of Hoxb3 during embryogenesis. Together our study shows that multiple control elements direct reporter gene expression in diverse tissue-, temporal-, and spatially restricted subset of the endogenous Hoxb3 expression domains and work in concert to control the neural and mesodermal patterns of expression.

Animals↗

Multiple sclerosis in Key West, Florida.

In 1984, a press release by a Miami, Florida, neurologist described a possible cluster of persons with multiple sclerosis in Key West, Florida. The authors examined the cluster using prevalence rates, which are recognized as having a latitudinal gradient for multiple sclerosis, being generally high at high latitudes and low at low latitudes. Case ascertainment showed 32 definite or probable cases among residents of the study area (latitude, 24.5 degrees N) on September 1, 1985, a prevalence rate of 70.1/100,000 population--14 times the rate estimated for this latitude by modeling techniques based on US and international data, 7-44 times the rate for areas at similar latitudes (Mexico City, Mexico; Hawaii; New Orleans, Louisiana; and Charles County, South Carolina), and 2.5 times the expected rate for all US latitudes below 37 degrees N. This finding could not be explained by changes in diagnostic criteria, case ascertainment bias, immigration of people from high-risk areas, an unusual population structure, a large percentage of related cases, or better survival. Prevalent cases (n = 22) were more likely than general population controls (n = 76), matched by sex and 10-year age group, to have: lived longer in Key West, been a nurse, ever owned a Siamese cat, had detectable antibody titers to coxsackievirus A2 and poliovirus 2, and ever visited a local military base (Fleming Key). Key West has an unusually high prevalence of multiple sclerosis that may be related to these risk factors.

Adult↗

Clustering of atoms in a model with multiple thermostats.

We propose a model for a one-dimensional chain of interacting particles in an external periodic potential. In this model the particles have a complex structure treated in a mean-field fashion: particle collisions are inelastic and also each particle is considered as having its own thermostat. We derived the Fokker-Planck equation for this model and demonstrated that the model has a truly equilibrium ground state. When an external dc force is applied to the atoms, the model exhibits a hysteresis even at high temperatures due to the clustering of atoms with the same velocity. Another effect of clustering is phase separation in the steady state when the system splits into regions of immobile atoms ("traffic jams") and regions of running atoms.

Journal Article↗

The gvpA/C cluster of Anabaena flos-aquae has multiple copies of a gene encoding GvpA.

Southern analysis of genomic DNA from Anabaena flos-aquae revealed that the genes encoding the two authenticated protein components of cyanobacterial gas vesicles, GvpA and GvpC, were carried on the same 4.9-kb HindIII restriction fragment. By comparing the hybridization intensities observed when either gvpA- or gvpC-specific oligonucleotides are bound to this HindIII fragment, we calculated that the A. flos-aquae genome contains seven copies of gvpA and a single copy of gvpC. The nucleotide sequence of the longest cloned section of the gvpA/C cluster of A. flos-aquae DNA revealed the presence of four complete copies of gvpA and part of a fifth copy located upstream from a single copy of gvpC; no clones carrying the entire gvpA/C-bearing HindIII fragment were identified. The distribution of Sau3A restriction sites throughout the gvpA/C-bearing genomic HindIII fragment resembled that seen in the cloned portion of the gvpA/C cluster and is consistent with that expected for a cluster containing seven copies of gvpA and one copy of gvpC. The length of transcripts that hybridize to both gvpA and gvpC on Northern blots was consistent with a 7gvpA + 1gvpC transcriptional unit.

Amino Acid Sequence↗

Spearman correlation identifies statistically significant gene expression clusters in spinal cord development and injury.

An important problem in the analysis of large-scale gene expression data is the validation of gene expression clusters. By examining the temporal expression patterns of 74 genes expressed in rat spinal cord under three different experimental conditions, we have found evidence that some genes cluster together under multiple conditions. Using RT-PCR data from spinal cord development and two sets of microarray data from spinal injury, we applied Spearman correlation to identify clusters and to assign P values to pairs of genes with highly similar temporal expression patterns. We found that 15% of genes occurred in statistically significant pairs in all three experimental conditions, providing both statistical and experimental support for the idea that genes that cluster together are co-regulated. In addition, we demonstrated that DNA microarray and RT-PCR data are comparable, and can be combined to confirm gene expression relationships.

Aging↗

A hybrid gene team model and its application to genome analysis.

It is well-known that functionally related genes occur in a physically clustered form, especially operons in bacteria. By leveraging on this fact, there has recently been an interesting problem formulation known as gene team model, which searches for a set of genes that co-occur in a pair of closely related genomes. However, many gene teams, even experimentally verified operons, frequently scatter within other genomes. Thus, the gene team model should be refined to reflect this observation. In this paper, we generalized the gene team model, that looks for gene clusters in a physically clustered form, to multiple genome cases with relaxed constraints. We propose a novel hybrid pattern model that combines the set and the sequential pattern models. Our model searches for gene clusters with and/or without physical proximity constraint. This model is implemented and tested with 97 genomes (120 replicons). The result was analyzed to show the usefulness of our model. We also compared the result from our hybrid model to those from the traditional gene team model. We also show that predicted gene teams can be used for various genome analysis: operon prediction, phylogenetic analysis of organisms, contextual sequence analysis and genome annotation. Our program is fast enough to provide a service on the web at http://platcom.informatics.indiana.edu/platcom/. Users can select any combination of 97 genomes to predict gene teams.

Algorithms↗

Multiple patch-test reactions: a pilot evaluation of a combination approach to visualize patterns of multiple sensitivity in patch-test databases and a proposal for a multiple sensitivity index.

BACKGROUND: The variety of patterns of multiple sensitivity in patch-test data remains poorly defined. Studies addressing this topic have primarily concerned the occurrence of pairs of allergens, and some reports hypothesize a predisposing factor that influences the individual sensitivity of patients to multiple reactions. OBJECTIVE: The aim of this study was to address this topic by reanalyzing a matched data set from two patch-test units in Cleveland, OH, and one unit in Cologne, Germany, focusing on multiple reactions to identical allergens of the standard screening trays over the same 4-year period. METHODS: Based on the statistical FREQ procedure (SAS Institute Inc., Cary, NC), we propose a program for addressing the difficulties in computing and visualizing patterns of multiple sensitivity. Additionally, we propose the "multiple sensitivity index" (MSI) as an absolute measure for characterizing the occurrence of an allergen with others on a selected panel. RESULTS: For the seventeen allergens examined, 131072 possible combinations were evaluated in a total of 2881 patients. Of patients tested, 12.4% had multiple positive patch-test reactions to two to seven allergens. However, because of the small number of patients with the crucial number of possible combinations, no cluster patterns were evident in the three- to seven-allergen combinations. Pairs of allergens most frequently observed were nickel sulfate and potassium dichromate (n = 23), formaldehyde and quaternium-15 (n = 18), and nickel sulfate and formaldehyde (n = 13). We found that nickel sulfate, once again the most frequent sensitizer, occurred in the majority of noncombined cases (MSI = -0.280). CONCLUSION: Larger patch-test databases require evaluation to obtain further evidence of cluster patterns of multiple sensitivity and to validate the MSI.

Allergens↗

Esophageal intelligibility training: back consonants and clusters.

Seven esophageal speakers recorded multiple choice intelligibility lists loaded with words beginning with +BACK consonants and clusters. (A third of the items began with -BACK consonants and clusters). After recording several lists, they played them back and scored them, noting their errors for independent practice. After eight sessions (four weeks) of practice, prepractice and postpractice recordings were randomized and presented to a group of naive listeners. The group scores for the +BACK words improved significantly from prepractice to postpractice (84.1% to 90.6%). The average gain per session for +BACK practice was 0.81%, a result that was in close agreement with prior research. The average gain for the less-practiced -BACK items was 0.46%.

Adult↗