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At least 343 records · Page 19Linked to original sources

Clustered localized pigmented villonodular synovitis.

The localized form of pigmented villonodular synovitis (PVNS) is a rare pathologic entity characterized by limited involvement of the synovium. In the knee joint, which is the most commonly affected joint, the disorder generally presents as a single nodular lesion, or rarely as 2 or 3 multiple nodular lesions into the joint. We report 2 cases of localized PVNS in which multiple nodules were clustered in a limited patella fat pad area. Clustered, multiple nodular lesions in a limited area suggested to us to consider a variant of localized forms.

Adult↗

Great occipital nerve blockade for cluster headache in the emergency department: case report.

A 44-year-old man with a past medical history of episodic cluster headache presented in our ED with complaints of multiple daily cluster headache attacks, with cervico-occipital spreading of pain from May to September 2004. The neurological examination showed no abnormalities as well as brain and spine MRI. Great Occipital Nerve (GON) blockade, with Lidocaine 2% (5 ml) and betamethasone (2 mg), were performed in the right occipital region (ipsilaterally to cluster headache), during attack. GON blockade was effective immediately for the attack and the cluster period resolved after the injection. We suppose that the action of GON blockade may involve the trigemino-cervical complex and we moreover strongly suggest to use GON blockade in emergency departments for cluster headache with cervico-occipital spreading as attack abortive therapy, especially in oxygen and sumatriptan resistant cluster headache attacks, in patients who complaints sumatriptan side-effects or have contraindications to use triptans.

Adult↗

Genomic analysis of regulatory mechanisms governing EPS66A biosynthesis in Streptomyces changanensis HL-66.

Streptomyces changanensis HL-66 produces the α-(1,4)/(1,6)-glucan exopolysaccharide EPS66A, a potent plant immune elicitor with promising applications in plant protection. However, its low native fermentation yield limits large-scale application. To investigate the biosynthetic potential and regulatory mechanisms underlying EPS66A production, the whole genome of HL-66 was sequenced and analyzed. The HL-66 genome is 6.82 Mb in size, with a GC content of 74%, and encodes 6081 predicted functional genes. Among these, 1390 genes were annotated to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, 4187 were assigned to Gene Ontology (GO) terms, and 143 were classified into Clusters of Orthologous Groups (COG) categories. antiSMASH analysis identified 22 secondary metabolite biosynthetic gene clusters, including multiple polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) clusters. Functional analyses revealed that the glycosyltransferase gene (GTy) and the global regulatory gene (bldD) are involved in EPS66A biosynthesis. bldD is involved in morphological development and EPS66A production, whereas GTy specifically regulates EPS66A production without affecting growth or development. In both in vivo and potted-plant experiments, EPS66A (200 μg/mL) significantly reduced the severity of tobacco mosaic virus, apple anthracnose leaf spot, walnut bacterial leaf spot, and jujube anthracnose, achieving control efficacies of 90.21%, 87.95%, 77.41%, and 68.55%, respectively, and outperforming a commercial chitosan oligosaccharide control. These findings provide new insights into the genetic architecture and regulatory mechanisms of EPS66A biosynthesis and support its development as a polysaccharide-based green pesticide.

Streptomyces↗

Ultrastructural characterization of the delimiting membranes of isolated autophagosomes and amphisomes by freeze-fracture electron microscopy.

The delimiting membranes of isolated autophagosomes from rat liver had extremely few transmembrane proteins, as indicated by the paucity of intramembrane particles in freeze-fracture images (about 20 particles/microm2, whereas isolated lysosomes had about 2000 particles/microm2). The autophagosomes also appeared to lack peripheral surface membrane proteins, since attempts to surface-biotinylate intact autophagosomes only yielded biotinylation of proteins from contaminating damaged mitochondria. All the membrane layers of multilamellar autophagosomes were equally particle-poor; the same was true of the autophagosome-forming, sequestering membrane complexes (phagophores). Isolated amphisomes (vacuoles formed by fusion between autophagosomes and endosomes) had more intramembrane particles than the autophagosomes (about 90 particles/microm2), and freeze-fracture images of these organelles frequently showed particle-rich endosomes fusing with particle-poor or particle-free autophagosomes. The appearence of multiple particle clusters suggested that a single autophagic vacuole could undergo multiple fusions with endosomes. Only the outermost membrane of bi- or multilamellar autophagic vacuoles appeared to engage in such fusions.

Animals↗

Modular organization of occipito-temporal pathways: cortical connections between visual area 4 and visual area 2 and posterior inferotemporal ventral area in macaque monkeys.

The modular organization of cortical pathways linking visual area 4 (V4) with occipital visual area 2 (V2) and inferotemporal posterior inferotemporal ventral area (PITv) was investigated through an analysis of the patterns of retrogradely labeled cell bodies after injections of tracers into V4 and PITv. Although cytochrome oxidase or other stains have failed to yield reliable independent anatomical markers for cortical modules beyond V1 and V2, V4 and PITv seem to have modular compartments with specific patterns of cortico-cortical connectivity. Tracer injections of V4 labeled cells in V2 (1) thin stripes exclusively, (2) interstripes exclusively, or (3) specific combinations of interstripe and thin stripe subcompartments. These labeling patterns suggest (1) that there is a complicated organization of inputs to V4, (2) that projections from V2 to V4 display a submodular selectivity, and (3) that projections from V2 to V4 display some degree of cross-stream convergence. Consistent with this framework, extensive regions of PITv provide feedback projections to interstripe-recipient portions of V4, whereas more restricted portions of PITv provide feedback to thin stripe-recipient portions of V4. Similarly, the feedforward projection from V4 to PITv often arose from multiple cell clusters across a wide expanse of V4. When distinguishable fluorescent tracers were injected into two PITv sites separated by 3-5 mm, a variety of projection patterns was observed in V4. In most cases, labeled cells were found in multiple, interdigitating, nonoverlapping clusters of 1-3 mm width, whereas in other cases the two labeled fields were highly intermixed. These results suggest that V4 and PITv contain functional modules that can be characterized by the specific patterns of segregated and convergent projections they receive from lower cortical areas. These specific patterns of intercortical input, in conjunction with intrinsic cortical circuitry, may endow extrastriate cortical neurons with new and more complex receptive field properties.

Animals↗

Automatic clustering of orthologs and inparalogs shared by multiple proteomes.

MOTIVATION: The complete sequencing of many genomes has made it possible to identify orthologous genes descending from a common ancestor. However, reconstruction of evolutionary history over long time periods faces many challenges due to gene duplications and losses. Identification of orthologous groups shared by multiple proteomes therefore becomes a clustering problem in which an optimal compromise between conflicting evidences needs to be found. RESULTS: Here we present a new proteome-scale analysis program called MultiParanoid that can automatically find orthology relationships between proteins in multiple proteomes. The software is an extension of the InParanoid program that identifies orthologs and inparalogs in pairwise proteome comparisons. MultiParanoid applies a clustering algorithm to merge multiple pairwise ortholog groups from InParanoid into multi-species ortholog groups. To avoid outparalogs in the same cluster, MultiParanoid only combines species that share the same last ancestor. To validate the clustering technique, we compared the results to a reference set obtained by manual phylogenetic analysis. We further compared the results to ortholog groups in KOGs and OrthoMCL, which revealed that MultiParanoid produces substantially fewer outparalogs than these resources. AVAILABILITY: MultiParanoid is a freely available standalone program that enables efficient orthology analysis much needed in the post-genomic era. A web-based service providing access to the original datasets, the resulting groups of orthologs, and the source code of the program can be found at http://multiparanoid.cgb.ki.se.

Algorithms↗

A comprehensive approach to clustering of expressed human gene sequence: the sequence tag alignment and consensus knowledge base.

The expressed human genome is being sequenced and analyzed by disparate groups producing disparate data. The majority of the identified coding portion is in the form of expressed sequence tags (ESTs). The need to discover exonic representation and expression forms of full-length cDNAs for each human gene is frustrated by the partial and variable quality nature of this data delivery. A highly redundant human EST data set has been processed into integrated and unified expressed transcript indices that consist of hierarchically organized human transcript consensi reflecting gene expression forms and genetic polymorphism within an index class. The expression index and its intermediate outputs include cleaned transcript sequence, expression, and alignment information and a higher fidelity subset, SANIGENE. The STACK_PACK clustering system has been applied to dbEST release 121598 (GenBank version 110). Sixty-four percent of 1,313, 103 Homo sapiens ESTs are condensed into 143,885 tissue level multiple sequence clusters; linking through clone-ID annotations produces 68,701 total assemblies, such that 81% of the original input set is captured in a STACK multiple sequence or linked cluster. Indexing of alignments by substituent EST accession allows browsing of the data structure and its cross-links to UniGene. STACK metaclusters consolidate a greater number of ESTs by a factor of 1. 86 with respect to the corresponding UniGene build. Fidelity comparison with genome reference sequence AC004106 demonstrates consensus expression clusters that reflect significantly lower spurious repeat sequence content and capture alternate splicing within a whole body index cluster and three STACK v.2.3 tissue-level clusters. Statistics of a staggered release whole body index build of STACK v.2.0 are presented.

Algorithms↗

Multiple turnover transfer of [2Fe2S] clusters by the iron-sulfur cluster assembly scaffold proteins IscU and IscA.

IscU/Isu and IscA/Isa (and related NifU and SufA proteins) have been proposed to serve as molecular scaffolds for preassembly of [FeS] clusters to be used in the biogenesis of iron-sulfur proteins. In vitro studies demonstrating transfer of preformed scaffold-[FeS] complexes to apoprotein acceptors have provided experimental support for this hypothesis, but investigations to date have yielded only single-cluster transfer events. We describe an in vitro assay system that allows for real-time monitoring of [FeS] cluster formation using circular dichroism spectroscopy and use this to investigate de novo [FeS] cluster formation and transfer from Escherichia coli IscU and IscA to apo-ferredoxin. Both IscU and IscA were found to be capable of multiple cycles of [2Fe2S] cluster formation and transfer suggesting that these scaffold proteins are capable of acting "catalytically." Kinetic studies further showed that cluster transfer exhibits Michaelis-Menten behavior indicative of complex formation of holo-IscU and holo-IscA with apoferredoxin and consistent with a direct [FeS] cluster transfer mechanism. Analysis of the dependence of the rate of cluster transfer, however, revealed enhanced efficiency at low ratios of scaffold to acceptor protein suggesting participation of a transient, labile scaffold-[FeS] species in the transfer process.

Carrier Proteins↗

Familial multiple sclerosis: volumetric assessment in clinically symptomatic and asymptomatic individuals.

A genetic basis for clustering of multiple sclerosis (MS) cases, based on studies of MS families, has been proposed for decades. Few reports provide detailed neurological as well as neuroradiological findings on these patients. We report total T2-weighted intracranial lesion volumes on members of three familial MS cohorts: a mother and father with conjugal MS with one affected son and a neurologically normal son and daughter, one pair of monozygotic twin sisters with MS, and a female sibling pair with MS. We hypothesized that asymptomatic siblings in a family with two affected parents and another affected child might demonstrate clinically silent T2-weighted lesions; and that monozygotic twins with MS are more likely to express similar T2-weighted lesion volumes than non-twin sibling pairs. We found clinically silent lesions in unaffected children of the symptomatic parent couple, with a significant difference in total T2 lesion volume between these unaffected siblings and their parents, as well as their affected brother. In our other sibling pairs, T2 lesion volumes were similar between the twins and significantly different in the non-twin pair, despite similar levels of clinical functioning as determined by EDSS scoring. These results suggest that foci of demyelination might be expected in clinically normal offspring of parents with MS, possibly reflecting a genetic predisposition to subsequent development of MS.

Adult↗

A model of frequency discrimination with optimal processing of auditory nerve spike intervals.

This paper investigates phase-lock coding of frequency in the auditory system. One objective with the current model was to construct an optimal central estimation mechanism able to extract frequency directly from spike trains. The model bases estimates of the stimulus frequency on inter-spike intervals of spike trains phase-locked to a pure tone stimulus. Phase-locking is the tendency of spikes to cluster around multiples of the stimulus period. It is assumed that these clusters have Gaussian distributions with variance that depends on the amount of phase-locking. Inter-spike intervals are then noisy measurements of the actual period of the stimulus waveform. The problem of estimating frequency from inter-spike intervals can be solved optimally with a Kalman filter. It is shown that the number of inter-spike intervals observed in the stimulus interval determines frequency discrimination at low frequencies, while the variance of spike clusters dominates at higher frequencies. Timing information in spike intervals is sufficient to account for human frequency discrimination performance up to 5000 Hz. When spikes are available on each stimulus cycle, the model can accurately predict frequency discrimination thresholds as a function of frequency, intensity and duration.

Acoustic Stimulation↗

Sequence-related human proteins cluster by degree of evolutionary conservation.

Gene duplication followed by adaptive evolution is thought to be a central mechanism for the emergence of novel genes. To illuminate the contribution of duplicated protein-coding sequences to the complexity of the human genome, we study the connectivity of pairwise sequence-related human proteins and construct a network (N) of linked protein sequences with shared similarities. We find that (i) the connectivity distribution P (k) for k sequence-related proteins decays as a power law P (k) approximately k(-gamma) with gamma approximately 1.2 , (ii) the top rank of N consists of a single large cluster of proteins ( approximately 70%) , while bottom ranks consist of multiple isolated clusters, and (iii) structural characteristics of N show both a high degree of clustering and an intermediate connectivity ("small-world" features). We gain further insight into structural properties of N by studying the relationship between the connectivity distribution and the phylogenetic conservation of proteins in bacteria, plants, invertebrates, and vertebrates. We find that (iv) the proportion of sequence-related proteins increases with increasing extent of evolutionary conservation. Our results support that small-world network properties constitute a footprint of an evolutionary mechanism and extend the traditional interpretation of protein families.

Chromosome Mapping↗

Wildfire: distributed, Grid-enabled workflow construction and execution.

BACKGROUND: We observe two trends in bioinformatics: (i) analyses are increasing in complexity, often requiring several applications to be run as a workflow; and (ii) multiple CPU clusters and Grids are available to more scientists. The traditional solution to the problem of running workflows across multiple CPUs required programming, often in a scripting language such as perl. Programming places such solutions beyond the reach of many bioinformatics consumers. RESULTS: We present Wildfire, a graphical user interface for constructing and running workflows. Wildfire borrows user interface features from Jemboss and adds a drag-and-drop interface allowing the user to compose EMBOSS (and other) programs into workflows. For execution, Wildfire uses GEL, the underlying workflow execution engine, which can exploit available parallelism on multiple CPU machines including Beowulf-class clusters and Grids. CONCLUSION: Wildfire simplifies the tasks of constructing and executing bioinformatics workflows.

Algorithms↗

Evolution and arrangement of the hsp70 gene cluster in two closely related species of the virilis group of Drosophila.

To investigate the genetic basis of differing thermotolerance in the closely related species Drosophila virilis and Drosophila lummei, which replace one another along a latitudinal cline, we characterized the hsp70 gene cluster in multiple strains of both species. In both species, all hsp70 copies cluster in a single chromosomal locus, 29C1, and each cluster includes two hsp70 genes arranged as an inverted pair, the ancestral condition. The total number of hsp70 copies is maximally seven in the more thermotolerant D. virilis and five in the less tolerant D. lummei, with some strains of each species exhibiting lower copy numbers. Thus, maximum hsp70 copy number corresponds to hsp70 mRNA and Hsp70 protein levels reported previously and the size of heat-induced puffs at 29C1. The nucleotide sequence and spacing of the hsp70 copies are consistent with tandem duplication of the hsp70 genes in a common ancestor of D. virilis and D. lummei followed by loss of hsp70 genes in D. lummei. These and other data for hsp70 in Drosophila suggest that evolutionary adaptation has repeatedly modified hsp70 copy number by several different genetic mechanisms.

Animals↗

The etiology of multiple sclerosis: temporal-spatial clustering indicating two environmental exposures before onset.

Studies in the Orkney and Shetland Islands have demonstrated the highest rates of multiple sclerosis (MS) recorded. Accumulated evidence suggests that an environmental factor is paramount in etiology. The role of an environmental exposure (infectious or toxic) is confirmed in this study by the demonstration in Orkney of clustering of cases in time and space. Lifetime data showed temporal-spatial clustering of MS patients (1) at least 21 years prior to onset, and (2) just prior to onset. Each of the two time clusters occurred on three separate islands. No clustering was seen at birth, by chronological age, or by schooling. Clustering was not demonstrated in Shetland. Previous efforts to demonstrate clustering may have failed because of lack of specificity of the data or inappropriate methodology. These data indicate that not one but two environmental factors play a role in the etiology of MS, representing exposures to two different environmental insults, or exposure twice to the same insult, prior to onset of MS.

Epidemiologic Methods↗

Decentralized formation flying control in a multiple-team hierarchy.

In recent years, formation flying has been recognized as an enabling technology for a variety of mission concepts in both the scientific and defense arenas. Examples of developing missions at NASA include magnetospheric multiscale (MMS), solar imaging radio array (SIRA), and terrestrial planet finder (TPF). For each of these missions, a multiple satellite approach is required in order to accomplish the large-scale geometries imposed by the science objectives. In addition, the paradigm shift of using a multiple satellite cluster rather than a large, monolithic spacecraft has also been motivated by the expected benefits of increased robustness, greater flexibility, and reduced cost. However, the operational costs of monitoring and commanding a fleet of close-orbiting satellites is likely to be unreasonable unless the onboard software is sufficiently autonomous, robust, and scalable to large clusters. This paper presents the prototype of a system that addresses these objectives-a decentralized guidance and control system that is distributed across spacecraft using a multiple team framework. The objective is to divide large clusters into teams of "manageable" size, so that the communication and computation demands driven by N decentralized units are related to the number of satellites in a team rather than the entire cluster. The system is designed to provide a high level of autonomy, to support clusters with large numbers of satellites, to enable the number of spacecraft in the cluster to change post-launch, and to provide for on-orbit software modification. The distributed guidance and control system will be implemented in an object-oriented style using a messaging architecture for networking and threaded applications (MANTA). In this architecture, tasks may be remotely added, removed, or replaced post launch to increase mission flexibility and robustness. This built-in adaptability will allow software modifications to be made on-orbit in a robust manner. The prototype system, which is implemented in Matlab, emulates the object-oriented and message-passing features of the MANTA software. In this paper, the multiple team organization of the cluster is described, and the modular software architecture is presented. The relative dynamics in eccentric reference orbits is reviewed, and families of periodic, relative trajectories are identified, expressed as sets of static geometric parameters. The guidance law design is presented, and an example reconfiguration scenario is used to illustrate the distributed process of assigning geometric goals to the cluster. Next, a decentralized maneuver planning approach is presented that utilizes linear-programming methods to enact reconfiguration and coarse formation keeping maneuvers. Finally, a method for performing online collision avoidance is discussed, and an example is provided to gauge its performance.

Journal Article↗

Folding and organization of a contiguous chromosome region according to the gene distribution pattern in primary genomic sequence.

Specific mammalian genes functionally and dynamically associate together within the nucleus. Yet, how an array of many genes along the chromosome sequence can be spatially organized and folded together is unknown. We investigated the 3D structure of a well-annotated, highly conserved 4.3-Mb region on mouse chromosome 14 that contains four clusters of genes separated by gene "deserts." In nuclei, this region forms multiple, nonrandom "higher order" structures. These structures are based on the gene distribution pattern in primary sequence and are marked by preferential associations among multiple gene clusters. Associating gene clusters represent expressed chromatin, but their aggregation is not simply dependent on ongoing transcription. In chromosomes with aggregated gene clusters, gene deserts preferentially align with the nuclear periphery, providing evidence for chromosomal region architecture by specific associations with functional nuclear domains. Together, these data suggest dynamic, probabilistic 3D folding states for a contiguous megabase-scale chromosomal region, supporting the diverse activities of multiple genes and their conserved primary sequence organization.

Animals↗

Geotoxicology of multiple sclerosis: the Henribourg, Saskatchewan, Cluster Focus. I. The water.

Some childhood-related, geographically-linked factor predisposes towards (or protects against) multiple sclerosis (MS). It is quite plausible that this factor could be one or more chemicals in the environment, and that chemical study of the environment or "focus" of an MS cluster might maximize the chances of detecting such an etiological link. The water chemistry of such a focus (Henribourg, Saskatchewan) was compared with North American norms, and with the chemistry of water from a nearby control area with a near-zero incidence of MS and of childhood homes of MS cases. Overall, the results suggest that an environment predisposing to MS may have a number of water chemistry characteristics such as: relative deficiency of selenium and sulfate, but relative abundance of barium, calcium, chloride, chromium, magnesium, manganese, molybdenum, nitrate plus nitrite, strontium and zinc. Possible explanations for the apparent link between the excess rate of MS and the water geochemistry findings at Henribourg are discussed.

Cohort Studies↗

Geotoxicology of multiple sclerosis: the Henribourg, Saskatchewan, cluster focus. II. The soil.

The childhood-related, geographically-linked factor which predisposes towards (or protects against) multiple sclerosis (MS) could be one or more chemicals in the environment. Chemical study of the environment or "focus" of an MS cluster may maximize the chances of detecting such an etiological link. The soil chemistry of an MS focus (Henribourg, Saskatchewan) was compared with North American norms, and with the chemistry of soil from a nearby control area with a near-zero incidence of MS and of childhood homes of MS cases. A combination of our present results with those reported in the literature suggests that an environment predisposing to MS may have a number of the following chemical characteristics: Calcareous; with soils (but not necessarily waters) generally low in copper, iron and vanadium; with excess lead, nickel and zinc in the upper soil layer; with waters relatively high in chloride, chromium, molybdenum, nitrate plus nitrite, and zinc; but low in selenium and sulfate. One possible causal pathway to explain the apparent link between the excess rate of MS and some of the curious geochemical findings at Henribourg is presented. Many other possible explanations could equally well be advanced, and methods for testing such alternative hypotheses are proposed.

Canada↗