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PubMed2003

Core-hole effects on the ELNES of absorption edges in SrTiO3.

Near-edge structures of absorption edges in electron energy-loss spectra (ELNES) of SrTiO(3) were calculated and compared to experimental inelastic electron scattering data. The goal of this study was to investigate final-state effects on the electronic structure. Two theoretical approaches were applied: density-functional theory with a band-structure supercell method and a real-space multiple-scattering cluster approach. Within both techniques, the Z+1 approximation was used to model the core hole generated by the inelastic scattering process. For the band-structure calculations, supercells of (SrTiO(3))(n)(n=1,4,8,16) composition with three-dimensional periodic boundary conditions were applied. The influence of supercell size and shape on calculated site- and symmetry-projected local densities of unoccupied states is assessed quantitatively. Relevant convergence criteria are the length scale set by the spatial extension of the valence-electron screening cloud around the core hole, and the interaction energy of neighbouring core hole centres. For a sufficiently large supercell size, the Z+1 approximation yields a reasonable description of the local densities of unoccupied states probed by the energy losses of inelastically scattered electrons of the Ti L(3)-, O K- and Sr L(3)-absorption edges. The quantitative equivalence of ELNES information extracted from the multiple-scattering cluster calculations and the band-structure supercell calculations is demonstrated. Discrepancies between theoretical and experimental results are discussed.

Journal Article↗
PubMed2002

Charge localization in collision-induced multiple ionization of van der Waals clusters with highly charged ions.

Charge localization in multiple ionization and fragmentation of small argon clusters is reported. The processes are initiated by interaction of the neutral cluster with highly charged Xe(q+) (5< or =q< or =25). Products are detected by means of multicoincidence time-of-flight methods. A strong dependence of the fragmentation pattern on the Xe charge state q is observed. In particular, we find evidence for formation of multiply charged atomic Ar(r+) fragment ions up to r = 7. Such high charge states have neither been observed in fission of multiply charged van der Waals clusters nor in ion-induced fragmentation of fullerenes or metal clusters. This hints at fundamentally different excitation and fragmentation dynamics.

Journal Article↗
PubMed2004

Meeting recommendations for multiple healthy lifestyle factors. Prevalence, clustering, and predictors among adolescent, adult, and senior health plan members.

BACKGROUND: Whereas much is known about single lifestyle-related health risk factor prevalence and covariates, more research is needed to elucidate the interactions among multiple healthy lifestyle factors and variables that may predict adherence to these factors. Such data may guide both clinical and health policy decision making and person-centered approaches to population health improvement. METHODS: We document the prevalence and cluster patterns of multiple healthy lifestyle factors among a random sample of adolescents (n =616), adults (n =585), and seniors (n =685) from a large Midwestern health plan. Modifiable, lifestyle-related health factors assessed included physical activity, nonsmoking, high-quality diet, and healthy weight for all subjects; adults and seniors were also asked about their alcohol consumption. Second, we sought to identify characteristics associated with the likelihood of meeting recommendations for healthy lifestyle factors. The healthy lifestyle factors sum score was categorized into three levels, that is, 0 to 2, 3, or 4 to 5 healthy lifestyle factors (4 for adolescents), and we used ordinal logistic regression to estimate the odds of meeting each of these criteria from several demographic characteristics and disease states. RESULTS: Overall, only 14.5% of adolescent, adult, and senior health plan members meet recommended guidelines for four common healthy lifestyle factors. Only 10.8% of adults and 12.8% of seniors met all five behavior-related factors. For adolescents, only being nondepressed was associated with an increased likelihood to be in adherence to multiple healthy lifestyle factors (odds ratio [OR]=2.15; p <0.05). For adults, being in the 50- to 64-year-old cohort (OR=1.46, p<0.05), having a college degree (OR=1.65; p <0.05), and having no chronic disease (OR=1.92; p <0.05) were all associated with an increased likelihood to be in adherence to multiple healthy lifestyle factors. For seniors, having a college degree (OR=1.61; p <0.05), was the only variable associated with an increased likelihood to be in adherence to multiple healthy lifestyle factors. CONCLUSIONS: A small proportion of health plan members meet multiple recommended healthy lifestyle guidelines at once. This analysis identifies population subgroups of specific interest and importance based on adherence to multiple healthy lifestyle factors, and predictors for increased likelihood to be in adherence to multiple healthy lifestyle factors. It presents a potentially useful summary measure based on person-centered measures of healthy lifestyle factors. Clinicians may derive meaningful information from analyses that address adherence to multiple healthy lifestyle factors. Health systems administrators may use this information to influence health policy and resource allocation decisions. Further studies are needed to assess the usefulness of this comprehensive lifestyle-related health measure as a metric of progress toward public health goals, or as a clinical metric that conveys information on future health status and directs interventions at the individual level.

Adolescent↗
PubMed2003

Iterative temporal clustering analysis for the detection of multiple response peaks in fMRI.

The temporal clustering analysis (TCA) is a novel and effective technique for obtaining brain activation maps when the timing and location of the activation are completely unknown. Performing the TCA method once can only detect the largest peak of the activation time windows well, if multiple response peaks at the same location of the brain occur. However, this limitation can be removed by using a TCA method in an iterative way in order for the smaller peaks to be detected. Our in vivo fMRI experiments with event-related visual tasks have demonstrated this ability.

Brain Mapping↗
PubMed2006

Evidence of early childhood as the susceptibility period in multiple sclerosis: space-time cluster analysis in a Sardinian population.

The authors analyzed the natural history of multiple sclerosis (MS) before onset to identify the period of susceptibility and exogenous factors that might play a role in causing the disease. Space-time cluster analysis was performed among northern Sardinians, a genetically stable Italian population that showed an increasing risk of MS between 1965 and 1999. Residence changes from birth to clinical onset were recorded for all MS patients with clinical onset between 1965 and 1999 in the province of Sassari. Closeness in space and time was defined as living in the same municipality and differing in year of birth by 1, 2, or 5 years. Analyses were performed for the period from birth to age 25 years or MS onset and in demographic and clinical subgroups. Clustering was substantial in early childhood. Clustering was most marked in the most recent cases, among women, and among patients with early age at onset, a relapsing-remitting course, and in the eastern subarea. No clustering was found when closeness in time was defined as a fixed number of years before onset, which argues against a fixed latency period. Early childhood seemed to be a period of increased susceptibility to MS. This evidence and the increasing incidence of MS in northern Sardinia are compatible with a change in environmental exposure.

Adolescent↗
PubMed1999

Susceptibility to multiple sclerosis mediated by HLA-DRB1 is influenced by a second gene telomeric of the TNF cluster.

Susceptibility to multiple sclerosis (MS) is clearly associated with human leukocyte antigen (HLA)-DRB1*1501, but some studies show associations with HLA-B7 and -B18. These are often co-expressed with DRB1*1501 in the ancestral haplotypes (AH) denoted 7.1 (HLA-A3, B7, tumor necrosis factor [TNF]a11b4, DRB1*1501) and 18.1 (HLA-A25, B18, TNFa10b4, DRB 1*1501). Here we present a systematic study of 218 patients and 274 controls typed at all standard class II and TNF microsatellite loci, and a novel non-synonymous polymorphism in the central major histocompatibility complex gene, inhibitor of kappa B-like protein (IKBL). The C allele at IKBL+738 is only found on the 7.1 haplotype. HLA-DRB1*1501 was associated with disease, as expected. When subjects expressing DRB 1*501 were analyzed separately, TNFa11b4 and IKBL+738C were less common in the patients and, hence, mark an allele that mediates resistance which lies telomeric of IKBL. TNFa10b4 and TNFa1b5 were more common in DRB1*1501 patients than in controls. These alleles have been associated with the 18.1 and 18.2 AH, respectively. Since no component of these haplotypes was an independent risk factor in this study, it appears likely that a gene linked to TNFa10b4 and TNFa1b5 modifies the effect of the susceptibility locus marked by HLA-DRB1*1501. Potential candidate genes telomeric of the TNF cluster are discussed.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

Clustering in small networks of excitatory neurons with heterogeneous coupling strengths.

Excitatory coupling with a slow rise time destabilizes synchrony between coupled neurons. Thus, the fully synchronous state is usually unstable in networks of excitatory neurons. Phase-clustered states, in which neurons are divided into multiple synchronized clusters, have also been found unstable in numerical studies of excitatory networks in the presence of noise. The question arises as to whether synchrony is possible in networks of neurons coupled through slow, excitatory synapses. In this paper, we show that robust, synchronous clustered states can occur in such networks. The effects of non-uniform distributions of coupling strengths are explored. Conditions for the existence and stability of clustered states are derived analytically. The analysis shows that a multi-cluster state can be stable in excitatory networks if the overall interactions between neurons in different clusters are stabilizing and strong enough to counter-act the destabilizing interactions between neurons within each cluster. When heterogeneity in the coupling strengths strengthens the stabilizing inter-cluster interactions and/or weakens the destabilizing in-cluster interactions, robust clustered states can occur in excitatory networks of all known model neurons. Numerical simulations were carried out to support the analytical results.

Cluster Analysis↗
PubMed2002

Multiple ionization of atom clusters by intense soft X-rays from a free-electron laser.

Intense radiation from lasers has opened up many new areas of research in physics and chemistry, and has revolutionized optical technology. So far, most work in the field of nonlinear processes has been restricted to infrared, visible and ultraviolet light, although progress in the development of X-ray lasers has been made recently. With the advent of a free-electron laser in the soft-X-ray regime below 100 nm wavelength, a new light source is now available for experiments with intense, short-wavelength radiation that could be used to obtain deeper insights into the structure of matter. Other free-electron sources with even shorter wavelengths are planned for the future. Here we present initial results from a study of the interaction of soft X-ray radiation, generated by a free-electron laser, with Xe atoms and clusters. We find that, whereas Xe atoms become only singly ionized by the absorption of single photons, absorption in clusters is strongly enhanced. On average, each atom in large clusters absorbs up to 400 eV, corresponding to 30 photons. We suggest that the clusters are heated up and electrons are emitted after acquiring sufficient energy. The clusters finally disintegrate completely by Coulomb explosion.

Journal Article↗
PubMed2003

Agrin is a chimeric proteoglycan with the attachment sites for heparan sulfate/chondroitin sulfate located in two multiple serine-glycine clusters.

Agrin is a large extracellular matrix protein that plays a key role in the formation and maintenance of the vertebrate neuromuscular junction. The amino acid sequence of agrin encodes a protein with a molecular size of 220 kDa, whereas SDS-PAGE shows a diffuse band around 400 kDa. Further studies showed that agrin is highly glycosylated and belongs to the family of heparan sulfate proteoglycans. By expressing different protein fragments, we localized the glycosaminoglycan (GAG) attachment sites to two locations within the agrin molecule. One site that is located between the seventh and eight follistatin-like domain includes 3 closely spaced serine-glycine (SG) consensus sequences and carries exclusively heparan sulfate side chains. The second site is located further downstream in the centrally located serine-threonine-rich domain and contains a cluster of 4 closely packed SG consensus sequences. This site predominantly carries chondroitin sulfate side chains. Investigating the contribution of individual serines in GAG priming by site-directed mutagenesis showed that each serine of the two SG clusters has the potential to carry GAGs. In accordance with the mixed GAG glycosylation of agrin peptide fragments, it was found that recombinant and in vivo-derived full-length agrin are not exclusively heparan sulfate proteoglycans but also carry chondroitin sulfate side chains.

Agrin↗
PubMed2006

In vivo membrane topology of Escherichia coli SecA ATPase reveals extensive periplasmic exposure of multiple functionally important domains clustering on one face of SecA.

The Sec-dependent protein translocation pathway promotes the transport of proteins into or across the bacterial plasma membrane. SecA ATPase has been shown to be a nanomotor that associates with its protein cargo as well as the SecYEG channel complex and to undergo ATP-driven cycles of membrane insertion and retraction that promote stepwise protein translocation. Previous studies have shown that both the 65-kDa N-domain and 30-kDa C-domain of SecA appear to undergo such membrane cycling. In the present study we performed in vivo sulfhydryl labeling of an extensive collection of monocysteine secA mutants under topologically specific conditions to identify regions of SecA that are accessible to the trans side of the membrane in its membrane-integrated state. Our results show that distinct regions of five of six SecA domains were labeled under these conditions, and such labeling clusters to a single face of the SecA structure. Our results demarcate an extensive face of SecA that interacts with SecYEG and is in fluid contact with the protein-conducting channel. The observed domain-specific labeling patterns should also provide important constraints on model building efforts in this dynamic system.

Adenosine Triphosphatases↗
PubMed1998

Complete sequence of a 93.4-kb contig from chromosome 3 of Trypanosoma cruzi containing a strand-switch region.

We have initiated large-scale sequencing of the third smallest chromosome of the CL Brener strain of Trypanosoma cruzi and we report here the complete sequence of a contig consisting of three cosmids. This contig covers 93.4 kb and has been found to contain 20-30 novel genes and several repeat elements, including a novel chromosome 3-specific 400-bp repeat sequence. The intergenic sequences were found to be rich in di- and trinucleotide repeats of varying lengths and also contained several known T. cruzi repeat elements. The sequence contains 29 open reading frames (ORFs) longer than 700 bp, the longest being 5157 bp, and a large number of shorter ORFs. Of the long ORFs, seven show homology to known genes in parasites and other organisms, whereas four ORFs were confirmed by sequencing of cDNA clones. Two shorter ORFs were confirmed by a database homology and a cDNA clone, respectively, and one RNA gene was identified. The identified genes include two copies of the gene for alanine-aminotransferase as well as genes for glucose-6-phosphate isomerase, protein kinases and phosphatases, and an ATP synthase subunit. An interesting feature of the sequence was that the genes appear to be organized in two long clusters containing multiple genes on the same strand. The two clusters are transcribed in opposite directions and they are separated by an approximately 20-kb long, relatively GC-rich sequence, that contains two large repetitive elements as well as a pseudogene for cruzipain and a gene for U2snRNA. It is likely that this strand switch region contains one or more regulatory and promoter regions. The reported sequence provides the first insight into the genome organization of T. cruzi and shows the potential of this approach for rapid identification of novel genes. [The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AF052831-AF052833.]

ATP Synthetase Complexes↗
PubMed2004

Factors that cause genotype by environment interaction and use of a multiple-trait herd-cluster model for milk yield of Holstein cattle from Brazil and Colombia.

Descriptive herd variables (DVHE) were used to explain genotype by environment interactions (G x E) for milk yield (MY) in Brazilian and Colombian production environments and to develop a herd-cluster model to estimate covariance components and genetic parameters for each herd environment group. Data consisted of 180,522 lactation records of 94,558 Holstein cows from 937 Brazilian and 400 Colombian herds. Herds in both countries were jointly grouped in thirds according to 8 DVHE: production level, phenotypic variability, age at first calving, calving interval, percentage of imported semen, lactation length, and herd size. For each DVHE, REML bivariate animal model analyses were used to estimate genetic correlations for MY between upper and lower thirds of the data. Based on estimates of genetic correlations, weights were assigned to each DVHE to group herds in a cluster analysis using the FASTCLUS procedure in SAS. Three clusters were defined, and genetic and residual variance components were heterogeneous among herd clusters. Estimates of heritability in clusters 1 and 3 were 0.28 and 0.29, respectively, but the estimate was larger (0.39) in Cluster 2. The genetic correlations of MY from different clusters ranged from 0.89 to 0.97. The herd-cluster model based on DVHE properly takes into account G x E by grouping similar environments accordingly and seems to be an alternative to simply considering country borders to distinguish between environments.

Analysis of Variance↗
PubMed1999

Cluster headache-like pain in multiple sclerosis.

We describe a case with simultaneous occurrence of cluster headache-like pain and multiple sclerosis. Both neuroimaging and neurophysiology (trigeminal evoked potentials) revealed a demyelination plaque in the pons, at the trigeminal root entry zone, on the side of pain. Although that type of lesion is usually associated with trigeminal neuralgia pain, we hypothesize that in this case it may be linked with the concomitant cluster headache, possibly by activation of trigemino-vascular mechanisms.

Adult↗
PubMed1989

The organization of spatial coding in the hippocampus: a study of neural ensemble activity.

Neural activity was recorded from local groups of hippocampal single units in rats performing a spatial-memory task. The organization of functional correlates in these neural ensembles was investigated by examining the spatial relationships among the place fields of single units in each ensemble. The distance and overlap between place fields were determined together with the tuning of cellular activity to behavioral variables, including direction, speed, and turning angle during movements within place fields. The place fields of recorded neural ensembles were significantly clustered: closer in space and considerably more overlapped than chance when compared statistically with Monte Carlo simulations. Just as single units often have significant firing in more than one distinct location in the environment (subfields), the ensembles had multiple and distinct clusters of overlapping subfields. In addition, proximity and overlap between place fields were significantly, but weakly, correlated with similarity in optimal movement tuning parameters. These results suggest that the hippocampus maintains a local organization with respect to place fields despite having no apparent large-scale isomorphism with the spatial environment. The organization of multiple, clustered place fields with correlated movement tuning properties in small neural ensembles suggests the existence of functional neural ensembles serving to encode multiple sensory and behavioral aspects of a place or event. Such an organization is similar to that observed for neocortical association areas afferent to the hippocampal system.

Animals↗
PubMed1996

The multiple-sugar metabolism (msm) gene cluster of Streptococcus mutans is transcribed as a single operon.

The multiple-sugar metabolism (msm) locus of Streptococcus mutans constitutes a non-PTS sugar uptake system responsible for the transport and utilization of raffinose, melibiose and isomaltotrioses. While previous studies have used polar mutations to suggest that these genes are co-transcribed, there has not been evidence to support this. In this report we present direct evidence that the msm genes can be transcribed as a single operon.

Base Sequence↗