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PubMed2006

Differential engagement of modules 1 and 4 of vascular cell adhesion molecule-1 (CD106) by integrins alpha4beta1 (CD49d/29) and alphaMbeta2 (CD11b/18) of eosinophils.

We have studied adhesion of eosinophils to various forms of vascular cell adhesion molecule 1 (VCAM-1, CD106), an integrin counter-receptor implicated in eosinophil recruitment to the airway in asthma. Full-length 7d-VCAM-1, with seven immunoglobulin-like modules, contains integrin-binding sites in modules 1 and 4. The alternatively spliced six-module protein, 6d-VCAM-1, lacks module 4. In static assays, unactivated purified human blood eosinophils adhered similarly to recombinant soluble human 6d-VCAM-1 and 7d-VCAM-1 coated onto polystyrene microtiter wells. Further experiments, however, revealed differences in recognition of modules 1 and 4. Antibody blocking indicated that eosinophil adhesion to 6d-VCAM-1 or a VCAM-1 construct containing only modules 1-3, 1-3VCAM-1, is mediated by alpha4beta1 (CD49d/29), whereas adhesion to a construct containing modules 4-7, 4-7VCAM-1, is mediated by bothalpha4beta1 andalphaMbeta2 (CD11b/18). Inhibitors of phosphoinositide 3-kinase, which block adhesion of eosinophils mediated by alphaMbeta2, blocked adhesion to 4-7VCAM-1 but had no effect on adhesion to 6d-VCAM-1. Consistent with the antibody and pharmacological blocking experiments, eosinophilic leukemic cell lines lacking alphaMbeta2 did not adhere to 4-7VCAM-1 but did adhere to 6d-VCAM-1 or 1-3VCAM-1. Activation of eosinophils by interleukin (IL)-5 enhanced static adhesion to 6d-VCAM-1, 7d-VCAM-1, or 4-7VCAM-1; IL-5-enhanced adhesion to all 3 constructs was blocked by anti-alphaMbeta2. Adhesion of unstimulated eosinophils to 7d-VCAM-1 under flow conditions was inhibited by anti-alpha4 or anti-alphaM. IL-5 treatment decreased eosinophil adhesion to 7d-VCAM-1 under flow, and anti-alphaM had the paradoxical effect of increasing adhesion. These results demonstrate that alphaMbeta2 modulatesalpha4beta1-mediated eosinophil adhesion to VCAM-1 under both static and flow conditions.

Binding Sites↗

PubMed1995

Dynamic beam modulation by using a single computer-controlled absorber.

The authors have developed an apparatus able to generate ID intensity-modulated beams, using only one moving absorber within the irradiation field. A procedure for deriving optimized absorber-speed profiles in order to produce the desired fluence/dose profiles has been suggested. Experimental tests show that the system should be sufficiently reliable in reproducing modulated beam profiles of different shape: expected relative doses against measured relative doses have been found to be in agreement in a number of situations within 3% using a nonfocused device. A better agreement should be expected using a focused apparatus (which is currently being developed). Beam modulation by single absorber cannot modulate the beam fluence in any was one wishes, due to physical constraints, which depend on the absorber and field widths and on the shape of the desired fluence profile. However, the authors show that this simple and low-cost tool could offer, with a sufficient degree of accuracy, the possibility of modulating the beam fluence with a high degree of versatility. In particular, a procedure or performing tissue-missing compensation by single-absorber dynamic beam modulation is suggested. Moreover, 'strongly' modulated beam profiles can be created, showing that this simple technique could also have some interesting applications in the field of conformal radiotherapy by non-uniform dose delivery.

Algorithms↗

PubMed1999

1D dynamic beam modulation: methods to counteract inertia effects.

Dynamic modulation can be affected by inaccuracies when the required acceleration is larger than the highest allowed by the mechanical characteristics of the whole apparatus. In this study, inertia effects have been investigated with regard to the single absorber 1D modulation, analysing primarily how the acceleration performed by the modulating system affects the realization of 'single absorber' fluence profiles and the type of correction which could be devised. The observed percentage deviations from desired modulation at the lowest fluence coordinate of single minimum fluence profiles, when no correction is applied, were almost negligible for 'easy' modulations of the incident fluence (i.e. slow gradients); deviations became increasingly relevant as the moving absorber executed steeper gradients (a 17.6% higher dose being delivered in the minimum position when a 0.2 modulation is required). By applying the proposed corrections, the single absorber performances were improved to a satisfactory level, with a maximum deviation from desired modulation in the minima within 1.6%.

Algorithms↗

PubMed1999

Functional promoter modules can be detected by formal models independent of overall nucleotide sequence similarity.

MOTIVATION: Gene regulation often depends on functional modules which feature a detectable internal organization. Overall sequence similarity of these modules is often insufficient for detection by general search methods like FASTA or even Gapped BLAST. However, it is of interest to evaluate whether modules, often known from experimental analysis of single sequences, are present in other regulatory sequences. RESULTS: We developed a new method (FastM) which combines a search algorithm for individual transcription factor binding sites (MatInspector) with a distance correlation function. FastM allows fast definition of a model of correlated binding sites derived from as little as a single promoter or enhancer. ModelInspector results are suitable for evaluation of the significance of the model. We used FastM to define a model for the experimentally verified NFkappaB/IRF1 regulatory module from the major histocompatibility complex (MHC) class I HLA-B gene promoter. Analysis of a test set of sequences as well as database searches with this model showed excellent correlation of the model with the biological function of the module. These results could not be obtained by searches using FASTA or Gapped BLAST, which are based on sequence similarity. We were also able to demonstrate association of a hypothetical GRE-GRE module with viral sequences based on analysis of several GenBank sections with this module. AVAILABILITY: The WWW version of FastM is accessible at: http://www.gsf.de/cgi-bin/fastm. pl and http://genomatix.gsf.de/cgi-bin/fastm2/fastm.pl

Algorithms↗

PubMed2000

Intermodal selective attention in monkeys. II: physiological mechanisms of modulation.

Of all areas studied in the accompanying study, attention effects were most consistent and well resolved in V4. In this study, to define some of the anatomical circuits and neural processes underlying the influence of attention, we examined the laminar distribution and physiology of attention effects in V4 and in two lower areas, V1 and V2. Laminar event-related potential (ERP), current source density (CSD) and multiunit activity (MUA) profiles allowed identification of processes occurring in the local ensembles, as well as their sequence and laminar distribution. These methods also permitted us to analyze the brain processes reflected in attention-sensitive components of the surface ERP. As outlined in the previous study, the first robust modulation by attention occurred in V4 during the 100-300 ms poststimulus interval. This is the time frame of the net refractoriness which follows the net local excitatory response to luminance increment. Over this interval, attention reduced CSD amplitudes and increased action potential firing rates, findings consistent with disinhibition as a mechanism for attention in V4. Similar effects were observed during the 100-300 ms time frame in V2. In V4, attention had no effect on the initial excitatory response at the depth of lamina 4, but it did produce large modulations in supragranular and deep laminae, origins of both feedforward and feedback projections. Attentional modulation in V2 was later than in V4 and concentrated in extragranular laminae, with no modulation of the initial layer 4 response. Attentional modulation in V1 was smaller and still later than that in V2 and was focused in the supragranular laminae. In this paradigm, attention did not modulate either the response in lateral geniculate nucleus (LGN) or the initial excitation in lamina 4C of V1. The timing of effects across areas and the laminar distribution of effects within areas indicate that attention effects are mediated by feedback projections. Moreover, our findings suggest that attention may increase the perceptual salience of stimuli by reducing stimulus-evoked refractoriness and/or inhibition in cortical ensembles. Finally, attentional modulation of transmembrane current flow in V4 produced a sustained negative deflection in the laminar ERP profile, that was manifested in the ERP over the occipital surface. This posits a mechanism for the 'selection negativity', a scalp ERP effect noted under similar experimental conditions in human subjects.

Animals↗

PubMed2002

Activity-dependent modulation of synaptic transmission in the intact human motor cortex revealed with transcranial magnetic stimulation.

Activity-dependent modulation of cortical synaptic transmission is a fundamental mechanism involved in learning and memory storage. This modulation has been widely studied in in vitro brain slices and in vivo animal models. More recently, transcranial magnetic stimulation has allowed detection of activity-dependent excitability modulation occurring in the intact human primary motor cortex (MI) after execution of different kinds of motor tasks. Both increased and decreased MI excitability have been described after exercise. While increased MI excitability is generally considered direct expression of cortical synaptic plasticity, a controversy still exists as to whether decreased MI excitability reflects fatigue of central nervous system (CNS) structures or cortical neuronal reorganization taking place after exercise. Here, we extend previous findings in order to provide further support for the latter hypothesis. Abduction- adduction movements of the thumb performed for 1 min at 2 Hz frequency rate produce a 55% decrease in MI excitability of mean 30 min duration. Similar decrements in amplitude and duration of motor evoked potentials (MEPs) are not reached if the same task is performed once again during the maximal inhibition phase (10 min post-exercise) produced by a previous activation. Moreover, the same task performed at a lower (1 Hz) frequency rate produces no significant MEP changes but can transiently reverse activity-dependent depression obtained after previous 2 Hz movements. Repeated execution of the same task (2 Hz), each being performed after recovery from a previously induced MEP depression, ceases to produce an MEP decrement, suggesting adaptation in MI excitability modulation. This adaptation is long lasting and task-specific, since a different motor task (1 min circular movement of the thumb) restores activity-dependent modulation. Overall, these findings suggest that the dynamic modulation of MEPs occurring after execution of different kinds of simple motor skills reflects some form of activity-dependent, plastic neuronal reorganization instead of CNS fatigue. Possible anatomo-functional mechanisms involved in this activity-dependent modulation of MI excitability are discussed.

Adult↗

PubMed1999

Antigen-induced TCR-CD3 down-modulation does not require CD3delta or CD3gamma cytoplasmic domains, necessary in response to anti-CD3 antibody.

We studied cytotoxic T lymphocyte (CTL) clones expressing cytoplasmic domain-deleted CD3delta and CD3gamma chains. These cells retained efficient antigen-specific cytolysis. Because the cytoplasmic domains of native CD3delta and CD3gamma chains contain a dileucine-based and a tyrosine-based motif thought to be important for receptor endocytosis, we compared TCR-CD3 down-modulation on the CTL clones expressing or not these domains. We found that antigen-induced TCR-CD3 down-modulation was not dependent on either the CD3delta or CD3gamma cytoplasmic domains. This contrasts with phorbol ester- and anti-CD3 mAb (soluble or plastic-coated)-induced TCR-CD3 down-modulation, that are respectively dependent on CD3gamma and on either CD3delta or CD3gamma cytoplasmic domains, suggesting that differences may exist between the mechanisms of TCR-CD3 down-modulation in response to the three stimuli. TCR-CD3 down-modulation in response to antigen was demonstrated by confocal microscopy to be associated with TCRbeta chain internalization, whether CD3delta and CD3gamma were native or truncated. Inhibition by the protein tyrosine kinase inhibitor PP1 of TCR-CD3 down-modulation in response to antigen was also similar whether CD3delta and CD3gamma cytoplasmic domains were present or not. These properties of receptor down-modulation are discussed with respect to the requirements for TCR engagement on antigen-presenting cells.

Animals↗

PubMed2004

Module-specific antibodies against human connective tissue growth factor: utility for structural and functional analysis of the factor as related to chondrocytes.

Connective tissue growth factor/hypertrophic chondrocyte specific gene product 24 (CTGF/Hcs24/CCN2) shows diverse functions in the process of endochondral ossification. It promotes not only the proliferation and differentiation of chondrocytes and osteoblasts in vitro, but also angiogenesis in vivo. The ctgf gene is a member of the gene family called CCN, and it encodes the characteristic 4-module structure of this family, with the protein containing IGFBP, VWC, TSP and CT modules. We raised several monoclonal antibodies and polyclonal antisera against CTGF, and located the epitopes in the modules by Western blotting. For mapping the epitopes, Brevibacillus-produced independent modules were utilized. As a result, at least 1 antibody or antiserum was prepared for the detection of each module in CTGF. Western blotting with these antibodies is expected to be useful for the analysis of CTGF fragmentation. Moreover, we examined the effects of these monoclonal antibodies on the biological functions of CTGF. One out of 3 humanized monoclonal antibodies was found to neutralize efficiently the stimulatory effect of CTGF on chondrocytic cell proliferation. This particular antibody bound to the CT module. In contrast, surprisingly, all of the 3 antibodies recognizing IGFBP, VWC and CT modules stimulated proteoglycan synthesis in chondrocytic cells. Together with previous findings, these results provide insight into the structural-functional relationships of CTGF in executing multiple functions.

Amino Acid Motifs↗

PubMed2005

Automatic tube-current modulation in CT--a comparison between different solutions.

In this study, tube-current modulation systems on two different CT equipments have been evaluated: Care Dose from Siemens and Auto mA from GE Medical Systems. Care Dose modulates the tube current in the xy-plane during rotation whereas Auto mA modulates the tube current in the z-direction. xy-Plane modulation was investigated by using an elliptic Polymethylmethacrylate phantom and a CTDI-ion chamber. To investigate modulation in the z-direction, an anthropomorphic dosimetry phantom (Atom) was used. Tests performed with and without tube-current modulation were compared with respect to absorbed dose and image quality. In the anthropomorphic phantom measurements, the dose savings were 15% using Care Dose and the photon starvation artefacts were negligible. Using Auto mA the absorbed dose depends on the chosen noise level. Image noise becomes more constant throughout the patient but photon starvation artefacts remain. We conclude that the two tube-current modulation techniques show different dose advantages and image quality artefacts.

Humans↗

PubMed2005

Age-related changes in the circadian modulation of sleep-spindle frequency during nap sleep.

STUDY OBJECTIVES: Sleep spindles exhibit a clear circadian modulation in healthy younger people. During the biological night (when melatonin is secreted), spindle density and spindle amplitude are high and spindle frequency and its variability are low, as compared with the biological day. We investigated whether this circadian modulation of spindle characteristics changes with age. DESIGN: A 40-hour multiple-nap paradigm under constant-routine conditions SETTING: Chronobiology Laboratory, University Psychiatric Hospitals, Basel, Switzerland PARTICIPANTS: Seventeen younger (20-31 years) and 15 older (57-74 years) volunteers. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Whereas the circadian modulation of spindle density, amplitude, duration, and intraspindle frequency variability was not greatly affected by age, we found significant changes in the circadian modulation of spindle frequency. The pronounced circadian modulation of spindle frequency in younger, but not older, subjects was phase locked with the circadian rhythm in melatonin secretion. In the latter, circadian modulation was attenuated and tended to be advanced with respect to the timing of melatonin secretion. There was no difference between age groups in the phase of the sleep-wake cycle or that of melatonin, nor did the phase angle between them differ. Although changes in the circadian modulation of spindle frequency in older subjects were accompanied by reduced amplitude in the sleep consolidation profile, there was no significant correlation between spindle frequency and sleep consolidation. CONCLUSION: This multiple-nap protocol under constant-routine conditions revealed an age-dependent weaker coupling of the circadian rhythms of spindle frequency and sleep propensity to the circadian rhythm of melatonin secretion.

Adult↗

PubMed2000

Effect of different recumbent positions on spectral indices of autonomic modulation of the heart during the acute phase of myocardial infarction.

OBJECTIVE: To examine which recumbent position can lead to the highest vagal modulation in patients during the acute phase of myocardial infarction. DESIGN: Descriptive study. SETTING: Intensive care unit in a medical center. PATIENTS: A total of 52 patients admitted to the intensive care unit because of acute myocardial infarction (AMI), 41 patients with coronary artery disease (CAD), and 28 patients with patent coronary arteriogram. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Heart rate variability analysis was performed in patients with AMI, patients with CAD, and patent coronary controls in supine, left lateral decubitus, and right lateral decubitus positions in random order. In the right lateral decubitus position, the vagal modulation was the highest and the sympathetic modulation was the lowest among three recumbent positions in three groups of patients. When the position was changed from supine to right lateral decubitus, the increase in vagal modulation was greater in patients who had more severely depressed vagal modulation in the supine position and the rate of increase was the greatest in patients with AMI, followed by patients with CAD and patent coronary controls. Detailed analysis showed that the vagal enhancing and sympathetic suppression effect of the right lateral decubitus position applied to patients with Q wave myocardial infarctions. CONCLUSIONS: The right lateral decubitus position can lead to the highest vagal modulation and the lowest sympathetic modulation among three recumbent positions in patients with Q wave myocardial infarction. The right lateral decubitus position can be used as an effective vagal enhancer in patients with Q wave myocardial infarction but without severe bradycardia or atrioventricular block.

Aged↗

PubMed2002

Auditory steady-state responses to exponential modulation envelopes.

OBJECTIVE: This study examined the steady-state responses evoked by tones modulated with exponential envelopes. The hypothesis was that stimuli with envelopes containing more rapid changes would evoke larger responses. DESIGN: Multiple auditory steady-state responses were recorded simultaneously to eight tonal stimuli, four in each ear. The carrier frequencies of the stimuli ranged from 500 to 6000 Hz and the modulation rates were between 75 and 95 Hz. The modulation envelopes were based on functions using sin' where N was 1, 2, 3, or 4. Setting N to 1 produced the traditional sinusoidal modulation. RESULTS: Exponential envelopes with N greater than 1 produced larger steady-state responses than a sinusoidal envelope. For amplitude-modulation (AM), exponential envelopes increased response amplitudes by 21% at 55 dB pSPL, and by 29% at 35 dB pSPL. The increases were smaller for carrier frequencies of 1500 to 2000 Hz than for lower and higher carrier frequencies. Latencies calculated from phase data increased significantly with increasing N. This was likely caused by the point of maximal envelope-slope shifting later in time as N increased. For frequency modulation (FM), the steady-state responses did not significantly change with changes in the power of the exponential envelopes. CONCLUSIONS: When tones are amplitude-modulated with exponential envelopes based on sin(N), the amplitude and latency of the steady-state response increased significantly with increasing N. Using exponential envelopes with N greater than 1 should considerably shorten the time needed for responses to become significant when using steady-state responses in objective audiometry.

Adult↗

PubMed2003

Use of data from the Behavioral Risk Factor Surveillance System optional diabetes module by states.

An optional diabetes module of the Behavioral Risk Factor Surveillance System was first made available to states in 1993. In 2002, 49 states administered this module. In October 2001 we asked state Diabetes Prevention and Control Program coordinators to complete a two-part questionnaire regarding the use of data from the diabetes module and their usefulness in guiding programmatic activities. Seventy percent of state coordinators reported using data from at least one module question to perform program evaluation, develop publications, and development of community interventions; 45 percent of coordinators used data from at least one module question for activities related to passage of legislation. Questions on self monitoring of blood glucose, hemoglobin A1c test, annual foot exam, annual dilated eye exam, and diabetes education were rated as highly useful by the state coordinators. The results from the optional diabetes module are widely used by states and are essential to Diabetes Prevention and Control Program activities. It is important that the optional diabetes module continue to be included in each state's yearly Behavioral Risk Factor Surveillance System.

Behavioral Risk Factor Surveillance System↗

PubMed2006

Optimizing the stimuli to evoke the amplitude modulation following response (AMFR) in neonates.

OBJECTIVE: The goal was to identify stimulus features that enhance the detection of the amplitude modulation following response (AMFR) in neonates. The features explored were (1) envelope type, sinusoidal versus a half-wave rectified sinusoid (transposed); (2) best modulation frequency; and (3) spectral content, i.e., tone versus band-pass noise. DESIGN: Results are based on recordings from 149 babies (80 babies in the neonatal intensive care unit and 69 newborn infants). All had passed hearing screening based on the click-evoked ABR. Babies were not sedated. We used carrier frequencies of approximately 500, 1000, 2000, and 4000 Hz and modulation frequencies between approximately 25 and 98 Hz. For the noise stimuli, we used band-pass noise at center frequencies of 500, 1000, 2000, and 4000 Hz. All stimuli were presented through insert earphones delivered simultaneously to both ears, at intensities ranging from 20 to 70 dB SPL. Magnitude squared coherence, phase coherence, and spectral criteria were used to detect criterion AMFRs. We analyzed four measures: (1) percent of satisfied runs; (2) the amplitude of criterion AMFR; (3) time to detect a criterion AMFR; and (4) response strength (e.g., the value of the magnitude squared coherence when it reached criterion minus the critical value it had to exceed for that number of averages all divided by the critical value). RESULTS: (1) The AMFRs evoked by transposed tones were larger and detected faster than those to sinusoidal amplitude modulated tones. Consequently, remaining protocols all used the transposed envelopes. (2) The range of effective modulation frequencies was broad (41 to 88 Hz) across carrier frequencies. (3) The AMFRs evoked by transposed noise were faster and more efficient than those to transposed tones. CONCLUSIONS: In neonates, transposed tones are more effective than sinusoidal amplitude modulated tones in evoking the AMFR, modulation frequencies between 41 to 88 Hz are almost equally effective in evoking the AMFR, and band-pass noises are more effective in evoking the AMFR than tones. These three stimulus factors all add incrementally to the efficiency of evoking the AMFR. The short detection times indicate that the AMFR could be an effective tool for hearing screening.

Acoustic Stimulation↗

PubMed2006

Static versus dynamic loading in the mechanical modulation of vertebral growth.

STUDY DESIGN: Measures of absolute and relative growth modulation were used to determine the effects of static and dynamic asymmetric loading of vertebrae in the rat tail. OBJECTIVES: To quantify the differences between static and dynamic asymmetric loading in vertebral bone growth modulation. SUMMARY OF BACKGROUND DATA: The creation and correction of vertebral wedge deformities have been previously described in a rat-tail model using static loading. The effects of dynamic loading on growth modulation in the spine have not been characterized. METHODS: A total of 36 immature Sprague-Dawley rats were divided among four different groups: static loading (n = 12, 0.0 Hz), dynamic loading (n = 12, 1.0 Hz), sham operated (n = 6), and growth controls (n = 6). An external fixator was placed across the sixth and eighth caudal vertebrae as the unviolated seventh caudal vertebra was evaluated for growth modulation. Static or dynamic asymmetric loads were applied at a loading magnitude of 55% body weight. After 3 weeks of loading, growth modulation was assessed using radiographic measurements of vertebral wedge angles and vertebral body heights. RESULTS: The dynamically loaded rats had a final average wedge deformity of 15.2+/- 6.4 degrees, which was significantly greater than the statically loaded rats whose final deformity averaged 10.3 degrees +/- 3.7 degrees (P < 0.03). The deformity in both groups was statistically greater than the sham-operated (1.1+/- 2.0 degrees) and growth control rats (0.0+/- 1.0 degrees) (P < 0.001). The longitudinal growth was significantly lower on the concavity compared with the convexity in both the dynamically (0.34 +/- 0.23 mm vs. 0.86 +/- 0.23 mm) and statically (0.46 +/- 0.19 mm vs. 0.83 +/- 0.32 mm) loaded rats (P < 0.001). These growth rates were significantly less than the sham operated and growth control rats (P < 0.001). CONCLUSIONS: A variety of fusionless scoliosis implant strategies have been proposed that use both rigid and flexible implants to modulate vertebral bone growth. The results from this study demonstrate that dynamic loading of the vertebrae provides the greatest growth modulation potential.

Animals↗

PubMed2005

Novel specificities emerge by stepwise duplication of functional modules.

A functional module can be defined as a spatially or chemically isolated set of functionally associated components that accomplishes a discrete biological process. Modularity is a key attribute of cellular systems, but the mechanisms that underlie the evolution of functional modules are largely unknown. Duplication of modules has been shown to be an efficient mechanism for the generation of functional innovation in the field of artificial intelligence, but has not been studied in biological networks. Therefore, we ask whether module duplication occurs in cellular networks. We developed a generic framework for the analysis of module duplication, and use it in a large-scale analysis of Saccharomyces cerevisiae protein complexes. Protein complexes are well defined, experimentally derived, functional modules. We observe that at least 6%-20% of the protein complexes have strong similarity to other complexes; thus a considerable fraction has evolved by duplication. Our results indicate that many complexes evolved by step-wise partial duplications. We show that duplicated complexes retain the same overall function, but have different binding specificities and regulation, revealing that duplication of these modules is associated with functional specialization.

Evolution, Molecular↗

PubMed2005

Diffuse scattering and ordering in the short-range modulated paraelectric phase of sodium nitrite, NaNO2.

The incommensurately modulated antiferroelectric phase of sodium nitrite, NaNO2, transforms at T(N) = 437.7 K to the short-range modulated paraelectric phase. The apparently discontinuous phase transition is accompanied by characteristic changes in the diffraction pattern. Contrary to the well known modulated structures with sharp satellite reflections, the diffraction pattern of a short-range modulated structure contains diffuse satellite reflections. The short-range modulated crystal structure of the paraelectric phase of sodium nitrite has been analysed by the Reverse Monte Carlo (RMC) simulation of X-ray diffuse scattering. The crystal structure of sodium nitrite may be regarded as consisting of [Na+NO2-]infinity rows running along the polar b axis. One can expect long fragments of rows with uniform polarity The assumption that single [Na+NO2-]infinity rows are polar with uniform polarity proved to be a convenient approximation which is in good agreement with the observed diffraction pattern. The distribution of (+)- and (-)-[Na+NO2-]infinity polar rows crossing the (010) plane of short-range modulated NaNO2 revealed by RMC shows nanodomains consisting of distorted fragments of a sinusoidally modulated crystal structure. The size of the nanodomains and the degree of order in paraelectric NaNO2 decreases with temperature.

Crystallography, X-Ray↗

PubMedDate not supplied

Combining sequence and time series expression data to learn transcriptional modules.

Our goal is to cluster genes into transcriptional modules--sets of genes where similarity in expression is explained by common regulatory mechanisms at the transcriptional level. We want to learn modules from both time series gene expression data and genome-wide motif data that are now readily available for organisms such as S. cereviseae as a result of prior computational studies or experimental results. We present a generative probabilistic model for combining regulatory sequence and time series expression data to cluster genes into coherent transcriptional modules. Starting with a set of motifs representing known or putative regulatory elements (transcription factor binding sites) and the counts of occurrences of these motifs in each gene's promoter region, together with a time series expression profile for each gene, the learning algorithm uses expectation maximization to learn module assignments based on both types of data. We also present a technique based on the Jensen-Shannon entropy contributions of motifs in the learned model for associating the most significant motifs to each module. Thus, the algorithm gives a global approach for associating sets of regulatory elements to "modules" of genes with similar time series expression profiles. The model for expression data exploits our prior belief of smooth dependence on time by using statistical splines and is suitable for typical time course data sets with relatively few experiments. Moreover, the model is sufficiently interpretable that we can understand how both sequence data and expression data contribute to the cluster assignments, and how to interpolate between the two data sources. We present experimental results on the yeast cell cycle to validate our method and find that our combined expression and motif clustering algorithm discovers modules with both coherent expression and similar motif patterns, including binding motifs associated to known cell cycle transcription factors.

Algorithms↗