Stability of proximal mandibular anatomical structures following bilateral sagittal split osteotomy.

The aim of this study was to investigate the stability of the proximal mandibular reference structures that have been proposed in the literature for superimposition. Forty proximal mandibular segments of 20 patients who underwent bilateral sagittal split osteotomy (BSSO) for advancement were reconstructed from a pair of pre- and postoperative (2 years) cone beam computed tomography scans, and spatially divided into the mandibular condyle, the coronoid process, and 20 mandibular ramus regions. To assess the stability of the anatomical regions, the volumetric and surface discrepancy between the superimposed pre- and postoperative regions were calculated. One-sample t-tests were applied to analyse the statistical stability of the individual regions. Two statistically stable (P < 0.05) structures in the proximal segment of the mandible following BSSO were identified: (1) the posterior part of the mandibular ramus above the gonial angle and below the condylar neck, and (2) the sub-coronoid area below the coronoid process/mandibular notch. Using these stable structures for superimposition resulted in an assessment discrepancy in the condylar displacement of up to 1.1 mm and in the volumetric change of up to 2.8%. Hence, it is suggested that these two identified stable structures are used as reference areas when assessing condylar displacement and change using superimposition.

Crystal structure of La24Ru11.

The compound La24Ru11 (tetra-cosa-lanthanum undeca-ruthenium) crystallizes in a Ce24Co11-type structure. The non-centrosymmetric crystal structure (space group P63 mc) contains RuLa6 trigonal prisms, La6 octa-hedra and LaRu4 tetra-hedra and is closely related to that of Ce23Ni7Mg4. This communication highlights the crystal-chemical similarities and points out the differences between the two structures. All of the tested crystals were inversion twins.

A molecular rheostat adjusts auxin flux to promote root protophloem differentiation.

Auxin influences plant development through several distinct concentration-dependent effects 1 . In the Arabidopsis root tip, polar auxin transport by PIN-FORMED (PIN) proteins creates a local auxin accumulation that is required for the maintenance of the stem-cell niche2-4. Proximally, stem-cell daughter cells divide repeatedly before they eventually differentiate. This developmental gradient is accompanied by a gradual decrease in auxin levels as cells divide, and subsequently by a gradual increase as the cells differentiate5,6. However, the timing of differentiation is not uniform across cell files. For instance, developing protophloem sieve elements (PPSEs) differentiate as neighbouring cells still divide. Here we show that PPSE differentiation involves local steepening of the post-meristematic auxin gradient. BREVIS RADIX (BRX) and PROTEIN KINASE ASSOCIATED WITH BRX (PAX) are interacting plasma-membrane-associated, polarly localized proteins that co-localize with PIN proteins at the rootward end of developing PPSEs. Both brx and pax mutants display impaired PPSE differentiation. Similar to other AGC-family kinases, PAX activates PIN-mediated auxin efflux, whereas BRX strongly dampens this stimulation. Efficient BRX plasma-membrane localization depends on PAX, but auxin negatively regulates BRX plasma-membrane association and promotes PAX activity. Thus, our data support a model in which BRX and PAX are elements of a molecular rheostat that modulates auxin flux through developing PPSEs, thereby timing PPSE differentiation.

DOT1L-mediated H3K79me2 modification critically regulates gene expression during cardiomyocyte differentiation.

Epigenetic changes on DNA and chromatin are implicated in cell differentiation and organogenesis. For the heart, distinct histone methylation profiles were recently linked to stage-specific gene expression programs during cardiac differentiation in vitro. However, the enzymes catalyzing these modifications and the genes regulated by them remain poorly defined. We therefore decided to identify the epigenetic enzymes that are potentially involved in cardiomyogenesis by analyzing the expression profile of the 85 genes encoding the epigenetic-related proteins in mouse cardiomyocytes (CMs), and then study how they affect gene expression during differentiation and maturation of this cell type. We show here with gene expression screening of epigenetic enzymes that the highly expressed H3 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) drives a transitional pattern of di-methylation on H3 lysine 79 (H3K79) in CMs at different stages of differentiation in vitro and in vivo. Through a genome-wide chromatin-immunoprecipitation DNA-sequencing approach, we found H3K79me2 enriched at genes expressed during cardiac differentiation. Moreover, knockdown of Dot1L affected the expression of H3K79me2-enriched genes. Our results demonstrate that histone methylation, and in particular DOT1L-mediated H3K79me2 modification, drives cardiomyogenesis through the definition of a specific transcriptional landscape.

Multi-level synchrotron radiation-based microtomography of the dental alveolus and its consequences for orthodontics.

Multilevel synchrotron radiation-based microtomography has been performed on a human jaw segment obtained at autopsy by cutting increasingly smaller samples from the original segment. The focus of this study lay on the microstructure of the interface between root, periodontal ligament (PDL) and alveolar bone in order to find an answer to the question why alveolar bone remodels during orthodontic loading, when the associated stress and strain levels calculated with finite element analyses are well below the established threshold levels for bone remodeling. While the inner surface of the alveolus appears to be rather smooth on the lower resolution scans, detailed scans of the root-PDL-bone interface reveal that on a microscopical scale it is actually quite rough and uneven with bony spiculae protruding into the PDL space. Any external (orthodontic) loading applied to the root, when transferred through the PDL to the alveolar bone, will cause stress concentrations in these spiculae, rather than be distributed over a "smooth surface". As osteocyte lacunae are shown to be present in these spiculae, the local amplified stresses and strain can well be registered by the mechano-sensory network of osteocytes. In addition, a second stress amplification mechanism, due to the very presence of the lacunae themselves, is evidence that stresses and strains calculated with FE analyses, based on macroscopical scale models of teeth and their supporting structures, grossly underestimate the actual mechanical loading of alveolar bone at tissue level. It is therefore hypothesized that remodeling of alveolar bone is subject to the same biological regulatory process as remodeling in other bones.

The relationship between upper airways and craniofacial morphology studied in 3D. A CBCT study.

OBJECTIVES: To assess whether morphology and dimension of the upper airway differ between patients characterized by various craniofacial morphology. SETTING AND SAMPLE POPULATION: Ninety young adult patients from the Postgraduate Clinic, Section of Orthodontics, Department of Dentistry, Health, Aarhus University, Denmark, with no obvious signs of respiratory diseases and no previous adeno-tonsillectomy procedures. Thirty patients were characterized as Class I (-0.5 < ANB < 4.5), 30 as Class II (ANB > 4.5), and 30 as Class III (ANB < -0.5). MATERIAL AND METHODS: Cone-beam computed tomography (CBCT) scans obtained in a supine position for all patients. Cephalometric landmarks were identified in 3D. Sagittal and transversal dimensions, cross sections, and partial and total volumes of the upper airway were correlated with the cephalometric measurements in all three planes of space. The cross-sectional minimal area of the upper airway was assessed as well. RESULTS: No statistical significant relationships between dimension and morphology of upper airways and skeletal malocclusion were found. CONCLUSION: Differences in craniofacial morphology as identified by the sagittal jaw relationship were not correlated with variation in upper airway volumes. A clinical significant relation was detected between minimal area and total upper airway volume.

Enhanced detection of terrestrial gamma-ray flashes by AGILE.

At the end of March 2015 the onboard software configuration of the Astrorivelatore Gamma a Immagini Leggero (AGILE) satellite was modified in order to disable the veto signal of the anticoincidence shield for the minicalorimeter instrument. The motivation for such a change was the understanding that the dead time induced by the anticoincidence prevented the detection of a large fraction of Terrestrial Gamma-Ray Flashes (TGFs). The configuration change was highly successful resulting in an increase of one order of magnitude in TGF detection rate. As expected, the largest fraction of the new events has short duration (<100 µs), and part of them has simultaneous association with lightning sferics detected by the World Wide Lightning Location Network. The new configuration provides the largest TGF detection rate surface density (TGFs/km2/yr) to date, opening prospects for improved correlation studies with lightning and atmospheric parameters on short spatial and temporal scales along the equatorial region.

New constraint on the existence of the µ+ → e+ γ decay.

The analysis of a combined data set, totaling 3.6 × 10(14) stopped muons on target, in the search for the lepton flavor violating decay µ(+) → e(+)γ is presented. The data collected by the MEG experiment at the Paul Scherrer Institut show no excess of events compared to background expectations and yield a new upper limit on the branching ratio of this decay of 5.7 × 10(-13) (90% confidence level). This represents a four times more stringent limit than the previous world best limit set by MEG.

Post-natal cardiomyocytes can generate iPS cells with an enhanced capacity toward cardiomyogenic re-differentation.

Adult mammalian cells can be reprogrammed to a pluripotent state by forcing the expression of a few embryonic transcription factors. The resulting induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers. It is well known that post-natal cardiomyocytes (CMs) lack the capacity to proliferate. Here, we report that neonatal CMs can be reprogrammed to generate iPS cells that express embryonic-specific markers and feature gene-expression profiles similar to those of mouse embryonic stem (mES) cell and cardiac fibroblast (CF)-derived iPS cell populations. CM-derived iPS cells are able to generate chimeric mice and, moreover, re-differentiate toward CMs more efficiently then either CF-derived iPS cells or mES cells. The increased differentiation capacity is possibly related to CM-derived iPS cells retaining an epigenetic memory of the phenotype of their founder cell. CM-derived iPS cells may thus lead to new information on differentiation processes underlying cardiac differentiation and proliferation.

New limit on the lepton-flavor-violating decay µ+→e+γ.

We present a new result based on an analysis of the data collected by the MEG detector at the Paul Scherrer Institut in 2009 and 2010, in search of the lepton-flavor-violating decay µ(+)e(+)γ. The likelihood analysis of the combined data sample, which corresponds to a total of 1.8×10(14) muon decays, gives a 90% C.L. upper limit of 2.4×10(-12) on the branching ratio of the µ(+)→e(+)γ decay, constituting the most stringent limit on the existence of this decay to date.

Transversal maxillary dento-alveolar changes in patients treated with active and passive self-ligating brackets: a randomized clinical trial using CBCT-scans and digital models.

OBJECTIVE: To assess transversal tooth movements and buccal bone modeling of maxillary lateral segments achieved with active or passive self-ligating bracket systems in a randomized clinical trial. MATERIALS AND METHODS: Sixty-four patients, with Class I, II, and mild Class III malocclusions, were randomly assigned to treatment with passive (Damon 3 MX) or active (In-Ovation R) SLBs. Impressions and cone-beam CT-scans were taken before (T0) and after treatment (T1). Displacement of maxillary canines, premolars and molars, and buccal alveolar bone modeling were blindly assessed. RESULTS: Twenty-one patients in the Damon and 20 in the In-Ovation group completed treatment according to the prescribed protocol. Eight Damon and 10 In-Ovation patients were excluded as the treatment approach had to be changed because of deviation from the recommended initial plan, while three Damon and two In-Ovation patients did not complete the treatment. Transversal expansion of the upper arch was achieved by buccal tipping in all but one patient in each group. No statistical significant difference in inter-premolar bucco-lingual inclination was found between the two groups from T0 to T1. The bone area buccal to the 2nd premolar decreased on average of 20% in the Damon and 14% in the In-Ovation group. Only few patients exhibited widening of the alveolar process. CONCLUSION: The anticipated translation and buccal bone modeling using active or passive SLBs could not be confirmed. Because of the large interindividual variation, a patient-specific analysis seems to be mandatory as individual factors like pre-treatment teeth inclination and occlusion influenced the treatment outcome of the individual patients.

Terrestrial gamma-ray flashes as powerful particle accelerators.

Strong electric discharges associated with thunderstorms can produce terrestrial gamma-ray flashes (TGFs), i.e., intense bursts of x rays and γ rays lasting a few milliseconds or less. We present in this Letter new TGF timing and spectral data based on the observations of the Italian Space Agency AGILE satellite. We determine that the TGF emission above 10 MeV has a significant power-law spectral component reaching energies up to 100 MeV. These results challenge TGF theoretical models based on runaway electron acceleration. The TGF discharge electric field accelerates particles over the large distances for which maximal voltages of hundreds of megavolts can be established. The combination of huge potentials and large electric fields in TGFs can efficiently accelerate particles in large numbers, and we reconsider here the photon spectrum and the neutron production by photonuclear reactions in the atmosphere.

Discovery of powerful gamma-ray flares from the Crab Nebula.

The well-known Crab Nebula is at the center of the SN1054 supernova remnant. It consists of a rotationally powered pulsar interacting with a surrounding nebula through a relativistic particle wind. The emissions originating from the pulsar and nebula have been considered to be essentially stable. Here, we report the detection of strong gamma-ray (100 mega-electron volts to 10 giga-electron volts) flares observed by the AGILE satellite in September 2010 and October 2007. In both cases, the total gamma-ray flux increased by a factor of three compared with the non-flaring flux. The flare luminosity and short time scale favor an origin near the pulsar, and we discuss Chandra Observatory x-ray and Hubble Space Telescope optical follow-up observations of the nebula. Our observations challenge standard models of nebular emission and require power-law acceleration by shock-driven plasma wave turbulence within an approximately 1-day time scale.

Gamma-ray localization of terrestrial gamma-ray flashes.

Terrestrial gamma-ray flashes (TGFs) are very short bursts of high-energy photons and electrons originating in Earth's atmosphere. We present here a localization study of TGFs carried out at gamma-ray energies above 20 MeV based on an innovative event selection method. We use the AGILE satellite Silicon Tracker data that for the first time have been correlated with TGFs detected by the AGILE Mini-Calorimeter. We detect 8 TGFs with gamma-ray photons of energies above 20 MeV localized by the AGILE gamma-ray imager with an accuracy of ∼5-10° at 50 MeV. Remarkably, all TGF-associated gamma rays are compatible with a terrestrial production site closer to the subsatellite point than 400 km. Considering that our gamma rays reach the AGILE satellite at 540 km altitude with limited scattering or attenuation, our measurements provide the first precise direct localization of TGFs from space.

Condylar lesions in relation to mandibular growth in untreated and intra-articular corticosteroid-treated experimental temporomandibular joint arthritis.

OBJECTIVES: To evaluate condylar lesions in relation to mandibular growth in experimental temporomandibular joint (TMJ) arthritis and to assess the outcome of treating this condition with repeated intra-articular corticosteroid injections (IACIs). METHODS: Forty-two 10-week-old rabbits were randomly divided into four groups. Seven animals served as controls. Experimental TMJ arthritis was induced in five animals which received intra-articular TMJ saline injections. Fifteen animals had TMJ arthritis induced and were left untreated and 15 animals had TMJ arthritis induced and were treated with IACIs one week after each TMJ antigen-challenge procedure. Inter-group growth differences were evaluated from head computerised tomography scans taken at the time of arthritis induction and 12 weeks later. The variables assessed were: progression of condylar lesions (erosions/flattening/osteophytes), mandibular bone volume changes, condylar and sagittal ramus growth. RESULTS: No inter-group differences in the progression of condylar lesions were observed despite reduced mandibular growth in all three experimental groups. The most pronounced unfavourable mandibular growth alterations were observed in the corticosteroid-treated arthritis animals. CONCLUSIONS: No evidence was found in support of a relation between reduced mandibular growth and condylar lesions. We propose that: 1) condylar lesions are not the only causative factor of reduced mandibular growth in experimental TMJ arthritis, and 2) repeated IACIs have a very unfavourable impact on mandibular growth in experimental TMJ arthritis - treatment is more detrimental to mandibular growth than the TMJ arthritis itself.

An analysis of different approaches to the assessment of upper airway morphology: a CBCT study.

BACKGROUND: Upper airway morphology and respiration have been assigned an important role in the development of the craniofacial complex. Several studies advocate lateral cephalograms to evaluate the upper airway. Although this method has been widely used, a two-dimensional projection of a three-dimensional anatomical structure is questionable. OBJECTIVE: To correlate linear measurements (sagittal and transversal), cross-sectional areas, and volumes of the upper airway determined on Cone Beam CT (CBCT) data sets. MATERIAL AND METHODS: CBCT-scans of 34 patients were used to perform a 3D evaluation of the upper airway. Linear sagittal measurements reproducing those usually performed on lateral cephalograms, linear transversal measurements, cross-sectional areas, partial and total volumes (TV) were computed. RESULTS: The analysis showed a weak correlation (r < 0.8) between most of the linear measurements. The correlations between sagittal, transversal, and cross-sectional area with partial volumes were weak, except for the lower part of the nasopharynx which was highly correlated (r > 0.9) with sagittal measurement and with area. The upper part of the velopharynx presented a good correlation (0.8 < r < 0.9) between area and volume. Good correlation between most transversal measurements and the corresponding areas was found. Minimal sagittal, minimal transversal, and minimal area were weakly correlated with TV. CONCLUSIONS: Upper airway cannot be accurately expressed by single linear measurements as performed on cephalograms. The TV alone does not depict the morphology of the airway. A CBCT-based 3D analysis gives a better picture of the anatomical characteristics of the upper airways and therefore can lead to an improvement of the diagnosis.

Detection of gamma-ray emission from the Vela pulsar wind nebula with AGILE.

Pulsars are known to power winds of relativistic particles that can produce bright nebulae by interacting with the surrounding medium. These pulsar wind nebulae are observed by their radio, optical, and x-ray emissions, and in some cases also at TeV (teraelectron volt) energies, but the lack of information in the gamma-ray band precludes drawing a comprehensive multiwavelength picture of their phenomenology and emission mechanisms. Using data from the AGILE satellite, we detected the Vela pulsar wind nebula in the energy range from 100 MeV to 3 GeV. This result constrains the particle population responsible for the GeV emission and establishes a class of gamma-ray emitters that could account for a fraction of the unidentified galactic gamma-ray sources.

Extreme particle acceleration in the microquasar Cygnus X-3.

Super-massive black holes in active galaxies can accelerate particles to relativistic energies, producing jets with associated gamma-ray emission. Galactic 'microquasars', which are binary systems consisting of a neutron star or stellar-mass black hole accreting gas from a companion star, also produce relativistic jets, generally together with radio flares. Apart from an isolated event detected in Cygnus X-1, there has hitherto been no systematic evidence for the acceleration of particles to gigaelectronvolt or higher energies in a microquasar, with the consequence that we are as yet unsure about the mechanism of jet energization. Here we report four gamma-ray flares with energies above 100 MeV from the microquasar Cygnus X-3 (an exceptional X-ray binary that sporadically produces radio jets). There is a clear pattern of temporal correlations between the gamma-ray flares and transitional spectral states of the radio-frequency and X-ray emission. Particle acceleration occurred a few days before radio-jet ejections for two of the four flares, meaning that the process of jet formation implies the production of very energetic particles. In Cygnus X-3, particle energies during the flares can be thousands of times higher than during quiescent states.

Strains in periodontal ligament and alveolar bone associated with orthodontic tooth movement analyzed by finite element.

INTRODUCTION: Orthodontic tooth movement (OTM) is achieved by applying an orthodontic force system to the brackets. The (re)modeling processes of the alveolar support structures are triggered by alterations in the stress/strain distribution in the periodontium. According to the classical OTM theories, symmetric zones of compression and tension are present in the periodontium, but these do not consider the complex mechanical properties of the PDL, the alveolar structures' morphology, and the magnitude of the force applied. MATERIALS AND METHODS: Human jaws segments obtained from autopsy were microCT-scanned and sample-specific finite element (FE) models were generated. The material behavior of the PDL was considered to be nonlinear and non-symmetric and the alveolar bone was modeled according to its actual morphology. A series of FE-analyzes investigated the influence of the moment-to-force ratio, force magnitude, and chewing forces on the stress/strain in the alveolar support structures and OTM. RESULTS: Stress/strain findings were dependent on alveolar bone's morphology. Because of the nonlinear behavior of the PDL, distinct areas of tension, and compression could not be detected. Secondary load transfer mechanisms were activated and the stress/strain distribution in the periodontium was concealed by occlusal forces. CONCLUSIONS: We could not confirm the classical ideas of distinct and symmetrical compressive and tensile areas in the periodontium in relation to different OTM scenarios. Light continuous orthodontics forces will be perceived as intermittent by the periodontium. Because roots and alveolar bone morphology are patient-specific, FE-analysis of orthodontic loading regime should not be based on general models.

Ejection fraction-velocity ratio for the assessment of aortic bioprosthetic valves in patients with systolic dysfunction.

BACKGROUND: The continuity equation (CE) represents the 'gold standard' for the evaluation of aortic valve area in patients with aortic stenosis, but it is time-consuming and subject to error, and can be technically demanding. Recently, a new echocardiographic nonflow corrected index was introduced and demonstrated excellent accuracy in quantifying the effective orifice area (EOA) in native aortic valves and bioprostheses. This new index, the ejection fraction (EF)-velocity ratio (EFVR), is obtained by dividing the percentage left ventricular EF by the maximum aortic gradient. OBJECTIVE: To assess the usefulness of this echocardiographic index for quantifying the EOA in patients with aortic bioprosthesis and left ventricular dysfunction. METHODS: A total of 70 patients (25 women and 45 men) with aortic bioprosthesis and left ventricular dysfunction (EF of 49% or less) were studied. The mean (+/- SD) age of the study population was 71.4+/-9 years. The EOA was evaluated, both by the CE and by the EFVR. RESULTS: A significant linear correlation between the CE and the EFVR was found (r=0.80; P<0.0001). The receiver operating characteristic curve analysis showed good agreement between the CE and the EFVR. An EFVR value of 1.15 or less was found to have a good sensitivity (89%) and good specificity (91%) in identifying patients with an EOA of 1.0 cm2 or smaller, with positive and negative predictive values of 79% and 95%, respectively. CONCLUSIONS: The EFVR, a simple index that is less time-consuming than the CE, allows the identification of patients with aortic bioprosthesis stenosis with excellent sensitivity and specificity. It may be taken into consideration in clinical practice for the evaluation of patients with aortic bioprosthesis stenosis and left ventricular dysfunction.