Characterization of the macromolecule baseline in localized (1)H-MR spectra of human brain

Short-echo-time magnetic resonance spectra of human brain contain broad contributions from macromolecules. As they are a priori of unknown shape and intensity, they pose a problem if one wants to quantitate the overlying spectral features from low-molecular-weight metabolites. On the other hand, the macromolecular contributions may provide relevant clinical information themselves, if properly evaluated. Several methods, based on T(1), T(2), or spectral shape, have previously been suggested to suppress or edit the macromolecule contributions. Here, a method is presented based on a series of saturation recovery scans and that allows for simultaneous recording of the macromolecular baseline and the fully relaxed metabolite spectrum. In comparison to an inversion recovery technique aimed at nulling signals from long-T(1) components, the saturation recovery method is less susceptible to T(1) differences inherent in signals from different metabolites or introduced by pathology. The saturation recovery method was used to quantitate the macromolecular baseline in white and/or gray matter locations of the human brain in 40 subjects. It was found that the content and composition of MR visible macromolecules depends on cerebral location, as well as the age of the investigated subject, while no gender dependence could be found.

3G network traffic sources measurement and analysis

In this paper, we show statistical analyses of several types of traffic sources in a 3G network, namely voice, video and data sources. For each traffic source type, measurements were collected in order to, on the one hand, gain better understanding of the statistical characteristics of the sources and, on the other hand, enable forecasting traffic behaviour in the network. The latter can be used to estimate service times and quality of service parameters. The probability density function, mean, variance, mean square deviation, skewness and kurtosis of the interarrival times are estimated by Wolfram Mathematica and Crystal Ball statistical tools. Based on evaluation of packet interarrival times, we show how the gamma distribution can be used in network simulations and in evaluation of available capacity in opportunistic systems. As a result, from our analyses, shape and scale parameters of gamma distribution are generated. Data can be applied also in dynamic network configuration in order to avoid potential network congestions or overflows. Copyright © 2013 John Wiley & Sons, Ltd.

Statistical characterization and development of summary measures of non-normal distributions of nuclear morphometry data from prostate cancer cells for use as prognostic indicators

Nuclear morphometry (NM) uses image analysis to measure features of the cell nucleus which are classified as: bulk properties, shape or form, and DNA distribution. Studies have used these measurements as diagnostic and prognostic indicators of disease with inconclusive results. The distributional properties of these variables have not been systematically investigated although much of the medical data exhibit nonnormal distributions. Measurements are done on several hundred cells per patient so summary measurements reflecting the underlying distribution are needed.^ Distributional characteristics of 34 NM variables from prostate cancer cells were investigated using graphical and analytical techniques. Cells per sample ranged from 52 to 458. A small sample of patients with benign prostatic hyperplasia (BPH), representing non-cancer cells, was used for general comparison with the cancer cells.^ Data transformations such as log, square root and 1/x did not yield normality as measured by the Shapiro-Wilks test for normality. A modulus transformation, used for distributions having abnormal kurtosis values, also did not produce normality.^ Kernel density histograms of the 34 variables exhibited non-normality and 18 variables also exhibited bimodality. A bimodality coefficient was calculated and 3 variables: DNA concentration, shape and elongation, showed the strongest evidence of bimodality and were studied further.^ Two analytical approaches were used to obtain a summary measure for each variable for each patient: cluster analysis to determine significant clusters and a mixture model analysis using a two component model having a Gaussian distribution with equal variances. The mixture component parameters were used to bootstrap the log likelihood ratio to determine the significant number of components, 1 or 2. These summary measures were used as predictors of disease severity in several proportional odds logistic regression models. The disease severity scale had 5 levels and was constructed of 3 components: extracapsulary penetration (ECP), lymph node involvement (LN+) and seminal vesicle involvement (SV+) which represent surrogate measures of prognosis. The summary measures were not strong predictors of disease severity. There was some indication from the mixture model results that there were changes in mean levels and proportions of the components in the lower severity levels. ^

Quantitative morphometric analysis of lakes using GIS: rectangularity R , ellipticity E , orientation O , and the rectangularity vs. ellipticity index, REi

Quantitative measures of polygon shapes and orientation are important elements of geospatial analysis. These kinds of measures are particularly valuable in the case of lakes, where shape and orientation patterns can help identifying the geomorphological agents behind lake formation and evolution. However, the lack of built-in tools in commercial geographic information system (GIS) software packages designed for this kind of analysis has meant that many researchers often must rely on tools and workarounds that are not always accurate. Here, an easy-to-use method to measure rectangularity R, ellipticity E, and orientation O is developed. In addition, a new rectangularity vs. ellipticity index, REi, is defined. Following a step-by-step process, it is shown how these measures and index can be easily calculated using a combination of GIS built-in functions. The identification of shapes and estimation of orientations performed by this method is applied to the case study of the geometric and oriented lakes of the Llanos de Moxos, in the Bolivian Amazon, where shape and orientation have been the two most important elements studied to infer possible formation mechanisms. It is shown that, thanks to these new indexes, shape and orientation patterns are unveiled, which would have been hard to identify otherwise.

The new bern PET cyclotron, its research beam line, and the development of an innovative beam monitor detector

The new Bern cyclotron laboratory aims at industrial radioisotope production for PET diagnostics and multidisciplinary research by means of a specifically conceived beam transfer line, terminated in a separate bunker. In this framework, an innovative beam monitor detector based on doped silica and optical fibres has been designed, constructed, and tested. Scintillation light produced by Ce and Sb doped silica fibres moving across the beam is measured, giving information on beam position, shape, and intensity. The doped fibres are coupled to commercial optical fibres, allowing the read-out of the signal far away from the radiation source. This general-purpose device can be easily adapted for any accelerator used in medical applications and is suitable either for low currents used in hadrontherapy or for currents up to a few μA for radioisotope production, as well as for both pulsed and continuous beams.

Experimental, theoretical and numerical investigation of the nonlinear micromechanical properties of bone

Aging societies suffer from an increasing incidence of bone fractures. Bone strength depends on the amount of mineral measured by clinical densitometry, but also on the micromechanical properties of the bone hierarchical organization. A good understanding has been reached for elastic properties on several length scales, but up to now there is a lack of reliable postyield data on the lower length scales. In order to be able to describe the behavior of bone at the microscale, an anisotropic elastic-viscoplastic damage model was developed using an eccentric generalized Hill criterion and nonlinear isotropic hardening. The model was implemented as a user subroutine in Abaqus and verified using single element tests. A FE simulation of microindentation in lamellar bone was finally performed show-ing that the new constitutive model can capture the main characteristics of the indentation response of bone. As the generalized Hill criterion is limited to elliptical and cylindrical yield surfaces and the correct shape for bone is not known, a new yield surface was developed that takes any convex quadratic shape. The main advantage is that in the case of material identification the shape of the yield surface does not have to be anticipated but a minimization results in the optimal shape among all convex quadrics. The generality of the formulation was demonstrated by showing its degeneration to classical yield surfaces. Also, existing yield criteria for bone at multiple length scales were converted to the quadric formulation. Then, a computational study to determine the influence of yield surface shape and damage on the in-dentation response of bone using spherical and conical tips was performed. The constitutive model was adapted to the quadric criterion and yield surface shape and critical damage were varied. They were shown to have a major impact on the indentation curves. Their influence on indentation modulus, hardness, their ratio as well as the elastic to total work ratio were found to be very well described by multilinear regressions for both tip shapes. For conical tips, indentation depth was not a significant fac-tor, while for spherical tips damage was insignificant. All inverse methods based on microindentation suffer from a lack of uniqueness of the found material properties in the case of nonlinear material behavior. Therefore, monotonic and cyclic micropillar com-pression tests in a scanning electron microscope allowing a straightforward interpretation comple-mented by microindentation and macroscopic uniaxial compression tests were performed on dry ovine bone to identify modulus, yield stress, plastic deformation, damage accumulation and failure mecha-nisms. While the elastic properties were highly consistent, the postyield deformation and failure mech-anisms differed between the two length scales. A majority of the micropillars showed a ductile behavior with strain hardening until failure by localization in a slip plane, while the macroscopic samples failed in a quasi-brittle fashion with microcracks coalescing into macroscopic failure surfaces. In agreement with a proposed rheological model, these experiments illustrate a transition from a ductile mechanical behavior of bone at the microscale to a quasi-brittle response driven by the growth of preexisting cracks along interfaces or in the vicinity of pores at the macroscale. Subsequently, a study was undertaken to quantify the topological variability of indentations in bone and examine its relationship with mechanical properties. Indentations were performed in dry human and ovine bone in axial and transverse directions and their topography measured by AFM. Statistical shape modeling of the residual imprint allowed to define a mean shape and describe the variability with 21 principal components related to imprint depth, surface curvature and roughness. The indentation profile of bone was highly consistent and free of any pile up. A few of the topological parameters, in particular depth, showed significant correlations to variations in mechanical properties, but the cor-relations were not very strong or consistent. We could thus verify that bone is rather homogeneous in its micromechanical properties and that indentation results are not strongly influenced by small de-viations from the ideal case. As the uniaxial properties measured by micropillar compression are in conflict with the current literature on bone indentation, another dissipative mechanism has to be present. The elastic-viscoplastic damage model was therefore extended to viscoelasticity. The viscoelastic properties were identified from macroscopic experiments, while the quasistatic postelastic properties were extracted from micropillar data. It was found that viscoelasticity governed by macroscale properties has very little influence on the indentation curve and results in a clear underestimation of the creep deformation. Adding viscoplasticity leads to increased creep, but hardness is still highly overestimated. It was possible to obtain a reasonable fit with experimental indentation curves for both Berkovich and spherical indenta-tion when abandoning the assumption of shear strength being governed by an isotropy condition. These results remain to be verified by independent tests probing the micromechanical strength prop-erties in tension and shear. In conclusion, in this thesis several tools were developed to describe the complex behavior of bone on the microscale and experiments were performed to identify its material properties. Micropillar com-pression highlighted a size effect in bone due to the presence of preexisting cracks and pores or inter-faces like cement lines. It was possible to get a reasonable fit between experimental indentation curves using different tips and simulations using the constitutive model and uniaxial properties measured by micropillar compression. Additional experimental work is necessary to identify the exact nature of the size effect and the mechanical role of interfaces in bone. Deciphering the micromechanical behavior of lamellar bone and its evolution with age, disease and treatment and its failure mechanisms on several length scales will help preventing fractures in the elderly in the future.

Morphologic characteristics, location, and associated complications of maxillary and mandibular supernumerary teeth as evaluated using cone beam computed tomography.

OBJECTIVES To evaluate the location and morphologic characteristics of supernumerary teeth and to assess the frequency and extent of root resorption of adjacent teeth using cone beam computed tomography (CBCT). MATERIALS AND METHODS CBCT scans of 82 patients with supernumerary teeth in the maxilla and mandible were evaluated by two orthodontists independently. Data regarding the type, shape, and three-dimensional (3D) location of the supernumeraries including the frequency and extent of root resorption of adjacent teeth were recorded and evaluated for possible associations. RESULTS The study comprised a total of 101 supernumerary teeth. Most of the patients (80.5 per cent) exhibited one single supernumerary tooth, while 15.8 per cent had two and 3.7 per cent had three supernumeraries. Males were affected more than females with a ratio of 1.65:1. Mesiodentes were the most frequently diagnosed type of supernumerary teeth (48.52 per cent), followed by supernumerary premolars (23.76 per cent) and lateral incisors (18.81 per cent). Supernumeraries were most commonly conical in shape (42.6 per cent) with a normal or inclined vertical position (61.4 per cent). Root resorption of adjacent teeth was detected for 22.8 per cent of the supernumerary teeth, most frequently for supernumerary premolars. There was a significant association between root resorption of adjacent teeth and type and shape of tooth. Interrater agreement for the measurements performed showed kappa values ranging from 0.55 to 1 with a kappa value of 1 for type and shape of the supernumerary teeth. CONCLUSIONS CBCT provides 3D information about location and shape of supernumerary teeth as well as prevalence and degree of root resorption of neighbouring teeth with moderate to high interrater correlation.

The tail plays a major role in the differing manoeuvrability of two sibling species of mouse-eared bats (Myotis myotis and Myotis blythii)

Two sympatrically occurring bat species, the greater mouse-eared bat (Myotis myotis (Borkhausen, 1797)) and the lesser mouse-eared bat (Myotis blythii (Tomes, 1857)) (Chiroptera, Vespertillionidae), share numerous similarities in morphology, roosting behaviour, and echolocation and are often difficult to distinguish. However, despite these similarities, their foraging behaviour is noticeably different. Our aim was to examine the extent to which these different foraging strategies reflect morphological adaptation. We assessed whether the morphology of the wing, body, and tail differed between M. myotis and M. blythii. In addition, in a laboratory experiment involving an obstacle course, we compared differences in manoeuvrability by relating them to our morphological measurements. The two species differed in their overall size, wing-tip shape, and tail-to-body length ratio. The generally smaller sized M. blythii performed better in the obstacle course and was therefore considered to be more manoeuvrable. Although differences in wing-tip shape were observed, we found the most important characteristic affecting manoeuvrability in both species to be the tail-to-body length ratio. Additionally, when we compared two bats with injured wing membranes with unharmed bats of the same species, we found no difference in manoeuvrability, even when the wing shape was asymmetric. We therefore postulate that morphometric differences between the two species in their overall size and, more importantly, in their tail-to-body length ratio are the main physical characteristics providing proof of adaptation to different foraging and feeding strategies.

Dissecting abdominal aortic aneurysm in Ang II-infused mice: suprarenal branch ruptures and apparent luminal dilatation.

AIMS In this work, we provide novel insight into the morphology of dissecting abdominal aortic aneurysms in angiotensin II-infused mice. We demonstrate why they exhibit a large variation in shape and, unlike their human counterparts, are located suprarenally rather than infrarenally. METHODS AND RESULTS We combined synchrotron-based, ultra-high resolution ex vivo imaging (phase contrast X-Ray tomographic microscopy) with in vivo imaging (high-frequency ultrasound and contrast-enhanced micro-CT) and image-guided histology. In all mice, we observed a tear in the tunica media of the abdominal aorta near the ostium of the celiac artery. Independently we found that, unlike the gradual luminal expansion typical for human aneurysms, the outer diameter increase of angiotensin II-induced dissecting aneurysms in mice was related to one or several intramural haematomas. These were caused by ruptures of the tunica media near the ostium of small suprarenal side branches, which had never been detected by the established small animal imaging techniques. The tear near the celiac artery led to apparent luminal dilatation, while the intramural haematoma led to a dissection of the tunica adventitia on the left suprarenal side of the aorta. The number of ruptured branches was higher in those aneurysms that extended into the thoracic aorta, which explained the observed variability in aneurysm shape. CONCLUSION Our results are the first to describe apparent luminal dilatation, suprarenal branch ruptures, and intramural haematoma formation in dissecting abdominal aortic aneurysms in mice. Moreover, we validate and demonstrate the vast potential of phase contrast X-ray tomographic microscopy in cardiovascular small animal applications.

Satellite laser ranging to GPS and GLONASS

Satellite laser ranging (SLR) to the satellites of the global navigation satellite systems (GNSS) provides substantial and valuable information about the accuracy and quality of GNSS orbits and allows for the SLR-GNSS co-location in space. In the framework of the NAVSTAR-SLR experiment two GPS satellites of Block-IIA were equipped with laser retroreflector arrays (LRAs), whereas all satellites of the GLONASS system are equipped with LRAs in an operational mode. We summarize the outcome of the NAVSTAR-SLR experiment by processing 20 years of SLR observations to GPS and 12 years of SLR observations to GLONASS satellites using the reprocessed microwave orbits provided by the center for orbit determination in Europe (CODE). The dependency of the SLR residuals on the size, shape, and number of corner cubes in LRAs is studied. We show that the mean SLR residuals and the RMS of residuals depend on the coating of the LRAs and the block or type of GNSS satellites. The SLR mean residuals are also a function of the equipment used at SLR stations including the single-photon and multi-photon detection modes. We also show that the SLR observations to GNSS satellites are important to validate GNSS orbits and to assess deficiencies in the solar radiation pressure models. We found that the satellite signature effect, which is defined as a spread of optical pulse signals due to reflection from multiple reflectors, causes the variations of mean SLR residuals of up to 15 mm between the observations at nadir angles of 0∘ and 14∘. in case of multi-photon SLR stations. For single-photon SLR stations this effect does not exceed 1 mm. When using the new empirical CODE orbit model (ECOM), the SLR mean residual falls into the range 0.1–1.8 mm for high-performing single-photon SLR stations observing GLONASS-M satellites with uncoated corner cubes. For best-performing multi-photon stations the mean SLR residuals are between −12.2 and −25.6 mm due to the satellite signature effect.

Retinal Cell Death Caused by Sodium Iodate Involves Multiple Caspase-Dependent and Caspase-Independent Cell-Death Pathways

Herein, we have investigated retinal cell-death pathways in response to the retina toxin sodium iodate (NaIO3) both in vivo and in vitro. C57/BL6 mice were treated with a single intravenous injection of NaIO3 (35 mg/kg). Morphological changes in the retina post NaIO3 injection in comparison to untreated controls were assessed using electron microscopy. Cell death was determined by TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining. The activation of caspases and calpain was measured using immunohistochemistry. Additionally, cytotoxicity and apoptosis in retinal pigment epithelial (RPE) cells, primary retinal cells, and the cone photoreceptor (PRC) cell line 661W were assessed in vitro after NaIO3 treatment using the ApoToxGlo™ assay. The 7-AAD/Annexin-V staining was performed and necrostatin (Nec-1) was administered to the NaIO3-treated cells to confirm the results. In vivo, degenerating RPE cells displayed a rounded shape and retracted microvilli, whereas PRCs featured apoptotic nuclei. Caspase and calpain activity was significantly upregulated in retinal sections and protein samples from NaIO3-treated animals. In vitro, NaIO3 induced necrosis in RPE cells and apoptosis in PRCs. Furthermore, Nec-1 significantly decreased NaIO3-induced RPE cell death, but had no rescue effect on treated PRCs. In summary, several different cell-death pathways are activated in retinal cells as a result of NaIO3.

How to be in a good shape? The influence of clone morphology on cell competition

Cell competition is a conserved mechanism where slow proliferating cells (so called losers) are eliminated by faster proliferating neighbors (so called winners) through apoptosis.(1) It is an important process which prevents developmental malformations and maintains tissue fitness in aging adults.(2) Recently, we have shown that the probability of elimination of loser cells correlates with the surface of contact between losers and winners in Myc-induced competition.(3) Moreover, we have characterized an active mechanism that increases the surface of contact between losers and winners, hence accelerating the elimination of loser cells. This is the first indication that cell shape and mechanics can influence cell competition. Here, we will discuss the consequence of the relationship between shape and competition, as well as the relevance of this model for other modes of competition.

Stand Structure Governs the Crown Collisions of Lodgepole Pine

We investigated tree sway and crown collision behavior of even-aged lodgepole pine (Pinus contorta Dougl. ex Loud. var. latifolia Engelm.) stands of different structure in Alberta, Canada, to examine how these factors might affect loss of leaf area as stands mature. The Two Creeks stand (TC) had high density and slender trees, while the Chickadee stand (CH) had stout trees. The TC stand was then thinned (TCT) to reduce the stand density. For each stand, simultaneous tree sways of a group of 10 trees were monitored with biaxial clinometers during wind speed of 5 m/s (canopy top). Crown collisions were reconstructed by combining sway displacement of individual trees with their respective crown dimensions. Comparing the sway statistics between stands with contrasting mean bole slenderness (TC and CH) indicated that more slender trees have greater sway displacements, faster sway speeds, and a greater depth of collision. Disturbance by thinning increased sway displacements, sway speeds, and depth of collisions at TCT. Tree sway patterns were circular in shape and not aligned with wind direction, but patterns were elongated after thinning. This demonstrates the high frequency of crown collision experienced by stands with slender trees and supports the notion that crown collisions result in empty space between crowns of trees.

NHERF1 recruits the tumor suppressors PTEN and PHLPP to synergistically inhibit the PI-3K pathway

Glioblastoma multiforme is the most common form of brain cancer that presents patients with a poor prognosis that has remained unchanged over the past few decades. The tumor suppressor phosphatase PTEN antagonizes one of the major oncogenic pathways involved in the progression of glioblastoma, and is frequently deleted in this cancer type. Contrary to our expectations, we found that most glioblastoma cells expressing endogenous PTEN also harbor basal PI-3K/AKT activation mainly attributable to impaired PTEN membrane localization. This alteration correlated with a shift of the adaptor protein NHERF1, which contributes to PTEN membrane recruitment in normal cells, from the membrane to the cytoplasm. In cells expressing membrane-localized NHERF1, only simultaneous PTEN and NHERF1 depletion achieved AKT activation, suggesting the involvement of additional PI-3K/AKT suppressor regulated by NHERF1. We identified these novel interactors of NHERF1 as the PHLPP1 and PHLPP2 phosphatases. ^ NHERF1 directly interacted and recruited both PHLPP proteins to the membrane and, through both NHERF1 PDZ domains, assembled ternary complexes consisting of PTEN-NHERF1-PHLPP. Only simultaneous depletion of PTEN and PHLPP1 significantly activated AKT and increased proliferation in cells with membrane-localized NHERF1. Analysis of glioblastoma human tumors revealed frequent loss of membrane-localized NHERF1. On the other hand, targeting of NHERF1 to the membrane achieved suppression of AKT and cell proliferation. Our findings reveal a novel mechanism for PI-3K/AKT regulation by the synergistic cooperation between two important tumor suppressors, PTEN and PHLPP, via the scaffold protein NHERF1. ^

Temperature, salinity and ikaite crystal characteristics in snow, slush and sea ice during R/V Lance cruise in April-May 2011

We identified ikaite crystals (CaCO3 · 6H2O) and examined their shape and size distribution in first-year Arctic pack ice, overlying snow and slush layers during the spring melt onset north of Svalbard. Additional measurements of total alkalinity (TA) were made for melted snow and sea-ice samples. Ikaite crystals were mainly found in the bottom of the snowpack, in slush and the surface layers of the sea ice where the temperature was generally lower and salinity higher than in the ice below. Image analysis showed that ikaite crystals were characterized by a roughly elliptical shape and a maximum caliper diameter of 201.0±115.9 µm (n = 918). Since the ice-melting season had already started, ikaite crystals may already have begun to dissolve, which might explain the lack of a relationship between ikaite crystal size and sea-ice parameters (temperature, salinity, and thickness of snow and ice). Comparisons of salinity and TA profiles for melted ice samples suggest that the precipitation/dissolution of ikaite crystals occurred at the top of the sea ice and the bottom of the snowpack during ice formation/melting processes.