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Abstract: New macro-cellular carbons, called carbon meringues, have been prepared by whipping until stiff an aqueous solution of tannin until liquid foam was obtained, which was next stabilized in an oven and pyrolysed, hence their name. With such cheap, fast and very easy process, flawless, homogeneous carbon foams were obtained in a wider range of density than that of more conventional cellular vitreous carbon (CVC) foams derived from similar formulations but made by physical foaming. The porosity, the average cell size and the cell wall thickness were only controlled by the initial concentration of tannin, all other things being equal. The resultant carbon meringues were fully investigated by electron microscopy, X-ray tomography, mercury porosimetry, Kr and N2 adsorption, thermal conductivity and mechanical compression studies. Differences with former CVC foams, and advantages of the new process and materials have been emphasised. [Copyright &y& Elsevier]

Abstract: Synchrotron radiation micro-computed tomography (SRμCT) is a very useful technique when it comes to three-dimensional (3D) imaging of complex internal and external geometries. Being a fully non-destructive technique, SRμCT can be combined with other experiments in situ for functional imaging. We are especially interested in the combination of SRμCT with mechanical testing in order to gain new insights in the failure mechanism of trabecular bone. This interest is motivated by the immense costs in health care due to patients suffering from osteoporosis, a systemic skeletal disease resulting in decreased bone stability and increased fracture risk. To better investigate the different failure mechanisms on the microlevel, we have developed a novel in situ mechanical compression device, capable of exerting both static and dynamic displacements on experimental samples. The device was calibrated for mechanical testing using solid aluminum and bovine trabecular bone samples. To study different failure mechanisms in trabecular bone, we compared a fatigued and a non-fatigued bovine bone sample with respect to failure initiation and propagation. The fatigued sample failed in a burst-like fashion in contrast to the non-fatigued sample, which exhibited a distinct localized failure band. Moreover, microscopic cracks – microcracks and microfractures – were uncovered in a 3D fashion illustrating the failure process in great detail. The majority of these cracks were connected to a bone surface. The data also showed that the classification of microcracks and -fractures from 2D section can sometimes be ambiguous, which is also true for the distinction of diffuse and distinct microdamage. Detailed investigation of the failure mechanism in these samples illustrated that trabecular bone often fails in delamination, providing a mechanism for energy dissipation while conserving trabecular bone architecture. In the future, this will allow an even better understanding of bone mechanics related to its hierarchical structural organization. [Copyright &y& Elsevier]

Grating interferometry CT (GI-CT) is a promising technology that could play an important role in future breast cancer imaging. Thanks to its sensitivity to refraction and small-angle scattering, GI-CT could augment the diagnostic content of conventional absorption-based CT. However, reconstructing GI-CT tomographies is a complex task because of ill problem conditioning and high noise amplitudes. It has previously been shown that combining data-driven regularization with iterative reconstruction is promising for tackling challenging inverse problems in medical imaging. In this work, we present an algorithm that allows seamless combination of data-driven regularization with quasi-Newton solvers, which can better deal with ill-conditioned problems compared to gradient descent-based optimization algorithms. Contrary to most available algorithms, our method applies regularization in the gradient domain rather than in the image domain. This comes with a crucial advantage when applied in conjunction with quasi-Newton solvers: the Hessian is approximated solely based on denoised data. We apply the proposed method, which we call GradReg, to both conventional breast CT and GI-CT and show that both significantly benefit from our approach in terms of dose efficiency. Moreover, our results suggest that thanks to its sharper gradients that carry more high spatial-frequency content, GI-CT can benefit more from GradReg compared to conventional breast CT. Crucially, GradReg can be applied to any image reconstruction task which relies on gradient-based updates.

X-ray grating interferometry CT (GI-CT) is an emerging imaging modality which provides three complementary contrasts that could increase the diagnostic content of clinical breast CT: absorption, phase, and dark-field. Yet, reconstructing the three image channels under clinically compatible conditions is challenging because of severe ill-conditioning of the tomographic reconstruction problem. In this work we propose to solve this problem with a novel reconstruction algorithm that assumes a fixed relation between the absorption and the phase-contrast channel to reconstruct a single image by automatically fusing the absorption and phase channels. The results on both simulations and real data show that, enabled by the proposed algorithm, GI-CT outperforms conventional CT at a clinical dose.

Introduction: Conventional irrigation techniques do not remove debris adequately. The remaining tissue debris cause infection inside the root canal and may also affect the seal of the root canal. The study aimed to compare the ability of EndoVac (EV) with XP-endo finisher (XPF) in debris removal using micro-CT analysis., Materials and Methods: We used 12 lower first permanent molar human teeth for this study. The root canals were instrumented using a small TF adaptive system. Then, the volume of debris was calculated. Teeth were divided into two groups, according to advanced irrigation methods, with six teeth per group: EV group and XPF group. The volume of debris was calculated again. The paired-sample t -test was used to compare the volume of the debris before and after the use of advanced irrigation methods with the statistical significance of P < 0.05. The percentage of debris reduction was also calculated., Results: Both EV and XPF showed a significant decrease of debris in the mesial canals ( P < 0.05), whereas EV only showed a significant reduction of debris in the distal canals., Conclusion: Both EV and XPF were able to significantly reduce debris after instrumentation in the mesial canals of lower first mandibular molars., Clinical Significance: The study provides insight into the recent advanced methods used in debris removal and canal disinfection., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of International Society of Preventive and Community Dentistry.)

We aimed to analyze the morpho-geometric changes of the root canal system created by two rotary systems (TF Adaptive and BioRace) using micro-CT technology. Two concepts of rotary file system kinematics, continuous rotation and adaptive kinematics, were used in root canal preparation. Twenty mandibular molars (n = 20) were selected with the following criteria: the teeth have mesial roots with a single and continuous isthmus connecting the mesiobuccal and mesiolingual canals (Vertucci's Type I configuration) and distal roots with independent canals. Teeth were scanned at a resolution of 14 μm. Canals were divided equally into two groups and then enlarged sequentially using the BioRace system and TF Adaptive system according to manufacturer protocol. Co-registered images, before and after preparation, were evaluated for morphometric measurements of canal surface area, volume, structure model index, thickness, straightening, and un-instrumented surface area. Before and after preparation, data were statistically analyzed using a paired sample t -test. After preparation, data were analyzed using an unpaired sample test. The preparation by both systems significantly changed canal surface area, volume, structure model index, and thickness in both systems. There were no significant differences between instrument types with respect to these parameters ( p > 0.05). TF Adaptive was associated with less straightening (8% compared with 17% for BioRace in the mesial canal, p > 0.05). Both instrumentation systems produced canal preparations with adequate geometrical changes. BioRace straightened the mesial canals more than TF Adaptive.

Objectives: Previous research revealed that autogenous tooth roots may be biologically equivalent to conventional bone grafts for lateral ridge augmentation. However, these analyses were limited to two dimensions, whereas healing is a volumetric process. The present study aimed at volumetrically assessing the microstructure following lateral ridge augmentation using extracted tooth roots., Material and Methods: The roots of differently conditioned maxillary premolars (i.e., healthy: PM-C; endodontically treated: PM-E; ligature-induced periodontitis: PM-P) and retromolar cortical autogenous bone (AB) blocks were used for lateral ridge augmentation at chronic-type defects in the lower quadrants of n = 16 foxhounds. At 12 weeks, titanium implants were inserted and left to heal for another 3 weeks. Tissue biopsies were scanned using microcomputed tomography (μCT), and volumes of interest were separated at the buccal and oral aspects to measure bone volume per tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and connectivity density (Conn.D)., Results: All groups investigated revealed comparable BV/TV, Tb.Th, Tb.Sp, and Conn.D values at either the augmented buccal or pristine oral aspects, respectively. A gradual but heterogeneous replacement of grafts was observed in all groups, but residual PM fragments were particularly noted in PM-C and PM-P groups., Conclusions: Differently conditioned PM and AB grafts were associated with a comparable bone microstructure within the grafted area. The duration of replacement resorption may vary considerably among the subjects., Clinical Relevance: Autogenous tooth roots may serve as potential alternative to AB for localized alveolar ridge augmentation.

Purpose: A personalized estimation of the cochlear shape can be used to create computational anatomical models to aid cochlear implant (CI) surgery and CI audio processor programming ultimately resulting in improved hearing restoration. The purpose of this work is to develop and test a method for estimation of the detailed patient-specific cochlear shape from CT images., Methods: From a collection of temporal bone [Formula: see text]CT images, we build a cochlear statistical deformation model (SDM), which is a description of how a human cochlea deforms to represent the observed anatomical variability. The model is used for regularization of a non-rigid image registration procedure between a patient CT scan and a [Formula: see text]CT image, allowing us to estimate the detailed patient-specific cochlear shape., Results: We test the accuracy and precision of the predicted cochlear shape using both [Formula: see text]CT and CT images. The evaluation is based on classic generic metrics, where we achieve competitive accuracy with the state-of-the-art methods for the task. Additionally, we expand the evaluation with a few anatomically specific scores., Conclusions: The paper presents the process of building and using the SDM of the cochlea. Compared to current best practice, we demonstrate competitive performance and some useful properties of our method.

Histomorphometry and microCT are the two dominant imaging techniques to study bone structure and quality to evaluate repair, regeneration, and disease. These two methods are complementary; where histology provides highly resolved tissue properties on a cellular level in 2D, microCT provides spatial information of bone micro-structure in 3D. For this reason, both of these modalities are commonly used in bone studies. As it is not trivial to combine the images of these two modalities, the two methods are typically applied to different specimens within a study. However, we believe that applying both imaging modalities to the same specimen with a suitable fusion strategy may further strengthen the value of each modality. Therefore, we propose a registration method to align 2D histology slices with a 3D microCT volume, without any prior knowledge of the sectioning direction. In a preprocessing step, bone is extracted from both images. Then, we use a strategy for initializing potential locations, and an iterative approach for searching for an ideal fitting plane using Radon-based rigid transforms and feature-based affine alignments. The algorithm was tested and validated with simulated and real data. For the latter, microCT images of trabecular bone with 76 corresponding histological sections acquired from decalcified and calcified specimens were used. The registration resulted in 94.7% acceptable solutions as defined by a registration orientation error of less than 3°. Average registration accuracy of the acceptable results was 0.6°, leading to a target registration error for our method of 106.3μm, computed based on landmarks annotated by an observer. This corresponds roughly to 10pixels in the images; although, the relation to actual visible structures that provide the features to register, is arguably more relevant., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Cilia play a major role in the regulation of numerous signaling pathways and are essential for embryonic development. Mutations in genes affecting ciliary function can cause a variety of diseases in humans summarized as ciliopathies. To facilitate the detection and visualization of cilia in a temporal and spatial manner in mouse tissues, we generated a Cre-inducible cilium-specific reporter mouse line expressing an ARL13B-tRFP fusion protein driven by a CMV enhancer/chicken β actin promotor (pCAG) from the Hprt locus. We detected bright and specific ciliary signals by immunostainings of various mono- and multiciliated tissues and by time-lapse live-cell analysis of cultured embryos and organ explant cultures. Additionally, we monitored cilium assembly and disassembly in embryonic fibroblast cells using live-cell imaging. Thus, the ARL13B-tRFP reporter mouse strain is a valuable tool for the investigation of ciliary structure and function in a tissue-specific manner to understand processes, such as ciliary protein trafficking or cilium-dependent signaling in vitro and in vivo., (© 2017 Wiley Periodicals, Inc.)

Understanding the human inner ear anatomy and its internal structures is paramount to advance hearing implant technology. While the emergence of imaging devices allowed researchers to improve understanding of intracochlear structures, the difficulties to collect appropriate data has resulted in studies conducted with few samples. To assist the cochlear research community, a large collection of human temporal bone images is being made available. This data descriptor, therefore, describes a rich set of image volumes acquired using cone beam computed tomography and micro-CT modalities, accompanied by manual delineations of the cochlea and sub-compartments, a statistical shape model encoding its anatomical variability, and data for electrode insertion and electrical simulations. This data makes an important asset for future studies in need of high-resolution data and related statistical data objects of the cochlea used to leverage scientific hypotheses. It is of relevance to anatomists, audiologists, computer scientists in the different domains of image analysis, computer simulations, imaging formation, and for biomedical engineers designing new strategies for cochlear implantations, electrode design, and others.

In humans and mice, motile cilia occur on the surface of the embryonic ventral node, on respiratory and ependymal epithelia and in reproductive organs where they ensure normal left-right asymmetry of the organism, mucociliary clearance of airways, homeostasis of the cerebrospinal fluid and fertility. The genetic programme for the formation of motile cilia, thus critical for normal development and health, is switched on by the key transcription factor FOXJ1. In previous microarray screens for murine FOXJ1 effectors, we identified candidates for novel factors involved in motile ciliogenesis, including both genes that are well conserved throughout metazoa and beyond, like FOXJ1 itself, and genes without overt homologues outside higher vertebrates. Here we examine one of the novel murine FOXJ1 effectors, the uncharacterised 1700012B09Rik whose homologues appear to be restricted to higher vertebrates. In mouse embryos and adults, 1700012B09Rik is predominantly expressed in motile ciliated tissues in a FOXJ1-dependent manner. 1700012B09RIK protein localises to basal bodies of cilia in cultured cells. Detailed analysis of 1700012B09Rik lacZ knock-out mice reveals no impaired function of motile cilia or non-motile cilia. In conclusion, this novel FOXJ1 effector is associated mainly with motile cilia but - in contrast to other known FOXJ1 targets - its putative ciliary function is not essential for development or health in the mouse, consistent with a late emergence during evolution of motile ciliogenesis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To (i) assess the impact of insertion depth and abutment microstructure on the three-dimensional crestal bone-level changes at endosseous titanium implant using μCT and computerized image processing and (ii) to correlate the findings with previously reported histology., Material & Methods: Titanium implants (conical abutment connection) were inserted in each hemimandible of n = 6 foxhounds with the implant shoulder (IS) located either in epicrestal (0 mm), supracrestal (+1 mm) or subcrestal (-1 mm) positions and randomly (split-mouth design) connected with machined or partially micro-grooved healing abutments. At 20 weeks, the tissue biopsies were processed for μCT and histological (HI) analyses. The volumetric dehiscence profile around the implants was computed as distance between the implant shoulder (IS) and the most coronal bone-to-implant contact (CBI) using MATLAB. The respective buccal and oral values were averaged, and agreement with the respective IS-CBI scores from HI was assessed using Bland-Altman plots., Results: A median net bone gain was observed for supracrestal insertion depths at both abutment types, but lower bounds of the 75% quartile experienced net bone losses. Epicrestal and subcrestal insertion depths were linked to slight bone losses, and the buccal and oral dehiscences were smaller compared to supracrestal positioning. Bland-Altman plots yielded a moderate agreement of IS-CBI values measured with μCT and HI., Conclusion: The novel image processing method allowed reliable evaluations and pointed to a direct impact of insertion depths on crestal bone-level changes. Additionally, it demonstrated that HI morphometry crucially depends on the chosen cutting position., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Fractures of the distal section of the radius (Colles' fractures) occur earlier in life than other osteoporotic fractures. Therefore, they can be interpreted as a warning signal for later, more deleterious fractures of vertebral bodies or the femoral neck. In the past decade, the advent of HR-pQCT allowed a detailed architectural analysis of the distal radius and an automated but time-consuming estimation of its strength with linear micro-finite element (μFE) analysis. Recently, a second generation of HR-pQCT scanner (XtremeCT II, SCANCO Medical, Switzerland) with a resolution beyond 61 μm became available for even more refined biomechanical investigations in vivo. This raises the question how biomechanical outcome variables compare between the original (LR) and the new (HR) scanner resolution. Accordingly, the aim of this work was to validate experimentally a patient-specific homogenized finite element (hFE) analysis of the distal section of the human radius for the fast prediction of Colles' fracture load based on the last generation HR-pQCT. Fourteen pairs of fresh frozen forearms (mean age = 77.5±9) were scanned intact using the high (61 μm) and the low (82 μm) resolution protocols that correspond to the new and original HR-pQCT systems. From each forearm, the 20mm most distal section of the radius were dissected out, scanned with μCT at 16.4 μm and tested experimentally under compression up to failure for assessment of stiffness and ultimate load. Linear and nonlinear hFE models together with linear micro finite element (μFE) models were then generated based on the μCT and HR-pQCT reconstructions to predict the aforementioned mechanical properties of 24 sections. Precision errors of the short term reproducibility of the FE analyses were measured based on the repeated scans of 12 sections. The calculated failure loads correlated strongly with those measured in the experiments: accounting for donor as a random factor, the nonlinear hFE provided a marginal coefficient of determination (R m 2 ) of 0.957 for the high resolution (HR) and 0.948 for the low resolution (LR) protocols, the linear hFE with R m 2 of 0.957 for the HR and 0.947 for the LR protocols. Linear μFE predictions of the ultimate load were similar with an R m 2 of 0.950 for the HR and 0.954 for the LR protocols, respectively. Nonlinear hFE strength computation led to precision errors of 2.2 and 2.3% which were higher than the ones calculated based on the linear hFE (1.6 and 1.9%) and linear μFE (1.2 and 1.6%) for the HR and LR protocols respectively. Computation of the fracture load with nonlinear hFE demanded in average 6h of CPU time which was 3 times faster than with linear μFE, while computation with linear hFE took only a few minutes. This study delivers an extensive experimental and numerical validation for the application of an accurate and fast hFE diagnostic tool to help in identifying individuals who may be at risk of an osteoporotic wrist fracture and to follow up pharmacological and other treatments in such patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Formation of motile cilia in vertebrate embryos is essential for proper development and tissue function. Key regulators of motile ciliogenesis are the transcription factors FOXJ1 and NOTO, which are conserved throughout vertebrates. Downstream target genes of FOXJ1 have been identified in a variety of species, organs and cultured cell lines; in murine embryonic and foetal tissues, however, FOXJ1 and NOTO effectors have not been comprehensively analysed and our knowledge of the downstream genetic programme driving motile ciliogenesis in the mammalian lung and ventral node is fragmentary. We compared genome-wide expression profiles of undifferentiated E14.5 vs. abundantly ciliated E18.5 micro-dissected airway epithelia as well as Foxj1 + vs. Foxj1-deficient foetal (E16.5) lungs of the mouse using microarray hybridisation. 326 genes deregulated in both screens are candidates for FOXJ1-dependent, ciliogenesis-associated factors at the endogenous onset of motile ciliogenesis in the lung, including 123 genes that have not been linked to ciliogenesis before; 46% of these novel factors lack known homologues outside mammals. Microarray screening of Noto + vs. Noto null early headfold embryos (E7.75) identified 59 of the lung candidates as NOTO/FOXJ1-dependent factors in the embryonic left-right organiser that carries a different subtype of motile cilia. For several uncharacterised factors from this small overlap - including 1700012B09Rik, 1700026L06Rik and Fam183b - we provide extended experimental evidence for a ciliary function., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Motile cilia move extracellular fluids or mediate cellular motility. Their function is essential for embryonic development, adult tissue homeostasis and reproduction throughout vertebrates. FOXJ1 is a key transcription factor for the formation of motile cilia but its downstream genetic programme is only partially understood. Here, we characterise a novel FOXJ1 target, Cfap157, that is specifically expressed in motile ciliated tissues in mouse and Xenopus in a FOXJ1-dependent manner. CFAP157 protein localises to basal bodies and interacts with tubulin and the centrosomal protein CEP350. Cfap157 knockout mice appear normal but homozygous males are infertile. Spermatozoa display impaired motility and a novel phenotype: Cfap157-deficient sperm exhibit axonemal loops, supernumerary axonemal profiles with ectopic accessory structures, excess cytoplasm and clustered mitochondria in the midpiece regions, and defective axonemes along the flagella. Our study thus demonstrates an essential sperm-specific function for CFAP157 and suggests that this novel FOXJ1 effector is part of a mechanism that acts during spermiogenesis to suppress the formation of supernumerary axonemes and ensures a correct ultrastructure., (© 2016. Published by The Company of Biologists Ltd.)

Objectives: Compared with multirow detector CT (MDCT), specimen (ex vivo) micro-CT (μCT) has a significantly higher (~ 30 x) spatial resolution and is considered the gold standard for assessing bone above the cellular level. However, it is expensive and time-consuming, and when applied in vivo, the radiation dose accumulates considerably. The aim of this study was to examine whether the lower resolution of the widely used MDCT is sufficient to qualitatively and quantitatively evaluate bone regeneration in rats., Methods: Forty critical-size defects (5mm) were placed in the mandibular angle of rats and covered with coated bioactive titanium implants to promote bone healing. Five time points were selected (7, 14, 28, 56 and 112 days). μCT and MDCT were used to evaluate the defect region to determine the bone volume (BV), tissue mineral density (TMD) and bone mineral content (BMC)., Results: MDCT constantly achieved higher BV values than μCT (10.73±7.84 mm3 vs. 6.62±4.96 mm3, p<0.0001) and consistently lower TMD values (547.68±163.83 mm3 vs. 876.18±121.21 mm3, p<0.0001). No relevant difference was obtained for BMC (6.48±5.71 mm3 vs. 6.15±5.21 mm3, p = 0.40). BV and BMC showed very strong correlations between both methods, whereas TMD was only moderately correlated (r = 0.87, r = 0.90, r = 0.68, p < 0.0001)., Conclusions: Due to partial volume effects, MDCT overestimated BV and underestimated TMD but accurately determined BMC, even in small volumes, compared with μCT. Therefore, if bone quantity is a sufficient end point, a considerable number of animals and costs can be saved, and compared with in vivo μCT, the required dose of radiation can be reduced., Competing Interests: Scanco Medical AG provided support in the form of salaries for MS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of MS is articulated in the ‘author contributions’ section. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To draft a clinical profile of mentally ill first-generation Spanish immigrants in Germany treated in a special setting in their native language and to identify possible correlations between time of onset of a mental disorder and migration and also between degree of utilization and clinical as well as care variables., Method: Statistical reanalysis of individual data (n = 100) of a previously published descriptive study with aggregated data corresponding to 15 variables. Correlations are calculated using chi-square as well as Fisher's exact test. Multivariate regression and logistic models were conducted. In addition to the explained variance of the models (R(2)), analyses of residuals as well as post-hoc power analyses (1-β) were performed., Results: A quarter of the sample (26 %) was mentally ill before migration; most of the patients received treatment very late (about 10 years after onset) and became chronically ill. Half of the sample shows a relevant somatic comorbidity and large average lengths of inpatient stays (54 days). In 16 % of treated cases, repatriation had to be organized. The degree of chronicity correlates with mental illness prior to migration. Severe mood disorders and psychoses occur late after having migrated, addictions and neurotic disorders are equally distributed over time., Discussion: Migration can not be set in a causal relationship with the development of mental disorders, although there is a positive correlation between affective disorders and the duration of the migration status. Chronicity is related to an outbreak of the disease before migration. The sample is relatively homogeneous (one nationality, first generation), but loses epidemiological representativeness (not related to a catchment area)., (© Georg Thieme Verlag KG Stuttgart · New York.)

We propose a novel 3D-2D registration approach for micro-computed tomography (μCT) and histology (HI), constructed for dental implant biopsies, that finds the position and normal vector of the oblique slice from μCT that corresponds to HI. During image pre-processing, the implants and the bone tissue are segmented using a combination of thresholding, morphological filters and component labeling. After this, chamfer matching is employed to register the implant edges and fine registration of the bone tissues is achieved using simulated annealing. The method was tested on n=10 biopsies, obtained at 20 weeks after non-submerged healing in the canine mandible. The specimens were scanned with μCT 100 and processed for hard tissue sectioning. After registration, we assessed the agreement of bone to implant contact (BIC) using automated and manual measurements. Statistical analysis was conducted to test the agreement of the BIC measurements in the registered samples. Registration was successful for all specimens and agreement of the respective binary images was high (median: 0.90, 1.-3. Qu.: 0.89-0.91). Direct comparison of BIC yielded that automated (median 0.82, 1.-3. Qu.: 0.75-0.85) and manual (median 0.61, 1.-3. Qu.: 0.52-0.67) measures from μCT were significant positively correlated with HI (median 0.65, 1.-3. Qu.: 0.59-0.72) between μCT and HI groups (manual: R(2)=0.87, automated: R(2)=0.75, p<0.001). The results show that this method yields promising results and that μCT may become a valid alternative to assess osseointegration in three dimensions., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Notch signalling is a fundamental pathway that shapes the developing embryo and sustains adult tissues by direct communication between ligand and receptor molecules on adjacent cells. Among the ligands are two Delta paralogues, DLL1 and DLL4, that are conserved in mammals and share a similar structure and sequence. They activate the Notch receptor partly in overlapping expression domains where they fulfil redundant functions in some processes (e.g. maintenance of the crypt cell progenitor pool). In other processes, however, they appear to act differently (e.g. maintenance of foetal arterial identity) raising the questions of how similar DLL1 and DLL4 really are and which mechanism causes the apparent context-dependent divergence. By analysing mice that conditionally overexpress DLL1 or DLL4 from the same genomic locus (Hprt) and mice that express DLL4 instead of DLL1 from the endogenous Dll1 locus (Dll1Dll4ki), we found functional differences that are tissue-specific: while DLL1 and DLL4 act redundantly during the maintenance of retinal progenitors, their function varies in the presomitic mesoderm (PSM) where somites form in a Notch-dependent process. In the anterior PSM, every cell expresses both Notch receptors and ligands, and DLL1 is the only activator of Notch while DLL4 is not endogenously expressed. Transgenic DLL4 cannot replace DLL1 during somitogenesis and in heterozygous Dll1Dll4ki/+ mice, the Dll1Dll4ki allele causes a dominant segmentation phenotype. Testing several aspects of the complex Notch signalling system in vitro, we found that both ligands have a similar trans-activation potential but that only DLL4 is an efficient cis-inhibitor of Notch signalling, causing a reduced net activation of Notch. These differential cis-inhibitory properties are likely to contribute to the functional divergence of DLL1 and DLL4.

Chiral control of crystallization has ample precedent in the small-molecule world, but relatively little is known about the role of chirality in protein crystallization. In this study, lysozyme was crystallized in the presence of the chiral additive 2-methyl-2,4-pentanediol (MPD) separately using the R and S enantiomers as well as with a racemic RS mixture. Crystals grown with (R)-MPD had the most order and produced the highest resolution protein structures. This result is consistent with the observation that in the crystals grown with (R)-MPD and (RS)-MPD the crystal contacts are made by (R)-MPD, demonstrating that there is preferential interaction between lysozyme and this enantiomer. These findings suggest that chiral interactions are important in protein crystallization.