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Abstract: Objective: Catecholamines released from β-adrenergic neurons upon stress can interfere with periodontal regeneration. The cellular mechanisms, however, are unclear. Here, we assessed the effect of catecholamines on proliferation of periodontal fibroblasts. Methods: Fibroblasts from the gingiva and the periodontal ligament were exposed to agonists of the β-adrenergic receptors; isoproterenol (ISO, non-selective β-adrenergic agonist), salbutamol (SAL, selective β2-adrenergic receptor agonist) and BRL 37344 (BRL selective β3-receptor agonist). Proliferation was stimulated with platelet-derived growth factor-BB (PDGF-BB). Pharmacological inhibitors and gene expression analysis further revealed β-adrenergic signalling. Results: Gingiva and periodontal ligament fibroblast express the β2-adrenergic receptor. ISO and SAL but not BRL decreased proliferation of fibroblasts in the presence of PDGF-BB. The inhibitory effect of β-adrenergic signalling on proliferation but not protein synthesis in response to PDGF-BB was reduced by propranolol, a non-selective β-adrenergic antagonist. Conclusions: These results suggest that β2-receptor agonists can reduce the mitogenic response of periodontal fibroblasts. These data add to the compelling concept that blocking of β2-receptor signalling can support tissue maintenance and regeneration. [Copyright &y& Elsevier]

Abstract: Purpose: To determine the accuracy of a probably benign assessment of non-palpable breast lesions (BI-RADS category 3) at mammography and/or ultrasound with immediate histological work-up. Materials and methods: Stereotactic or ultrasound guided core needle breast biopsy (NBB) was performed to evaluate 288 lesions, which were prospectively assessed as BI-RADS category 3. Imaging findings included 195 masses, 73 calcification cases, 16 focal asymmetries, and four architectural distortion cases. After NBB, patients underwent either open surgical biopsy (OSB) (n =204) or mammographic follow-up (n =84) for at least 24 months. Histological results of NBB were compared with those of OSB. Results: Three of the 288 lesions (1.0%) proved to be malignant at histological work-up, two of them were ductal carcinoma in situ (DCIS) and one of them was an invasive carcinoma. NBB revealed invasive carcinoma in 1/288 (0.35%) and atypical ductal hyperplasia (ADH) in 13/288 (4.5%) lesions. OSB revealed DCIS in 2/204 (1%) and invasive carcinoma in 1/204 (0.5%) lesions. The two DCIS were underestimated as ADH by NBB. The remaining 285 (99%) lesions proved to be benign at OSB or remained stable during follow-up. Conclusion: Confirmed by tissue diagnosis, the low likelihood of malignancy of prospectively assessed probably benign lesions is below the 2% threshold established for BI-RADS category 3. Imaging follow-up is a safe and effective alternative to immediate histological work-up for such lesions. [Copyright &y& Elsevier]

Abstract: Purpose: To determine the frequency with which stereotactic 11-g vacuum-assisted breast biopsy (11-g SVAB) obviates an open surgical biopsy (OSB), to compare the costs of these two biopsy methods, and to estimate the potential cost savings attributable to 11-g SVAB in the diagnosis of suspicious breast lesions in patients in Austria. Materials and methods: We retrospectively reviewed 318 consecutive breast lesions of BI-RADS categories IV and V (microcalcifications n =166; masses n =152) on which 11-g SVAB and OSB were performed. Cost savings were calculated using nationally allowed flat rates and patient charges. Costs were measured from a hospital and a socioeconomic perspective. Common clinical scenarios and sensitivity analyses assessed the extent of achievable cost savings. Results: 11-g SVAB obviated the need for an OSB in 93 (29%) of 318 women. Overall cost savings per 11-g SVAB over OSB were € 242 per case from a hospital perspective, and € 422 per case from a socioeconomic perspective. The use of 11-g SVAB decreased the cost of diagnosis by 7% from a hospital perspective, and by 10% from a socioeconomic perspective. Conclusion: In Austria, annual national savings of over 5 million Euro could be realized with the use of 11-g SVAB for the diagnosis of suspicious breast lesions. Although savings per case are modest, the national health care system realizes significant cost reduction as women benefit from a faster and less invasive approach to diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To examine the budget impact of ultrasound-guided 14-g large core breast biopsy (US-guided LCBB) by comparing the costs of US-guided LCBB and open surgical biopsy (OSB); to calculate the cost savings attributable to US-guided LCBB; and to assess the frequency with which US-guided LCBB obviates the need for an OSB. Materials and methods: In a retrospective study, we reviewed 399 suspicious breast lesions on which US-guided LCBB and OSB or, in cases of benign histology, clinical follow-up, were performed. Cost savings were calculated using nationally allowed flat rates (A-drg) and patient charges. Costs were measured from both, a hospital and a socioeconomic perspective. Deterministic sensitivity analyses were simulated to assess the extent of achievable cost savings. Results: Overall cost savings for US-guided LCBB over OSB were €977 (€2,337/€3,314) per case from a hospital perspective, resulting in a total cost decrease of 30% for the diagnosis of suspicious breast lesions. From a socioeconomic perspective, cost savings were €1,542 (€2,600/€4,142) per case, resulting in a 37% reduction in biopsy cost. US-guided LCBB obviated the need for a surgical procedure in 240 (60%) of 399 women. In all four sensitivity analyses, costs of US-guided LCBB remained lower than that of OSB. Conclusion: From an economic perspective, US-guided LCBB is highly recommended for the diagnosis of suspicious breast lesions, as this procedure reduces the cost of diagnosis substantially. In Austria, annual cost savings would be €18.5 million. [Copyright &y& Elsevier]

Time-of-flight (TOF) experiments in the low energy ion scattering (LEIS) regime are reported for He projectiles and a copper target for a scattering angle of 129°, aiming at a more profound physical understanding of the neutralization process. In our experiment, the ions are separated from the neutrals by post-acceleration along the flight path between the target and the detector. The spectrum of the neutrals yields information about deeper layers, as in Rutherford backscattering (RBS). Ions originate from scattering by surface atoms, the ion yield being characterized by the ion fraction P+. Our P+ results indicate that at energies >2 keV a second neutralisation mechanism sets in that is similarly effective as the one that is important at low energies. Above the threshold energy for reionization, a non-monotonous behavior of P+ as function of the reciprocal velocity is found. Our data are compared to available data from the literature, yielding mutual agreement within the combined error bars. [Copyright &y& Elsevier]

Platelets are activated at fracture sites or upon the insertion of implants as a consequence of vascular disruption and secrete the contents of their granules into the developing hematoma. The regeneration of injured tissue requires bone remodeling and the resorbing activity of osteoclasts. To test our hypothesis that platelets can stimulate osteoclastogenesis, we examined the effects of supernatants released from thrombin-activated platelets on osteoclast-like cell formation in murine bone marrow cultures. Histochemical analysis indicated the presence of bone-resorbing, tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. Transcripts that are characteristically expressed in native osteoclasts were increased in these cultures, as determined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. The inhibition of both cyclooxygenases with indomethacin, as well as the addition of the cyclooxygenase-2 (COX-2)-selective antagonist, NS398, completely blocked osteoclast-like cell formation and decreased endogenous prostaglandin E2 production. Platelet-released supernatants stimulated the expression of receptor activator of NF-κB ligand (RANKL), whereas mRNA levels of osteoprotegerin (OPG) were decreased. The formation of osteoclast-like cells was prevented by recombinant OPG. Our results suggest that COX-2 activity is necessary for osteoclast-like cell formation in response to platelet-released supernatants, and that endogenously produced prostaglandin E2 can, in turn, increase the RANKL:OPG ratio, indicating that platelets can contribute to bone remodeling by stimulation of osteoclastogenesis. [Copyright &y& Elsevier]

In this study a close to reality one component (1K) structural epoxy adhesive is introduced. The physical properties have been investigated by means of gravimetric water uptake, bulk tensile tests, and lap shear tests. The influence of two different types of hollow glass microspheres (HGM) on the ageing behaviour has been observed via accelerated ageing tests followed by lap shear tests of galvanized steel. Results show that the formulation described outperforms very brittle and basic systems consisting of bisphenol A diglycidyl ether (DGEBA) and dicyandiamide (DICY) in terms of ductility. The addition of HGM resulted in higher water absorption suggesting that water gathers as a liquid in the HGM. Further, the addition of HGM led to an increase of the cohesion failure percentage on unaged lap shear specimens without significantly influencing the tensile shear strength and the addition of the bigger HGM observed led to a change in fracture mechanism from substrate-near cohesion failure to cohesion failure. The results of this study on the long-term durability of bonded steel joints indicate that the addition of HGM into the adhesive system has no significant effect on the ageing behaviour in two of three corrosion tests. It can be concluded that the incorporation of HGM is a possible solution not only reducing the amount of chemicals required for automotive adhesive production, but also promoting lightweight construction because of the decreased density of the adhesive system. • A novel, near to realism structural epoxy adhesive for scientific purposes. • Gravimetric water uptake in structural epoxy adhesive. • Ageing resistance of adhesively bonded steel sheets. • Addition of hollow glass microspheres changes fracture mechanism. [ABSTRACT FROM AUTHOR]

In the current paper, we first introduce the research themes of the attention, behaviour and sleep (ABS) laboratory, namely, sleep and ADHD, sleep and obesity, and sleep and academic performance. We then focus in on the topic to be reviewed in the current paper – the association between sleep restriction and neurobehavioral functioning (NBF) in typically developing children. We review the research thus far conducted by the ABS lab specific to this topic and posit the unique methodological contributions of the ABS lab (e.g. home-based assessment of sleep architecture and patterns, extensive phenotyping, etc.) in terms of advancing this research area. In the second section of the paper, we review 13 studies investigating the causal association between experimental sleep restriction and NBF in normally developing pediatric populations. Eight of the 13 studies found that sleep restriction causes impairments in neurobehavioural functioning. However, given the inconsistency in outcome measures, experimental protocols and statistical power, the studies reviewed herein are difficult to interpret. Strategies used by the ABS including implementing home assessments of sleep, restricting sleep relative to the participants’ typical sleep schedules, blinding raters who assess NBF, and using valid and reliable NBF assessments are an attempt to address the gaps in this research area and clarify the causal relationship between sleep restriction and NBF in typically developing children and adolescents. [ABSTRACT FROM AUTHOR]

Abstract: This paper describes a new hp method for the numerical solution of the two-dimensional eigenvalue problem in primal variational formulation. In standard methods with triangular or quadrangular finite elements, or with spectral elements, the spectrum contains spurious modes if the mesh is non-Cartesian. With the new hp method described in this paper we show that, although it delivers a approximation on the same grid for both velocity components, the spectrum is represented without any spurious mode whether a Cartesian or a non-Cartesian quadrangular grid is chosen. Spectra computed with standard high-order methods and with the new element are presented and compared with the analytic solutions. [Copyright &y& Elsevier]

The antibiotic Beauvericin (BEA) was previously shown to express ionophoric properties under simple experimental systems. Its channel-forming activity was examined in inside–out patches of ventricular myocytes and synthetic membranes with the patch clamp and fluorescence imaging techniques. Current transitions to several open state levels were evident after wash-in. The BEA channel is cation-selective. Conductance and kinetics are presented for K+ and Na+ substates and main states. The pore was blocked by La3+. In myocytes, the [K+]i was reduced, while [Na+]i and [Ca2+]i increased, leading to cytolysis. These results indicate that BEA forms cation-selective channels in lipid membranes, which can affect the ionic homeostasis. [Copyright &y& Elsevier]

The preparation of active carbons containing nitrogen surface functions is considered by ammoxidation of various raw materials like pinewood, peat and lignite. To have an accurate knowledge of the nitrogen functions introduced, diffuse reflectance IR/FT and X-ray photoelectron spectroscopies were used. Taking into account the complexity of the raw materials, the structural characterisation of the cellulose ammoxidation products was undertaken in the first step of our study, since cellulose is one of the major compounds of woods. The thermal treatment of cellulose, at around 250 °C and at different durations (1, 2, 4 h), was realised for comparison under several conditions: air, argon, ammonia and air–ammonia mixtures (ammoxidation). Several nitrogenated structures were characterised. The mechanism of their formation from the C4 fragment formed from the heterolytic cleavage of cellulose by thermal treatment was proposed pointing out the fundamental role of intermediate imine function. [Copyright &y& Elsevier]

Soil management techniques, such as mulching, are used to enhance soil organic carbon sequestration. However, we demonstrate that the potential of crop residue mulching to increase soil organic carbon (SOC) sequestration varies by cropping system and soil type in Austrian agricultural soils. Effects of mulch (as harvested crop residues applied at 1.0 t C ha −1 ) on soil and microbial carbon (C) and nitrogen (N) and soil δ 13 C were measured in an Austrian Cambisol field experiment with sole maize or vetch or vetch-maize rotation cropping systems after five years with or without mulching to elucidate how SOC is affected. The direct role of mulch on SOC in different soil types was also investigated in a similar greenhouse mesocosm study with controlled moisture using the same Cambisols and an Austrian agricultural Chernozem. Only sole maize cropping in the field experiment resulted in higher SOC with mulching and when legumes were included in a legume-maize rotation SOC did not improve. Mulching in the field experiment only resulted in higher SOC in the top 0–5 cm of soils with sole maize cropping (by 22%) compared to soils without mulch. Although mulch did not increase SOC in vetch-maize rotation, the δ 13 C of SOC was less negative with mulch indicating larger C contribution from maize than vetch mulch. After four years of annual soybean-maize rotation in the mesocosm experiment, no significant differences in SOC were observed in Cambisols with or without mulch. Again, δ 13 C of both soil types was less negative with mulching indicating a larger C contribution from maize than soybean mulch. No relationships between microbial biomass C and N and SOC were observed in either experiment and only soil N concentration was positively correlated with SOC. Together these studies indicate that maize can increase SOC when crop residues are applied in Austrian Cambisols but that inclusion of legume production and legume mulch in rotation can mute these benefits. [ABSTRACT FROM AUTHOR]

Abstract: Destruxins (Dtx) are secondary metabolites of the entomopathogenic fungus Metarhizium anisopliae. Recently, Dtx came into focus of interest as anticancer therapeutics. However, data on human and especially on cancer cells are fragmentary. In order to successfully establish novel anticancer therapeutics, a broad knowledge on the cellular and molecular mechanisms underlying their activity is essential. Consequently, this study aimed to investigate the impact of the most common Dtx derivatives A, B and E on human cancer cell growth and survival with a focus on colon cancer cell models. Summarizing, the experimental data showed that (i) Dtx A and B exert potent antiproliferative activity in the micromolar and Dtx E in the nanomolar range in KB-3-1, A549, CaCo-2, and especially in HCT116 colon cancer cells, (ii) all three Dtx derivatives cause imbalance of cell cycle distribution, (iii) their cytostatic/cytotoxic effects are widely p53-independent but reduced by p21- and bax-deletion, respectively, (iv) cytotoxicity is based on intrinsic apoptosis induction and associated with phosphoinositide-3-kinase (PI3K)/Akt pathway inhibition, (v) anticancer activity of Dtx E but not Dtx A and B involves disturbance of the intracellular redox balance, (vi) Dtx inhibit the migration and tube formation of human endothelial cells indicating antiangiogenic potential, and (vii) all three Dtx derivatives possess ionophoric properties not differing in conductivity, ion selectivity and single channel kinetics. Thus, Dtx represent feasible, multifunctional anticancer drug candidates for preclinical development especially against colorectal cancer. [Copyright &y& Elsevier]

Abstract: Objective: Ageing, hypogonadism, malnutrition, and the application of glucocorticoids have adverse effects on skeletal homeostasis. Herein we determined to which extent the periodontium undergoes catabolic changes under these conditions in a sheep model. Methods: Six old sheep with a mean age of 7.5±1.0 years were subjected to ovariectomy, calcium/vitamin D-restricted diet, and intramuscular administration of approximately 2g methylprednisolone. Six adult sheep with a mean age of 3.8±0.9 years remained untreated and served as controls. First and second premolars of both jaws were subjected to histological analysis. The distances from the gingival margin (GM) and from the alveolar bone crest (ABC) to the cemento-enamel junction (CEJ) were determined. Periodontal attachment was given as the ratio between the dimension of the periodontal ligament and the alveolar bone. Clinical data were collected by counting the number of teeth missing, teeth with gingival recession, and teeth with a probing depth>4mm. Results: We report that distance between GM and CEJ (2.1±1.7mm and 6.6±2.6mm maxilla; −0.4±1.4mm and 3.2±1.5mm mandible), and between ABC and CEJ (−3.4±1.3mm and 1.8±2.7mm maxilla; −3.5±1.1mm and −0.1±1.4mm mandible) are significantly lower in test than in control animals. In line with these findings, periodontal attachment was 67% in the maxilla and 86% in the mandible of the test group and almost completely preserved in the control group. Clinical evaluation showed that the overall number of teeth with recessions was significantly higher in the test compared to the control group (4.9±2.4 and 2.3±3.6), but not the number of teeth missing and teeth with a probing depth>4mm. Conclusions: Together these findings suggest that in sheep, the cumulating effects of ageing, hypogonadism, malnutrition and glucocorticoid application can cause substantial catabolic changes of the periodontium. [Copyright &y& Elsevier]

Abstract: Nematode infections cause human morbidity and enormous economic loss in livestock. Since resistance against currently available anthelmintics is a worldwide problem, there is a continuous need for new compounds. The cyclooctadepsipeptide PF1022A is a novel anthelmintic that binds to the latrophilin-like transmembrane receptor important for pharyngeal pumping in nematodes. Furthermore, PF1022A binds to GABA receptors, which might contribute to the anthelmintic effect. Like other cyclodepsipeptides, PF1022A acts as an ionophore. However, no correlation between ionophoric activity and anthelmintic properties was found. This is the first study describing the effect of PF1022A on mammalian cells and tissues. While channel-forming activity was observed already at very low concentrations, changes in intracellular ion concentrations and reduction of contractility in isolated guinea pig ileum occurred at multiples of anthelmintically active concentrations. PF1022A did not induce necrotic cell death indicated by complete lack of cellular lactate dehydrogenase release. In contrast, apoptosis induction via the mitochondrial pathway was suggested for long-term drug treatment at high concentrations due to numerous apoptotic morphological changes as well as mitochondrial membrane depolarisation. Short time effects were based on cell cycle blockade in G0/G1 phase. Additionally, the cell cycle and apoptosis regulating proteins p53, p21 and bax, but not Bcl-2 were shown to impact on PF1022A-induced cytotoxicity. However, since PF1022A-induced cytotoxicity was found at drug concentrations higher than those used in anthelmintic treatment, it can be suggested that PF1022A intake might not impair human or animal health. Thus, PF1022A seems to be a safe alternative to other anthelmintic drugs. [Copyright &y& Elsevier]

Abstract: This paper presents spectral approaches on staggered grids to extract the solenoidal (i.e. divergence free) and non-solenoidal (i.e. curl free or, gradient of a scalar field) components of a given vector field. Basically, the vector field is described using a polynomial expansion on a GLL/GL-GL/GLL mesh, and the scalar field is computed using a polynomial expansion on the GL/GL grid. These approaches use the same spectral element and consist in a projection either onto the kernel of the operator, or onto its range. Two variational formulations are presented and studied to approximate the divergence free and the curl free parts of the spectrum. Each one is well adapted to ensure the expected constraints. The approaches are detailed and illustrated by several numerical examples. [Copyright &y& Elsevier]

Abstract: Secondary metabolites produced by Fusarium spp. including beauvericin, enniatin and moniliformin are mycotoxins identified in cereal samples. The two cyclohexadepsipeptide mycotoxins beauvericin and enniatin have cytotoxic, antibiotic, insecticidal and ionophoric properties, while moniliformin primarily acts as a cardiotoxic mycotoxin. In this study, we examined the electromechanical and electrophysiological effects of moniliformin and moniliformin with ionophoric mycotoxins on cells (ventricular myocytes, Caco-2 cells) and in multicellular preparations (papillary muscles and terminal ilea of the guinea pig). Additionally, we investigated the influence of moniliformin on cell homeostasis in absence and presence of the cyclodepsipeptide mycotoxins (ventricular myocytes, Caco-2 cells). Experiments were performed using isometric measurements of contractility, intracellular microelectrode and patch-clamp techniques, and fluorescence imaging. While ionophoric cyclohexadepsipeptides affect action potential parameters and cell homeostasis, moniliformin did not change spontaneous rates of activity or cardiac action potentials. Furthermore, moniliformin had no effect on intracellular concentrations of ions and ATP, and did not affect pH. Moniliformin reduced contractility in papillary muscle, terminal ileum, the aorta and the pulmonary artery. However, moniliformin did not alter beauvericin and enniatin induced effects. From our studies, we conclude that moniliformin is not solely a cardiotoxic secondary metabolite, but also exerts its effects on smooth muscle. Moreover, there is no synergistic relationship between moniliformin and the concurrently produced cyclohexadepsipeptide mycotoxins beauvericin and enniatin. [Copyright &y& Elsevier]

The experimental set-up for analysis of the charge of light ions scattered from surface atoms (ACOLISSA) is described in the following paper. ACOLISSA is used for determination of flight times of low-energy ions. It permits time-of-flight low energy ion scattering spectra of all scattered projectiles (TOF-LEIS-AP) as well as charge separated (TOF-LEIS-CS) spectra to be recorded. The evaluation of TOF-LEIS-AP spectra allows subsurface layers of the target to be studied. The analysis of TOF-LEIS-CS spectra together with ions only spectra (TOF-LEIS-IO) is used for investigation of the neutralization behaviour of projectiles at the outermost atomic layer. The performance of the set-up is described and, as an example, spectra are shown for a polycrystalline Cu target and a 7 A˚ Cu layer deposited on top of an alumina substrate. [Copyright &y& Elsevier]

Low energy ion scattering is very surface sensitive if scattered ions are analyzed. By time-of-flight (TOF) techniques, also neutral and charge integrated spectra (ions plus neutrals) can be obtained, which yield information about deeper layers. In the literature, the observation of a more or less pronounced surface peak was reported for charge integrated spectra, the intensity of the surface peak being higher at low energies and for heavy projectiles.Aiming at a more profound physical understanding of this surface peak, we performed TOF-experiments and computer simulations for He projectiles and a copper target. Experiments were done in the range 1–9 keV for a scattering angle of 129°. The simulation was performed using the MARLOWE code for the given experimental parameters and a polycrystalline target. At low energies, a pronounced surface peak was observed, which fades away at higher energies. This peak is quantitatively reproduced by the simulation, and corresponds to scattering from ∼2 atomic layers.Analyzing the contributions of the individual outermost atomic layers, one finds that the surface peak is due to binary collisions of projectiles with atoms in the first and second layer, while the contribution from deeper layers is dominated by multiple scattering. [Copyright &y& Elsevier]