Variable ventilation ages in the equatorial Indian Ocean thermocline during the LGM.

Variations of atmospheric CO2 during the Pleistocene ice-ages have been associated with changes in the drawdown of carbon into the deep-sea. Modelling studies suggest that about one third of the glacial carbon drawdown may not be associated to the deep ocean, but to the thermocline or intermediate ocean. However, the carbon storage capacity of thermocline waters is still poorly constrained. Here we present paired 230Th/U and 14C measurements on scleractinian cold-water corals retrieved from ~ 450 m water depth off the Maldives in the Indian Ocean. Based on these measurements we calculate ∆14C, ∆∆14C and Benthic-Atmosphere (Batm) ages in order to understand the ventilation dynamics of the equatorial Indian Ocean thermocline during the Last Glacial Maximum (LGM). Our results demonstrate a radiocarbon depleted thermocline as low as -250 to -345‰ (∆∆14C), corresponding to ~ 500-2100 years (Batm) old waters at the LGM compared to ~ 380 years today. More broadly, we show that thermocline ventilation ages are one order of magnitude more variable than previously thought. Such a radiocarbon depleted thermocline can at least partly be explained by variable abyssal upwelling of deep-water masses with elevated respired carbon concentrations. Our results therefore have implications for radiocarbon-only based age models and imply that upper thermocline waters as shallow as 400 m depth can also contribute to some of the glacial carbon drawdown.

Relative size of fungiform papillae in patients with neurofibromatosis Type 1.

OBJECTIVE: To explore possible manifestations of neurofibromatosis on the tongue, especially, enlarged papillae fungiformes. According to the literature, enlarged fungiform papillae of the tongue are a very common oral finding in patients with Neurofibromatosis Type 1 (NF1). MATERIALS AND METHODS: Firstly, photos of 18 NF1 patients' tongues, taken at different times were compared to rule of possible fluctuating papillae size. Secondly, 60 photos of 60 patients with NF1 were age/sex matched, blinded and compared to 60 photos of 60 healthy patients. Three independent medical doctors rated the photos in regard of the fungiform papillae as smaller/same/larger at two different times. The inter- and intraindividual results were compared. Thirdly, fungiform papillae of 11 NF1 patients were quantitatively measured using the Denver protocol. RESULTS: The fungiform papillae showed a stable size. The comparison of the healthy individuals to the NF1 patients suggests that the larger papillae are significantly more frequent in NF1 patients than in age- and gender-matched non-NF1 individuals. The agreement between two ratings of each of the 3 raters at different time points was two moderate and one substantial, the agreement among raters was only fair, since the Fleiss' Kappa value of all 6 ratings was 0.38. CONCLUSION: Although this study confirms that the evaluation of the size of the fungiform papillae by visual inspection only is very subjective, the fungiform papillae in NF1 patients do seem to be enlarged at a statistically significant level. Nonetheless the statistical difference is not distinctive enough to establish this as a diagnostic tool in diagnosing NF1. CLINICAL RELEVANCE: Facilitating the diagnosis of NF1 is an important factor in finding the correct treatment for these patients. A clinical inspection of the tongue is a simple and non-invasive procedure. This paper addresses the question if an inspection of the tongue, especially the fungiform papillae is a reliable indicator for the diagnosis of NF1.

A blast without power - cell death induced by the tuberculosis-necrotizing toxin fails to elicit adequate immune responses.

In this study, we deploy a doxycycline-dependent suicide switch integrated in a tumor challenge model. With this experimental setup, we characterized the immunological consequences of cells dying by four distinct cell death stimuli in vivo. We observed that apoptotic cell death induced by expression of the truncated form of BH3 interacting-domain death agonist (tBid) and a constitutively active form of caspase 3 (revC3), respectively, showed higher immunogenicity than cell death induced by expression of the tuberculosis-necrotizing toxin (TNT). Our data indicate that the early release of ATP induces the silent clearance of dying cells, whereas the simultaneous presence of 'find me' signals and danger-associated molecular patterns (DAMPs) promotes inflammatory reactions and increased immunogenicity. This proposed model is supported by findings showing that the production and release of high concentrations of IL-27 by bone-marrow-derived macrophages (BMDM) is limited to BMDM exposed to those forms of death that simultaneously released ATP and the DAMPs heat-shock protein 90 (HSP90) and high-mobility group box-1 protein (HMGB1). These results demonstrate that the tissue microenvironment generated by dying cells may determine the subsequent immune response.

Nanoencapsulation of tacrolimus in lipid-core nanocapsules showed similar immunosuppressive activity after oral and intraperitoneal administrations.

Tacrolimus is widely used in the prophylaxis of solid-organ transplant rejection. Several studies have reported that tacrolimus has variable and poor bioavailability after oral administration, apart from adverse effects such as gastrointestinal disorders, hyperglycemia, nephro- and neurotoxicity. The aim of this work was to encapsulate tacrolimus (TAC) in lipid-core nanocapsules (LNC) as an oral strategy to deliver the drug. To validate our hypothesis, the pharmacodynamic effect of TAC-LNC was determined after oral and intraperitoneal (i.p.) administrations to mice. TAC-LNC had z-average diameter of 210 nm (unimodal), and 99.5% of encapsulation efficiency. In vitro sustained release was determined for TAC-LNC fitting an anomalous transport mechanism (n = 0.8). TAC-LNC demonstrated higher immunosuppressive activity after oral and i.p. administrations, when compared to the drug solution. TAC-LNC administered at 6.0 mg kg(-1) day(-1) showed equivalent percent reduction in lymphocyte when both routes of administration were used. After oral administration, drug nanoencapsulation allows reducing the dose by at least 40%. Furthermore, the nanoencapsulation of TAC in lipid-core nanocapsules showed pharmacodynamic effect similar for the oral and the i.p. routes. In conclusion, the lipid-core nanocapsules were able to improve the TAC deliver across the oral absorption barrier.

Spiral defect chaos in an advection-reaction-diffusion system.

This paper comprises numerical and theoretical studies of spatiotemporal patterns in advection-reaction-diffusion systems in which the chemical species interact with the hydrodynamic fluid. Due to the interplay between the two, we obtained the spiral defect chaos in the activator-inhibitor-type model. We formulated the generalized Swift-Hohenberg-type model for this system. Then the evolution of fractal boundaries due to the effect of the strong nonlinearity at the interface of the two chemical species is studied numerically. The purpose of the present paper is to point out that spiral defect chaos, observed in model equations of the extended Swift-Hohenberg equation for low Prandtl number convection, may actually be obtained also in certain advection-reaction-diffusion systems.

Generalized vortex model for the inverse cascade of two-dimensional turbulence.

We generalize Kirchhoff's point vortex model of two-dimensional fluid motion to a rotor model which exhibits an inverse cascade by the formation of rotor clusters. A rotor is composed of two vortices with like-signed circulations glued together by an overdamped spring. The model is motivated by a treatment of the vorticity equation representing the vorticity field as a superposition of vortices with elliptic Gaussian shapes of variable widths, augmented by a suitable forcing mechanism. The rotor model opens up the way to discuss the energy transport in the inverse cascade on the basis of dynamical systems theory.

Instabilities of localized structures in dissipative systems with delayed feedback.

We report on a novel behavior of solitary localized structures in a real Swift-Hohenberg equation subjected to a delayed feedback. We shall show that variation in the product of the delay time and the feedback strength leads to nontrivial instabilities resulting in the formation of oscillons, soliton rings, labyrinth patterns, or moving structures. We provide a bifurcation analysis of the delayed system and derive a system of order parameter equations explicitly describing the temporal behavior of the localized structure in the vicinity of the bifurcation point. We demonstrate that a normal form of the bifurcation, responsible for the emergence of moving solitary structures, can be obtained and show that spontaneous motion to the lowest order occurs without change of the shape.

Langevin description of superdiffusive Lévy processes.

The description of diffusion processes is possible in different frameworks such as random walks or Fokker-Planck or Langevin equations. Whereas for classical diffusion the equivalence of these methods is well established, in the case of anomalous diffusion it often remains an open problem. In this paper we aim to bring three approaches describing anomalous superdiffusive behavior to a common footing. While each method clearly has its advantages it is crucial to understand how those methods relate and complement each other. In particular, by using the method of subordination, we show how the Langevin equation can describe anomalous diffusion exhibited by Lévy-walk-type models and further show the equivalence of the random walk models and the generalized Kramers-Fokker-Planck equation. As a result a synergetic and complementary description of anomalous diffusion is obtained which provides a much more flexible tool for applications in real-world systems.

[IOL multifocality combined with the compensation for corneal spherical aberration: a new concept of presbyopia correcting IOL]. / Multifokalität in Kombination mit Aberrationskorrektur: ein neues Konzept einer Presbyopie korrigierenden IOL.

Further developments in the field of intraocular lenses have resulted in improvements of multifocal lenses (MIOL) which enable spectacle-free vision at near and far distance under most conditions. In our prospective study we investigated a new aberration-corrected MIOL, whereby 31 eyes of 19 patients, aged between 40 and 81 years, received a Tecnis ZMB00 MIOL (Abbott Medical Optics). Postoperative visual results were documented. Patients were enrolled if they were at least 40 years old and if they were scheduled for cataract surgery or presbyobic lens exchange. Exclusion criteria were any other visually relevant pathologies and a corneal astigmatism of 1.5 D or more. After 6 months, 94.7 % of the patients had a binocular uncorrected distance vision of 0.1 LogMAR or better, 67.7 % of eyes could read Jaeger 1+ (0.0 LogMAR) and 93.6 % could read Jaeger 1 (0.1 LogMAR) or better. There was no correlation between the power of the implanted lens and the postoperative distance or near vision or between IOL power and best-corrected distance vision. The aspheric diffractive multifocal IOL Tecnis ZMB00 provides a restoration of far and near visual function after cataract surgery or presbyopia correction. The correction provided by the IOL is predictable and independent from the optical power of the IOL implanted. The combination of diffractive multifocality and compensation for corneal spherical aberration is an effective alternative for cataract surgery and presbyopia correction.

Critical evaluation of phosphate solubilizing pseudomonads isolated from a partially recultivated potash tailings pile.

Ten phosphate solubilizing pseudomonads isolated from a partially recultivated potash tailings pile in Germany were characterized and tested for their potential to assist in the ongoing recultivation process. Despite fertilization, the plants which are grown for recultivation show phosphate deficiency symptoms, and therefore the isolates are intended to be used as biofertilizer inoculants. On agar plates incubated at five different temperatures, some of the strains showed a temperature-dependent ability to solubilize tricalcium phosphate, while others performed the same at any given temperature. In liquid medium, the isolates solubilized between 271 and 730 µg ml(-1) of phosphate from tricalcium phosphate. Both the weakest (designated S10) and the strongest solubilizing strain (S06) were further tested for their viability during solubilization. In an assay over the course of 1 week, both strains released their maximum amount of phosphate after 2-4 days. At that later point of time, however, viable cells of isolate S06 were no longer detectable, whereas the weaker strain S10 could be cultured after 1 week in broth. Taking all in vitro observations into account, the usability of the isolates as biofertilizers is critically discussed regarding both the in situ conditions on the tailings pile and the lowered viability due to the excess production of organic acids.

Electronic states and the influence of oxygen addition on the optical absorption behaviour of manganese phthalocyanine.

The effects of electronic states and air exposure on the spectroscopic properties of manganese phthalocyanine (MnPc) have been examined. The observed features of the Q-band in the absorption spectra can be explained by intrinsic electronic properties of MnPc, i.e., the formation of singly charged molecules by charge transfer excitations. However, the reaction of MnPc with atmospheric molecular oxygen leads to deviations in peak intensities but does not change the fundamental characteristics of the spectra. Nevertheless, the reaction with oxygen changes the spin state from S = 3/2 to S = 1/2. X-ray diffraction measurements also indicate a slow diffusion process of the oxygen into the MnPc crystal. We discuss both influences to explain the behaviour of MnPc in various spectroscopic methods (EELS, ellipsometry, PES). Furthermore, we support the experimental investigations by detailed ab-initio calculations of spectroscopic properties using methods of the density functional theory framework.

Statistical analysis of global wind dynamics in vigorous Rayleigh-Bénard convection.

Experimental and numerical studies of thermal convection have shown that sufficiently vigorous convective flows exhibit a large-scale thermal wind component sweeping along small-scale thermal boundary layer instabilities. A characteristic feature of these flows is an intermittent behavior in the form of irregular reversals in the orientation of the large-scale circulation. There have been several attempts toward a better understanding and description of the phenomenon of flow reversals, but so far most of these models are based on a statistical analysis of few-point measurements or on simplified theoretical assumptions. The analysis of long-term data sets (>5×10(5) turnover times τ(t)=d/u(rms)) obtained by numerical simulations of turbulent two-dimensional Rayleigh-Bénard convection allows us to get a more comprehensive view of the spatio-temporal flow behavior. By means of a global statistical analysis of the characteristic spatial modes of the flow we extract information about the stability of dominant large-scale modes as well as the reversal paths in state subspace. We examine probability density functions and drift vector fields of two-dimensional state subspaces spanned by different large-scale spatial modes. This also provides information about the coexistence of dominant modes.

Different methods to estimate the Einstein-Markov coherence length in turbulence.

We study the Markov property of experimental velocity data of different homogeneous isotropic turbulent flows. In particular, we examine the stochastic "cascade" process of nested velocity increments ξ(r):=u(x+r)-u(x) as a function of scale r for different nesting structures. It was found in previous work that, for a certain nesting structure, the stochastic process of ξ(r) has the Markov property for step sizes larger than the so-called Einstein-Markov coherence length l(EM), which is of the order of magnitude of the Taylor microscale λ [Phys. Lett. A 359, 335 (2006)]. We now show that, if a reasonable definition of the effective step size of the process is applied, this result holds independently of the nesting structure. Furthermore, we analyze the stochastic process of the velocity u as a function of the spatial position x. Although this process does not have the exact Markov property, a characteristic length scale l(u(x))≈l(EM) can be identified on the basis of a statistical test for the Markov property. Using a method based on the matrix of transition probabilities, we examine the significance of the non-Markovian character of the velocity u(x) for the statistical properties of turbulence.

Overexpression of TACE and TIMP3 mRNA in head and neck cancer: association with tumour development and progression.

BACKGROUND: TACE/ADAM17 is a transmembranous protease that cleaves membrane-bound growth factors like EGFR ligands. TACE-dependent proteolysis is regulated by its inhibitor, tissue inhibitor of metalloproteinases 3 (TIMP3). This study analyses the role of TACE and TIMP3 mRNA expression in squamous cell carcinomas of the head and neck (HNSCCs). METHODS: We analysed TACE and TIMP3 mRNA expression in HNSCCs from 106 patients by RNA in situ hybridisation. RESULTS: TACE mRNA was upregulated in HNSCCs compared with dysplastic (P<0.05) and normal epithelia (P<0.001), with strong hybridisation signals in 21.9% of invasive tumour tissues and 4.5% of dysplasia. Elevated mRNA levels were accompanied by increased amounts of TACE protein in HNSCCs. TIMP3 mRNA expression in HNSCC-associated stroma was significantly higher than in the stroma adjacent to dysplastic or normal epithelia. Expression of TACE mRNA in HNSCCs was associated with tumour stage (P=0.019) and regional lymph node metastasis (P=0.009). Furthermore, levels of TACE mRNA in HNSCCs correlated with the expression of TIMP3 mRNA in HNSCC-associated stroma. Concomitantly, patients expressing high levels of TACE and TIMP3 mRNA showed significantly reduced overall survival compared with those with low mRNA levels. CONCLUSION: Our results indicate an important role of TACE and TIMP3 during development and progression of HNSCCs.

Long-term follow-up of blowout fractures of the orbital floor reconstructed with a polyglactin 910/PDS implant.

PURPOSE: Resorbable alloplastic materials are used in many surgical applications. This retrospective study evaluated the clinical outcome after reconstruction of traumatic orbital floor defects using a polyglactin 910/PDS implant (Ethisorb™). PATIENTS AND METHODS: Seventy patients with isolated blowout fractures of the orbital floor resulting in defect sizes of up to 2.5 cm(2) were included in this study. All patients were clinically examined 5 days after surgery at the time of suture removal (T1) and 18 months postoperatively (T2). Diplopia was graded as significant diplopia or diplopia in extreme gaze. RESULTS: At T1, diplopia was observed in 9% of the patients, swelling of the periorbital region in 6%, and enophthalmus in none of the patients. No persistent complications were observed at T2. CONCLUSION: Reconstructive surgery of the orbit is one of the most demanding challenges in maxillofacial surgery. For traumatic defects of the orbital floor, reconstruction using a polyglactin 910/PDS implant (Ethisorb(™)) seems to be a reliable method for the repair of small-to-moderate defects.

Tablets containing drug-loaded polymeric nanocapsules: an innovative platform.

The aim of the present work was to evaluate the feasibility to convert drug-loaded nanocapsule suspensions in a solid dosage form (tablets). Dexamethasone was used as a model drug due to its low aqueous solubility and fast drug release from conventional tablets. Granules containing dexamethasone-loaded nanocapsules were obtained by a wet granulation process using a dispersion of polyvinylpirrolidone/nanocapsules as a binder system. Granules were compressed in an eccentric compression machine (D-NC-T). A control formulation (tablets without nanocapsules) was also prepared (D-T). Tablets were characterized by means of mean weight, hardness, friability, diameter, thickness, disintegration time, drug content, morphological analysis by scanning electron microscopy (SEM), and in vitro drug release studies. D-NC-T showed adequate physicochemical characteristics according to the pharmacopeial requirements in terms of mean weight, hardness, friability, disintegration time and drug content. Intact nanocapsules in tablets were observed by SEM. In vitro drug release studies showed a slower release of dexamethasone from these tablets (D-NC-T) compared to the control formulation (D-T). Results showed that these tablets represent an interesting platform to the development of oral drug delivery systems containing polymeric nanocapsules.

Hypercementosis and odontogenic epithelial hyperplasia associated with a tooth root remnant mimicking a neoplasm. A case report.

Hypercementosis presents as painless, single or multiple non-neoplastic cementum formation beyond the physiological limits of the tooth. It often occurs in the apical area of the involved tooth following infection, chemical or mechanical trauma. We report on radiographic and histopathological findings in a single case of late intraosseous hypercementosis and odontogenic epithelial hyperplasia associated with a minute apical tooth root remnant years after its extraction, mimicking a tumour.

Expression and distribution of tenascin in rat submandibular glands following irradiation.

UNLABELLED: The aim of this study was to investigate the late changes in the expression of tenascin-C (TN-C) in salivary glands (SG) following irradiation (IRR). MATERIALS AND METHODS: In 124 submandibular SG from 62 Wistar rats, the effect of IRR dose (fractionated IRR, 2 Gy per day, total dose of 20, 40, or 60 Gy), time since IRR (6 months vs. 12 months), and animal age (1 year vs. 1.5 years) on TN-C expression profile and its distribution pattern was investigated. RESULTS: Expression of TN-C showed slight to moderate alterations in the irradiated specimens. The expression differed in frequency and degree among various tissue structures. The most striking finding was pronounced dose-dependent heterogeneity, with increases, decreases and fluctuations in staining. CONCLUSION: The staining of TN-C predominantly showed notable dose-dependent heterogeneity, persisting for up to 1 year after completion of IRR. Thus, these findings can be attributed to late radiation effects. The altered expression of tenascin-C may play at least a partial role in late radiogenic dysfunction of the submandibular SG.

Hydrogel containing dexamethasone-loaded nanocapsules for cutaneous administration: preparation, characterization, and in vitro drug release study.

CONTEXT: Our group previously reported the development of dexamethasone-loaded polymeric nanocapsules as an alternative for topical dermatological treatments. OBJECTIVE: Our study aimed to prepare and characterize a hydrogel containing this system to improve the effectiveness of the glucocorticoid for cutaneous disorders. METHODS: For the antiproliferative activity assay, a dexamethasone solution and D-NC were tested on Allium cepa root meristem model. D-NC were prepared by the interfacial deposition of preformed polymer. Hydrogels were prepared using Carbopol Ultrez 10 NF, as polymer, and characterized according to the following characteristics: pH, drug content, spreadability, viscosity, and in vitro drug release. RESULTS AND DISCUSSION: Nanocapsules showed mean particle size and zeta potential of 201 +/- 6 and -5.73 +/- 0.42 nm, respectively. They demonstrated a lower mitotic index (4.62%) compared to free dexamethasone (8.60%). Semisolid formulations presented acidic pH values and adequate drug content (between 5.4% and 6.1% and 100% and 105%, respectively). The presence of nanocapsules in hydrogels led to a decrease in their spreadability factor. Intact nanoparticles were demonstrated by TEM as well as by dynamic light scattering (mean particle size < 300 nm). In vitro studies showed a controlled dexamethasone release from hydrogels containing the drug associated to the nanocapsules following the Higuchi's squared root model (k = 20.21 +/- 2.96 mg/cm(2)/h(1/2)) compared to the hydrogels containing the free drug (k = 26.65 +/- 2.09 mg/cm(2)/h(1/2)). CONCLUSION: Taking all these results together, the hydrogel containing D-NC represent a promising approach to treat antiproliferative-related dermatological disorders.