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The study employs the semantic similarity measures to determine the phenotypic similarities between the various hereditary and other diseases based on their ontologies. The approach is shown to be extremely beneficial in determining the semantic structure of the human phenotypic abnormalities.

Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated regarding its therapeutic properties in several several conditions such as epilepsy, migraine and major depressive disorder and was shown to access similar neural pathways as invasive vagus nerve stimulation. While the vagus nerve's role in gut motility is physiologically established, the effect of taVNS has scarcely been investigated in humans and yielded conflicting results. Real-time gastric magnetic resonance imaging (rtMRI) is an established reproducible method to investigate gastric motility non-invasively. To investigate the influence of taVNS on gastric motility of healthy participants using rtMRI. We conducted a randomized, double-blind study using high-frequency (HF) stimulation at 25Hz or low-frequency (LF) taVNS at 1Hz after ingestions of a standardized meal in 57 healthy participants. The gastric motility index (GMI) was determined by measuring the amplitude and velocity of the peristaltic waves using rtMRI. After HF taVNS, GMI was significantly higher than after LF stimulation (p = 0.005), which was mainly attributable to a higher amplitude of the peristaltic waves (p = 0.003). We provide evidence that 4-h of taVNS influences gastric motility in healthy human participants for the first time using rtMRI. HF stimulation is associated with higher amplitudes of peristaltic waves in the gastric antrum compared to LF stimulation. Further studies are needed to investigate the effect of different frequencies of taVNS and its therapeutic properties in conditions with impaired gastric motility. • Transcutaneous vagus nerve stimulation influences gut motility on healthy subjects. • First use of real-time MRI in humans to asses the effect of taVNS on gut motility. • High frequency stimulation is associated with higher GMI than low frequency. [ABSTRACT FROM AUTHOR]

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the "Integrated Epilepsy Classification". This consists of five categories derived to different degrees from both of the classification systems: 1) a "Headline" summarizing localization and etiology for the less specialized users, 2) "Seizure type(s)", 3) "Epilepsy type" (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) "Etiology", and 5) "Comorbidities & patient preferences". [ABSTRACT FROM AUTHOR]

• Preoperative estimates corresponded well to observed outcome after epilepsy surgery. • Patient counselling about expected outcome in clinical practice was appropriate. • The use of prediction models did not improve the accuracy of clinical predictions. Epilepsy surgery is an evidence-based treatment for drug-refractory focal epilepsy. We aimed to evaluate how well preoperative outcome estimates of epilepsy surgery in clinical practice correlated with postoperative outcome and to compare prediction by the clinical team with available scores (m-SFS, ESN). Retrospective cohort study including patients with drug-refractory focal epilepsy who underwent resective epilepsy surgery at Epilepsy Center Hessen, Marburg, between 1998-2016. Patients were categorized into four groups based on their estimated chance of postoperative seizure freedom documented in preoperative medical records. Variables required for calculation of m-SFS and ESN were also extracted from presurgical medical records. Seizure outcome using Engel/ILAE classifications was extracted from postoperative medical records. 148 patients were included and 98 had follow-up at 5 years. 69 (70%) had Engel I and 50 (51%) ILAE 1 outcome. Observed 5-year outcome for very good candidates was 20/22 (91%) Engel I and 14/22 (64%) ILAE 1, for good candidates 29/40 (73%) Engel I and 21/40 (53%) ILAE 1, for candidates with slightly reduced chance 11/18 (61%) Engel I and 9/18 (50%) ILAE 1 and for candidates with considerably reduced chance 1/5 (20%) Engel I and 1/5 (20%) ILAE 1.There were no significant differences in discrimination or overall performance between predictions by the clinical team, ESN and m-SFS. Preoperative outcome estimates corresponded well with observed outcome indicating adequate patient counseling. [ABSTRACT FROM AUTHOR]

Up to 80% of mesial temporal lobe epilepsy patients with hippocampal sclerosis (mTLE-HS) are resistant to pharmacological treatment, often necessitating surgical resection. Deep brain stimulation (DBS) has emerged as an alternative treatment for patients who do not qualify for resective brain surgery. Brain stimulation may also exert disease-modifying effects, and noncoding microRNAs have recently been proposed to shape the gene expression landscape in epilepsy. We compared the effect of DBS of 4 different hippocampal target regions on epileptogenesis and manifest epilepsy in a rat model of mTLE-HS. To explore mechanisms, we profiled the effect of the most effective DBS paradigm on hippocampal microRNA levels. MTLE-HS was induced by electrical stimulation of the perforant pathway (PP) in rats. This paradigm leads to spontaneous seizures within 4 weeks. We investigated DBS of 4 targets: PP, fimbria fornix (FF) formation, dentate gyrus (DG) and ventral hippocampal commissure (VHC). We applied both high- (130 Hz) and low-frequency (5 Hz or 1 Hz) stimulation. Functional microRNAs were identified in the hippocampus immediately after VHC-DBS and after a 97-day recording period by sequencing small RNAs bound to Argonaute-2, a component of the miRNA silencing complex. Low frequency DBS of the VHC significantly delayed the occurrence of the first spontaneous recurrent seizure in the PPS model by ∼300%, from 19 to 56 days. No other stimulation regime altered the latency phase. Upregulation of 5 microRNAs during epileptogenesis was suppressed by VHC-stimulation. We conclude that DBS of the VHC delays epilepsy in the PPS model in rats and is associated with differential regulation of several miRNAs. Additional studies are required to determine whether VHC-regulated miRNAs serve causal roles in the anti-epileptogenic effects of this DBS model. • Stimulation of the ventral hippocampal commissure (VHC) significantly delays epileptogenesis. • VHC stimulation suppresses epileptogenesis-related upregulation of 5 miRNAs. • MiRNA target analysis revealed a possible impact on mRNAs previously associated with epilepsy. [ABSTRACT FROM AUTHOR]

Abstract A synthetic diabatic compressed air energy storage (CAES) based on an existing surface facility and using the Rhaetian sandstone formation in the North German Basin as porous storage reservoir is investigated for induced geochemical reactions. A daily storage cycle with a 6-h injection and a 6-h extraction phase in the early morning and late afternoon is applied. The chosen mineral assemblage shows the presence of pyrite in the Rhaetian sandstone, so that operating CAES in this porous formation introduces oxygen in the formation and induces geochemical reactions governed mainly by pyrite oxidation. A consistent geochemical reaction system for the Rhaetian sandstone is developed and kinetic batch simulations are used to quantify the changes due to the induced geochemical reactions in both stored air as well as storage formation. The injection of air into this geological formation leads to pyrite oxidation, changes in stored air composition, air pressure and formation properties. Results show that only a very small change up to 0.29% in the oxygen mole fraction is found within one storage cycle, which does not affect flammability of the stored air. Considering a longer residence time, the oxygen concentration in the stored air may drop below the minimum oxygen concentration for flame propagation and thus cannot be used for burning natural gas as required for a diabatic CAES. The pH of the formation fluid after 20-year cyclic daily operation can drop significantly below one near the gas wells increasing the risk of well corrosion, but with smaller effects at larger distances. However, mineral dissolution and precipitation found in the storage formation results in only minor increases of porosity and permeability with relative changes up to 1.0% and 5.0%, respectively. The uncertainties in mineral reactive surface area and pyrite oxidation kinetic strongly affect the rate of oxygen reduction and fluid acidification. Analysis of these parameters of the reservoir mineral phases from the target location, especially for pyrite, are therefore required for a reliable estimate of possible induced geochemical reactions and impacts. [ABSTRACT FROM AUTHOR]

Large-scale compressed air energy storage (CAES) in porous formations can contribute to compensate the strong daily fluctuations in renewable energy production. This work presents a hypothetical CAES scenario using a representative geological anticlinal structure in Northern Germany and performs numerical simulations to estimate pressure response in the storage formation. The results show that the induced pressure changes laterally throughout the storage formation are due to initial fill of the air storage. Because of high air compressibility, the pressure fluctuations caused by daily cyclic operation can only be observed in the gas phase which reaches a distance of roughly 500 m. [ABSTRACT FROM AUTHOR]

In this work, an innovative modular heat storage system is investigated experimentally and by numerical modeling. A single storage module consists of a helical heat exchanger in a water saturated porous cement matrix. The experiment comprises a 5 day thermal loading stage, followed by 16.5 days of passive cooling, and was especially designed to quantify the thermal insulation efficiency. An inverse modeling approach was applied to successfully match temperature measurements within the storage by numerical simulation. The thus determined heat loss rates amount to 130 W for the fully loaded storage and to 50 W on average during passive cooling. [ABSTRACT FROM AUTHOR]

The geological subsurface offers large potential renewable energy storage sites through cavern or porous media storage systems. This work presents a methodology for assessing the size of the storage systems required, for modelling the storage operation and for predicting the induced effects and impacts on the environment by numerical simulations. The methodology is demonstrated for a hypothetical porous medium hydrogen storage and for geothermal heat storage. It is found that induced pressure effects may range over kilometers for gas storage, while temperature effects are limited to a few tens of meters for heat storage. [ABSTRACT FROM AUTHOR]

Subsurface porous media hydrogen storage could be a viable option to mitigate shortages in energy supply from renewable sources. In this work, a scenario for such a storage is developed and the operation is simulated using a numerical model. A hypothetical storage site is developed, based on an actual geological structure. The results of the simulations show that the storage can supply about 20% of the average demand in electrical energy of the state of Schleswig-Holstein, Germany, for a week-long period. [ABSTRACT FROM AUTHOR]

Seasonal heat storage in the shallow subsurface is gaining relevance due to the increasing production of energy from renewable sources. This work presents model extensions of the code OpenGeoSys for simulating impacts of heat storages on groundwater quality. Application of the non-isothermal model is demonstrated for scenarios of heat storage in a TCE contaminated aquifer. Simulation results show slightly elevated TCE emissions due to increases in flow and solubility, but also increases in contaminant biodegradation caused by widening of the plume. Further experimental and modeling work is required for a quantitative assessment of such complex systems and process interactions. [ABSTRACT FROM AUTHOR]

Abstract: We show how the abstract concept of a labeled interface theory can be canonically extended to an abstract framework for component interfaces with ports. The resulting theory satisfies itself the general laws of an interface theory for composition, refinement and communication compatibility. The ports of a component interface represent the interaction points of a component. Each port is equipped with a contract specifying the assumptions on and the guarantees for the environment of a component. We study reliable component interfaces and we provide methodological guidelines how to design reliable interfaces and how to adapt them to changing environments. Two instances of our approach are presented. First, we consider modal component interfaces such that component behaviors and the assume and guarantee behaviors of ports are given in terms of modal I/O-transition systems with weak notions of refinement and compatibility. The second instance uses I/O-predicates as interface specifications. [Copyright &y& Elsevier]

Hamiltonian dielectric solvent (HADES) is a recent method [7,25] , which enables Hamiltonian molecular dynamics (MD) simulations of peptides and proteins in dielectric continua. Sample simulations of an α -helical decapeptide with and without explicit solvent demonstrate the high efficiency of HADES-MD. Addressing the folding of this peptide by replica exchange MD we study the properties of HADES by comparing melting curves, secondary structure motifs and salt bridges with explicit solvent results. Despite the unoptimized ad hoc parametrization of HADES, calculated reaction field energies correlate well with numerical grid solutions of the dielectric Poisson equation. [ABSTRACT FROM AUTHOR]

Purpose There is growing evidence that complex interactions between seizures and the immune system shape the course of epilepsy. However, systematic analyses of the effects of antiepileptic drugs (AED) on the immune system in humans are rare. We performed a prospective study on the influence of the widely used AED valproate and levetiracetam on interictal immunological parameters. Methods 36 patients were prospectively included. 15 were started on valproate (5 female (33%), age 54±27 years, 12 (80%) on monotherapy), 21 on levetiracetam (10 female (48%), age 45±19 years, 17 (81%) on monotherapy). Before treatment and after 3 months, we performed a differential blood count and analyzed the distribution of CD3+CD4+-, CD3+CD8+- and CD4+CD25+-leukocyte subsets using flow cytometry. In addition, we determined the concentrations of IL-1β, IL-6, TNF-α and MCP-1 in the peripheral blood using ELISAs. Results Valproate intake resulted in a significant decrease of the total white blood count (6.96±1.23/nl vs. 6.13±1.57/nl, p=0.026) and of absolute count and percentage of neutrophils (4.60±1.05/nl vs. 3.69±1.30/nl, p=0.01; 65.4±7.9% vs. 59.5±11.5%, p=0.01, respectively). The percentage of CD3+CD4+-lymphocytes dropped significantly (50.4±10.9% vs. 45.3±12.3%, p=0.002). Levetiracetam treatment resulted in a decrease of the percentage of CD4+CD25+-lymphocytes (26.1±8.0% vs. 21.5±9.2%, p=0.01) but did not significantly alter absolute counts. Neither valproate nor levetiracetam were associated with significant changes in cytokines. Conclusion Valproate intake results in profound changes of white blood cell count and subset distribution. Cytokine levels were not influenced by valproate or levetiracetam. [ABSTRACT FROM AUTHOR]

Abstract: Modal specification is a well-known formalism used as an abstraction theory for transition systems. Modal specifications are transition systems equipped with two types of transitions: must-transitions that are mandatory to any implementation, and may-transitions that are optional. The duality of transitions allows for developing a unique approach for both logical and structural compositions, and eases the step-wise refinement process for building implementations. We propose Modal Specifications with Data (MSDs), the first modal specification theory with explicit representation of data. Our new theory includes the most commonly seen ingredients of a specification theory; that is parallel composition, conjunction and quotient. As MSDs are by nature potentially infinite-state systems, we propose symbolic representations based on effective predicates. Our theory serves as a new abstraction-based formalism for transition systems with data. [Copyright &y& Elsevier]

Highlights: [•] Investigation of large-scale vertical pressure monitoring. [•] Pressure signals vertically offset may be strongly delayed relative to injection. [•] Maximum vertical leakage risk may occur significantly after injection end. [•] Formation entry pressure does not influence vertical pressure propagation. [Copyright &y& Elsevier]

Alveolar soft part sarcoma (ASPS) is a distinct type of soft tissue sarcoma holding a specific ASPL-TFE3 fusion transcript. Curative therapy is based on surgical removal, whereas lately, antiangiogenic targeted therapy regimens have proven effective. In ASPS, analysis of small series additionally display mTOR (mammalian target of rapamycin) pathway activity, thus making mTOR a possible additive target in ASPS, because it is in other tumor entities. Therefore, we systematically evaluated mTOR pathway activity in a large series of ASPS in comparison with soft tissue sarcomas of other differentiation (non-ASPS). Upstream and downstream factors of mTOR signaling and ancillary targets were analyzed in 103 cases (22 ASPS, 81 non-ASPS) by immunohistochemistry mostly using phospho-specific antibodies. TFE3 (transcription factor for immunoglobulin heavy-chain enhancer 3) translocation status was determined by FISH and RT-PCR. All ASPS were positive in TFE3 break-apart FISH and exhibited specific fusion products when RNA was available (type 1: 9x, type 2: 11x), whereas TFE3-immunoreactive non-ASPS did not. In ASPS, TFE3-, cMET-, pAKT T308- (all P < .0001), pp70S6K- (P = .002), and p4EBP1 (P = .087) expression levels were elevated, whereas pAKT S473 was decreased (P < .0001). In addition, ASPS exhibited higher TFE3-, cMET-, pAKT T308-, and pp70S6K- expression levels compared with TFE3-immunopositive non-ASPS sarcomas (all P < .001). We demonstrate elevated mTOR complex 1 (mTORC1) activity in ASPS independent of mTOR complex 2 (mTORC2) activation. mTORC1 activity seems to be related to the existence of ASPL-TFE3 fusion transcripts because TFE3-immunoreactive non-ASPS without ASPL-TFE3 fusion transcripts exhibit significantly lower mTORC1 activation status. Small molecule-based targeting of mTOR might therefore represent a potential mechanism in ASPS alone or in combination with contemporary upstream approaches. [ABSTRACT FROM AUTHOR]

Abstract: Due to their widespread occurrence and large capacities, deep geological saline formations are regarded as an important storage option for anthropogenic CO2. Injection of supercritical CO2 into such a formation will result in a multi-phase flow porous media system. Both the CO2 and brine phase compositions are influenced by multiphase flow and mass transport processes as well as by interfacial reactions (gas dissolution, water vaporization, mineral dissolution and precipitation). For a model based assessment of CO2 storage, most simulation codes apply an operator-splitting approach to solve the coupled problem, where multi-phase flow and geochemical reactions are handled by separate routines sequentially. This approach relies on two approximations: (I) the dissolution of CO2 in the brine, which is usually quantified by the multiphase flow routine by using an equation of state approach, is treated as instantaneous, and (II) the amount of CO2 consumed during geochemical reactions quantified by the reaction routine is small compared to the amount dissolved, as during geochemical reactions CO2 is not resupplied from the CO2 phase by dissolution. To investigate these two approximations, the multiphase flow and multi-component reactive transport simulator OpenGeoSys was extended and now allows to simulate mineral-brine as well as the brine-CO2 interface reactions either kinetically controlled or by using an equilibrium approach, and to account for the presence of a CO2 phase during brine-mineral reactions. The code is used here to investigate a simple gas-liquid-solid phase (CO2-H2O- CaCO3) system controlled by fast reaction rates. Batch reaction calculations are performed for the multiphase system at various temperature and pressure conditions for different initial CO2 saturations. Two methods of approximating the equilibrium state of the system by an operator splitting approach are compared. The first method determines the gas-liquid and solid-liquid equilibria in separate subsequent steps. At reservoir conditions relevant for storage of CO2 (323K, 100bar) and for high CO2 saturations the error in predicted CO2 concentrations in the liquid phase reaches up to -2%. This error can be reduced to less than -0.5% by the second method, where a conjoint gas-liquid-solid equilibrium is accounted for in the reaction calculations. Accordingly, the latter approach should preferably be employed in multiphase flow reactive transport modeling based on operator splitting techniques. [Copyright &y& Elsevier]

Abstract: This paper presents a code comparison of coupled multiphase flow and geomechanical processes resulting from CO2 injection into deep saline formations. The coupled simulator OpenGeoSys-Eclipse as well as Eclipse-Visage, GEM and OpenGeoSys are used for this purpose. Comparison of the results of the different simulators shows a strong dependence of the results on the grid discretization and the numerical methods applied. Further investigations of the one-way coupled geomechanical simulations shows that even if the multiphase flow results are nearly identical for the simulators used, the geomechanical response on the pressure build up can be different. [Copyright &y& Elsevier]

Abstract: Purpose: To further elucidate possible immune-modulatory effects of valproate (VPA) or levetiracetam (LEV), we investigated their influence on apoptosis and cytotoxic function of CD8+ T lymphocytes in humans. Methods: In 15 healthy subjects (9 female (60%), 35.7±12.1 years), apoptosis and cytotoxic function of CD8+ T lymphocytes were measured using flow cytometry following in vitro exposure to LEV (5mg/L and 50mg/L) and VPA (10mg/L and 100mg/L). Apoptosis rates were determined after incubation with LEV or VPA for 1h or 24h. Cytotoxic function was assessed following 2h stimulation with mixed virus peptides, using perforin release, CD107a/b expression and proliferation. The presence of synaptic vesicle protein 2A (SV2A) was investigated in human CD8+ T lymphocytes by flow cytometry analysis, Western blot and real time polymerase chain reaction (rtPCR). Results: High concentration of LEV decreased perforin release of CD8+ T lymphocytes (LEV 50mg/L vs. CEF only: 21.4% (interquartile range (IQR) 16.5–35.9%) vs. 16.6% (IQR 12–24.9%), p =0.002). LEV had no influence on apoptosis and proliferation (p >0.05). VPA (100mg/L) slowed apoptosis of CD8+ T lymphocytes after 24h (VPA 100mg/L vs. control: 7.3% (IQR 5.4–9.5%) vs. 11.3% (IQR 8.2–15.1%), p <0.001), but had no effects on perforin release (p >0.05). SV2A protein was detected in CD8+ T lymphocytes. Conclusion: LEV decreased degranulation of CD8+ T lymphocytes which may contribute to the increased incidence of upper respiratory tract infections in LEV treated patients. Inhibition of SV2A may be responsible for this effect. [Copyright &y& Elsevier]

Abstract: During recent decades vast and continuously increasing numbers of biomedical implants have been introduced for continuous use in the human body. Since the early cemented hip replacements in the 1960s there has been a constant spread of new materials, and ever more complex designs are being used in these implant devices. But still the rate of failure and loss of implants is undesirably high and leaves space for improvements. The challenge is to understand the interactions of implant surface with the surrounding tissue sufficiently, to actively tailor desired interactions. Bulk and surface properties of biomaterials used for implants have been shown to directly influence, and in some cases, control the dynamic interactions that take place at the tissue–implant interface. It is critical to recognize that synthetic materials have specific bulk and surface properties or characteristics that determine their in vitro and in vivo characteristics. This article reviews the interdisciplinary field of biocompatible implant surfaces from the viewpoint of materials science, biochemistry and cell biology. It compiles an overview on basic information about bulk and surface properties of implants based on metallic materials (particularly titanium and its alloys) and surface modification including functionalization with adhesion and growth promoting species. It describes how cells recognize surfaces and respond to different biomaterials, outlines common assays on cell behavior in culture, and reports on cell types and proteins involved in tissue response, acute and chronic responses to implanted biomaterials. [Copyright &y& Elsevier]

Abstract: By electrochemical anodization, highly ordered nanotubular TiO2 structures were formed on titanium surfaces with diameters of 15 and 100nm. In previous work we showed that 15nm tubes strongly enhanced adhesion and vitality of many cell types, whereas on 100nm diameter tubes the induction of apoptosis was observed. In the present work we produce mixed (15nm contrasted with 100nm) nanotube microstructures that combine highly defined micro- and nanostructures using a photolithographic approach to achieve a direct comparison of adhesion and spreading of mesenchymal stem cells on different diameter nanotubes present on a single surface. On these coupled different nanoscale surfaces mesenchymal stem cell adhesion is initially favoured on 15nm tube areas but, with time, a gradient in cell number and shape to the “unfavourable” regions of the substrate (100nm tubes) can be observed. This can be explained by cells on the “favourable” 15nm regions that strongly produce and shed extracellular matrix onto the “unfavourable” locations. These findings contribute to the design of cell guiding surfaces, but also demonstrate the need for a long-range defined homogeneous order when studying cell behaviour on nanostructured surfaces. [Copyright &y& Elsevier]

Abstract: Aim: Resection of the primary tumor with intraoperative staging is the standard procedure in patients with gastrointestinal stromal tumors (GIST). FDG-PET/CT has shown high accuracy when assessing treatment response in GIST patients. This study was designed to assess the accuracy of postoperative FDG-PET/CT to stage for occult tumor seeding in patients with R0 resection and without intraoperative detection of metastases. Patients and methods: 48 consecutive patients (mean age: 59y) with histologically proven GIST underwent whole-body FDG-PET/CT after R0-resection without intraoperative detection of metastases. Fused data sets were assessed for metastases by a nuclear medicine physician and a radiologist. Histology of potential lesions and a clinical/radiological follow-up with a mean of 614±415d served as standards of reference. Results: FDG-PET/CT detected occult peritoneal metastases in 2 patients (4%). In 6 patients (13%) who later developed metastases postoperative FDG-PET/CT was falsely negative. False-positive findings were detected in 5 cases (10%) caused by increased FDG-uptake due to tissue regeneration postoperatively. In 3 patients (6%) other, formerly unknown malignancies were detected. The sensitivity and specificity of FDG-PET/CT for the detection of intraoperatively occult GIST metastases were 25% and 88%, respectively. Conclusion: FDG-PET/CT performed immediately after R0-resection of GIST without intraoperative detection of metastases does not seem to be a sufficient tool to detect clinically occult metastases. [Copyright &y& Elsevier]

Abstract: In the present work we demonstrate that amorphous anodic TiO2 nanotubes show upon annealing a tube diameter dependent phase stabilization. For tube diameters <30nm the formation of rutile is observed while for larger diameters anatase is formed. This effect is induced by the presence of the metallic substrate — in its absence all tube diameters are converted to anatase. As the nature of the stable phase strongly affects electronic, optical and biomedical properties of TiO2, the finding is of a high significance for many applications of TiO2 nanotubes. [Copyright &y& Elsevier]

Abstract: Adaptive systems are systems capable of adapting their behaviour to changes in their environment. Creating such systems is not an easy task, however. Especially, creating such a system as one monolithic software component taking all eventualities and environments into account bears the risk of bad system design. To circumvent this risk, an adaptive system can be composed from partial solutions handling only a subset of all possible circumstances and environments. Then, the system can be changed through reconfigurations as the environment evolves. In this paper, we propose an approach for the verification of systems using reconfiguration as means of adaptation. For the specification of such systems and their components we introduce reMitl which is based on Metric Interval Temporal Logic Mitl and allows to express connectivity of components. Based on an example from the domain of pervasive computing, we show how a system undergoing reconfigurations can be verified to satisfy a global assume-guarantee contract expressed as a pair of reMitl formulas. [Copyright &y& Elsevier]

Abstract: Epilepsy is a common chronic neurological disorder affecting approximately 8 out of 1000 people. Its pathophysiology, however, has remained elusive in many regards. Consequently, adequate seizure control is still lacking in about one third of patients. Cytokines are soluble mediators of cell communication that are critical in immune regulation. In recent years, studies have shown that epileptic seizures can induce the production of cytokines, which in turn influence the pathogenesis and course of epilepsies. At the time of this review, the focus is mostly on interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα). In this review, we summarize the current knowledge regarding these cytokines and their potential roles in epilepsy. The focus concentrates on their expression and influence on induced seizures in animal models of epilepsy, as well as findings in human studies. Both proconvulsive and anticonvulsive effects have been reported for each of these molecules. One possible explanation for this phenomenon is that cytokines play dichotomous roles through multiple pathways, each of which is dependent on free concentration and available receptors. Furthermore, the immune-mediated leakage in the blood–brain-barrier also plays an important role in epileptogenesis. Nonetheless, these observations demonstrate the multifarious nature of cytokine networks and the complex relationship between the immune system and epilepsy. Future studies are warranted to further clarify the influence of the immune system on epilepsy and vice versa. [Copyright &y& Elsevier]

Abstract: A liquid density model for the H2O–CO2–NaCl ternary system is established, based on previous methods (Duan et al. Energy & Fuels 2008, 22, 1666–1674), and combined with a recent density model for H2O–NaCl binary solution (Mao and Duan. The Journal of Chemical Thermodynamics 2008, 40, 1046–1063). The applicable range of the model is 273–573 K, 0.001–1000 bar and 0–6 mol/kg NaCl concentration as well as CO2 concentrations from 0 up to saturated conditions. The model is accurate and its total error is within 0.5%. The applicable range totally covers conditions for geological storage of CO2. Therefore it is suited for simulation studies of CO2 geological storage, especially for fluid convection processes due to density differences. In order to facilitate the model application, a Matlab © program is provided which can be downloaded from our web page. Three examples are presented to demonstrate the model application. The first one is the calculation of pure water density varying with pressure at different temperature conditions. Second application is on the fluid density calculation under different CO2 saturations which is relevant for convection process simulation. The last application shows the total pressure change caused by temperature changes under isometric conditions. [Copyright &y& Elsevier]

Abstract: The storage of CO2 in deep saline aquifers is due to the large available capacities and the common occurrence of these formations one of the major options for carbon dioxide sequestration. Besides the multiphase flow aspects geochemical, thermal and mechanical processes may alter the conditions within the reservoir as well as in the cap rock. Whereas single aspects of these processes can be investigated with experiments a multi-process simulator allows evaluating their combined consequences for the storage system over short and long time scales. In this paper the newly coupled software ECLIPSE-OpenGeoSys is presented that allows a combined simulation of multiphase flow, transport and geochemical reactions. ECLIPSE provides a fast and efficient solution for the multiphase flow whereas the open-source scientific software OpenGeoSys is used for calculating transport and geochemical reactions. This paper presents the code structure of the interface. Furthermore the coupled software is successfully applied to benchmarks [Copyright &y& Elsevier]

Abstract: TiO2 nanotube layers can provide greatly enhanced kinetics for hydroxyapatite formation from simulated body fluid compared with smooth, compact TiO2 surfaces. In the present work we show how this contrast in reactivity can be used to create highly defined lateral microstructures where bone-like hydroxyapatite can be deposited with very high selectivity. For this we used a photolithographic approach to produce micropatterned TiO2 nanotube layers surrounded by compact oxide that were then immersed in a simulated body fluid (SBF) solution. Not only the tubular vs. flat geometry but also the finding that compact oxides created in phosphate electrolytes in particular suppress apatite deposition are crucial for a very high reactivity contrast. Overall the results show the feasibility of stimulating hydroxyapatite deposition at surface locations where needed or desired. This provides a valuable tool for biomedical device design. [ABSTRACT FROM AUTHOR]

Abstract: Background: Inadequate response to cisplatin-based chemotherapy is associated with poor prognosis in patients with advanced malignant testicular germ cell tumours (TGCTs), especially of the nonseminomatous type. Novel chemotherapeutic agents have failed so far to significantly improve the outcome of such patients. The majority of these tumours express low levels of p53, and TP53 mutations are rarely observed. Murine double minute 2 (Mdm2) inhibitors enhance apoptosis in tumours harbouring wild-type p53. Objective: We sought to investigate the potential therapeutic value of Mdm2 in TGCT-derived cell lines with the histology of nonseminoma. Design, setting, and participants: The Mdm2 inhibitor nutlin-3 was evaluated alone and in combination with cisplatin in a panel of germ cell tumour (GCT)–derived cell lines (embryonal carcinomas, being the nonseminomatous stem-cell component) with wild-type (NT2 and 2102EP cells) and mutant (NCCIT cells) p53 status. Measurements: Biological consequences of Mdm2 inhibition were determined by analysis of the p53 pathway, cell proliferation, and apoptosis. Results and limitations: Nutlin-3 exhibited significant activity (IC50 2.8μM) in NT2 and 2102EP (wild-type p53) but not in p53-mutant NCCIT cells (<10% inhibition at 10μM). At concentrations beyond 500nM, additive effects were seen for the combination of nutlin-3 and cisplatin in NT2 and 2102EP cells but not in NCCIT cells. This correlated with the induction of p53 and its target p21, suggesting an on-target effect of nutlin-3. Moreover, nutlin-3 (5μM) and cisplatin (0.5μM) additively induced caspase cleavage and apoptosis in NT2 cells and 2102-EP cells but not in p53-mutant NCCIT cells. Conclusions: These results provide strong evidence for further development of pharmacologic Mdm2 inhibition for the treatment of patients suffering from high-risk nonseminomatous TGCT with wild-type p53 status. [Copyright &y& Elsevier]