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Keywords
Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16) is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism.
Selective Laser Melting (SLM) is one of the Additive Manufacturing (AM) technologies applicable for producing complex geometries which are typically expensive or difficult to fabricate using conventional methods. This process has been extensively investigated experimentally for various metals and the fabrication process parameters have been established for different applications; however, fabricating 3D glass objects using SLM technology has remained a challenge so far although it could have many applications. This paper presents a summery on various experimental evaluations of a material database incorporating the build parameters of glass powder using the SLM process for jewelry applications.
Molecular-genetic identification of emerged novel invasive pathogens of Asiatic Elm Ulmus pumila L
(2014)
The dwarf elm Ulmus pumila L. (Ulmaceae) is one of indigenous species of flora in Kazakhstan and forms a basis of dendroflora in virtually all settlements of the region. In the past decade, multiple outbreaks of previously unknown diseases of the small-leaved elm have been registered. In our study, by the molecular-genetic analysis it was found that the pathogens responsible for the outbreaks are microfungi belonging to the genus Fusarium – F. solani and F. oxysporum. The nucleotide sequences (ITS regions) isolated from the diseased trees showed very high similarity with the GenBank control numbers EU625403.1 and FJ478128.1 (100.0 and 99.0 % respectively). Oncoming research will focus on the search of natural microbial antagonists of the discovered phytopathogens.
Network theory provides novel concepts that promise an improved characterization of interacting dynamical systems. Within this framework, evolving networks can be considered as being composed of nodes, representing systems, and of time-varying edges, representing interactions between these systems. This approach is highly attractive to further our understanding of the physiological and pathophysiological dynamics in human brain networks. Indeed, there is growing evidence that the epileptic process can be regarded as a large-scale network phenomenon. We here review methodologies for inferring networks from empirical time series and for a characterization of these evolving networks. We summarize recent findings derived from studies that investigate human epileptic brain networks evolving on timescales ranging from few seconds to weeks. We point to possible pitfalls and open issues, and discuss future perspectives.
The scope of this study is the measurement of endotoxin adsorption rate for carbonized rice husk. It showed good adsorption properties for LPS. During the batch experiments, several techniques were used and optimized for improving the material’s adsorption behavior. Also, with the results obtained it was possible to differentiate the materials according to their adsorption capacity and kinetic characteristics.
Background
True date palms (Phoenix dactylifera L.) are impressive trees and have served as an indispensable source of food for mankind in tropical and subtropical countries for centuries. The aim of this study is to differentiate date palm tree varieties by analysing leaflet cross sections with technical/optical methods and artificial neural networks (ANN).
Results
Fluorescence microscopy images of leaflet cross sections have been taken from a set of five date palm tree cultivars (Hewlat al Jouf, Khlas, Nabot Soltan, Shishi, Um Raheem). After features extraction from images, the obtained data have been fed in a multilayer perceptron ANN with backpropagation learning algorithm.
Conclusions
Overall, an accurate result in prediction and differentiation of date palm tree cultivars was achieved with average prediction in tenfold cross-validation is 89.1% and reached 100% in one of the best ANN.
A technology reference study for a multiple near-Earth object (NEO) rendezvous mission with solar sailcraft is currently carried out by the authors of this paper. The investigated mission builds on previous concepts, but adopts a strong micro-spacecraft philosophy based on the DLR/ESA Gossamer technology. The main scientific objective of the mission is to explore the diversity of NEOs. After direct interplanetary insertion, the solar sailcraft should—within less than 10 years—rendezvous three NEOs that are not only scientifically interesting, but also from the point of human spaceight and planetary defense. In this paper, the objectives of the study are outlined and a preliminary potential mission profile is presented.
This paper describes the modeling of a high-temperature storage system for an existing solar tower power plant with open volumetric receiver technology, which uses air as heat transfer medium (HTF). The storage system model has been developed in the simulation environment Matlab/Simulink®. The storage type under investigation is a packed bed thermal energy storage system which has the characteristics of a regenerator. Thermal energy can be stored and discharged as required via the HTF air. The air mass flow distribution is controlled by valves, and the mass flow by two blowers. The thermal storage operation strategy has a direct and significant impact on the energetic and economic efficiency of the solar tower power plants.
A new trend in automation is to deploy so-called cyber-physical systems (CPS) which combine computation with physical processes. The novel RoboCup Logistics League Sponsored by Festo (LLSF) aims at such CPS logistic scenarios in an automation setting. A team of robots has to produce products from a number of semi-finished products which they have to machine during the game. Different production plans are possible and the robots need to recycle scrap byproducts. This way, the LLSF is a very interesting league offering a number of challenging research questions for planning, coordination, or communication in an application-driven scenario. In this paper, we outline the objectives of the LLSF and present steps for developing the league further towards a benchmark for logistics scenarios for CPS. As a major milestone we present the new automated referee system which helps in governing the game play as well as keeping track of the scored points in a very complex factory scenario.
Bacillus pumilus reveals a remarkably high resistance to hydrogen peroxide provoked oxidative stress
(2014)
Bacillus pumilus is characterized by a higher oxidative stress resistance than other comparable industrially relevant Bacilli such as B. subtilis or B. licheniformis. In this study the response of B. pumilus to oxidative stress was investigated during a treatment with high concentrations of hydrogen peroxide at the proteome, transcriptome and metabolome level. Genes/proteins belonging to regulons, which are known to have important functions in the oxidative stress response of other organisms, were found to be upregulated, such as the Fur, Spx, SOS or CtsR regulon. Strikingly, parts of the fundamental PerR regulon responding to peroxide stress in B. subtilis are not encoded in the B. pumilus genome. Thus, B. pumilus misses the catalase KatA, the DNA-protection protein MrgA or the alkyl hydroperoxide reductase AhpCF. Data of this study suggests that the catalase KatX2 takes over the function of the missing KatA in the oxidative stress response of B. pumilus. The genome-wide expression analysis revealed an induction of bacillithiol (Cys-GlcN-malate, BSH) relevant genes. An analysis of the intracellular metabolites detected high intracellular levels of this protective metabolite, which indicates the importance of bacillithiol in the peroxide stress resistance of B. pumilus.
Shakedown analysis of Reissner-Mindlin plates using the edge-based smoothed finite element method
(2014)
This paper concerns the development of a primal-dual algorithm for limit and shakedown analysis of Reissner-Mindlin plates made of von Mises material. At each optimization iteration, the lower bound of the shakedown load multiplier is calculated simultaneously with the upper bound using the duality theory. An edge-based smoothed finite element method (ES-FEM) combined with the discrete shear gap (DSG) technique is used to improve the accuracy of the solutions and to avoid the transverse shear locking behaviour. The method not only possesses all inherent features of convergence and accuracy from ES-FEM, but also ensures that the total number of variables in the optimization problem is kept to a minimum compared with the standard finite element formulation. Numerical examples are presented to demonstrate the effectiveness of the present method.
Two single-incision mini-slings used for treating urinary incontinence in women are compared with respect to the stresses they produce in their surrounding tissue. In an earlier paper we experimentally observed that these implants produce considerably different stress distributions in a muscle tissue equivalent. Here we perform 2D finite element analyses to compare the shear stresses and normal stresses in the tissue equivalent for the two meshes and to investigate their failure behavior. The results clearly show that the Gynecare TVT fails for increasing loads in a zipper-like manner because it gradually debonds from the surrounding tissue. Contrary to that, the tissue at the ends of the DynaMesh-SIS direct may rupture but only at higher loads. The simulation results are in good agreement with the experimental observations thus the computational model helps to interpret the experimental results and provides a tool for qualitative evaluation of mesh implants.
Successful bone sawing requires a high level of skill and experience, which could be gained by the use of Virtual Reality-based simulators. A key aspect of these medical simulators is realistic force feedback. The aim of this paper is to model the bone sawing process in order to develop a valid training simulator for the bilateral sagittal split osteotomy, the most often applied corrective surgery in case of a malposition of the mandible. Bone samples from a human cadaveric mandible were tested using a designed experimental system. Image processing and statistical analysis were used for the selection of four models for the bone sawing process. The results revealed a polynomial dependency between the material removal rate and the applied force. Differences between the three segments of the osteotomy line and between the cortical and cancellous bone were highlighted.
There is significant interest in sampling subglacial environments for geobiological studies, but they are difficult to access. Existing ice-drilling technologies make it cumbersome to maintain microbiologically clean access for sample acquisition and environmental stewardship of potentially fragile subglacial aquatic ecosystems. The IceMole is a maneuverable subsurface ice probe for clean in situ analysis and sampling of glacial ice and subglacial materials. The design is based on the novel concept of combining melting and mechanical propulsion. It can change melting direction by differential heating of the melting head and optional side-wall heaters. The first two prototypes were successfully tested between 2010 and 2012 on glaciers in Switzerland and Iceland. They demonstrated downward, horizontal and upward melting, as well as curve driving and dirt layer penetration. A more advanced probe is currently under development as part of the Enceladus Explorer (EnEx) project. It offers systems for obstacle avoidance, target detection, and navigation in ice. For the EnEx-IceMole, we will pay particular attention to clean protocols for the sampling of subglacial materials for biogeochemical analysis. We plan to use this probe for clean access into a unique subglacial aquatic environment at Blood Falls, Antarctica, with return of a subglacial brine sample.
A technology reference study for a solar polar mission is presented. The study uses novel analytical methods to quantify the mission design space including the required sail performance to achieve a given solar polar observation angle within a given timeframe and thus to derive mass allocations for the remaining spacecraft sub-systems, that is excluding the solar sail sub-system. A parametric, bottom-up, system mass budget analysis is then used to establish the required sail technology to deliver a range of science payloads, and to establish where such payloads can be delivered to within a given timeframe. It is found that a solar polar mission requires a solar sail of side-length 100–125 m to deliver a ‘sufficient value’ minimum science payload, and that a 2.5 μm sail film substrate is typically required, however the design is much less sensitive to the boom specific mass.
A 3D finite element model of the female pelvic floor for the reconstruction of urinary incontinence
(2014)
Developing a new production host from a blueprint: Bacillus pumilus as an industrial enzyme producer
(2014)
This paper develops a new finite element method (FEM)-based upper bound algorithm for limit and shakedown analysis of hardening structures by a direct plasticity method. The hardening model is a simple two-surface model of plasticity with a fixed bounding surface. The initial yield surface can translate inside the bounding surface, and it is bounded by one of the two equivalent conditions: (1) it always stays inside the bounding surface or (2) its centre cannot move outside the back-stress surface. The algorithm gives an effective tool to analyze the problems with a very high number of degree of freedom. Our numerical results are very close to the analytical solutions and numerical solutions in literature.
Today, the assembly of laser systems requires a large share of manual operations due to its complexity regarding the optimal alignment of optics. Although the feasibility of automated alignment of laser optics has been shown in research labs, the development effort for the automation of assembly does not meet economic requirements – especially for low-volume laser production. This paper presents a model-based and sensor-integrated assembly execution approach for flexible assembly cells consisting of a macro-positioner covering a large workspace and a compact micromanipulator with camera attached to the positioner. In order to make full use of available models from computer-aided design (CAD) and optical simulation, sensor systems at different levels of accuracy are used for matching perceived information with model data. This approach is named "chain of refined perception", and it allows for automated planning of complex assembly tasks along all major phases of assembly such as collision-free path planning, part feeding, and active and passive alignment. The focus of the paper is put on the in-process image-based metrology and information extraction used for identifying and calibrating local coordinate systems as well as the exploitation of that information for a part feeding process for micro-optics. Results will be presented regarding the processes of automated calibration of the robot camera as well as the local coordinate systems of part feeding area and robot base.
1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug–drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described.
2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created.
3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug–drug interactions as well as in human metabolite testing and risk assessment.
4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed.
The impact of wake model effects is investigated for two highly
non-planar lifting systems. Dependent on the geometrical
arrangement of the configuration, the wake model shape is found
to considerably affect the estimation. Particularly at higher angles
of attack, an accurate estimation based on the common linear wake
model approaches is involved.
Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in development of less common isotopes. Herein, we describe the production of ⁴⁴Sc (t₁⸝₂ = 3.97 h, Eavg,β⁺ = 1.47 MeV, branching ratio = 94.27%) in a solution target and an automated loading system which allows a quick turn-around between different radiometallic isotopes and therefore greatly improves their availability for tracer development. Experimental yields are compared to theoretical calculations.
Does stiffer electoral competition reduce political shirking? For a micro-analysis of this question, I construct a new data set spanning the years 2005 to 2012 covering biographical and political information about German Members of Parliament (MPs), including their attendance rates in voting sessions. For the parliament elected in 2009, I show that indeed opposition party MPs who expect to face a close race in their district show significantly and relevantly lower absence rates in parliament beforehand. MPs of governing parties seem not to react significantly to electoral competition. These results are confirmed by an analysis of the parliament elected in 2005, by several robustness checks, and also by employing an instrumental variable strategy exploiting convenient peculiarities of the German electoral system. The study also shows how MPs elected via party lists react to different levels of electoral competition.
Planning the layout and operation of a technical system is a common task
for an engineer. Typically, the workflow is divided into consecutive stages: First,
the engineer designs the layout of the system, with the help of his experience or of
heuristic methods. Secondly, he finds a control strategy which is often optimized
by simulation. This usually results in a good operating of an unquestioned sys-
tem topology. In contrast, we apply Operations Research (OR) methods to find a
cost-optimal solution for both stages simultaneously via mixed integer program-
ming (MILP). Technical Operations Research (TOR) allows one to find a provable
global optimal solution within the model formulation. However, the modeling error
due to the abstraction of physical reality remains unknown. We address this ubiq-
uitous problem of OR methods by comparing our computational results with mea-
surements in a test rig. For a practical test case we compute a topology and control
strategy via MILP and verify that the objectives are met up to a deviation of 8.7%.
Molecular Modeling Approach to the Prediction of Mechanical Properties of Silica-Reinforced Rubbers
(2014)
Recently, we have suggested a nanomechanical model for dissipative loss in filled elastomer networks in the context of the Payne effect. The mechanism is based on a total interfiller particle force exhibiting an intermittent loop, due to the combination of short-range repulsion and dispersion forces with a long-range elastic attraction. The sum of these forces leads, under external strain, to a spontaneous instability of “bonds” between the aggregates in a filler network and attendant energy dissipation. Here, we use molecular dynamics simulations to obtain chemically realistic forces between surface modified silica particles. The latter are combined with the above model to estimate the loss modulus and the low strain storage modulus in elastomers containing the aforementioned filler-compatibilizer systems. The model is compared to experimental dynamic moduli of silica filled rubbers. We find good agreement between the model predictions and the experiments as function of the compatibilizer's molecular structure and its bulk concentration.
Objectives
To assess the image quality of T2-weighted (T2w) magnetic resonance imaging of the prostate and the visibility of prostate cancer at 7 Tesla (T).
Materials & methods
Seventeen prostate cancer patients underwent T2w imaging at 7T with only an external transmit/receive array coil. Three radiologists independently scored images for image quality, visibility of anatomical structures, and presence of artefacts. Krippendorff’s alpha and weighted kappa statistics were used to assess inter-observer agreement. Visibility of prostate cancer lesions was assessed by directly linking the T2w images to the confirmed location of prostate cancer on histopathology.
Results
T2w imaging at 7T was achievable with ‘satisfactory’ (3/5) to ‘good’ (4/5) quality. Visibility of anatomical structures was predominantly scored as ‘satisfactory’ (3/5) and ‘good’ (4/5). If artefacts were present, they were mostly motion artefacts and, to a lesser extent, aliasing artefacts and noise. Krippendorff’s analysis revealed an α = 0.44 between three readers for the overall image quality scores. Clinically significant cancer lesions in both peripheral zone and transition zone were visible at 7T.
Conclusion
T2w imaging with satisfactory to good quality can be routinely acquired, and cancer lesions were visible in patients with prostate cancer at 7T using only an external transmit/receive body array coil.
Vestibular effects of a 7 Tesla MRI examination compared to 1.5 T and 0 T in healthy volunteers
(2014)
Ultra-high-field MRI (7 Tesla (T) and above) elicits more temporary side-effects compared to 1.5 T and 3 T, e.g. dizziness or “postural instability” even after exiting the scanner. The current study aims to assess quantitatively vestibular performance before and after exposure to different MRI scenarios at 7 T, 1.5 T and 0 T. Sway path and body axis rotation (Unterberger's stepping test) were quantitatively recorded in a total of 46 volunteers before, 2 minutes after, and 15 minutes after different exposure scenarios: 7 T head MRI (n = 27), 7 T no RF (n = 22), 7 T only B₀ (n = 20), 7 T in & out B₀ (n = 20), 1.5 T no RF (n = 20), 0 T (n = 15). All exposure scenarios lasted 30 minutes except for brief one minute exposure in 7 T in & out B₀. Both measures were documented utilizing a 3D ultrasound system. During sway path evaluation, the experiment was repeated with eyes both open and closed. Sway paths for all long-lasting 7 T scenarios (normal, no RF, only B₀) with eyes closed were significantly prolonged 2 minutes after exiting the scanner, normalizing after 15 minutes. Brief exposure to 7 T B₀ or 30 minutes exposure to 1.5 T or 0 T did not show significant changes. End positions after Unterberger's stepping test were significantly changed counter-clockwise after all 7 T scenarios, including the brief in & out B₀ exposure. Shorter exposure resulted in a smaller alteration angle. In contrast to sway path, reversal of changes in body axis rotation was incomplete after 15 minutes. 1.5 T caused no rotational changes. The results show that exposure to the 7 Tesla static magnetic field causes only a temporary dysfunction or “over-compensation” of the vestibular system not measurable at 1.5 or 0 Tesla. Radiofrequency fields, gradient switching, and orthostatic dysregulation do not seem to play a role.
Objectives
The aim of this study was to identify characteristics of phosphorus (³¹P) spectra of the human prostate and to investigate changes of individual phospholipid metabolites in prostate cancer through in vivo ³¹P magnetic resonance spectroscopic imaging (MRSI) at 7 T.
Materials and Methods
In this institutional review board–approved study, 15 patients with biopsy-proven prostate cancer underwent T₂-weighted magnetic resonance imaging and 3-dimensional ³¹P MRSI at 7 T. Voxels were selected at the tumor location, in normal-appearing peripheral zone tissue, normal-appearing transition zone tissue, and in the base of the prostate close to the seminal vesicles. Phosphorus metabolite ratios were determined and compared between tissue types.
Results
Signals of phosphoethanolamine (PE) and phosphocholine (PC) were present and well resolved in most ³¹P spectra in the prostate. Glycerophosphocholine signals were observable in 43% of the voxels in malignant tissue, but in only 10% of the voxels in normal-appearing tissue away from the seminal vesicles. In many spectra, independent of tissue type, 2 peaks resonated in the chemical shift range of inorganic phosphate, possibly representing 2 separate pH compartments. The PC/PE ratio in the seminal vesicles was highly elevated compared with the prostate in 5 patients. A considerable overlap of ³¹P metabolite ratios was found between prostate cancer and normal-appearing prostate tissue, preventing direct discrimination of these tissues. The only 2 patients with high Gleason scores tumors (≥4+5) presented with high PC and glycerophosphocholine levels in their cancer lesions.
Conclusions
Phosphorus MRSI at 7 T shows distinct features of phospholipid metabolites in the prostate gland and its surrounding structures. In this exploratory study, no differences in ³¹P metabolite ratios were observed between prostate cancer and normal-appearing prostate tissue possibly because of the partial volume effects of small tumor foci in large MRSI voxels.
Purpose
To demonstrate that high quality T₂-weighted (T2w) turbo spin-echo (TSE) imaging of the complete prostate can be achieved routinely and within safety limits at 7 T, using an external transceive body array coil only.
Methods
Nine healthy volunteers and 12 prostate cancer patients were scanned on a 7 T whole-body system. Preparation consisted of B₀ and radiofrequency shimming and localized flip angle calibration. T₁ and T₂ relaxation times were measured and used to define the T2w-TSE protocol. T2w imaging was performed using a TSE sequence (pulse repetition time/echo time 3000–3640/71 ms) with prolonged excitation and refocusing pulses to reduce specific absorption rate.
Results
High quality T2w TSE imaging was performed in less than 2 min in all subjects. Tumors of patients with gold-standard tumor localization (MR-guided biopsy or prostatectomy) were well visualized on 7 T imaging (n = 3). The number of consecutive slices achievable within a 10-g averaged specific absorption rate limit of 10 W/kg was ≥28 in all subjects, sufficient for full prostate coverage with 3-mm slices in at least one direction.
Conclusion
High quality T2w TSE prostate imaging can be performed routinely and within specific absorption rate limits at 7 T with an external transceive body array.
This paper investigates the extent to which corporate governance affects the cost of debt and equity capital of German exchange-listed companies. I examine corporate governance along three dimensions: financial information quality, ownership structure and board structure. The results suggest that firms with high levels of financial transparency and bonus compensations face lower cost of equity. In addition, block ownership is negatively related to firms' cost of equity when the blockholders are other firms, managers or founding-family members. Consistent with the conjecture that agency costs increase with firm size, I find significant cost of debt effects only in the largest German companies. Here, the creditors demand lower cost of debt from firms with block ownerships held by corporations or banks. My findings demonstrate that a uniform set of governance attributes is unlikely to satisfy suppliers of debt and equity capital equally.
New coupled finite-infinite element approach for wave propagation simulation of unbounded soil media
(2014)
Because of its minor environmental impact, electricity generation using wind power is getting remarkable. The further growth of the wind industry depends on technological solutions to the challenges in production and construction of the turbines. Wind turbine tower vibrations, which limit power generation efficiency and cause fatigue problems with high maintenance costs, count as one of the main structural difficulties in the wind energy sector. To mitigate tower vibrations auxiliary measures are necessary. The effectiveness of tuned mass damper is verified by means of a numeric study on a 5 MW onshore reference wind turbine. Hereby, also seismic-induced vibrations and soil–structure interaction are considered. Acquired results show that tuned mass damper can effectively reduce resonant tower vibrations and improve the fatigue life of wind turbines. This chapter is also concerned with tuned liquid column damper and a semiactive application of it. Due to its geometric versatility and low prime costs, tuned liquid column dampers are a good alternative to other damping measures, in particular for slender structures like wind turbines.
The Gram-positive endospore-forming bacterium Bacillus licheniformis can be found widely in nature and it is exploited in industrial processes for the manufacturing of antibiotics, specialty chemicals, and enzymes. Both in its varied natural habitats and in industrial settings, B. licheniformis cells will be exposed to increases in the external osmolarity, conditions that trigger water efflux, impair turgor, cause the cessation of growth, and negatively affect the productivity of cell factories in biotechnological processes. We have taken here both systems-wide and targeted physiological approaches to unravel the core of the osmostress responses of B. licheniformis. Cells were suddenly subjected to an osmotic upshift of considerable magnitude (with 1 M NaCl), and their transcriptional profile was then recorded in a time-resolved fashion on a genome-wide scale. A bioinformatics cluster analysis was used to group the osmotically up-regulated genes into categories that are functionally associated with the synthesis and import of osmostress-relieving compounds (compatible solutes), the SigB-controlled general stress response, and genes whose functional annotation suggests that salt stress triggers secondary oxidative stress responses in B. licheniformis. The data set focusing on the transcriptional profile of B. licheniformis was enriched by proteomics aimed at identifying those proteins that were accumulated by the cells through increased biosynthesis in response to osmotic stress. Furthermore, these global approaches were augmented by a set of experiments that addressed the synthesis of the compatible solutes proline and glycine betaine and assessed the growth-enhancing effects of various osmoprotectants. Combined, our data provide a blueprint of the cellular adjustment processes of B. licheniformis to both sudden and sustained osmotic stress.
Members of the species Bacillus pumilus get more and more in focus of the biotechnological industry as potential new production strains. Based on exoproteome analysis, B. pumilus strain Jo2, possessing a high secretion capability, was chosen for an omics-based investigation. The proteome and metabolome of B. pumilus cells growing either in minimal or complex medium was analyzed. In total, 1542 proteins were identified in growing B. pumilus cells, among them 1182 cytosolic proteins, 297 membrane and lipoproteins and 63 secreted proteins. This accounts for about 43% of the 3616 proteins encoded in the B. pumilus Jo2 genome sequence. By using GC–MS, IP-LC/MS and H NMR methods numerous metabolites were analyzed and assigned to reconstructed metabolic pathways. In the genome sequence a functional secretion system including the components of the Sec- and Tat-secretion machinery was found. Analysis of the exoproteome revealed secretion of about 70 proteins with predicted secretion signals. In addition, selected production-relevant genome features such as restriction modification systems and NRPS clusters of B. pumilus Jo2 are discussed.
In co-operation with the German Aerospace Center, the Solar-Institut Jülich has been analyzing the different technologies that are available for methanol production from CO2 using solar energy. The aim of the project is to extract CO2 from industrial exhaust gases or directly from the atmosphere to recycle it by use of solar energy. Part of the study was the modeling and simulating of a methane reformer for the production of synthesis gas, which can be operated by solar or hybrid heat sources. The reformer has been simplified in such a way that the model is accurate and enables fast calculations. The developed pseudo-homogeneous one- dimensional model can be regarded as a kind of counter-current heat exchanger and is able to incorporate a steam reforming reaction as well as a dry reforming reaction.
A semiconductor field-effect device has been used for an enzymatically catalyzed degradation of biopolymers for the first time. This novel technique is capable to monitor the degradation process of multiple samples in situ and in real-time. As model system, the degradation of the biopolymer poly(D, L-lactic acid) has been monitored in the degradation medium containing the enzyme lipase from Rhizomucor miehei. The obtained results demonstrate the potential of capacitive field-effect sensors for degradation studies of biodegradable polymers.
Among the variety of transducer concepts proposed for label-free detection of biomolecules, the semiconductor field-effect device (FED) is one of the most attractive platforms. As medical techniques continue to progress towards diagnostic and therapies based on biomarkers, the ability of FEDs for a label-free, fast and real-time detection of multiple pathogenic and physiologically relevant molecules with high specificity and sensitivity offers very promising prospects for their application in point-of-care and personalized medicine for an early diagnosis and treatment of diseases. The presented paper reviews recent advances and current trends in research and development of different FEDs for label-free, direct electrical detection of charged biomolecules by their intrinsic molecular charge. The authors are mainly focusing on the detection of the DNA hybridization event, antibody-antigen affinity reaction as well as clinically relevant biomolecules such as cardiac and cancer biomarkers.
It is well known that the degradation environment can strongly influence the biodegradability and kinetics of biodegradation processes of polymers. Therefore, besides the monitoring of the degradation process, it is also necessary to control the medium in which the degradation takes place. In this work, a micromachined multi-parameter sensor chip for the control of the polymer-degradation medium has been developed. The chip combines a capacitive field-effect pH sensor, a four-electrode electrolyte-conductivity sensor and a thin-film Pt-temperature sensor. The results of characterization of individual sensors are presented. In addition, the multi-parameter sensor chip together with an impedimetric polymer-degradation sensor was simultaneously characterized in degradation solutions with different pH and electrolyte conductivity. The obtained results demonstrate the feasibility of the multi-parameter sensor chip for the control of the polymer-degradation medium.
Planar and three-dimensional (3D) interdigitated electrodes (IDE) with electrode digits separated by an insulating barrier of different heights were electrochemically characterized and compared in terms of their sensing properties. Due to the impact of the surface resistance, both types of IDE structures display a non-linear behavior in low-ionic strength solutions. The experimental data were fitted to an electrical equivalent circuit and interpreted taking into account the surface-charge-governed properties. The effect of a charged polyelectrolyte layer electrostatically assembled onto the sensor surface on the surface resistance in solutions with different KCl concentration is studied. In case of the same electrode footprint, 3D-IDEs show a larger cell constant and a higher sensitivity to molecular adsorption than that of planar IDEs. The obtained results demonstrate the potential of 3D-IDEs as a new transducer structure for a direct label-free sensing of charged molecules.
An enzyme system organized in a flow device was used to mimic a reversible Controlled NOT (CNOT) gate with two input and two output signals. Reversible conversion of NAD⁺ and NADH cofactors was used to perform a XOR logic operation, while biocatalytic hydrolysis of p-nitrophenyl phosphate resulted in an Identity operation working in parallel. The first biomolecular realization of a CNOT gate is promising for integration into complex biomolecular networks and future biosensor/biomedical applications.
A technology reference study for a displaced Lagrange point space weather mission is presented. The mission builds on previous concepts, but adopts a strong micro-spacecraft philosophy to deliver a low mass platform and payload which can be accommodated on the DLR/ESA Gossamer-3 technology demonstration mission. A direct escape from Geostationary Transfer Orbit is assumed with the sail deployed after the escape burn. The use of a miniaturized, low mass platform and payload then allows the Gossamer-3 solar sail to potentially double the warning time of space weather events. The mission profile and mass budgets will be presented to achieve these ambitious goals.
High-k perovskite oxide of barium strontium titanate (BST) represents a very attractive multi-functional transducer material for the development of (bio-)chemical sensors for liquids. In this work, BST films have been applied as a sensitive transducer material for a label-free detection of adsorbed charged macromolecules (positively charged polyelectrolytes) and concentration of hydrogen peroxide vapor as well as protection insulator layer for a contactless electrolyte-conductivity sensor. The experimental results of characterization of individual sensors are presented. Special emphasis is devoted towards the development of a capacitively-coupled contactless electrolyte-conductivity sensor.
The development of a cost-effective hydrolysis for crude cellulose is an essential part of biorefinery developments. To establish such high solid hydrolysis, a new solid state reactor with static mixing is used. However, concentrations >10% (w/w) cause a rate and yield reduction of enzymatic hydrolysis. By optimizing the synergetic activity of cellulolytic enzymes at solid concentrations of 9%, 17% and 23% (w/w) of crude Organosolv cellulose, glucose concentrations of 57, 113 and 152 g L⁻¹ are reached. However, the glucose yield decreases from 0.81 to 0.72gg⁻¹ at 17% (w/w). Optimal conditions for hydrolysis scale-up under minimal enzyme addition are identified. As result, at 23% (w/w) crude cellulose the glucose yield increases from 0.29 to 0.49gg⁻¹. As proof of its applicability, biobutanol, succinic and itaconic acid are produced with the crude hydrolysate. The potential of the substrate is proven e.g. by a high butanol yield of 0.33gg⁻¹.
A major part of edible oil is subjected to bleaching procedures, primarily with minerals applied as adsorbers. Their recycling is currently done either by regaining the oil via organic solvent extraction or by using the spent bleaching earth (SBE) as additive for animal feed, etc. As a new method, the reutilization of the by-product SBE for the microbiologic formation of acetone, butanol, and ethanol (ABE) is presented as proof-of-concept. The SBE was taken from a palm oil cleaning process. The recycling concept is based on the application of lipolytic clostridia strains. Due to considerably long fermentation times, co-fermentation with Candida rugosa and enzymatic hydrolyses of the bound oil with a subsequent clostridia fermentation are shown as alternative routes. Anaerobic fermentations under comparison of different clostridia strains were performed with glycerol media, enzymatically hydrolyzed palm oil and SBE. Solutes, side product compositions and productivities were quantified via HPLC. A successful production of ABE solutes from SBE has been done with a yield of 0.15 g butanol per gram of bound glycerol. Thus, the biotechnological recycling of the waste stream is possible in principle. Inhibition of the substrate suspension has been observed. A chromatographic ion-exchange of substrates increased the biomass concentration.
It is well known that biochemical and biotechnological processes are strongly dependent and affected by a variety of physico-chemical parameters such as pH value, temperature, pressure and electrolyte conductivity. Therefore, these quantities have to be monitored or controlled in order to guarantee a stable process operation, optimization and high yield. In this work, a sensor chip for the multiparameter detection of three physico-chemical parameters such as electrolyte conductivity, pH and temperature is realized using barium strontium titanate (BST) as multipurpose material. The chip integrates a capacitively coupled four-electrode electrolyte-conductivity sensor, a capacitive field-effect pH sensor and a thin-film Pt-temperature sensor. Due to the multifunctional properties of BST, it is utilized as final outermost coating layer of the processed sensor chip and serves as passivation and protection layer as well as pH-sensitive transducer material at the same time. The results of testing of the individual sensors of the developed multiparameter sensor chip are presented. In addition, a quasi-simultaneous multiparameter characterization of the sensor chip in buffer solutions with different pH value and electrolyte conductivity is performed. To study the sensor behavior and the suitability of BST as multifunctional material under harsh environmental conditions, the sensor chip was exemplarily tested in a biogas digestate.
A multi-spot (4 × 4 spots) light-addressable potentiometric sensor (MLAPS) consisting of an Al–p-Si–SiO2 structure has been applied for the label-free electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization by the intrinsic molecular charge for the first time. Single-stranded probe ssDNA molecules (20 bases) were covalently immobilized onto the silanized SiO2 gate surface. The unspecific adsorption of mismatch ssDNA on the MLAPS gate surface was blocked by bovine serum albumin molecules. To reduce the screening effect and to achieve a high sensor signal, the measurements were performed in a low ionic-strength solution. The photocurrent–voltage (I–V) curves were simultaneously recorded on all 16 spots after each surface functionalization step. Large shifts of I–V curves of 25 mV were registered after the DNA immobilization and hybridization event. In contrast, a small potential shift (∼5 mV) was observed in case of mismatch ssDNA, revealing good specificity of the sensor. The obtained results demonstrate the potential of the MLAPS as promising transducer platform for the multi-spot label-free electrical detection of DNA molecules by their intrinsic molecular charge.
RGB-D sensors such as the Microsoft Kinect or the Asus Xtion are inexpensive 3D sensors. A depth image is computed by calculating the distortion of a known infrared light (IR) pattern which is projected into the scene. While these sensors are great devices they have some limitations. The distance they can measure is limited and they suffer from reflection problems on transparent, shiny, or very matte and absorbing objects. If more than one RGB-D camera is used the IR patterns interfere with each other. This results in a massive loss of depth information. In this paper, we present a simple and powerful method to overcome these problems. We propose a stereo RGB-D camera system which uses the pros of RGB-D cameras and combine them with the pros of stereo camera systems. The idea is to utilize the IR images of each two sensors as a stereo pair to generate a depth map. The IR patterns emitted by IR projectors are exploited here to enhance the dense stereo matching even if the observed objects or surfaces are texture-less or transparent. The resulting disparity map is then fused with the depth map offered by the RGB-D sensor to fill the regions and the holes that appear because of interference, or due to transparent or reflective objects. Our results show that the density of depth information is increased especially for transparent, shiny or matte objects.
The problem of fair and privacy-preserving ordered set reconciliation arises in a variety of applications like auctions, e-voting, and appointment reconciliation. While several multi-party protocols have been proposed that solve this problem in the semi-honest model, there are no multi-party protocols that are secure in the malicious model so far. In this paper, we close this gap. Our newly proposed protocols are shown to be secure in the malicious model based on a variety of novel non-interactive zero-knowledge-proofs. We describe the implementation of our protocols and evaluate their performance in comparison to protocols solving the problem in the semi-honest case.
Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization of these models will help to better understand their utility for predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis of these mouse lines by evaluating the compensatory changes in mRNA expression, quantifying the amounts of OATP1B1 and -1B3 protein by liquid chromatography–tandem mass spectrometry, and studying the active uptake in isolated hepatocytes and the pharmacokinetics of some prototypical substrates including statins. Major outcomes from these studies were 1) mostly moderate compensatory changes in only a few genes involved in drug metabolism and disposition, 2) a robust hepatic expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models, and 3) functional activities of the human transporters in hepatocytes isolated from the humanized models with several substrates tested in vitro and with pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized models did not significantly alter liver or plasma concentrations of rosuvastatin and pitavastatin compared with Oatp1a/1b knockout controls under the conditions used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed in vitro and/or in vivo functional activity with some statins, further characterization of these models is required to define their potential use and limitations in the prediction of drug disposition and drug-drug interactions in humans.
Up in the clouds and above fuels and construction materials must be very carefully selected to ensure a smooth flight and touchdown. Out of around 38,000 single and dual-engined propeller aeroplanes, roughly a third are affected by a new trend in the fuel sector that may lead to operating troubles or even emergency landings: The admixture of bio-ethanol to conventional gasoline. Experiences with these fuels may be projected to alternative mixtures containing new components.
Our knowledge on tree responses to drought is mainly based on short-term manipulation experiments which do not capture any possible long-term adjustments in this response. Therefore, historical water channels in inner-Alpine dry valleys were used as century-long irrigation experiments to investigate adjustments in tree growth to contrasting water supply. This involved quantifying the tree-ring growth of irrigated and non-irrigated (control) Scots pine (Pinus sylvestris L.) in Valais (Switzerland), as well as European larch (Larix decidua Mill.) and black pine (Pinus nigra Arnold) in Vinschgau (Italy). Furthermore, the adjustments in radial growth of Scots pine and European larch to an abrupt stop in irrigation were analyzed.
Irrigation promoted the radial growth of all tree species investigated compared to the control: (1) directly through increased soil water availability, and (2) indirectly through increased soil nutrients and humus contents in the irrigated plots. Irrigation led to a full elimination of growth responses to climate for European larch and black pine, but not for Scots pine, which might become more sensitive to drought with increasing tree size in Valais. For the control trees, the response of the latewood increment to water availability in July/August has decreased in recent decades for all species, but increased in May for Scots pine only. The sudden irrigation stop caused a drop in radial growth to a lower level for Scots pine or similar level for larch compared to the control for up to ten years. However, both tree species were then able to adjust to the new conditions and subsequently grew with similar (Scots pine) or even higher growth rates (larch) than the control.
To estimate the impact of climate change on future forest development, the duration of manipulation experiments should be on longer time scales in order to capture adjustment processes and feedback mechanisms of forest ecosystems.
Numerical Study on Increased Energy Density for the DLN Micromix Hydrogen Combustion Principle
(2014)
In der Reihe der nachwachsenden Rohstoffe besitzt Holz als erneuerbare und umweltfreundliche Ressource ein großes Potenzial. Über 11 Mio. ha Holz, das laut der Fachagentur für nachwachsende Rohstoffe (FNR) auch für industrielle Zwecke genutzt werden kann, wuchsen im Jahr 2013 allein auf bundesdeutscher Fläche. 56,8 Mio. m³ jährlicher Holzeinschlag in den letzten zehn Jahren wurde zu knapp der Hälfte stofflich und der Rest energetisch verwertet. Im Rahmen dieser Arbeit konnte auf der Basis vom Holz der Buche, die nach Fichte und Kiefer die dritthäufigste Baumart in Deutschland ist und 15% der deutschen Waldfläche ausmacht, die Fraktionierung der polymeren Hauptbestandteile mit niedrigem energetischen Einsatz erreicht werden. Hierbei werden in einem nachgeschalteten Extraktionsprozess die beiden Komponenten Hemicellulose und Lignin in flüssiger Form von der finalen festen Cellulosefraktion abgetrennt. Die Extraktion der Hemicellulose erfolgt durch eine Liquid Hot Water (LHW)-Behandlung. Untersucht wird der katalytische Zusatz anorganischer Säuren wie H₃PO₄ und H₂SO₄. Im Hinblick auf die weitere Verwertung von Lignin zu aromatischen Synthesebausteinen kommt die Organosolv-Extraktion mit einem Ethanol/Wasser-Gemisch zum Einsatz. Von Vorteil ist die weitere Verwendung beider Stoffströme ohne Fällungsschritt und nachteiliger Verdünnung der Hemicellulose.
DNA-hybridization detection using light-addressable potentiometric sensor modified with gold layer
(2014)
Multi-parameter detection for supporting monitoring and control of biogas processes in agriculture
(2014)
High-intensity discharge lamps can be driven by radio-frequency signals in the ISM frequency band at 2.45 GHz, using a matching network to transform the impedance of the plasma to the source impedance. To achieve an optimal operating condition, a good characterization of the lamp in terms of radio frequency equivalent circuits under operating conditions is necessary, enabling the design of an efficient matching network. This paper presents the characterization technique for such lamps and presents the design of the required matching network. For the characterization, a high-intensity discharge lamp was driven by a monofrequent large signal at 2.45 GHz, whereas a frequency sweep over 300 MHz was performed across this signal to measure so-called small-signal hot S-parameters using a vector network analyzer. These parameters are then used as an equivalent load in a circuit simulator to design an appropriate matching network. Using the measured data as a black-box model in the simulation results in a quick and efficient method to simulate and design efficient matching networks in spite of the complex plasma behavior. Furthermore, photometric analysis of high-intensity discharge lamps are carried out, comparing microwave operation to conventional operation.
Therefore Fermat is right
(2014)
It was Fernat's idea to investigate how many numbers would fulfill the equation according to the Pythagorean Theorem if the exponent were increased to random, e.g. to a3 + b3 = c3. His question became therefore: are there two whole numbers the cubes of which add up to the volume of the cube of a third whole number? He posed this same question, of course, for all kinds of higher exponents, so that the equation could be generalized: is there an integral solution for the equation an + bn = cn, if the exponent n is higher than 2? Although in 1993, the English mathematician Andrew Wiles was able to produce an arithmetical proof for Fermat's famous theorem, I will show that there is a simple logical explanation which is also pragmatic and plausible and what is the result of a fundamental alternative idea how our world seems to be constructed.
In any books about genetics it can still today be read that our genetic code is called “degenerate” because it is still believed that 43 = 64 triplets encode the 20 essential amino acids. Indeed we have to assume the inverse law, what means that 34 = 81 exact code positions are really effective for our genetic code and encode the amino acids, compiled to proteins. This very important discovery leads to two completely new results that are limits-overlooking: 1) 34 (=81) genetic code positions mean exactly the same number as there are stable and naturally existing chemical elements in our universe. This famous argument should now lead to some alternative, as well as new fundamental conclusions about our existence. 2) A genetic code positioning system shows that nature is much smarter than expected: mutations are made less dangerous than believed, because they won't be that easily able any more to cause severe damages in the protein-synthesis. This should also lead to some alternative views upon evolution of life.