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Preclinical development of highly effective and safe DNA vaccines directed against HPV 16 E6 and E7
(2011)
The anticancer activity of titanium complexes has been known since the groundbreaking studies of Köpf and Köpf-Maier on titanocen dichloride. Unfortunately, possibly due to their fast hydrolysis, derivatives of titanocen dichloride failed in clinical studies. Recently, the new family of titanium salan complexes containing tetradentate ONNO ligands with anti-cancer properties has been discovered. These salan complexes are much more stabile in aqueous media. In this study we describe the biological activity of two titanium salan complexes in a mouse model of cervical cancer. High efficiency of this promising complex family was demonstrated for the first time in vivo. From these data we conclude that titanium salan complexes display very strong antitumor properties exhibiting only minor side effects. Our results may influence the chemotherapy with metallo therapeutics in the future.
Digital elevation models (DEMs), represent the three-dimensional terrain and are the basic input for numerical snow avalanche dynamics simulations. DEMs can be acquired using topographic maps or remote-sensing technologies, such as photogrammetry or lidar. Depending on the acquisition technique, different spatial resolutions and qualities are achieved. However, there is a lack of studies that investigate the sensitivity of snow avalanche simulation algorithms to the quality and resolution of DEMs. Here, we perform calculations using the numerical avalance dynamics model RAMMS, varying the quality and spatial resolution of the underlying DEMs, while holding the simulation parameters constant. We study both channelized and open-terrain avalanche tracks with variable roughness. To quantify the variance of these simulations, we use well-documented large-scale avalanche events from Davos, Switzerland (winter 2007/08), and from our large-scale avalanche test site, Valĺee de la Sionne (winter 2005/06). We find that the DEM resolution and quality is critical for modeled flow paths, run-out distances, deposits, velocities and impact pressures. Although a spatial resolution of ~25 m is sufficient for large-scale avalanche modeling, the DEM datasets must be checked carefully for anomalies and artifacts before using them for dynamics calculations.
HisT/PLIER : A Two-Fold Provenance Approach for Grid-Enabled Scientific Workflows Using WS-VLAM
(2011)
Future evolution of risk management for structures : Advancement for the future IEC 62305-2 Ed3
(2011)
Understanding Additive Manufacturing : Rapid Prototyping - Rapid Tooling - Rapid Manufacturing
(2011)
Can vascular function be assessed by the interpretation of retinal vascular diameter changes?
(2011)
Air-pulse corneal applanation signal curve parameters for the characterisation of keratoconus
(2011)
Modification and testing of an engine and fuel control system for a hydrogen fuelled gas turbine
(2011)
Numerical and experimental investigation of tensile behavior of laser beam welded TRIP700 steel
(2011)
The proposed Den Haag Zuidwest district heating system of the city of The Hague consists of a deep doublet in a Jurassic sandstone layer that is designed for a production temperature of 75 °C and a reinjection temperature of 40 °C at a flow rate of 150 m3 h−1. The prediction of reservoir temperature and production behavior is crucial for success of the proposed geothermal doublet. This work presents the results of a study of the important geothermal and geohydrological issues for the doublet design. In the first phase of the study, the influences of the three-dimensional (3D) structures of anticlines and synclines on the temperature field were examined. A comprehensive petrophysical investigation was performed to build a large scale 3D-model of the reservoir. Several bottomhole temperatures (BHTs), as well as petrophysical logs were used to calibrate the model using thermal conductivity measurements on 50 samples from boreholes in different lithological units in the study area. Profiles and cross sections extracted from the calculated temperature field were used to study the temperature in the surrounding areas of the planned doublet. In the second phase of the project, a detailed 3D numerical reservoir model was set up, with the aim of predicting the evolution of the producer and injector temperatures, and the extent of the cooled area around the injector. The temperature model from the first phase provided the boundary conditions for the reservoir model. Hydraulic parameters for the target horizons, such as porosity and permeability, were taken from data available from the nearby exploration wells. The simulation results are encouraging as no significant thermal breakthrough is predicted. For the originally planned location of the producer, the extracted water temperature is predicted to be around 79 °C, with an almost negligible cooling in the first 50 years of production. When the producer is located shallower parts of the reservoir, the yield water temperatures is lower, starting at ≈76 °C and decreasing to ≈74 °C after 50 years of operation. This comparatively larger decrease in temperature with time is caused by the structural feature of the reservoir, namely a higher dip causes the cooler water to easily move downward. In view of the poor reservoir data, the reservoir simulation model is constructed to allow iterative updates using data assimilation during planned drilling, testing, and production phases. Measurements during an 8 h pumping test carried out in late 2010 suggest that a flow rate of 150 m3 h−1 is achievable. Fluid temperatures of 76.5 °C were measured, which is very close to the predicted value.
Meiotic functions of RAD18
(2011)
The contribution of altered post-transcriptional gene silencing to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. Here, we demonstrate that expression of microRNA (miR)-143 and 145 is upregulated in the liver of genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. Conversely, mice deficient for the miR-143–145 cluster are protected from the development of obesity-associated insulin resistance. Quantitative-mass-spectrometry-based analysis of hepatic protein expression in miR-143-overexpressing mice revealed miR-143-dependent downregulation of oxysterol-binding-protein-related protein (ORP) 8. Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation. Our experiments provide direct evidence that dysregulated post-transcriptional gene silencing contributes to the development of obesity-induced insulin resistance, and characterize the miR-143–ORP8 pathway as a potential target for the treatment of obesity-associated diabetes.
Plant physiology and plant stress: Plant physiology will be much more important for human mankind because of yield and cultivation limits of crops determined by their resistance to stress. To assess and counteract various stress factors it is necessary to conduct plant research to gain information and results on plant physiology.
Grass silage provides a great potential as renewable feedstock. Two fractions of the grass silage, a press juice and the fiber fraction, were evaluated for their possible use for bioethanol production. Direct production of ethanol from press juice is not possible due to high concentrations of organic acids. For the fiber fraction, alkaline peroxide or enzymatic pretreatment was used, which removes the phenolic acids in the cell wall. In this study, we demonstrate the possibility to integrate the enzymatic pretreatment with a simultaneous saccharification and fermentation to achieve ethanol production from grass silage in a one-process step. Achieved yields were about 53 g ethanol per kg silage with the alkaline peroxide pretreatment and 91 g/kg with the enzymatic pretreatment at concentrations of 8.5 and 14.6 g/L, respectively. Furthermore, it was shown that additional supplementation of the fermentation medium with vitamins, trace elements and nutrient salts is not necessary when the press juice is directly used in the fermentation step.
Flight times to the heliopause using a combination of solar and radioisotope electric propulsion
(2011)
We investigate the interplanetary flight of a low-thrust space probe to the heliopause,located at a distance of about 200 AU from the Sun. Our goal was to reach this distance within the 25 years postulated by ESA for such a mission (which is less ambitious than the 15-year goal set by NASA). Contrary to solar sail concepts and combinations of allistic and electrically propelled flight legs, we have investigated whether the set flight time limit could also be kept with a combination of solar-electric propulsion and a second, RTG-powered upper stage. The used ion engine type was the RIT-22 for the first stage and the RIT-10 for the second stage. Trajectory optimization was carried out with the low-thrust optimization program InTrance, which implements the method of Evolutionary Neurocontrol,using Artificial Neural Networks for spacecraft steering and Evolutionary Algorithms to optimize the Neural Networks’ parameter set. Based on a parameter space study, in which the number of thrust units, the unit’s specific impulse, and the relative size of the solar power generator were varied, we have chosen one configuration as reference. The transfer time of this reference configuration was 29.6 years and the fastest one, which is technically
more challenging, still required 28.3 years. As all flight times of this parameter study were longer than 25 years, we further shortened the transfer time by applying a launcher-provided hyperbolic excess energy up to 49 km2/s2. The resulting minimal flight time for the reference configuration was then 27.8 years. The following, more precise optimization to a launch with the European Ariane 5 ECA rocket reduced the transfer time to 27.5 years. This is the fastest mission design of our study that is flexible enough to allow a launch every
year. The inclusion of a fly-by at Jupiter finally resulted in a flight time of 23.8 years,which is below the set transfer-time limit. However, compared to the 27.5-year transfer,this mission design has a significantly reduced launch window and mission flexibility if the
escape direction is restricted to the heliosphere’s “nose".
Summary: This paper presents a methodology to study and understand the mechanics of stapled anastomotic behaviors by combining empirical experimentation and finite element analysis. Performance of stapled anastomosis is studied in terms of leakage and numerical results which are compared to in vitro experiments performed on fresh porcine tissue. Results suggest that leaks occur between the tissue and staple legs penetrating through the tissue.
The importance of the availability of stored blood or blood cells, respectively, for urgent transfusion cannot be overestimated. Nowadays, blood storage becomes even more important since blood products are used for epidemiological studies, bio-technical research or banked for transfusion purposes. Thus blood samples must not only be processed, stored, and shipped to preserve their efficacy and safety, but also all parameters of storage must be recorded and reported for Quality Assurance. Therefore, blood banks and clinical research facilities are seeking more accurate, automated means for blood storage and blood processing.
This paper presents a novel numerical procedure for computing limit and shakedown loads of structures using a node-based smoothed FEM in combination with a primal–dual algorithm. An associated primal–dual form based on the von Mises yield criterion is adopted. The primal-dual algorithm together with a Newton-like iteration are then used to solve this associated primal–dual form to determine simultaneously both approximate upper and quasi-lower bounds of the plastic collapse limit and the shakedown limit. The present formulation uses only linear approximations and its implementation into finite element programs is quite simple. Several numerical examples are given to show the reliability, accuracy, and generality of the present formulation compared with other available methods.
An Interstellar – Heliopause mission using a combination of solar/radioisotope electric propulsion
(2011)
There is common agreement within the scientific community that in order to understand our local galactic environment it will be necessary to send a spacecraft into the region beyond the solar wind termination shock. Considering distances of 200 AU for a new mission, one needs a spacecraft travelling at a speed of close to 10 AU/yr in order to keep the mission duration in the range of less than 25 yrs, a transfer time postulated by ESA.Two propulsion options for the mission have been proposed and discussed so far: the solar sail propulsion and the ballistic/radioisotope electric propulsion. As a further alternative, we here investigate a combination of solar-electric propulsion and radioisotope-electric propulsion. The solar-electric propulsion stage consists of six 22 cm diameter “RIT-22”ion thrusters working with a high specific impulse of 7377 s corresponding to a positive grid voltage of 5 kV. Solar power of 53 kW BOM is provided by a light-weight solar array. The REP-stage consists of four space-proven 10 cm diameter “RIT-10” ion thrusters that will be operating one after the other for 9 yrs in total. Four advanced radioisotope generators provide 648 W at BOM. The scientific instrument package is oriented at earlier studies. For its mass and electric power requirement 35 kg and 35 W are assessed, respectively. Optimized trajectory calculations, treated in a separate contribution, are based on our “InTrance” method.The program yields a burn out of the REP stage in a distance of 79.6 AU for a usage of 154 kg of Xe propellant. With a C3 = 45,1 (km/s)2 a heliocentric probe velocity of 10 AU/yr is reached at this distance, provided a close Jupiter gravity assist adds a velocity increment of 2.7 AU/yr. A transfer time of 23.8 yrs results for this scenario requiring about 450 kg Xe for the SEP stage, jettisoned at 3 AU. We interpret the SEP/REP propulsion as a competing alternative to solar sail and ballistic/REP propulsion. Omiting a Jupiter fly-by even allows more launch flexibility, leaving the mission duration in the range of the ESA specification.
The purpose of this study was to investigate whether sprint performance is related to lower leg musculoskeletal geometry within a homogeneous group of highly trained 100-m sprinters. Using a cluster analysis, eighteen male sprinters were divided into two groups based on their personal best (fast: N = 11, 10.30 ± 0.07 s; slow: N = 7, 10.70 ± 0.08 s). Calf muscular fascicle arrangement and Achilles tendon moment arms (calculated by the gradient of tendon excursion versus ankle joint angle) were analyzed for each athlete using ultrasonography. Achilles tendon moment arm, foot and ankle skeletal geometry, fascicle arrangement as well as the ratio of fascicle length to Achilles tendon moment arm showed no significant (p > 0.05) correlation with sprint performance, nor were there any differences in the analyzed musculoskeletal parameters between the fast and slow sprinter group. Our findings provide evidence that differences in sprint ability in world-class athletes are not a result of differences in the geometrical design of the lower leg even when considering both skeletal and muscular components.
The msprop program presented in this work is capable of solving the Maxwell–Schrödinger equations for one or several laser fields propagating through a medium of quantum optical few-level systems in one spatial dimension and in time. In particular, it allows to numerically treat systems in which a laser field interacts with the medium with both its electric and magnetic component at the same time. The internal dynamics of the few-level system is modeled by a quantum optical master equation which includes coherent processes due to optical transitions driven by the laser fields as well as incoherent processes due to decay and dephasing. The propagation dynamics of the laser fields is treated in slowly varying envelope approximation resulting in a first order wave equation for each laser field envelope function. The program employs an Adams predictor formula second order in time to integrate the quantum optical master equation and a Lax–Wendroff scheme second order in space and time to evolve the wave equations for the fields. The source function in the Lax–Wendroff scheme is specifically adapted to allow taking into account the simultaneous coupling of a laser field to the polarization and the magnetization of the medium. To reduce execution time, a customized data structure is implemented and explained. In three examples the features of the program are demonstrated and the treatment of a system with a phase-dependent cross coupling of the electric and magnetic field component of a laser field is shown.
Market changes have forced telecommunication companies to transform their business. Increased competition, short innovation cycles, changed usage patterns, increased customer expectations and cost reduction are the main drivers. Our objective is to analyze to what extend transformation projects have improved the orientation towards the end-customers. Therefore, we selected 38 real-life case studies that are dealing with customer orientation. Our analysis is based on a telecommunication-specific framework that aligns strategy, business processes and information systems. The result of our analysis shows the following: transformation projects that aim to improve the customer orientation are combined with clear goals on costs and revenue of the enterprise. These projects are usually directly linked to the customer touch points, but also to the development and provisioning of products. Furthermore, the analysis shows that customer orientation is not the sole trigger for transformation. There is no one-fits-all solution; rather, improved customer orientation needs aligned changes of business processes as well as information systems related to different parts of the company.
Harmful effects of electromagnetic fields (EMF) on cognitive and behavioural features of humans and rodents have been controversially discussed and raised persistent concern about adverse effects of EMF on general brain functions. In the present study we applied radio-frequency (RF) signals of the Universal Mobile Telecommunications System (UMTS) to full brain exposed male Wistar rats in order to elaborate putative influences on stress hormone release (corticosteron; CORT and adrenocorticotropic hormone; ACTH) and on hippocampal derived synaptic long-term plasticity (LTP) and depression (LTD) as electrophysiological hallmarks for memory storage and memory consolidation. Exposure was computer controlled providing blind conditions. Nominal brain-averaged specific absorption rates (SAR) as a measure of applied mass-related dissipated RF power were 0, 2, and 10 W/kg over a period of 120 min. Comparison of cage exposed animals revealed, regardless of EMF exposure, significantly increased CORT and ACTH levels which corresponded with generally decreased field potential slopes and amplitudes in hippocampal LTP and LTD. Animals following SAR exposure of 2 W/kg (averaged over the whole brain of 2.3 g tissue mass) did not differ from the sham-exposed group in LTP and LTD experiments. In contrast, a significant reduction in LTP and LTD was observed at the high power rate of SAR (10 W/kg). The results demonstrate that a rate of 2 W/kg displays no adverse impact on LTP and LTD, while 10 W/kg leads to significant effects on the electrophysiological parameters, which can be clearly distinguished from the stress derived background. Our findings suggest that UMTS exposure with SAR in the range of 2 W/kg is not harmful to critical markers for memory storage and memory consolidation, however, an influence of UMTS at high energy absorption rates (10 W/kg) cannot be excluded.
Purpose:
At 1.5 T, real-time MRI of joint movement has been shown to be feasible. However, 7 T, provides higher SNR and thus an improved potential for parallel imaging acceleration. The purpose of this work was to build an open, U-shaped eight-channel transmit/receive microstrip coil for 7 T MRI to enable high-resolution and real-time imaging of the moving ankle joint.
Methods:
A U-shaped eight-channel transmit/receive array for the human ankle was built.urn:x-wiley:00942405:mp3399:equation:mp3399-math-0001-parameters and urn:x-wiley:00942405:mp3399:equation:mp3399-math-0002-factor were measured. SAR calculations of different ankle postures were performed to ensure patient safety. Inhomogeneities in the transmit field consequent to the open design were compensated for by the use of static RF shimming. High-resolution and real-time imaging was performed in human volunteers.
Results:
The presented array showed good performance with regard to patient comfort and image quality. High acceleration factors of up to 4 are feasible without visible acceleration artifacts. Reasonable image homogeneity was achieved with RF shimming.
Conclusions:
Open, noncylindrical designs for transmit/receive coils are practical at 7 T and real-time imaging of the moving joint is feasible with the presented coil design.