Showing papers by "University of Jena published in 2010"

Poly(ethylene glycol) in Drug Delivery: Pros and Cons as Well as Potential Alternatives

Abstract: Poly(ethylene glycol) (PEG) is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer-based drug delivery. The properties that account for the overwhelming use of PEG in biomedical applications are outlined in this Review. The first approved PEGylated products have already been on the market for 20 years. A vast amount of clinical experience has since been gained with this polymer--not only benefits, but possible side effects and complications have also been found. The areas that might need consideration and more intensive and careful examination can be divided into the following categories: hypersensitivity, unexpected changes in pharmacokinetic behavior, toxic side products, and an antagonism arising from the easy degradation of the polymer under mechanical stress as a result of its ether structure and its non-biodegradability, as well as the resulting possible accumulation in the body. These possible side effects will be discussed in this Review and alternative polymers will be evaluated.

The Einstein Telescope: a third-generation gravitational wave observatory

Abstract: Advanced gravitational wave interferometers, currently under realization, will soon permit the detection of gravitational waves from astronomical sources. To open the era of precision gravitational wave astronomy, a further substantial improvement in sensitivity is required. The future space-based Laser Interferometer Space Antenna and the third-generation ground-based observatory Einstein Telescope (ET) promise to achieve the required sensitivity improvements in frequency ranges. The vastly improved sensitivity of the third generation of gravitational wave observatories could permit detailed measurements of the sources' physical parameters and could complement, in a multi-messenger approach, the observation of signals emitted by cosmological sources obtained through other kinds of telescopes. This paper describes the progress of the ET project which is currently in its design study phase.

Nilotinib versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia

Abstract: Background Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia (CML) in the chronic phase. Methods In this phase 3, randomized, open-label, multicenter study, we assigned 846 patients with chronic-phase Philadelphia chromosome–positive CML in a 1:1:1 ratio to receive nilotinib (at a dose of either 300 mg or 400 mg twice daily) or imatinib (at a dose of 400 mg once daily). The primary end point was the rate of major molecular response at 12 months. Results At 12 months, the rates of major molecular response for nilotinib (44% for the 300-mg dose and 43% for the 400-mg dose) were nearly twice that for imatinib (22%) (P<0.001 for both comparisons). The rates of complete cytogenetic response by 12 months were significantly higher for nilotinib (80% for the 300-mg dose and 78% for the 400-mg dose) than for imatinib (65%) (P<0.001 for both comparisons). Patients receiving either the 300-mg dose or the 400-mg dose of nilotinib twice daily had a significant improvement in the time to progression to the accelerated phase or blast crisis, as compared with those receiving imatinib (P = 0.01 and P = 0.004, respectively). No patient with progression to the accelerated phase or blast crisis had a major molecular response. Gastrointestinal and fluid-retention events were more frequent among patients receiving imatinib, whereas dermatologic events and headache were more frequent in those receiving nilotinib. Discontinuations due to aminotransferase and bilirubin elevations were low in all three study groups. Conclusions Nilotinib at a dose of either 300 mg or 400 mg twice daily was superior to imatinib in patients with newly diagnosed chronic-phase Philadelphia chromosome–positive CML. (ClinicalTrials.gov number, NCT00471497.)

Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia.

Abstract: Background Treatment with dasatinib, a highly potent BCR-ABL kinase inhibitor, has resulted in high rates of complete cytogenetic response and progression-free survival among patients with chronic myeloid leukemia (CML) in the chronic phase, after failure of imatinib treatment. We assessed the efficacy and safety of dasatinib, as compared with imatinib, for the first-line treatment of chronic-phase CML. Methods In a multinational study, 519 patients with newly diagnosed chronic-phase CML were randomly assigned to receive dasatinib at a dose of 100 mg once daily (259 patients) or imatinib at a dose of 400 mg once daily (260 patients). The primary end point was complete cytogenetic response by 12 months, confirmed on two consecutive assessments at least 28 days apart. Secondary end points, including major molecular response, were tested at a significance level of 0.0001 to adjust for multiple comparisons. Results After a minimum follow-up of 12 months, the rate of confirmed complete cytogenetic response was higher with dasatinib than with imatinib (77% vs. 66%, P = 0.007), as was the rate of complete cytogenetic response observed on at least one assessment (83% vs. 72%, P = 0.001). The rate of major molecular response was higher with dasatinib than with imatinib (46% vs. 28%, P<0.0001), and responses were achieved in a shorter time with dasatinib (P<0.0001). Progression to the accelerated or blastic phase of CML occurred in 5 patients who were receiving dasatinib (1.9%) and in 9 patients who were receiving imatinib (3.5%). The safety profiles of the two treatments were similar. Conclusions Dasatinib, administered once daily, as compared with imatinib, administered once daily, induced significantly higher and faster rates of complete cytogenetic response and major molecular response. Since achieving complete cytogenetic response within 12 months has been associated with better long-term, progression-free survival, dasatinib may improve the long-term outcomes among patients with newly diagnosed chronic-phase CML. (ClinicalTrials.gov number, NCT00481247.)

A guide to super-resolution fluorescence microscopy

Abstract: For centuries, cell biology has been based on light microscopy and at the same time been limited by its optical resolution. However, several new technologies have been developed recently that bypass this limit. These new super-resolution technologies are either based on tailored illumination, nonlinear fluorophore responses, or the precise localization of single molecules. Overall, these new approaches have created unprecedented new possibilities to investigate the structure and function of cells.

Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.

Abstract: We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.

Review of climate and cryospheric change in the Tibetan Plateau

Abstract: The Tibetan Plateau (TP), with an average elevation of over 4000 m asl and an area of approximately 2.5 × 10 6 km 2 , is the highest and most extensive highland in the world and has been called the ‘Third Pole’. The TP exerts a huge influence on regional and global climate through thermal and mechanical forcing mechanisms. Because the TP has the largest cryospheric extent outside the polar region and is the source region of all the large rivers in Asia, it is widely recognized to be the driving force for both regional environmental change and amplification of environmental changes on a global scale. Within China it is recognized as the ‘Asian water tower’. In this letter, we summarize the recent changes observed in climate elements and cryospheric indicators on the plateau before discussing current unresolved issues concerning climate change in the TP, including the temporal and spatial components of this change, and the consistency of change as represented by different data sources. Based on meteorological station data, reanalyses and remote sensing, the TP has shown significant warming during the last decades and will continue to warm in the future. While the warming is predominantly caused by increased greenhouse gas emissions, changes in cloud amount, snow-albedo feedback, the Asian brown clouds and land use changes also partly contribute. The cryosphere in the TP is undergoing rapid change, including glacier retreat, inconsistent snow cover change, increasing permafrost temperatures and degradation, and thickening of the active layer. Hydrological processes impacted by glacial retreat have received much attention in recent years. Future attention should be paid to additional perspectives on climate change in the TP, such as the variations of climate extremes, the reliability of reanalyses and more detailed comparisons of reanalyses with surface observations. Spatial issues include the identification of whether an elevational dependency and weekend effect exist, and the identification of spatial contrasts in temperature change, along with their causes. These issues are uncertain because of a lack of reliable data above 5000 m asl.

Bottom-up effects of plant diversity on multitrophic interactions in a biodiversity experiment

Abstract: Biodiversity is rapidly declining, and this may negatively affect ecosystem processes, including economically important ecosystem services Previous studies have shown that biodiversity has positive effects on organisms and processes across trophic levels However, only a few studies have so far incorporated an explicit food-web perspective In an eight-year biodiversity experiment, we studied an unprecedented range of above- and below-ground organisms and multitrophic interactions A multitrophic data set originating from a single long-term experiment allows mechanistic insights that would not be gained from meta-analysis of different experiments Here we show that plant diversity effects dampen with increasing trophic level and degree of omnivory This was true both for abundance and species richness of organisms Furthermore, we present comprehensive above-ground/below-ground biodiversity food webs Both above ground and below ground, herbivores responded more strongly to changes in plant diversity than did carnivores or omnivores Density and richness of carnivorous taxa was independent of vegetation structure Below-ground responses to plant diversity were consistently weaker than above-ground responses Responses to increasing plant diversity were generally positive, but were negative for biological invasion, pathogen infestation and hyperparasitism Our results suggest that plant diversity has strong bottom-up effects on multitrophic interaction networks, with particularly strong effects on lower trophic levels Effects on higher trophic levels are indirectly mediated through bottom-up trophic cascades

Printed electronics: the challenges involved in printing devices, interconnects, and contacts based on inorganic materials

Abstract: Printed electronics represent an emerging area of research that promises large markets due to the ability to bypass traditional expensive and inflexible silicon-based electronics to fabricate a variety of devices on flexible substrates using high-throughput printing approaches. This article presents a summary of work to date in the field of printed electronics and the materials chemistry involved. In particular, the focus is upon the use of metal- and metal oxide-containing inks in the preparation of contacts and interconnects. The review discusses the challenges associated with processing these types of inks and ways to successfully obtain the desired features.

The role of prenucleation clusters in surface-induced calcium phosphate crystallization

Abstract: Unravelling the processes of calcium phosphate formation is important in our understanding of both bone and tooth formation, and also of pathological mineralization, for example in cardiovascular disease. Serum is a metastable solution from which calcium phosphate precipitates in the presence of calcifiable templates such as collagen, elastin and cell debris. A pathological deficiency of inhibitors leads to the uncontrolled deposition of calcium phosphate. In bone and teeth the formation of apatite crystals is preceded by an amorphous calcium phosphate (ACP) precursor phase. ACP formation is thought to proceed through prenucleation clusters--stable clusters that are present in solution already before nucleation--as was recently demonstrated for CaCO(3) (refs 15,16). However, the role of such nanometre-sized clusters as building blocks for ACP has been debated for many years. Here we demonstrate that the surface-induced formation of apatite from simulated body fluid starts with the aggregation of prenucleation clusters leading to the nucleation of ACP before the development of oriented apatite crystals.

Asymmetric transmission of linearly polarized light at optical metamaterials.

Abstract: We experimentally demonstrate a three-dimensional chiral optical metamaterial that exhibits an asymmetric transmission for forwardly and backwardly propagating linearly polarized light. The observation of this novel effect requires a metamaterial composed of three-dimensional chiral meta-atoms without any rotational symmetry. Our analysis is supported by a systematic investigation of the transmission matrices for arbitrarily complex, generally lossy media that allows deriving a simple criterion for asymmetric transmission in an arbitrary polarization base. Contrary to physical intuition, in general the polarization eigenstates in such three-dimensional and low-symmetry metamaterials do not obey fixed relations and the associated transmission matrices cannot be symmetrized.

Femtosecond fiber CPA system emitting 830 W average output power.

Abstract: In this Letter we report on the generation of 830 W compressed average power from a femtosecond fiber chirped pulse amplification (CPA) system In the high-power operation we achieved a compressor throughput of about 90% by using high-efficiency dielectric gratings The output pulse duration of 640 fs at 78 MHz repetition rate results in a peak power of 12 MW Additionally, we discuss further a scaling potential toward and beyond the kilowatt level by overcoming the current scaling limitations imposed by the transversal spatial hole burning

Multiscale parameter regionalization of a grid-based hydrologic model at the mesoscale

Abstract: [1] The requirements for hydrological models have increased considerably during the previous decades to cope with the resolution of extensive remotely sensed data sets and a number of demanding applications. Existing models exhibit deficiencies such as overparameterization, the lack of an effective technique to integrate the spatial heterogeneity of physiographic characteristics, and the nontransferability of parameters across scales and locations. A multiscale parameter regionalization (MPR) technique is proposed as a way to address these issues simultaneously. Using this technique, parameters at a coarser scale, in which the dominant hydrological processes are represented, are linked with their corresponding ones at a finer resolution in which input data sets are available. The linkage is done with upscaling operators such as the harmonic mean, among others. Parameters at the finer scale are regionalized through nonlinear transfer functions which link basin predictors with global parameters to be determined through calibration. MPR was compared with a standard regionalization (SR) method in which basin predictors instead of model parameters are first aggregated. Both methods were tested in a basin located in Germany using a distributed hydrologic model. Results indicate that MPR is superior to SR in many respects, especially if global parameters are transferred from coarser to finer scales. Furthermore, MPR, as opposed to SR, preserves the spatial variability of state variables and conserves the mass balance with respect to a control scale. Cross-validation tests indicate that the transferability of the global parameters to ungauged locations is possible.

Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema

Abstract: BACKGROUND Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

Discrete optics in femtosecond-laser-written photonic structures

Abstract: Over the last few years arrays of evanescently coupled waveguides have been brought into focus as a particular representation of functionalized optical materials, in which the dispersion and diffraction of propagating light can be specifically tuned Moreover, it turns out that the light evolution in these systems shares fundamental similarities to the quantum evolution of particle wavefunctions, so that waveguide arrays can act as a model system for emulating quantum mechanics Recently, a novel technique was developed with which waveguides can be directly 'written' into various optical bulk materials using femtosecond laser pulses, which allows for the realization of a variety of innovative concepts which are not feasible using other fabrication methods The aim of this tutorial is to give an introduction to this topic

Genome sequence of the model mushroom Schizophyllum commune

Abstract: Much remains to be learned about the biology of mushroom-forming fungi, which are an important source of food, secondary metabolites and industrial enzymes. The wood-degrading fungus Schizophyllum commune is both a genetically tractable model for studying mushroom development and a likely source of enzymes capable of efficient degradation of lignocellulosic biomass. Comparative analyses of its 38.5-megabase genome, which encodes 13,210 predicted genes, reveal the species's unique wood-degrading machinery. One-third of the 471 genes predicted to encode transcription factors are differentially expressed during sexual development of S. commune. Whereas inactivation of one of these, fst4, prevented mushroom formation, inactivation of another, fst3, resulted in more, albeit smaller, mushrooms than in the wild-type fungus. Antisense transcripts may also have a role in the formation of fruiting bodies. Better insight into the mechanisms underlying mushroom formation should affect commercial production of mushrooms and their industrial use for producing enzymes and pharmaceuticals.

Advanced Jones calculus for the classification of periodic metamaterials

Abstract: By relying on an advanced Jones calculus, we analyze the polarization properties of light upon propagation through metamaterial slabs in a comprehensive manner. Based on symmetry considerations, we show that all periodic metamaterials may be divided into five different classes only. It is shown that each class differently affects the polarization of the transmitted light and sustains different eigenmodes. We show how to deduce these five classes from symmetry considerations and provide a simple algorithm that can be applied to decide to which class a given metamaterial belongs by measuring only the transmitted intensities.

Stable internal reference genes for normalization of real-time RT-PCR in tobacco ( Nicotiana tabacum ) during development and abiotic stress

Abstract: Real-time RT-PCR is a powerful technique for the measurement of gene expression, but its accuracy depends on the stability of the internal reference gene(s) used for data normalization. Tobacco (Nicotiana tabacum) is an important model in studies of plant gene expression, but stable reference genes have not been well-studied in the tobacco system. We address this problem by analysing the expression stability of eight potential tobacco reference genes. Primers targeting each gene (18S rRNA, EF-1α, Ntubc2, α- and β-tubulin, PP2A, L25 and actin) were developed and optimized. The expression of each gene was then measured by real-time PCR in a diverse set of 22 tobacco cDNA samples derived from developmentally distinct tissues and from plants exposed to several abiotic stresses. L25 and EF-1α demonstrated the highest expression stability, followed by Ntubc2. Measurement of L25 and EF-1α was sufficient for accurate normalization in either the developmental or stress-treated samples, but Ntubc2 was also required when considering the entire sample set. Analysis of a tobacco circadian gene (NTCP-23) verified these reference genes in an additional context, and all techniques were optimized to enable a high-throughput approach. These results provide a foundation for the more accurate and widespread use of real-time RT-PCR in tobacco.

Plant diversity effects on soil microorganisms support the singular hypothesis.

Abstract: The global decline in biodiversity has generated concern over the consequences for ecosystem functioning and services. Although ecosystem functions driven by soil microorganisms such as plant productivity, decomposition, and nutrient cycling are of particular importance, interrelationships between plant diversity and soil microorganisms are poorly understood. We analyzed the response of soil microorganisms to variations in plant species richness (1-60) and plant functional group richness (1-4) in an experimental grassland system over a period of six years. Major abiotic and biotic factors were considered for exploring the mechanisms responsible for diversity effects. Further, microbial growth characteristics were assessed following the addition of macronutrients. Effects of plant diversity on soil microorganisms were most pronounced in the most diverse plant communities though differences only became established after a time lag of four years. Differences in microbial growth characteristics indicate successional changes from a disturbed (zymogeneous) to an established (autochthonous) microbial community four years after establishment of the experiment. Supporting the singular hypothesis for plant diversity, the results suggest that plant species are unique, each contributing to the functioning of the belowground system. The results reinforce the need for long-term biodiversity experiments to fully appreciate consequences of current biodiversity loss for ecosystem functioning.

Examining student satisfaction with higher education services: using a new measurement tool

Abstract: Purpose – This paper aims to investigate how students perceive the services they are offered at a German university and how satisfied they are with them.Design/methodology/approach – An evaluation study using a new tool to measure 15 dimensions of student satisfaction at an institutional level that covers most aspects of student life was used. It was decided to develop a new measurement tool as many existing surveys are poorly designed, lack standardization and give no evidence concerning reliability or validity. Questionnaires were handed out in eight lectures for the pilot study and 18 lectures for the main study. The response rate was 99 percent. A total of 374 students (pilot study) and 544 students (main study) filled in the newly developed questionnaires using Likert scales.Findings – The study gave a valuable insight into how students perceive the quality of the services offered at a university and how satisfied they are with these offerings. The results show that students' satisfaction with their ...

Production of Extracellular Traps against Aspergillus fumigatus In Vitro and in Infected Lung Tissue Is Dependent on Invading Neutrophils and Influenced by Hydrophobin RodA

Abstract: Aspergillus fumigatus is the most important airborne fungal pathogen causing life-threatening infections in immunocompromised patients. Macrophages and neutrophils are known to kill conidia, whereas hyphae are killed mainly by neutrophils. Since hyphae are too large to be engulfed, neutrophils possess an array of extracellular killing mechanisms including the formation of neutrophil extracellular traps (NETs) consisting of nuclear DNA decorated with fungicidal proteins. However, until now NET formation in response to A. fumigatus has only been demonstrated in vitro, the importance of neutrophils for their production in vivo is unclear and the molecular mechanisms of the fungus to defend against NET formation are unknown. Here, we show that human neutrophils produce NETs in vitro when encountering A. fumigatus. In time-lapse movies NET production was a highly dynamic process which, however, was only exhibited by a sub-population of cells. NETosis was maximal against hyphae, but reduced against resting and swollen conidia. In a newly developed mouse model we could then demonstrate the existence and measure the kinetics of NET formation in vivo by 2-photon microscopy of Aspergillus-infected lungs. We also observed the enormous dynamics of neutrophils within the lung and their ability to interact with and phagocytose fungal elements in situ. Furthermore, systemic neutrophil depletion in mice almost completely inhibited NET formation in lungs, thus directly linking the immigration of neutrophils with NET formation in vivo. By using fungal mutants and purified proteins we demonstrate that hydrophobin RodA, a surface protein making conidia immunologically inert, led to reduced NET formation of neutrophils encountering Aspergillus fungal elements. NET-dependent killing of Aspergillus-hyphae could be demonstrated at later time-points, but was only moderate. Thus, these data establish that NET formation occurs in vivo during host defence against A. fumigatus, but suggest that it does not play a major role in killing this fungus. Instead, NETs may have a fungistatic effect and may prevent further spreading.

Matching post-Newtonian and numerical relativity waveforms: Systematic errors and a new phenomenological model for nonprecessing black hole binaries

Abstract: We present a new phenomenological gravitational waveform model for the inspiral and coalescence of nonprecessing spinning black hole binaries. Our approach is based on a frequency-domain matching of post-Newtonian inspiral waveforms with numerical relativity based binary black hole coalescence waveforms. We quantify the various possible sources of systematic errors that arise in matching post-Newtonian and numerical relativity waveforms, and we use a matching criteria based on minimizing these errors; we find that the dominant source of errors are those in the post-Newtonian waveforms near the merger. An analytical formula for the dominant mode of the gravitational radiation of nonprecessing black hole binaries is presented that captures the phenomenology of the hybrid waveforms. Its implementation in the current searches for gravitational waves should allow cross-checks of other inspiral-merger-ringdown waveform families and improve the reach of gravitational-wave searches.