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In object-oriented programming, polymorphic dispatch of operations decouples clients from specific providers of services and allows implementations to be modified or substituted without affecting clients.
The Uniform Access Principle (UAP) tries to extend these qualities to resource access by demanding that access to state be indistinguishable from access to operations. Despite language features supporting the UAP, the overall goal of substitutability has not been achieved for either alternative resources such as keyed storage, files or web pages, or for alternate access mechanisms: specific kinds of resources are bound to specific access mechanisms and vice versa. Changing storage or access patterns either requires changes to both clients and service providers and trying to maintain the UAP imposes significant penalties in terms of code-duplication and/or performance overhead.
We propose introducing first class identifiers as polymorphic names for storage locations to solve these problems. With these Polymorphic Identifiers, we show that we can provide uniform access to a wide variety of resource types as well as storage and access mechanisms, whether parametrized or direct, without affecting client code, without causing code duplication or significant performance penalties.
H-1 NMR relaxation is used to study the self-assembly of a double thermoresponsive diblock copolymer in dilute aqueous solution. Above the first transition temperature, at which aggregation into micellar structures is observed, the trimethylsilyl (TMS)-labeled end group attached to the shell-forming block shows a biphasic T-2 relaxation. The slow contribution reflects the TMS groups located at the periphery of the hydrophilic shell, in agreement with a star-like micelle. The fast T-2 contribution corresponds to the TMS groups, which fold back toward the hydrophobic core, reflecting a flower-like micelle. These results confirm the formation of block copolymer micelles of an intermediate nature (i.e., of partial flower-like and star-like character), in which a part of the TMS end groups folds back to the core due to hydrophobic interactions.
Identifying drivers of species diversity is a major challenge in understanding and predicting the dynamics of species-rich semi-natural grasslands. In particular in temperate grasslands changes in land use and its consequences, i.e. increasing fragmentation, the on-going loss of habitat and the declining importance of regional processes such as seed dispersal by livestock, are considered key drivers of the diversity loss witnessed within the last decades.
We investigated the role of GPER as a potential tumor suppressor in triple-negative breast cancer cells MDA-MB-231 and MDA-MB-468 using cell cycle analysis and apoptosis assay. The constitutive activity of GPER was investigated.
GPER-specific activation with G-1 agonist inhibited breast cancer cell growth in concentration-dependent manner via induction of the cell cycle arrest in G2/M phase, enhanced phosphorylation of histone H3 and caspase-3-mediated apoptosis. Analysis of the methylation status of the GPER promoter in the triple-negative breast cancer cells and in tissues derived from breast cancer patients revealed that GPER amount is regulated by epigenetic mechanisms and GPER expression is inactivated by promoter methylation. Furthermore, GPER expression was induced by stress factors, such as radiation, and GPER amount inversely correlated with the p53 expression level.
Overall, our results establish the protective role in breast cancer tumorigenesis, and the cell surface expression of GPER makes it an excellent potential therapeutic target for triple-negative breast cancer.
Harnessing the evolvability of tricyclic microviridins to dissect protease-inhibitor interactions
(2014)
Understanding and controlling proteolysis is an important goal in therapeutic chemistry. Among the natural products specifically inhibiting proteases microviridins are particularly noteworthy. Microviridins are ribosomally produced and posttranslationally modified peptides that are processed into a unique, cagelike architecture. Here, we report a combined rational and random mutagenesis approach that provides fundamental insights into selectivity-conferring moieties of microviridins. The potent variant microviridin J was co-crystallized with trypsin, and for the first time the three-dimensional structure of microviridins was determined and the mode of inhibition revealed.
This article summarizes the latest results on the proton-to-electron mass ratio derived from H-2 observations at high redshift in the light of possible variations of fundamental physical constants. The focus lies on UVES observations of the past years as enormous progress was achieved since the first positive results on / were published. With the better understanding of systematics, dedicated observation runs, and numerous approaches to improve wavelength calibration accuracy, all current findings are in reasonable good agreement with no variation and provide an upper limit of / < 1 x 10(-5) for the redshift range of 2 < z < 3. ((
The cultivation of plants for use as energy resources is an agricultural and industrial sector with potentially synergistic benefits related to protecting the environment and generating income. Against the background of increasing land-use changes and new agricultural approaches to the production of energy crops, we present a method for identifying future-oriented crop rotations that supports both the economic and environmental components of decision-making strategies with respect to agriculture-related policy decisions (regional mission statements). The conflicting aspects of these objectives can be addressed with the analytic hierarchy process (AHP), a multi-attribute decision-making method that was integrated here. Three models are used to generate simulations of the defined objectives over a planning period of 30 years under the current climate scenario and provide input data for the multi-attribute assessment of several crop rotations. Based on the entire evaluation process, dimensionless global priority vectors are used to indicate how well the crop rotations meet the requirements of the defined mission statement. The method is tested in a municipality in NE Germany. (C) 2014 Elsevier Ltd. All rights reserved.
New porous materials based on covalently connected monomers are presented. The key step of the synthesis is an acetalisation reaction. In previous years we used acetalisation reactions extensively to build up various molecular rods. Based on this approach, investigations towards porous polymeric materials were conducted by us. Here we wish to present the results of these studies in the synthesis of 1D polyacetals and porous 3D polyacetals. By scrambling experiments with 1D acetals we could prove that exchange reactions occur between different building blocks (evidenced by MALDI-TOF mass spectrometry). Based on these results we synthesized porous 3D polyacetals under the same mild conditions.
New porous materials based on covalently connected monomers are presented. The key step of the synthesis is an acetalisation reaction. In previous years we used acetalisation reactions extensively to build up various molecular rods. Based on this approach, investigations towards porous polymeric materials were conducted by us. Here we wish to present the results of these studies in the synthesis of 1D polyacetals and porous 3D polyacetals. By scrambling experiments with 1D acetals we could prove that exchange reactions occur between different building blocks (evidenced by MALDI-TOF mass spectrometry). Based on these results we synthesized porous 3D polyacetals under the same mild conditions.
New porous materials based on covalently connected monomers are presented. The key step of the synthesis is an acetalisation reaction. In previous years we used acetalisation reactions extensively to build up various molecular rods. Based on this approach, investigations towards porous polymeric materials were conducted by us. Here we wish to present the results of these studies in the synthesis of 1D polyacetals and porous 3D polyacetals. By scrambling experiments with 1D acetals we could prove that exchange reactions occur between different building blocks (evidenced by MALDI-TOF mass spectrometry). Based on these results we synthesized porous 3D polyacetals under the same mild conditions.
With the growth of virtualization and cloud computing, more and more forensic investigations rely on being able to perform live forensics on a virtual machine using virtual machine introspection (VMI). Inspecting a virtual machine through its hypervisor enables investigation without risking contamination of the evidence, crashing the computer, etc. To further access to these techniques for the investigator/researcher we have developed a new VMI monitoring language. This language is based on a review of the most commonly used VMI-techniques to date, and it enables the user to monitor the virtual machine's memory, events and data streams. A prototype implementation of our monitoring system was implemented in KVM, though implementation on any hypervisor that uses the common x86 virtualization hardware assistance support should be straightforward. Our prototype outperforms the proprietary VMWare VProbes in many cases, with a maximum performance loss of 18% for a realistic test case, which we consider acceptable. Our implementation is freely available under a liberal software distribution license. (C) 2014 Digital Forensics Research Workshop. Published by Elsevier Ltd. All rights reserved.
Whilst sophisticated multiphase fluid flow models are routinely employed to understand behaviour of oil and gas reservoirs, high-resolution data describing the three-dimensional (3D) distribution of rock characteristics is rarely available to populate models. We present a new approach to developing a quantitative understanding of the effect of individual controls on the distribution of petrophysical properties and their impact on fluid flow. This involves simulating flow through high-detail permeability architectures generated by forward modelling of the coupled depositional-diagenetic evolution of isolated platforms using CARB3D(+). This workflow is exemplified by an investigation of interactions between subsidence and climate, and their expression in spatial variations in reservoir quality in an isolated carbonate platform of similar size and subsidence history to the Triassic Latemar Platform.
Dissolutional lowering during subaerial exposure controls platform-top graininess via platform top hydrodynamics during the subsequent transgression. Dissolved carbonate is reprecipitated as cements by percolating meteoric waters. However, associated subsurface meteoric dissolution generates significant secondary porosity under a more humid climate. Slower subsidence enhances diagenetic overprinting during repeated exposure events. Single-phase streamline simulations show how early diagenesis develops more permeable fairways within the finer-grained condensed units that can act as thief zones for flow from the grainier but less diagenetically altered cyclic units.
Magnetite is an iron oxide, which is ubiquitous in rocks and is usually deposited as small nanoparticulate matter among other rock material. It differs from most other iron oxides because it contains divalent and trivalent iron. Consequently, it has a special crystal structure and unique magnetic properties. These properties are used for paleoclimatic reconstructions where naturally occurring magnetite helps understanding former geological ages. Further on, magnetic properties are used in bio- and nanotechnological applications –synthetic magnetite serves as a contrast agent in MRI, is exploited in biosensing, hyperthermia or is used in storage media.
Magnetic properties are strongly size-dependent and achieving size control under preferably mild synthesis conditions is of interest in order to obtain particles with required properties. By using a custom-made setup, it was possible to synthesize stable single domain magnetite nanoparticles with the co-precipitation method. Furthermore, it was shown that magnetite formation is temperature-dependent, resulting in larger particles at higher temperatures. However, mechanistic approaches about the details are incomplete.
Formation of magnetite from solution was shown to occur from nanoparticulate matter rather than solvated ions. The theoretical framework of such processes has only started to be described, partly due to the lack of kinetic or thermodynamic data. Synthesis of magnetite nanoparticles at different temperatures was performed and the Arrhenius plot was used determine an activation energy for crystal growth of 28.4 kJ mol-1, which led to the conclusion that nanoparticle diffusion is the rate-determining step.
Furthermore, a study of the alteration of magnetite particles of different sizes as a function of their storage conditions is presented. The magnetic properties depend not only on particle size but also depend on the structure of the oxide, because magnetite oxidizes to maghemite under environmental conditions. The dynamics of this process have not been well described. Smaller nanoparticles are shown to oxidize more rapidly than larger ones and the lower the storage temperature, the lower the measured oxidation. In addition, the magnetic properties of the altered particles are not decreased dramatically, thus suggesting that this alteration will not impact the use of such nanoparticles as medical carriers.
Finally, the effect of biological additives on magnetite formation was investigated. Magnetotactic bacteria¬¬ are able to synthesize and align magnetite nanoparticles of well-defined size and morphology due to the involvement of special proteins with specific binding properties. Based on this model of morphology control, phage display experiments were performed to determine peptide sequences that preferably bind to (111)-magnetite faces. The aim was to control the shape of magnetite nanoparticles during the formation. Magnetotactic bacteria are also able to control the intracellular redox potential with proteins called magnetochromes. MamP is such a protein and its oxidizing nature was studied in vitro via biomimetic magnetite formation experiments based on ferrous ions. Magnetite and further trivalent oxides were found.
This work helps understanding basic mechanisms of magnetite formation and gives insight into non-classical crystal growth. In addition, it is shown that alteration of magnetite nanoparticles is mainly based on oxidation to maghemite and does not significantly influence the magnetic properties. Finally, biomimetic experiments help understanding the role of MamP within the bacteria and furthermore, a first step was performed to achieve morphology control in magnetite formation via co-precipitation.
The mental chronometry of the human brain's processing of sounds to be categorized as targets has intensively been studied in cognitive neuroscience. According to current theories, a series of successive stages consisting of the registration, identification, and categorization of the sound has to be completed before participants are able to report the sound as a target by button press after similar to 300-500 ms. Here we use miniature eye movements as a tool to study the categorization of a sound as a target or nontarget, indicating that an initial categorization is present already after 80-100 ms. During visual fixation, the rate of microsaccades, the fastest components of miniature eye movements, is transiently modulated after auditory stimulation. In two experiments, we measured microsaccade rates in human participants in an auditory three-tone oddball paradigm (including rare nontarget sounds) and observed a difference in the microsaccade rates between targets and nontargets as early as 142 ms after sound onset. This finding was replicated in a third experiment with directed saccades measured in a paradigm in which tones had to be matched to score-like visual symbols. Considering the delays introduced by (motor) signal transmission and data analysis constraints, the brain must have differentiated target from nontarget sounds as fast as 80-100 ms after sound onset in both paradigms. We suggest that predictive information processing for expected input makes higher cognitive attributes, such as a sound's identity and category, available already during early sensory processing. The measurement of eye movements is thus a promising approach to investigate hearing.
A Little Piece of the Shire
(2014)
Rezensiertes Werk:
George, Rosemary Marangoly, Indian English and the Fiction of National Literature - Cambridge: Cambridge University Press, 2013. - Hb. viii, 285 pp. - (Zeitschrift für Anglistik und Amerikanistik ; 62(4)) ISBN 978-1-107-04000-7.