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101.
Hans‐Jörg Breyholz Dr. Stefan Wagner Dr. Andreas Faust Dr. Burkhard Riemann Prof. Dr. Carsten Höltke Dr. Sven Hermann Dr. Otmar Schober Prof. Dr. Michael Schäfers Prof. Dr. Klaus Kopka Priv.‐Doz. Dr. 《ChemMedChem》2010,5(5):777-789
Matrix metalloproteinases (MMPs) are zinc‐ and calcium‐dependent endopeptidases. Representing a subfamily of the metzincin superfamily, MMPs are involved in the proteolytic degradation of components of the extracellular matrix. Unregulated MMP expression, MMP dysregulation and locally increased MMP activity are common features of various diseases, such as cancer, atherosclerosis, stroke, arthritis, and others. Therefore, activated MMPs are suitable biological targets for the specific visualization of such pathologies, in particular by using radiolabeled MMP inhibitors (MMPIs). The aim of this work was to develop a radiofluorinated molecular probe for noninvasive in vivo imaging for the detection of up‐regulated levels of activated MMPs in the living organism. Fluorinated MMPIs ( 26 , 31 and 38 ) based on the pyrimidine‐2,4,6‐trione lead structure RO 28‐2653 ( 1 ) were synthesized, and their MMP inhibition potency was evaluated in vitro. The radiosynthesis and the in vivo biodistribution of the first 18F‐labeled prototype, MMP‐targeted tracer [18F] 26 , suitable for molecular imaging by means of positron emission tomography (PET) were realized. 相似文献
102.
Kristin Engels Dr. Carsten Beyer Dr. Maria L. Suárez Fernández Frank Bender Michael Gaßel Dr. Gottfried Unden Prof. Dr. Richard J. Marhöfer Dr. Jeremy C. Mottram Prof. Dr. Paul M. Selzer Prof. Dr. 《ChemMedChem》2010,5(8):1259-1271
Apicomplexan parasites encompass several human‐ and animal‐pathogenic protozoans such as Plasmodium falciparum, Toxoplasma gondii, and Eimeria tenella. E. tenella causes coccidiosis, a disease that afflicts chickens, leading to tremendous economic losses to the global poultry industry. The considerable increase in drug resistance makes it necessary to develop new therapeutic strategies against this parasite. Cyclin‐dependent kinases (CDKs) are key molecules in cell‐cycle regulation and are therefore prominent target proteins in parasitic diseases. Bioinformatics analysis revealed four potential CDK‐like proteins, of which one—E. tenella CDK‐related kinase 2 (EtCRK2)—has already been characterized by gene cloning and expression. 1 By using the CDK‐specific inhibitor flavopiridol in EtCRK2 enzyme assays and schizont maturation assays (SMA), we could chemically validate CDK‐like proteins as potential drug targets. An X‐ray crystal structure of human CDK2 (HsCDK2) served as a template to build protein models of EtCRK2 by comparative homology modeling. Structural differences in the ATP binding site between EtCRK2 and HsCDK2, as well as chicken CDK3, were addressed for the optimization of selective ATP‐competitive inhibitors. Virtual screening and “wet‐bench” high‐throughput screening campaigns on large compound libraries resulted in an initial set of hit compounds. These compounds were further analyzed and characterized, leading to a set of four promising lead compounds for development as EtCRK2 inhibitors. 相似文献
103.
Fatty acid profiles and antioxidants of organic and conventional milk from low‐ and high‐input systems during outdoor period
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104.
Incineration of diesel particulate matter for the regeneration of a mesh-type particulate-filter is achieved using induction heating technique. Heating of the diesel particulates deposited on the mesh-type particulate-filter at around 600 °C is investigated. In the case of the particulate filter, stainless-steel mesh-type filters are considered and the influence on filtering efficiency, the engine performance due to back-pressure generation is studied. Theoretical estimation shows that induction heating approach for the regeneration via exhaust gas heating requires high power (>3 kW). On the other hand, regeneration of mesh-type particulate-filter using induction heating technique requires a low input power of around 0.5 kW in the off-line condition. The proposed mesh-type particulate-filter allowed a filtration efficiency of around 30–40% at lower engine speeds and part loads. Particulate combustion through induction heating at static condition is studied and power required for mesh-type filter and sintered metal filter regeneration during engine operation is estimated theoretically. 相似文献
105.
Matthias M. M��ller Harald R. Haakh Tommaso Calarco Christiane P. Koch Carsten Henkel 《Quantum Information Processing》2011,10(6):771-792
Atom chips are a promising candidate for a scalable architecture for quantum information processing provided a universal set
of gates can be implemented with high fidelity. The difficult part in achieving universality is the entangling two-qubit gate.
We consider a Rydberg phase gate for two atoms trapped on a chip and employ optimal control theory to find the shortest gate
that still yields a reasonable gate error. Our parameters correspond to a situation where the Rydberg blockade regime is not
yet reached. We discuss the role of spontaneous emission and the effect of noise from the chip surface on the atoms in the
Rydberg state. 相似文献
106.
Carsten Steger 《Pattern recognition letters》2012,33(3):349-355
Pose estimation is a problem that occurs in many applications. In machine vision, the pose is often a 2D affine pose. In several applications, a restricted class of 2D affine poses with five degrees of freedom consisting of an anisotropic scaling, a rotation, and a translation must be determined from corresponding 2D points. A closed-form least-squares solution for this problem is described. The algorithm can be extended easily to robustly deal with outliers. 相似文献
107.
Baas Matthijs; De Dreu Carsten K. W.; Nijstad Bernard A. 《Canadian Metallurgical Quarterly》2011,100(5):794
Promotion-focused states generally boost creativity because they associate with enhanced activation and cognitive flexibility. With regard to prevention-focused states, research evidence is less consistent, with some findings suggesting prevention-focused states promote creativity and other findings pointing to no or even negative effects. We proposed and tested the hypothesis that whether prevention-focused states boost creativity depends on regulatory closure (whether a goal is fulfilled or not). We predicted that prevention-focused states that activate the individual (unfulfilled prevention goals, fear) would lead to similar levels of creativity as promotion-focused states but that prevention-focused states that deactivate (closed prevention goals, relief) would lead to lower levels of creativity. Moreover, we predicted that this effect would be mediated by feelings of activation. Predictions were tested in 3 studies on creative insights and 1 on original ideation. Results supported predictions. Implications for self-regulation, motivation, mood, and creativity are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved) 相似文献
108.
Matthias P. Wymann Carsten Schultz 《Chembiochem : a European journal of chemical biology》2012,13(14):2022-2035
Since its discovery in the late 1980s, phosphoinositide 3‐kinase (PI3K), and its isoforms have arguably reached the forefront of signal transduction research. Regulation of this lipid kinase, its functions, its effectors, in short its entire signaling network, has been extensively studied. PI3K inhibitors are frequently used in biochemistry and cell biology. In addition, many pharmaceutical companies have launched drug‐discovery programs to identify modulators of PI3Ks. Despite these efforts and a fairly good knowledge of the PI3K signaling network, we still have only a rudimentary picture of the signaling dynamics of PI3K and its lipid products in space and time. It is therefore essential to create and use novel biological and chemical tools to manipulate the phosphoinositide signaling network with spatial and temporal resolution. In this review, we discuss the current and potential future tools that are available and necessary to unravel the various functions of PI3K and its isoforms. 相似文献
109.
Carsten Clemen 《Structural and Multidisciplinary Optimization》2011,44(1):125-136
The aero-mechanical optimisation of a fan outlet guide vane (OGV) in the bypass duct of a modern turbofan engine is presented.
The purpose of the described outlet guide vane arrangement is to remove the swirl from the flow coming from the fan and to
connect the engine core structurally with the bypass duct and the engine mounts respectively. For that reason the outlet guide
vanes have to fulfill aerodynamic requirements—such as low pressure loss and large working range and turning of the absolute
flow to 0 degree—as well as the structural requirement to withstand the engine loads in all operating conditions. Such an
arrangement has the advantage, that additional struts downstream of the fan outlet guide vane become obsolete, which is beneficial
for the engine length and weight and hence the engine specific fuel consumption. At the same time the structural and aerodynamic
requirements on such an outlet guide vane are intuitively contradictory. Therefore the design is more complex than for a conventional
purely aerodynamic guide vane. To achieve the different requirements the conventional iterative design process has been replaced
by a multi-disciplinary approach, which delivers an aero-mechanically optimised fan outlet guide vane geometry based on aerodynamic
and mechanical boundary conditions and constraints. The prescribed boundary conditions are the structural load cases (flight
conditions) and the aerodynamic inlet and outlet conditions for the fan design point. In addition an existing bypass duct
geometry is used to get a valid comparison with a conventionally designed outlet guide vane/strut arrangement. In the structural
optimisation, carried out as a parameter study, the effect of several geometrical parameters is investigated using the software
ABAQUS. The aerodynamic optimisation is performed using the 2D-CFD-solver MISES on individual profile sections such that a
minimum pressure loss and a maximum working range is achieved. For that purpose the profile shape is modified freely taking
into account the constraints from the structural optimisation. A 3D-RANS-CFD analysis of the optimised vane and the comparison
with the conventional vane/strut arrangement confirmed the improved performance of the chosen design approach and showed a
significant reduction in pressure loss (ΔP/D) of nearly 20% compared to the conventional OGV/strut arrangement, leading to
an SFC reduction of about 0.5%. 相似文献
110.