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1.
Viktoria M. S. Kjær Loukas Ieremias Dr. Viktorija Daugvilaite Dr. Michael Lückmann Prof. Thomas M. Frimurer Prof. Trond Ulven Prof. Mette M. Rosenkilde Dr. Jon Våbenø 《ChemMedChem》2021,16(17):2623-2627
The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca2+ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch. 相似文献
2.
Haralabidis N. Loukas D. Misiakos K. Katsafouros S. 《Solid-State Circuits, IEEE Journal of》1997,32(1):135-138
A fast transimpedance multichannel amplifier has been designed, fabricated in CMOS 1.2-μm technology and tested. Each channel consists of a current sensitive preamplifier followed by a voltage amplification stage and an on-chip buffer able to drive 50 Ω loads with an output range of ±800 mV. Measured peaking time at the output is 40 ns and the circuit recovers to baseline in 90 ns. This results in a counting capability of more than 107 hits/s, Signals of both polarities can be handled. The first two stages consume a total of 2 mW per channel and the 50 Ω buffer consumes another 17 mW. The equivalent noise charge (ENC) is 1100 e- rms with a slope of 40e-/pF. The IC is intended for use in gas and solid-state detectors with high particle rate and extensive charge release as in high energy calorimetry 相似文献
3.
Passas Nikos Loukas Nikos Merakos Lazaros 《International Journal of Wireless Information Networks》1997,4(1):55-62
Future generation wireless personalcommunication networks (PCN) are expected to providemultimedia capable wireless extensions of fixedATM/B-ISDN. This paper presents a scheduling techniquefor PCN based on TDMA and the leaky bucket regulator, thewell known bandwidth enforcement mechanism for fixedATM. The main objective of the proposed technique is toensure fair and efficient treatment of various types oftraffic on the air interface, includingconstant-bit-rate (CBR) voice and variable-bit-rate(VBR) video. Two alternative priority mechanisms areintroduced and their performance is evaluated. Theperformance comparison of the alternatives reveals aninteresting tradeoff between fairness and quality ofservice (QoS). 相似文献
4.
Two forms of a sampling theorem for concentric circles are established for a bandlimited two-dimensional (2-D) function. The location of the samples is prescribed either on equidistant circles or on the roots of the Bessel function J0( ). Both methods give comparable results, however, the number of samples required for their numerical evaluation is significantly less for the root-sampling formulation. 相似文献
5.
This study estimates hydrological drought characteristics using a water balance derived drought index in Pinios river basin, Thessaly, Greece. The concept of hydrological management at subwatershed scale has been adopted because it encompasses the areal extent of a drought event. Fourteen (14) sub-watersheds of Pinios river basin were delineated according to the major tributaries of Pinios river using GIS. For the assessment of hydrological drought, because none of the sub-watersheds have flow gauge stations at their outlets, a six-parameter monthly conceptual water balance model (UTHBAL model), has been applied regionally to simulate runoff for the period October 1960?CSeptember 2002. The synthetic runoff was normalized through Box-Cox transformation and standardized to the mean runoff to produce the water balance derived drought index for hydrological drought assessment. The standardized precipitation index (SPI) at multiple time scales and four indices of the Palmer method (i.e. PDSI, WPLM, PHDI and the Palmer moisture anomaly Z-index) were also calculated to assess hydrological droughts. The results showed that the water balance derived drought index is a good indicator of hydrological drought in all sub-watersheds, since is capable to quantify drought severity and duration. Furthermore, the drought index provides guidance on the selection of an appropriate meteorological drought index for operational hydrological drought monitoring. Hence, SPI at 3- and 6-month timescales and the WPLM could be used along with the water balance derived drought index in risk and decision analyses at the study area. 相似文献
6.
DF Loukas 《Canadian Metallurgical Quarterly》1976,42(10):367-370
Leukemic reticuloendotheliosis (LRE) or "hairy cell leukemia" is a unique form of leukemia which possesses features of both a chronic and acute leukemia. Its characteristic morphology, clinical diagnosis, and treatment are discussed. A high index of suspicion should make this entity easily diagnosed by the medical technologist. 相似文献
7.
Time‐domain hybrid formulations for wave simulations in three‐dimensional PML‐truncated heterogeneous media 下载免费PDF全文
Arash Fathi Babak Poursartip Loukas F. Kallivokas 《International journal for numerical methods in engineering》2015,101(3):165-198
We are concerned with the numerical simulation of wave motion in arbitrarily heterogeneous, elastic, perfectly‐matched‐layer‐(PML)‐truncated media. We extend in three dimensions a recently developed two‐dimensional formulation, by treating the PML via an unsplit‐field, but mixed‐field, displacement‐stress formulation, which is then coupled to a standard displacement‐only formulation for the interior domain, thus leading to a computationally cost‐efficient hybrid scheme. The hybrid treatment leads to, at most, third‐order in time semi‐discrete forms. The formulation is flexible enough to accommodate the standard PML, as well as the multi‐axial PML. We discuss several time‐marching schemes, which can be used à la carte, depending on the application: (a) an extended Newmark scheme for third‐order in time, either unsymmetric or fully symmetric semi‐discrete forms; (b) a standard implicit Newmark for the second‐order, unsymmetric semi‐discrete forms; and (c) an explicit Runge–Kutta scheme for a first‐order in time unsymmetric system. The latter is well‐suited for large‐scale problems on parallel architectures, while the second‐order treatment is particularly attractive for ready incorporation in existing codes written originally for finite domains. We compare the schemes and report numerical results demonstrating stability and efficacy of the proposed formulations. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
8.
The characterization of the structure and internal dynamics of biomolecules is essential to understanding their biological function. Neutron scattering probes similar time- and length-scales to molecular dynamics simulation. Hence, simulation models of biomolecules have become invaluable in the interpretation of experimental neutron data. Here, we report on advances in the application of simulation in developing neutron scattering to investigate internal protein motions and, as an example of industrial relevance, in the derivation of physical models of use in biofuel renewable energy research. 相似文献
9.
Sterols regulate low density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase gene
expressions by end product repression. Studies on cultured cells have shown that growing cells have a higher LDL uptake than
quiescent cells and that incubation of cells with growth factors or mitogenic compounds leads to sterol-resistant upregulation
of LDL receptor gene expression. The recent finding that elevated LDL receptor activity in acute myelogenous leukemia cells
was characterized by a decreased sensitivity to downregulation by sterols raises the possibility that the mechanism behind
this is related to the cellular growth rate. By using cultured human fibroblasts as a model system we therefore studied whether
growth modulation of sterol sensitivity takes place in normal actively growing cells. Judging from the ability of sterols
(25-hydroxycholesterol+cholesterol) to inhibit 125I-LDL degradation, we found that the sensitivity to sterols varied markedly between cells of different densities. The lowest
sensitivity to sterols and highest 125I-LDL degradation rate were found in subconfluent cells, whereas sparse and confluent cells were the most sensitive ones.
In contrast to the LDL receptor, HMG-CoA reductase sterol sensitivity did not appear to be growth regulated. We conclude that
growth-dependent modulation of sterol sensitivity and LDL receptor activity takes place in normal human fibroblasts. Modulation
of sterol sensitivity may be an important mechanism to ensure an adequate cholesterol supply in growing cells. 相似文献
10.
This paper focuses on various coevolutionary robotic experiments where all parameters except for the fitness function remain the same. Initially an attempt to categorize coevolutionary experiments is made and subsequently three experiments of competitive coevolution (hunt, battle and mating) are presented. The experiment concerning implicit competition of two species (mating) is given special attention as it shows emergence of compromise and collaboration through a competitive environment. The co-evolution progress monitoring is evaluated through fitness graphs, CIAO and Hamming maps and the results are interpreted for each experimental setup. The paper concludes that despite the alteration of fitness functions, several evasion–pursuit elements emerge. Furthermore, conciliatory strategies can emerge in implicit competitional cases. 相似文献