The Antibacterial Drug Candidate SBC3 is a Potent Inhibitor of Bacterial Thioredoxin Reductase

Antibiotic resistance is a growing problem for public health and associated with increasing economic costs and mortality rates. Silver and silver-related compounds have been used for centuries due to their antimicrobial properties. In this work, we show that 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate/NHC*-Ag-OAc (SBC3) is a reversible, high affinity inhibitor of E. coli thioredoxin reductase (TrxR; K_i=10.8±1.2 nM). Minimal inhibition concentration (MIC) tests with different E. coli and P. aeruginosa strains demonstrated that SBC3 can efficiently inhibit bacterial cell growth, especially in combination with established antibiotics like gentamicin. Our results show that SBC3 is a promising antibiotic drug candidate targeting bacterial TrxR.     

Magnetic resonance imaging of disseminated sclerosis

Multiple sclerosis is a chronic demyelinating disease. Paraclinical examinations may contribute to the diagnosis of multiple sclerosis. Magnetic resonance imaging (MRI) has a very high sensitivity concerning multiple sclerosis, and has made it possible to visualize multiple sclerosis plaques in vivo, to follow each plaque over the course of time and in this way to obtain information about the pathogenesis. MRI has shown that the size of plaques may vary considerably, and that plaques are dynamic structures with the ability to change in size over few weeks. By using MRI and the contrast agent Gadolinium-DTPA, it is possible to distinguish a newly developed plaque from an older one. Therefore, MRI has become an important examination in therapeutic trials. Just now, MRI with Gadolinium-DTPA is being used to evaluate the efficacy of plasmapheresis and immunoglobulin treatment in a joint study between Rigshospitalet and Hvidovre Hospital.     

Inhibition of monocyte leukotriene B4 production after aspirin desensitization

Aspirin-sensitive patients may be desensitized through a graded series of exposures to aspirin. We investigated the underlying mechanism of aspirin desensitization by measuring the release of leukotrienes B4 and C4 from calcium ionophore-stimulated peripheral blood monocytes. Compared with monocytes from normal volunteers (n = 5), monocytes from patients with aspirin-sensitive asthma (n = 10) released increased amounts of thromboxane B2 (1060 +/- 245 pg/ml vs 456 +/- 62 pg/ml), leukotriene B4 (861 +/- 139 pg/ml vs 341 +/- 44 pg/ml), and leukotriene C4 (147 +/- 31 pg/ml vs 56 +/- 6 pg/ml) at baseline. After aspirin desensitization, thromboxane B2 release was almost completely suppressed in both groups. Leukotriene B4 release was significantly decreased in the aspirin-sensitive group (484 +/- 85 pg/ml) but not in the normal subject group (466 +/- 55 pg/ml). The need for prednisone decreased significantly after patients were desensitized to aspirin (10.4 +/- 2.2 mg/day to 1.6 +/- 2.8 mg/day). These results demonstrate that desensitization to aspirin results in decreased monocyte leukotriene B4 release. On the basis of the bronchospastic and inflammatory potential of leukotrienes, the decrease in leukotriene release may contribute to the clinical improvement seen after aspirin desensitization.     

Accuracy in perceptions of interpersonal interactions: Effects of dysphoria, friendship, and similarity.

Addressed conflicting views of depressives' interpersonal accuracy in an investigation of the accuracy of mild depressives (dysphorics) across differing social contexts. Women who were either friends or strangers and who were either similar or dissimilar in level of dysphoria conversed about 3 topics: a neutral topic, their own disclosure of a personal problem, and their partner's disclosure. Dysphorics were not more accurate in general than nondysphorics. After self-disclosure, all women more accurately detected sympathy from a similar stranger. After the partner's disclosure, women also better detected the mood of a similar partner. When interacting with nondysphoric strangers, however, dysphorics underestimated their partner's sympathy toward them. Implications for cognitive and interpersonal theories of depression and for depressives' relationships are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dynamic averaging and foraging decisions in horses (Equus callabus).

The variability of most environments taxes foraging decisions by increasing the uncertainty of the information available. One solution to the problem is to use dynamic averaging, as do some granivores and carnivores. Arguably, the same strategy could be useful for grazing herbivores, even though their food renews and is more homogeneously distributed. Horses (Equus callabus) were given choices between variable patches after short or long delays. When patch information was current, horses returned to the patch that was recently best, whereas those without current information matched choices to the long-term average values of the patches. These results demonstrate that a grazing species uses dynamic averaging and indicate that, like granivores and carnivores, they can use temporal weighting to optimize foraging decisions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Investigations of two-stage-pseudospark switches for high-currentapplications

To avoid the lowering of the holdoff voltage due to the electrode erosion in one stage high current pseudospark switches (PSS), a two stage PSS with no axial aperture in the intermediate electrode was tested. For investigations a pulse generator was used generating peak currents up to 120 kA at a maximum voltage of 30 kV with a period length of 5 μs of a weakly damped sine wave with 90% current reversal. In comparison with a one stage PSS the breakdown characteristic was shifted to higher pressure. With a free floating intermediate electrode, the device could not be triggered, however, with additional capacities of a few nF between the three electrodes the discharge was ignited. The discharge in the second gap is triggered by the pseudospark discharge in the cathode gap, discharging the auxiliary capacities. Simultaneously, observation of both gaps with fast shutter photography showed an independent movement of the discharges in the two gaps. In the cathode gap as current increases, the discharge moves away from the center to the plane electrode surface as has been observed in the one stage PSS. However, in the anode gap the discharge moves away from the center after a contraction to the center. The two discharges are transmitted to metal vapor arc type discharges as the erosion patterns prove. With this kind of a two stage PSS holdoff voltages exceeding 35 kV would be possible. The characteristic switch data, i.e., delay and jitter, are nearly equal to a one stage PSS     

Adult rats stressed as neonates show exaggerated behavioral responses to both pharmacological and environmental challenges.

Adult rats that were isolated from the mother and nest for 1 hr per day from Postnatal Day 2 to 9 were studied. Controls consisted of handled littermates as well as separate litters that were never handled. As adults, animals were given either a pharmacological challenge (1.0 or 2.0 mg/kg amphetamine) or an environmental challenge (restraint). Previously isolated animals demonstrated increased activity compared to controls at both drug doses. Similarly, isolated animals manifested exaggerated inhibition of activity after restraint. Previously isolated animals usually did not show differences compared to controls under baseline conditions (saline injection or no restraint). The neuroplastic changes that result from the neonatal experience are long lasting and appear when the system is challenged. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identification of intra-individual variation in intracranial arterial flow by MRI and the effect on computed hemodynamic descriptors

Magnetic Resonance Materials in Physics, Biology and Medicine - To determine the intra-individual flow variation in serially acquired studies, and the influence of this variation on subsequent...     

Creating geometrically robust designs for highly sensitive problems using topology optimization

Resonance and wave-propagation problems are known to be highly sensitive towards parameter variations. This paper discusses topology optimization formulations for creating designs that perform robustly under spatial variations for acoustic cavity problems. For several structural problems, robust topology optimization methods have already proven their worth. However, it is shown that direct application of such methods is not suitable for the acoustic problem under consideration. A new double filter approach is suggested which makes robust optimization for spatial variations possible. Its effect and limitations are discussed. In addition, a known explicit penalization approach is considered for comparison. For near-uniform spatial variations it is shown that highly robust designs can be obtained using the double filter approach. It is finally demonstrated that taking non-uniform variations into account further improves the robustness of the designs.     

3D interactive topology optimization on hand-held devices

This educational paper describes the implementation aspects, user interface design considerations and workflow potential of the recently published TopOpt 3D App. The app solves the standard minimum compliance problem in 3D and allows the user to change design settings interactively at any point in time during the optimization. Apart from its educational nature, the app may point towards future ways of performing industrial design. Instead of the usual geometrize, then model and optimize approach, the geometry now automatically adapts to the varying boundary and loading conditions. The app is freely available for iOS at Apple’s App Store and at http://www.topopt.dtu.dk/TopOpt3D for Windows and OSX.