Doxorubicin Impairs Smooth Muscle Cell Contraction: Novel Insights in Vascular Toxicity

Clinical and animal studies have demonstrated that chemotherapeutic doxorubicin (DOX) increases arterial stiffness, a predictor of cardiovascular risk. Despite consensus about DOX-impaired endothelium-dependent vasodilation as a contributing mechanism, some studies have reported conflicting results on vascular smooth muscle cell (VSMC) function after DOX treatment. The present study aimed to investigate the effects of DOX on VSMC function. To this end, mice received a single injection of 4 mg DOX/kg, or mouse aortic segments were treated ex vivo with 1 μM DOX, followed by vascular reactivity evaluation 16 h later. Phenylephrine (PE)-induced VSMC contraction was decreased after DOX treatment. DOX did not affect the transient PE contraction dependent on Ca²⁺ release from the sarcoplasmic reticulum (0 mM Ca²⁺), but it reduced the subsequent tonic phase characterised by Ca²⁺ influx. These findings were supported by similar angiotensin II and attenuated endothelin-1 contractions. The involvement of voltage-gated Ca²⁺ channels in DOX-decreased contraction was excluded by using levcromakalim and diltiazem in PE-induced contraction and corroborated by similar K⁺ and serotonin contractions. Despite the evaluation of multiple blockers of transient receptor potential channels, the exact mechanism for DOX-decreased VSMC contraction remains elusive. Surprisingly, DOX reduced ex vivo but not in vivo arterial stiffness, highlighting the importance of appropriate timing for evaluating arterial stiffness in DOX-treated patients.     

Decision support for rehabilitation hospital scheduling

We present a detailed analysis of the patient and resource scheduling problem in rehabilitation hospitals. In practice, the predominantly therapeutical treatments and activities which are prescribed for the patients are typically scheduled manually. This leads to rigid and inefficient schedules which can have negative effects on the quality of care and the patients’ satisfaction. We outline the conceptual framework of a decision support system for the scheduling process that is based on formal optimization models. To this end, we first develop a large-scale monolithic optimization model. Then we derive a numerically tractable hierarchical model system in order to deal with problem instances of realistic sizes. We report numerical results with respect to solution times, model sizes and solution quality.     

High-temperature thermoelectric properties of Ca0.9Y0.1Mn1−x Fe x O3 (0 ≤ x ≤ 0.25)

Polycrystalline compounds of Ca_0.9Y_0.1Mn_{1? x} Fe _x O₃ for 0 ≤ x ≤ 0.25 were prepared by solid-state reaction, followed by spark plasma sintering process, and their thermoelectric properties from 300 to 1200 K were systematically investigated in terms of Y and Fe co-doping at the Ca- and Mn-sites, respectively. Crystal structure refinement revealed that all the investigated samples have the O′-type orthorhombic structure, and the lattice parameters slightly increased with increasing Fe concentration, causing a crystal distortion. It was found that with increasing the content of Fe doping, the Seebeck coefficient of Ca_0.9Y_0.1Mn_{1? x} Fe _x O₃ tended to increase, while the tendency toward the electrical conductivity was more complicated. The highest power factor was found to be 2.1 × 10^?4 W/mK² at 1150 K for the sample with x = 0.05 after annealing at 1523 K for 24 h in air. Thermal conductivity of the Fe-doped samples showed a lower value than that of the x = 0 sample, and the highest dimensionless figure of merit, ZT was found to be improved about 20 % for the sample with x = 0.05 as compared to that of the x = 0 sample at 1150 K.     

Performance evaluation of three optical particle counters with an efficient “multimodal” calibration method

The sizing accuracies of two widely used yet hitherto unevaluated optical particle counters (OPCs—Grimm Model 1.109 and Palas Model WELAS 2100) as well as one high-resolution, non-commercial OPC were evaluated. The measured data were compared to scattering intensity calculations based on Mie theory. Additionally, the counting efficiency for all three counters was measured, as was the influence of coincidence effects for the OPC with the lowest (manufacturer specified) upper concentration limit.Beside the traditional polystyrene latex calibration, a little-known, very fast and precise “multimodal” calibration method was used, which is based on the simultaneous generation of up to eight sharp multiple-charge modes from polydisperse di-ethyl-hexyl-sebacate (DEHS) particles by electrical mobility classification.     

Nano-cones formation on a surface of Ge, Si crystals and Si1-xGe(x) solid solution by laser radiation

The study of self-assembling nano-cones induced by irradiation of nanosecond Nd:YAG laser pulses on a surface of a Si1-xGe(x) solid solution is reported. It is shown that dynamics of nano-cones formation depends on concentration of Ge atoms (x) in Si lattice and on the intensity of laser radiation. Two different processes of nano-cones formation depending on x are observed. The first one-at higher concentration of Ge atoms x = 0.3-0.4 and the second one-at lower concentration of Ge atoms at x = 0.15 take place. At the first stage, similar processes of nano-cones formation occur. It means, at low intensity of laser radiation 1 < 2.0 MW/cm2 Ge atoms drift to the irradiated surface due to Thermo-gradient effect and Ge-rich phase is formed for both concentration ranges. The second stage is different for low and high Ge content ranges. At the higher concentration of Ge atoms and intensity of laser radiation 1 > 2.0 MW/cm2 nano-cones formation takes place by Stransky-Krastanov mode. On the same time, at lower concentration of Ge atoms cones look like "tree ring" growth due to melting of Ge separated islands on the irradiated surface at intensity of laser radiation 1 = 20 MW/cm2.     

Quantum interference effects at room temperature in OPV-based single-molecule junctions

Interference effects on charge transport through an individual molecule can lead to a notable modulation and suppression on its conductance. In this letter, we report the observation of quantum interference effects occurring at room temperature in single-molecule junctions based on oligo(3)-phenylenevinylene (OPV3) derivatives, in which the central benzene ring is coupled to either para- or meta-positions. Using the break-junction technique, we find that the conductance for a single meta-OPV3 molecule wired between gold electrodes is one order of magnitude smaller than that of a para-OPV3 molecule. Theoretical calculations confirm the occurrence of constructive and destructive interference in the para- and meta-OPV3 molecules respectively, which arises from the phase difference of the transmission coefficients through the molecular orbitals.     

Isomer-specific combustion chemistry in allene and propyne flames

A combined experimental and modeling study is performed to clarify the isomer-specific combustion chemistry in flames fueled by the C₃H₄ isomers allene and propyne. To this end, mole fraction profiles of several flame species in stoichiometric allene (propyne)/O₂/Ar flames are analyzed by means of a chemical kinetic model. The premixed flames are stabilized on a flat-flame burner under a reduced pressure of 25 Torr (=33.3 mbar). Quantitative species profiles are determined by flame-sampling molecular-beam mass spectrometry, and the isomer-specific flame compositions are unraveled by employing photoionization with tunable vacuum-ultraviolet synchrotron radiation. The temperature profiles are measured by OH laser-induced fluorescence. Experimental and modeled mole fraction profiles of selected flame species are discussed with respect to the isomer-specific combustion chemistry in both flames. The emphasis is put on main reaction pathways of fuel consumption, of allene and propyne isomerization, and of isomer-specific formation of C₆ aromatic species. The present model includes the latest theoretical rate coefficients for reactions on a C₃H₅ potential [J.A. Miller, J.P. Senosiain, S.J. Klippenstein, Y. Georgievskii, J. Phys. Chem. A 112 (2008) 9429-9438] and for the propargyl recombination reactions [Y. Georgievskii, S.J. Klippenstein, J.A. Miller, Phys. Chem. Chem. Phys. 9 (2007) 4259-4268]. Larger peak mole fractions of propargyl, allyl, and benzene are observed in the allene flame than in the propyne flame. In these flames virtually all of the benzene is formed by the propargyl recombination reaction.