Frequency-dependence of myocardial energetics in failing human myocardium as quantified by a new method for the measurement of oxygen consumption in muscle strip preparations

Diastolic dysfunction at high heart rates may be associated with increased myocardial energy consumption. Frequency-dependent changes of isometric force and oxygen consumption (MVO2) were investigated in strip preparations from endstage failing human hearts exhibiting various degrees of diastolic dysfunction. MVO2 was determined by a new method which was validated. When stimulation rate was increased from 40 to 200 min-1 (n=7), developed force decreased from 16.5+/-4.3 to 7.9+/-2.9 mN/mm2 (P<0.01), diastolic force increased from 15.9+/-3.2 to 22.0+/-3.0 mN/mm2 (P<0.01), and total MVO2 increased from 2.6+/-0.6 to 4.7+/-0.9 ml/min/100 g (P<0.025). Resting MVO2 and resting force were 1.8+/-0.4 ml/min/100 g and 15.9+/-3.0 mN/mm2, respectively. After addition of 30 mm 2,3-butanedione monoxime (BDM) to inhibit crossbridges, resting MVO2 and resting force decreased by 46% (P<0.05) and 15% (P<0.01), respectively, indicating the presence of active force generation in unstimulated failing human myocardium. In each muscle preparation, there was a significant correlation between force-time integral (FTI) and total MVO2 (r=0.96+/-0.01). The strength of these correlations did not vary with the contribution of diastolic FTI to total FTI. The ratio of activity related MVO2 to developed FTI, an inverse index of the economy of contraction, increased depending on the rise of diastolic FTI at higher stimulation rates. In conclusion, in failing human myocardium, diastolic force development is occurring at the same energy expenditure as systolic force generation. Therefore, in muscle preparations with disturbed diastolic function economy of contraction decreases with higher stimulation rates, depending on the rise of diastolic force.     

X-SAR interferometry: first results

Repeat-pass interferometry data were acquired during the first and second SIR-C/X-SAR missions in April and October 1994. This paper presents the first results from X-SAR interferometry at four different sites. The temporal separations were one day and six months. At two sites the coherence requirements were met, resulting in high quality interferograms. A digital elevation model in ground range geometry has been derived. The limitations of the X-SAR interferometry are discussed     

Automatic recognition fingerspelling gestures in multiple languages for a communication interface for the disabled

This paper presents the design and evaluation of a multi-lingual fingerspelling recognition module that is designed for an information terminal. Through the use of multimodal input and output methods, the information terminal acts as a communication medium between deaf and blind people. The system converts fingerspelled words to speech and vice versa using fingerspelling recognition, fingerspelling synthesis, speech recognition and speech synthesis in Czech, Russian, and Turkish languages. We describe an adaptive skin color based fingersign recognition system with a close to real-time performance and present recognition results on 88 different letters signed by five different signers, using above four hours of training and test videos.     

Molecular Genetics of Conjunctival Melanoma and Prognostic Value of TERT Promoter Mutation Analysis

The aim of this study was exploration of the genetic background of conjunctival melanoma (CM) and correlation with recurrent and metastatic disease. Twenty-eight CM from the Rotterdam Ocular Melanoma Study group were collected and DNA was isolated from the formalin-fixed paraffin embedded tissue. Targeted next-generation sequencing was performed using a panel covering GNAQ, GNA11, EIF1AX, BAP1, BRAF, NRAS, c-KIT, PTEN, SF3B1, and TERT genes. Recurrences and metastasis were present in eight (29%) and nine (32%) CM cases, respectively. TERT promoter mutations were most common (54%), but BRAF (46%), NRAS (21%), BAP1 (18%), PTEN (14%), c-KIT (7%), and SF3B1 (4%) mutations were also observed. No mutations in GNAQ, GNA11, and EIF1AX were found. None of the mutations was significantly associated with recurrent disease. Presence of a TERT promoter mutation was associated with metastatic disease (p-value = 0.008). Based on our molecular findings, CM comprises a separate entity within melanoma, although there are overlapping molecular features with uveal melanoma, such as the presence of BAP1 and SF3B1 mutations. This warrants careful interpretation of molecular data, in the light of clinical findings. About three quarter of CM contain drug-targetable mutations, and TERT promoter mutations are correlated to metastatic disease in CM.     

Multi-Stage Phase-Segregation of Mixed Halide Perovskites under Illumination: A Quantitative Comparison of Experimental Observations and Thermodynamic Models

Photo- and charge-carrier-induced ion migration is a major challenge when utilizing metal halide perovskite semiconductors for optoelectronic applications. For mixed iodide/bromide perovskites, the compositional instability due to light- or electrical bias induced phase-segregation restricts the exploitation of the entire bandgap range. Previous experimental and theoretical work suggests that excited states or charge carriers trigger the process, but the exact mechanism is still under debate. To identify the mechanism and cause of light-induced phase-segregation phenomena, the full compositional range of methylammonium lead bromide/iodide samples are investigated, MAPb(Br_xI_1-x)₃ with x = 0…1, by simultaneous in situ X-ray diffraction (XRD) and photoluminescence (PL) spectroscopy during illumination. The quantitative comparison of composition-dependent in situ XRD and PL shows that at excitation densities of 1 sun, only the initial stage of photo-segregation is rationalized with the previously established thermodynamic models. However, a progression of the phase segregation is observed that is rationalized by considering long-lived accumulative photo-induced material alterations. It is suggested that (additional) photo-induced defects, possibly halide vacancies and interstitials, need to be considered to fully rationalize light-induced phase segregation and anticipate the findings to provide crucial insight for the development of more sophisticated models.     

Particle flow control by induced dipolar interaction of superparamagnetic microbeads

Magnetic particles diluted in liquid agglomerate in rod-like particle arrays if an external homogeneous magnetic field is applied. This work introduces a method to specifically exploit particle–particle interaction to obtain flow control of magnetic particles without changing the motion state of the carrier liquid. Experiments show the possibility to uncouple the particle flux from the motion state of liquid. We show how this method may be applied to design a microfluidic geometry in which the particle flow in a specific direction is either enabled or suppressed by the relative orientation of the fluid velocity and the external field.     

Controlled counter-flow motion of magnetic bead chains rolling along microchannels

We demonstrate controlled transport of superparamagnetic beads in the opposite direction of a laminar flow. A permanent magnet assembles 200 nm magnetic particles into about 200 μm long bead chains that are aligned in parallel to the magnetic field lines. Due to a magnetic field gradient, the bead chains are attracted towards the wall of a microfluidic channel. A rotation of the permanent magnet results in a rotation of the bead chains in the opposite direction to the magnet. Due to friction on the surface, the bead chains roll along the channel wall, even in counter-flow direction, up to at a maximum counter-flow velocity of 8 mm s⁻¹. Based on this approach, magnetic beads can be accurately manoeuvred within microfluidic channels. This counter-flow motion can be efficiently be used in Lab-on-a-Chip systems, e.g. for implementing washing steps in DNA purification.