Monitoring intracellular calcium in response to GPCR activation using thin-film silicon photodiodes with integrated fluorescence filters.

G-protein coupled receptor (GPCRs) drug discovery is a thriving strategy in the pharmaceutical industry. The standard approach uses living cells to test millions of compounds in a high-throughput format. Typically, changes in the intracellular levels of key elements in the signaling cascade are monitored using fluorescence or luminescence read-out systems, which require external equipment for signal acquisition. In this work, thin-film amorphous silicon photodiodes with an integrated fluorescence filter were developed to capture the intracellular calcium dynamics in response to the activation of the endogenous muscarinic M1 GPCR of HEK 293T cells. Using the new device it was possible to characterize the potency of carbachol (EC50=10.5 µM) and pirenzepine (IC50=4.2 µM), with the same accuracy as standard microscopy optical systems. The smaller foot-print provided by the detection system makes it an ideal candidate for the future integration in microfluidic devices for drug discovery.

Atomic-scale engineering of magnetic anisotropy of nanostructures through interfaces and interlines.

The central goals of nanoscale magnetic materials science are the self-assembly of the smallest structure exhibiting ferromagnetic hysteresis at room temperature, and the assembly of these structures into the highest density patterns. The focus has been on chemically ordered alloys combining magnetic 3d elements with polarizable 5d elements having high spin-orbit coupling and thus yielding the desired large magneto-crystalline anisotropy. The chemical synthesis of nanoparticles of these alloys yields disordered phases requiring annealing to transform them to the high-anisotropy L1(0) structure. Despite considerable efforts, so far only part of the nanoparticles can be transformed without coalescence. Here we present an alternative approach to homogeneous alloys, namely the creation of nanostructures with atomically sharp bimetallic interfaces and interlines. They exhibit unexpectedly high magnetization reversal energy with values and directions of the easy magnetization axes strongly depending on chemistry and texture. We find significant deviations from the expected behaviour for commonly used element combinations. Ab-initio calculations reproduce these results and unravel their origin.

Correlation of bacteriological flora of the urethra, glans and perineum with organisms causing urinary tract infection in the spinal injured male patient.

Positive urine cultures are common and often asymptomatic in the male spinal injured patient performing self clean intermittent catheterisation. It is possible that the positive urine cultures result from contamination from the colonised urethra at the time of catheterisation. This contamination could result in true infection of the bladder urine or yield false positive results, explaining the frequently seen asymptomatic cases. In a prospective study positive urine cultures were found on 58 occasions (74%) in 10 asymptomatic patients studied. In 19% of screenings, with positive urine cultures, an identical organism was cultured from the catheter specimen of urine, the perineum and the urethra. The flora of the anterior urethra is strongly correlated to that of the perineum (37.1%), as well as that of the bladder (52.6%). In 4 patients a correlation also existed between the urethra and fingers, and the perineum and fingers. This was associated with an increased incidence of positive urine culture in these patients. Suprapubic aspirates of urine before and after catheterisation cultured the same organisms. However, quantitative culture revealed colony counts that approached a 10-fold increase following catheterisation in one patient. This suggests that catheterisation is at least partially responsible for ascending infection in this group of patients. Catheter specimens were found to be a good representation of the bladder urine, with an 87.5% correlation.