Universal ultrafast detector for short optical pulses based on graphene

Graphene has unique optical and electronic properties that make it attractive as an active material for broadband ultrafast detection. We present here a graphene-based detector that shows 40-picosecond electrical rise time over a spectral range that spans nearly three orders of magnitude, from the visible to the far-infrared. The detector employs a large area graphene active region with interdigitated electrodes that are connected to a log-periodic antenna to improve the long-wavelength collection efficiency, and a silicon carbide substrate that is transparent throughout the visible regime. The detector exhibits a noise-equivalent power of approximately 100 µW·Hz–½ and is characterized at wavelengths from 780 nm to 500 µm

Light-Induced Switching of Tunable Single-Molecule Junctions

A major goal of molecular electronics is the development and implementation of devices such as single-molecular switches. Here, measurements are presented that show the controlled in situ switching of diarylethene molecules from their nonconductive to conductive state in contact to gold nanoelectrodes via controlled light irradiation. Both the conductance and the quantum yield for switching of these molecules are within a range making the molecules suitable for actual devices. The conductance of the molecular junctions in the opened and closed states is characterized and the molecular level E 0, which dominates the current transport in the closed state, and its level broadening Γ are identified. The obtained results show a clear light-induced ring forming isomerization of the single-molecule junctions. Electron withdrawing side-groups lead to a reduction of conductance, but do not influence the efficiency of the switching mechanism. Quantum chemical calculations of the light-induced switching processes correlate these observations with the fundamentally different lowlying electronic states of the opened and closed forms and their comparably small modification by electron-withdrawing substituents. This full characterization of a molecular switch operated in a molecular junction is an important step toward the development of real molecular electronics devices

Translational PK–PD modelling of molecular target modulation for the AMPA receptor positive allosteric modulator Org 26576

Introduction The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor potentiator Org 26576 represents an interesting pharmacological tool to evaluate the utility of glutamatergic enhancement towards the treatment of psychiatric disorders. In this study, a rat–human translational pharmacokinetic–pharmacodynamic (PK–PD) model of AMPA receptor modulation was used to predict human target engagement and inform dose selection in efficacy clinical trials. Methods Modelling and simulation was applied to rat plasma and cerebrospinal fluid (CSF) pharmacokinetic and pharmacodynamic measurements to identify a target concentration (EC80) for AMPA receptor modulation. Human plasma pharmacokinetics was determined from 33 healthy volunteers and eight major depressive disorder patients. From four out of these eight patients, CSF PK was also determined. Simulations of human CSF levels were performed for several doses of Org 26576. Results Org 26576 (0.1–10 mg/kg, i.v.) potentiated rat hippocampal AMPA receptor responses in an exposure-dependant manner. The rat plasma and CSF PK data were fitted by one-compartment model each. The rat CSF PK–PD model yielded an EC80 value of 593 ng/ml (90% confidence interval 406.8, 1,264.1). The human plasma and CSF PK data were simultaneously well described by a two-compartment model. Simulations showed that in humans at 100 mg QD, CSF levels of Org 26576 would exceed the EC80 target concentration for about 2 h and that 400 mg BID would engage AMPA receptors for 24 h. Conclusion The modelling approach provided useful insight on the likely human dose–molecular target engagement relationship for Org 26576. Based on the current analysis, 100 and 400 mg BID would be suitable to provide ‘phasic’ and ‘continuous’ AMPA receptor engagement, respectively

Bayesian pharmacokinetics of lithium after an acute self-intoxication and subsequent haemodialysis: a case report

We report a case of a 39-year-old male with bipolar affective disorder who was admitted to hospital with an intentional acute lithium intoxication resulting in renal insufficiency. The patient had previously been treated with lithium, risperidone, fluoxetine and lorazepam, and successfully titrated to lithium levels of 0.7 mmol/l. After overdosing, the lithium level was 5.89 mmol/l and haemodialysis was initiated. A full pharmacokinetic time profile of lithium was obtained. After successful haemodialysis treatment, lithium levels recovered below toxic levels of 1.5 mmol/l in 53 hr. Without intervention non-toxic levels were not expected to have been reached within 6 days, based on computer simulation of predialysis levels. The patient was discharged 6 days after admission without residual symptoms. It was concluded that the lithium intoxication resulted from a combination of lithium overdose and subsequent renal insufficiency due to the overdose. A possible fluoxetine-risperidone interaction was not considered clinically apparen