Dynamics of synaptic damage in severe traumatic brain injury revealed by cerebrospinal fluid SNAP-25 and VILIP-1.

BACKGROUND: Biomarkers of neuronal, glial cells and inflammation in traumatic brain injury (TBI) are available but they do not specifically reflect the damage to synapses, which represent the bulk volume of the brain. Experimental models have demonstrated extensive involvement of synapses in acute TBI, but biomarkers of synaptic damage in human patients have not been explored. METHODS: Single-molecule array assays were used to measure synaptosomal-associated protein-25 (SNAP-25) and visinin-like protein 1 (VILIP-1) (along with neurofilament light chain (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillar acidic protein (GFAP), interleukin-6 (IL-6) and interleukin-8 (IL-8)) in ventricular cerebrospinal fluid (CSF) samples longitudinally acquired during the intensive care unit (ICU) stay of 42 patients with severe TBI or 22 uninjured controls. RESULTS: CSF levels of SNAP-25 and VILIP-1 are strongly elevated early after severe TBI and decline in the first few days. SNAP-25 and VILIP-1 correlate with inflammatory markers at two distinct timepoints (around D1 and then again at D5) in follow-up. SNAP-25 and VILIP-1 on the day-of-injury have better sensitivity and specificity for unfavourable outcome at 6 months than NFL, UCH-L1 or GFAP. Later elevation of SNAP-25 was associated with poorer outcome. CONCLUSION: Synaptic damage markers are acutely elevated in severe TBI and predict long-term outcomes, as well as, or better than, markers of neuroaxonal injury. Synaptic damage correlates with initial injury and with a later phase of secondary inflammatory injury.

Visinin-like protein 1 levels in blood and CSF as emerging markers for Alzheimer's and other neurodegenerative diseases.

BACKGROUND: Visinin-like protein 1 (VILIP-1) belongs to the group of emerging biomarkers with the potential to support the early diagnosis of Alzheimer's disease (AD). However, studies investigating the differential diagnostic potential in cerebrospinal fluid (CSF) are rare and are not available for blood. METHODS: We set up a novel, sensitive single molecule array (Simoa) assay for the detection of VILIP-1 in CSF and serum. In total, paired CSF and serum samples from 234 patients were investigated: 73 AD, 18 behavioral variant frontotemporal dementia (bvFTD), 26 parkinsonian syndromes, 20 amyotrophic lateral sclerosis (ALS), 22 Creutzfeldt-Jakob disease (CJD), and 75 non-neurodegenerative control (Con) patients. The differential diagnostic potential of CSF and serum VILIP-1 was assessed using the receiver operating characteristic curve analysis and findings were compared to core AD biomarkers. RESULTS: CSF and serum VILIP-1 levels correlated weakly (r=0.32 (CI: 0.20-0.43), p<0.0001). VILIP-1 concentrations in CSF and serum were elevated in AD compared to Con (p<0.0001 and p<0.01) and CJD (p<0.0001 for CSF and serum), and an increase in CSF was observed already in early AD stages (p<0.0001). In the discrimination of AD versus Con, we could demonstrate a strong diagnostic potential for CSF VILIP-1 alone (area under the curve (AUC): 0.87), CSF VILIP-1/CSF Abeta 1-42 (AUC: 0.98), and serum VILIP-1/CSF Abeta 1-42 ratio (AUC: 0.89). CONCLUSIONS: We here report on the successful establishment of a novel Simoa assay for VILIP-1 and illustrate the potential of CSF and serum VILIP-1 in the differential diagnosis of AD with highest levels in CJD.

A gated quantum dot strongly coupled to an optical microcavity.

The strong-coupling regime of cavity quantum electrodynamics (QED) represents the light-matter interaction at the fully quantum level. Adding a single photon shifts the resonance frequencies-a profound nonlinearity. Cavity QED is a test bed for quantum optics1-3 and the basis of photon-photon and atom-atom entangling gates4,5. At microwave frequencies, cavity QED has had a transformative effect6, enabling qubit readout and qubit couplings in superconducting circuits. At optical frequencies, the gates are potentially much faster; the photons can propagate over long distances and can be easily detected. Following pioneering work on single atoms1-3,7, solid-state implementations using semiconductor quantum dots are emerging8-15. However, miniaturizing semiconductor cavities without introducing charge noise and scattering losses remains a challenge. Here we present a gated, ultralow-loss, frequency-tunable microcavity device. The gates allow both the quantum dot charge and its resonance frequency to be controlled electrically. Furthermore, cavity feeding10,11,13-17, the observation of the bare-cavity mode even at the quantum dot-cavity resonance, is eliminated. Even inside the microcavity, the quantum dot has a linewidth close to the radiative limit. In addition to a very pronounced avoided crossing in the spectral domain, we observe a clear coherent exchange of a single energy quantum between the 'atom' (the quantum dot) and the cavity in the time domain (vacuum Rabi oscillations), whereas decoherence arises mainly via the atom and photon loss channels. This coherence is exploited to probe the transitions between the singly and doubly excited photon-atom system using photon-statistics spectroscopy18. The work establishes a route to the development of semiconductor-based quantum photonics, such as single-photon sources and photon-photon gates.

Advanced Fabrication of Single-Crystal Diamond Membranes for Quantum Technologies.

Many promising applications of single crystal diamond and its color centers as sensor platform and in photonics require free-standing membranes with a thickness ranging from several micrometers to the few 100 nm range. In this work, we present an approach to conveniently fabricate such thin membranes with up to about one millimeter in size. We use commercially available diamond plates (thickness 50 µ m) in an inductively coupled reactive ion etching process which is based on argon, oxygen and SF 6 . We thus avoid using toxic, corrosive feed gases and add an alternative to previously presented recipes involving chlorine-based etching steps. Our membranes are smooth (RMS roughness <1 nm) and show moderate thickness variation (central part: <1 µ m over ≈200 × 200 µ m 2 ). Due to an improved etch mask geometry, our membranes stay reliably attached to the diamond plate in our chlorine-based as well as SF 6 -based processes. Our results thus open the route towards higher reliability in diamond device fabrication and up-scaling.

Increasing organic solar cell efficiency with polymer interlayers.

We demonstrate how organic solar cell efficiency can be increased by introducing a pure polymer interlayer between the PEDOT:PSS layer and the polymer:fullerene blend. We observe an increase in device efficiency with three different material systems over a number of devices. Using both electrical characterization and numerical modeling we show that the increase in efficiency is caused by optical absorption in the pure polymer layer and hence efficient charge separation at the polymer bulkheterojunction interface.