Wavelength-Sensitive Superconducting Single-Photon Detectors on Thin Film Lithium Niobate Waveguides.

Lithium niobate, because of its nonlinear and electro-optical properties, is one of the materials of choice for photonic applications. The development of nanostructuring capabilities of thin film lithium niobate (TFLN) permits fabrication of small footprint, low-loss optical circuits. With the recent implementation of on-chip single-photon detectors, this architecture is among the most promising for realizing on-chip quantum optics experiments.

Biomarker Discovery in Rare Malignancies: Development of a miRNA Signature for RDEB-cSCC.

Machine learning has been proven to be a powerful tool in the identification of diagnostic tumor biomarkers but is often impeded in rare cancers due to small patient numbers. In patients suffering from recessive dystrophic epidermolysis bullosa (RDEB), early-in-life development of particularly aggressive cutaneous squamous-cell carcinomas (cSCCs) represents a major threat and timely detection is crucial to facilitate prompt tumor excision. As miRNAs have been shown to hold great potential as liquid biopsy markers, we characterized miRNA signatures derived from cultured primary cells specific for the potential detection of tumors in RDEB patients.

5'RNA -Splicing Repair of Mutant Transcripts in Epidermolysis Bullosa.

Mutations within the gene underlie the inherited recessive subtype of the blistering skin disease dystrophic epidermolysis bullosa (RDEB). Although gene replacement approaches for genodermatoses are clinically advanced, their implementation for RDEB is challenging and requires endogenous regulation of transgene expression. Thus, we are using spliceosome-mediated RNA -splicing (SMaRT) to repair mutations in at the mRNA level.

Strain-Controlled Quantum Dot Fine Structure for Entangled Photon Generation at 1550 nm.

Entangled photon generation at 1550 nm in the telecom C-band is of critical importance as it enables the realization of quantum communication protocols over long distance using deployed telecommunication infrastructure. InAs epitaxial quantum dots have recently enabled on-demand generation of entangled photons in this wavelength range. However, time-dependent state evolution, caused by the fine-structure splitting, currently limits the fidelity to a specific entangled state.

On-Demand Generation of Entangled Photon Pairs in the Telecom C-Band with InAs Quantum Dots.

Entangled photons are an integral part in quantum optics experiments and a key resource in quantum imaging, quantum communication, and photonic quantum information processing. Making this resource available on-demand has been an ongoing scientific challenge with enormous progress in recent years. Of particular interest is the potential to transmit quantum information over long distances, making photons the only reliable flying qubit.

Personalized Development of Antisense Oligonucleotides for Exon Skipping Restores Type XVII Collagen Expression in Junctional Epidermolysis Bullosa.

Intermediate junctional epidermolysis bullosa caused by mutations in the gene is characterized by the frequent development of blisters and erosions on the skin and mucous membranes. The rarity of the disease and the heterogeneity of the underlying mutations renders therapy developments challenging. However, the high number of short in-frame exons facilitates the use of antisense oligonucleotides (AON) to restore collagen 17 (C17) expression by inducing exon skipping.

Crux of Using the Cascaded Emission of a Three-Level Quantum Ladder System to Generate Indistinguishable Photons.

We investigate the degree of indistinguishability of cascaded photons emitted from a three-level quantum ladder system; in our case the biexciton-exciton cascade of semiconductor quantum dots. For the three-level quantum ladder system we theoretically demonstrate that the indistinguishability is inherently limited for both emitted photons and determined by the ratio of the lifetimes of the excited and intermediate states. We experimentally confirm this finding by comparing the quantum interference visibility of noncascaded emission and cascaded emission from the same semiconductor quantum dot.

Origin of Antibunching in Resonance Fluorescence.

Resonance fluorescence has played a major role in quantum optics with predictions and later experimental confirmation of nonclassical features of its emitted light such as antibunching or squeezing. In the Rayleigh regime where most of the light originates from the scattering of photons with subnatural linewidth, antibunching would appear to coexist with sharp spectral lines. Here, we demonstrate that this simultaneous observation of subnatural linewidth and antibunching is not possible with simple resonant excitation.

Proximitized Josephson junctions in highly-doped InAs nanowires robust to optical illumination.

We have studied the effects of optical-frequency light on proximitized InAs/Al Josephson junctions based on highly n-doped InAs nanowires at varying incident photon flux and at three different photon wavelengths. The experimentally obtained IV curves were modeled using a resistively shunted junction model which takes scattering at the contact interfaces into account. Despite the fact that the InAs weak link is photosensitive, the Josephson junctions were found to be surprisingly robust, interacting with the incident radiation only through heating, whereas above the critical current our devices showed non-thermal effects resulting from photon exposure.

A cancer stem cell-like phenotype is associated with miR-10b expression in aggressive squamous cell carcinomas.

Background: Cutaneous squamous cell carcinomas (cSCC) are the primary cause of premature deaths in patients suffering from the rare skin-fragility disorder recessive dystrophic epidermolysis bullosa (RDEB), which is in marked contrast to the rarely metastasizing nature of these carcinomas in the general population. This remarkable difference is attributed to the frequent development of chronic wounds caused by impaired skin integrity. However, the specific molecular and cellular changes to malignancy, and whether there are common players in different types of aggressive cSCCs, remain relatively undefined.

GaAs Quantum Dot in a Parabolic Microcavity Tuned to Rb D.

We develop a structure to efficiently extract photons emitted by a GaAs quantum dot tuned to rubidium. For this, we employ a broadband microcavity with a curved gold backside mirror that we fabricate by a combination of photoresist reflow, dry reactive ion etching in an inductively coupled plasma, and selective wet chemical etching. Precise reflow and etching control allows us to achieve a parabolic backside mirror with a short focal distance of 265 nm.

Optimizing the stoichiometry of ultrathin NbTiN films for high-performance superconducting nanowire single-photon detectors.

The requirements in quantum optics experiments for high single-photon detection efficiency, low timing jitter, low dark count rate and short dead time have been fulfilled with the development of superconducting nanowire single-photon detectors. Although they offer a detection efficiency above 90%, achieving a high time resolution in devices made of amorphous materials is a challenge, particularly at temperatures above 0.8 K.

Gene Editing-Mediated Disruption of Epidermolytic Ichthyosis-Associated KRT10 Alleles Restores Filament Stability in Keratinocytes.

Epidermolytic ichthyosis is a skin fragility disorder caused by dominant-negative mutations in KRT1 or KRT10. No definitive restorative therapies exist that target these genetic faults. Gene editing can be used to efficiently introduce frameshift mutations to inactivate mutant genes.

Resonance Fluorescence of GaAs Quantum Dots with Near-Unity Photon Indistinguishability.

Photonic quantum technologies call for scalable quantum light sources that can be integrated, while providing the end user with single and entangled photons on demand. One promising candidate is strain free GaAs/AlGaAs quantum dots obtained by aluminum droplet etching. Such quantum dots exhibit ultra low multi-photon probability and an unprecedented degree of photon pair entanglement.

Strain-Tunable Quantum Integrated Photonics.

Semiconductor quantum dots are crucial parts of the photonic quantum technology toolbox because they show excellent single-photon emission properties in addition to their potential as solid-state qubits. Recently, there has been an increasing effort to deterministically integrate single semiconductor quantum dots into complex photonic circuits. Despite rapid progress in the field, it remains challenging to manipulate the optical properties of waveguide-integrated quantum emitters in a deterministic, reversible, and nonintrusive manner.

Basal pharmacokinetic parameters of topically applied diacerein in pediatric patients with generalized severe epidermolysis bullosa simplex.

Generalized severe epidermolysis bullosa simplex (EBS-gen sev) is caused by mutations within either the KRT5 or KRT14 gene, phenotypically resulting in blistering and wounding of the skin and mucous membranes after minor mechanical friction. In a clinical phase 2/3 trial, diacerein has recently been shown to significantly reduce blister numbers upon topical application. In this study we addressed basic pharmacokinetic parameters of locally applied diacerein in vitro and in vivo.

Diacerein orphan drug development for epidermolysis bullosa simplex: A phase 2/3 randomized, placebo-controlled, double-blind clinical trial.

Background: Epidermolysis bullosa simplex (EBS) is a rare genetic, blistering skin disease for which there is no cure. Treatments that address the pathophysiology of EBS are needed.

Objective: Compare the impact of 1% diacerein cream with placebo in reducing the number of blisters in EBS.

Threonine 150 Phosphorylation of Keratin 5 Is Linked to Epidermolysis Bullosa Simplex and Regulates Filament Assembly and Cell Viability.

A characteristic feature of the skin blistering disease epidermolysis bullosa simplex is keratin filament (KF) network collapse caused by aggregation of the basal epidermal keratin type II (KtyII) K5 and its type I partner keratin 14 (K14). Here, we examine the role of keratin phosphorylation in KF network rearrangement and cellular functions. We detect phosphorylation of the K5 head domain residue T150 in cytoplasmic epidermolysis bullosa simplex granules containing R125C K14 mutants.

Cut and Paste: Efficient Homology-Directed Repair of a Dominant Negative KRT14 Mutation via CRISPR/Cas9 Nickases.

With the ability to induce rapid and efficient repair of disease-causing mutations, CRISPR/Cas9 technology is ideally suited for gene therapy approaches for recessively and dominantly inherited monogenic disorders. In this study, we have corrected a causal hotspot mutation in exon 6 of the keratin 14 gene (KRT14) that results in generalized severe epidermolysis bullosa simplex (EBS-gen sev), using a double-nicking strategy targeting intron 7, followed by homology-directed repair (HDR). Co-delivery into EBS keratinocytes of a Cas9 D10A nickase (Cas9n), a predicted single guide RNA pair specific for intron 7, and a minicircle donor vector harboring the homology donor template resulted in a recombination efficiency of >30% and correction of the mutant KRT14 allele.

Electrically-Pumped Wavelength-Tunable GaAs Quantum Dots Interfaced with Rubidium Atoms.

We demonstrate the first wavelength-tunable electrically pumped source of nonclassical light that can emit photons with wavelength in resonance with the D transitions of Rb atoms. The device is fabricated by integrating a novel GaAs single-quantum-dot light-emitting diode (LED) onto a piezoelectric actuator. By feeding the emitted photons into a 75 mm long cell containing warm Rb vapor, we observe slow-light with a temporal delay of up to 3.

Comparison of different bonding techniques for efficient strain transfer using piezoelectric actuators.

In this paper, strain transfer efficiencies from a single crystalline piezoelectric lead magnesium niobate-lead titanate substrate to a GaAs semiconductor membrane bonded on top are investigated using state-of-the-art x-ray diffraction (XRD) techniques and finite-element-method (FEM) simulations. Two different bonding techniques are studied, namely, gold-thermo-compression and polymer-based SU8 bonding. Our results show a much higher strain-transfer for the "soft" SU8 bonding in comparison to the "hard" bonding via gold-thermo-compression.

MMP-9 and CXCL8/IL-8 are potential therapeutic targets in epidermolysis bullosa simplex.

Epidermolysis bullosa refers to a group of genodermatoses that affects the integrity of epithelial layers, phenotypically resulting in severe skin blistering. Dowling-Meara, the major subtype of epidermolysis bullosa simplex, is inherited in an autosomal dominant manner and can be caused by mutations in either the keratin-5 (K5) or the keratin-14 (K14) gene. Currently, no therapeutic approach is known, and the main objective of this study was to identify novel therapeutic targets.

K14 mRNA reprogramming for dominant epidermolysis bullosa simplex.

The major challenge to a successful gene therapy of autosomal dominant genetic diseases is a highly efficient and specific knock-down or repair of the disease-causing allele. In epidermolysis bullosa simplex-type Dowling-Meara (EBS-DM), a single amino acid exchange in exon 1 of the keratin 14 gene (K14) triggers a severe skin phenotype, characterized by blistering of the skin and mucous membranes after minor trauma. We chose spliceosome-mediated RNA trans-splicing to specifically replace exons 1-7 of the K14 gene.