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We present a detailed analysis of the physics governing the collection efficiency and the Purcell enhancement of the nanopost single-photon source. We show that a standard single-mode Fabry-P\'erot model is insufficient to describe the device performance, which benefits significantly from scattering from the fundamental mode to radiation modes. We show how the scattering mechanism decouples the collection efficiency from the Purcell enhancement, such that maximum collection efficiency is obtained off-resonance. Finally, we discuss how this scattering mechanism can be beneficial for future single-photon source designs.

Recent trials have reported the ability of triheptanoin to improve clinical outcomes for the severe symptoms associated with long-chain fatty acid oxidation disorders, including very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. However, the milder myopathic symptoms are still challenging to treat satisfactorily. Myopathic pathogenesis is multifactorial, but oxidative stress is an important component. We have previously shown that metabolic stress increases the oxidative burden in VLCAD-deficient cell lines and can deplete the antioxidant glutathione (GSH). We investigated whether medium-chain fatty acids provide protection against GSH depletion during metabolic stress in VLCAD-deficient fibroblasts. To investigate the effect of differences in anaplerotic capacity, we included both even-(octanoate) and odd-numbered (heptanoate) medium-chain fatty acids. Overall, we show that modulation of the concentration of medium-chain fatty acids in culture media affects levels of GSH retained during metabolic stress in VLCAD-deficient cell lines but not in controls. Lowered glutamine concentration in the culture media during metabolic stress led to GSH depletion and decreased viability in VLCAD deficient cells, which could be rescued by both heptanoate and octanoate in a dose-dependent manner. Unlike GSH levels, the levels of total thiols increased after metabolic stress exposure, the size of this increase was not affected by differences in cell culture medium concentrations of glutamine, heptanoate or octanoate. Addition of a PPAR agonist further exacerbated stress-related GSH-depletion and viability loss, requiring higher concentrations of fatty acids to restore GSH levels and cell viability. Both odd- and even-numbered medium-chain fatty acids efficiently protect VLCADdeficient cells against metabolic stress-induced antioxidant depletion.

Single-photon sources with near-unity efficiency and indistinguishability play a major role in the development of quantum technologies. However, on-demand excitation of the emitter imposes substantial limitations to the source performance. Here, we show that coherent two-color pumping allows for population inversion arbitrarily close to unity in bulk quantum dots thanks to a decoupling effect between the emitter and its phonon bath. Driving a micropillar single-photon source with this scheme, we calculate very high photon emission into the cavity mode (0.95 photons per pulse) together with excellent indistinguishability (0.975) in a realistic configuration, thereby removing the limitations imposed by the excitation scheme on single-photon source engineering., Comment: Replacement of a previous version entitled "Phonon-decoupled di-chromatic pumping scheme for highly efficient and indistinguishable single-photon sources"

We theoretically investigate the potential of the extreme mode-confinement waveguides for single-photon sources. Confining light far below the diffraction limit in a V-groove GaAs-on-insulator waveguide, we enhance the Purcell factor by a factor of eight.

Historically, the analyses used for newborn screening (NBS) were biochemical, but increasingly, molecular genetic analyses are being introduced in the workflow. We describe the application of molecular genetic analyses in the Danish NBS programme and show that second-tier molecular genetic testing is useful to reduce the false positive rate while simultaneously providing information about the precise molecular genetic variant and thus informing therapeutic strategy and easing providing information to parents. When molecular genetic analyses are applied as second-tier testing, valuable functional data from biochemical methods are available and in our view, such targeted NGS technology should be implemented when possible in the NBS workflow. First-tier NGS technology may be a promising future possibility for disorders without a reliable biomarker and as a general approach to increase the adaptability of NBS for a broader range of genetic diseases, which is important in the current landscape of quickly evolving new therapeutic possibilities. However, studies on feasibility, sensitivity, and specificity are needed as well as more insight into what views the general population has towards using genetic analyses in NBS. This may be sensitive to some and could have potentially negative consequences for the NBS programme.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous, debilitating, and complex disease. Along with disabling fatigue, ME/CFS presents an array of other core symptoms, including autonomic nervous system (ANS) dysfunction, sustained inflammation, altered energy metabolism, and mitochondrial dysfunction. Here, we evaluated patients’ symptomatology and the mitochondrial metabolic parameters in peripheral blood mononuclear cells (PBMCs) and plasma from a clinically well-characterised cohort of six ME/CFS patients compared to age- and gender-matched controls. We performed a comprehensive cellular assessment using bioenergetics (extracellular flux analysis) and protein profiles (quantitative mass spectrometry-based proteomics) together with self-reported symptom measures of fatigue, ANS dysfunction, and overall physical and mental well-being. This ME/CFS cohort presented with severe fatigue, which correlated with the severity of ANS dysfunction and overall physical well-being. PBMCs from ME/CFS patients showed significantly lower mitochondrial coupling efficiency. They exhibited proteome alterations, including altered mitochondrial metabolism, centred on pyruvate dehydrogenase and coenzyme A metabolism, leading to a decreased capacity to provide adequate intracellular ATP levels. Overall, these results indicate that PBMCs from ME/CFS patients have a decreased ability to fulfill their cellular energy demands.

Ethylmalonic acid (EMA) is a major and potentially cytotoxic metabolite associated with short-chain acyl-CoA dehydrogenase (SCAD) deficiency, a condition whose status as a disease is uncertain. Unexplained high EMA is observed in some individuals with complex neurological symptoms, who carry the SCAD gene (ACADS) variants, c.625G>A and c.511C>T. The variants have a high allele frequency in the general population, but are significantly overrepresented in individuals with elevated EMA. This has led to the idea that these variants need to be associated with variants in other genes to cause hyperexcretion of ethylmalonic acid and possibly a diseased state. Ethylmalonyl-CoA decarboxylase (ECHDC1) has been described and characterized as an EMA metabolite repair enzyme, however, its clinical relevance has never been investigated. In this study, we sequenced the ECHDC1 gene (ECHDC1) in 82 individuals, who were reported with unexplained high EMA levels due to the presence of the common ACADS variants only. Three individuals with ACADS c.625G>A variants were found to be heterozygous for ECHDC1 loss-of-function variants. Knockdown experiments of ECHDC1, in healthy human cells with different ACADS c.625G>A genotypes, showed that ECHDC1 haploinsufficiency and homozygosity for the ACADS c.625G>A variant had a synergistic effect on cellular EMA excretion. This study reports the first cases of ECHDC1 gene defects in humans and suggests that ECHDC1 may be involved in elevated EMA excretion in only a small group of individuals with the common ACADS variants. However, a direct link between ECHDC1/ACADS deficiency, EMA and disease could not be proven.

We introduce a scalable photonic platform that enables efficient generation of entangled photon pairs from a semiconductor quantum dot. Our system, which is based on a self-aligned quantum dot- micro-cavity structure, erases the need for complex steps of lithography and nanofabrication. We experimentally show collection efficiency of 0.17 combined with a Purcell enhancement of up to 1.7. We harness the potential of our device to generate photon pairs entangled in time bin, reaching a fidelity of 0.84(5) with the maximally entangled state. The achieved pair collection efficiency is 4 times larger than the state-of-the art for this application. The device, which theoretically supports pair extraction efficiencies of nearly 0.5 is a promising candidate for the implementation of bright sources of time-bin, polarization- and hyper entangled photon pairs in a straightforward manner.

We report on a simple nanopost single-photon source geometry based on a quantum dot in a mesa placed on a metal mirror. A remarkably large Purcell enhancement of 9 for the smallest structure is obtained.

We present a numerical investigation of the performance of the micropillar cavity single-photon source featuring an elliptical cross section. While ellipticity serves to establish polarization control of the emitted photons, it introduces a trade-off due to reduced coupling to a Gaussian profile in the far field and the need for significantly increased pumping power when a resonant excitation pumping scheme is implemented. Starting from a circular micropillar, we identify optimum geometrical parameters leading to a maximum polarized coupling efficiency of 0.90 to a Gaussian profile in the far field combined with a modest relative increase in the pump power of 16 dB.

We demonstrate high single-photon purity from an InAs/InP QD sources on Si operating at 1.55 µm. The single-photon extraction efficiency reaches up to 10% using a simple mesa structure.

BACKGROUND: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD) is the most frequent fatty acid oxidation (FAO) defect in humans. MCAD-deficient fibroblasts are more resistant to oxidative stress-induced cell death than other FAO defects and healthy controls.METHODS: Herein we investigate the antioxidant response and mitochondrial function in fibroblasts from MCAD-deficient patients (c.985 A>G/c.985 A>G) and healthy controls.RESULTS: MCAD-deficient fibroblasts showed increased level of mitochondrial superoxide, while lipids were less oxidatively damaged, and higher amount of manganese superoxide dismutase were detected compared to healthy controls, showing forceful antioxidant system in MCADD. We showed increased maximal respiration and reserve capacity in MCAD-deficient fibroblasts compared to controls, indicating more capacity through the tricarboxylic acid (TCA) cycle and subsequently respiratory chain. This led us to study the pyruvate dehydrogenase complex (PDC), the key enzyme in the glycolysis releasing acetyl-CoA to the TCA cycle. MCAD-deficient fibroblasts displayed not only significantly increased PDC but also increased lipoylated PDC protein levels compared to healthy controls.CONCLUSIONS: Based on these findings, we raise the interesting hypothesis that increased PDC-bound lipoic acid, synthesized from accumulated octanoic acid in MCADD, may affect the cellular antioxidant pool in MCADD.

In this paper, we introduce a novel quantum photonic device, which we term photonic Bier-Glass cavity. We discuss its fabrication and functionality, which is based on the coupling of integrated In(Ga)As quantum dots to a broadband photonic cavity resonance. By design, the device architecture uniquely combines the Purcell enhancement of a photonic micropillar structure with broadband photonic mode shaping of a vertical, tapered waveguide, making it an interesting candidate to enable the efficient extraction of entangled photon pairs. We detail the epitaxial growth of the heterostructure and the necessary lithography steps to approach a GaAs-based photonic device with a height exceeding 15 $\mu$m, supported on a pedestal that can be as thin as 20 nm. We present an optical characterization, which confirms the presence of broadband optical resonances, in conjunction with amplified spontaneous emission of single photons., Comment: 14 pages, 9 figures

We present a numerical investigation of the performance of the micropillar cavity single-photon source in terms of collection efficiency and indistinguishability of the emitted photons in the presence of non-Markovian phonon-induced decoherence. We analyze the physics governing the efficiency using a single-mode model, and we optimize efficiency $\ensuremath{\varepsilon}$ and the indistinguishability $\ensuremath{\eta}$ on an equal footing by computing $\ensuremath{\varepsilon}\ensuremath{\eta}$ as function of the micropillar design parameters. We show that $\ensuremath{\varepsilon}\ensuremath{\eta}$ is limited to $\ensuremath{\sim}0.96$ for the ideal geometry due to an inherent tradeoff between efficiency and indistinguishability. Finally, we subsequently consider the influence of realistic fabrication imperfections and Markovian pure dephasing noise on the performance.

As an essential vitamin, the role of riboflavin in human diet and health is increasingly being highlighted. Insufficient dietary intake of riboflavin is often reported in nutritional surveys and population studies, even in non-developing countries with abundant sources of riboflavin-rich dietary products. A latent subclinical riboflavin deficiency can result in a significant clinical phenotype when combined with inborn genetic disturbances or environmental and physiological factors like infections, exercise, diet, aging and pregnancy. Riboflavin, and more importantly its derivatives, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), play a crucial role in essential cellular processes including mitochondrial energy metabolism, stress responses, vitamin and cofactor biogenesis, where they function as cofactors to ensure the catalytic activity and folding/stability of flavoenzymes. Numerous inborn errors of flavin metabolism and flavoenzyme function have been described, and supplementation with riboflavin has in many cases been shown to be lifesaving or to mitigate symptoms. This review discusses the environmental, physiological and genetic factors that affect cellular riboflavin status. We describe the crucial role of riboflavin for general human health, and the clear benefits of riboflavin treatment in patients with inborn errors of metabolism.

Tapered nanowire antennas have emerged as a versatile solid-state platform for quantum optics. These broadband photonic structures efficiently funnel the spontaneous emission of an embedded quantum dot into a directive free-space beam. They find application in the realization of bright sources of quantum light, and enable the implementation of giant optical non-linearities, at the single-photon level. In this work, we discuss advances aiming at further optimizing this light-matter interface. In particular, recent measurements revealed that the thermal excitation of a single nanowire vibration mode can have a sizeable influence on the quantum dot optical linewidth. This motivated a comprehensive theoretical analysis, which shows that the thermally-driven vibrations of the nanowire have a major impact on the quantum dot light emission spectrum. Even at liquid helium temperatures, these prevent the emission of indistinguishable photons. To overcome this intrinsic limitation, we propose several designs that restore photon indistinguishability thanks to a specific engineering of the mechanical properties of the nanowire. We anticipate that such a mechanical optimization will also play a key role in the development of other high-performance light-matter interfaces based on nanostructures.

Epitaxially grown self-assembled quantum dots (QDs) are promising candidates for an efficient single-photon generation. In order to maximize the number of photons extracted from the device, QDs are frequently embedded into photonic structures such as micro-cavities. Once the QD is positioned inside an optical cavity, the Purcell effect ensures that light is emitted predominantly into the cavity mode. In this contribution, we demonstrate results of emission tuning of QDs inserted in micro-cavities. A sample containing an InAs/GaAs QDs embedded in a planar cavity based on Bragg reflectors has been integrated onto the PMN-PT piezo crystal. Subsequently, micro-cavities have been fabricated by electron-beam lithography and reactive ion etching. The application of external stress produces linear shifts of QDs emission which could be tuned into the resonance with fundamental cavity mode and allow enhancement of QD emission due to the Purcell effect.

True monomode operation and polarization control capability of elliptical nanowires leads to the need of efficient solvers for open elliptical nanophotonic structures. In this contribution, a full-wave vectorial modal method for open boundary elliptical geometries is presented for designing quantum-dot elliptical nanowire structures. The method exploits symmetry properties, provides insight into the physical behavior of the system giving direct access to propagation constants and mode profiles, which will be used in the efficiency calculations of the single-photon sources.

Newborn screening is a public health programme for early diagnosis of treatable diseases.The subjects included were newborns born 2002-2019. Expanded newborn screening (eNBS) for metabolic diseases was introduced as a pilot project from 2002 to 2009, followed by routine screening with informed dissent. A total of 967,780 newborns were screened; 82,930 were unscreened. Furthermore, a historic cohort of clinically diagnosed children born in the 1992-2001 period was included. Children in the unscreened and historic cohorts were evaluated for the same diseases as were the screened children. Dried blood spot samples were collected locally and sent for screening analyses. We recorded newborns with true and false positive results as well as false negative results and their clinical signs at screening and at the last follow-up.A total of 603 samples were screen positive: 354 false positives and 249 true positives (222 newborns and 27 mothers). The positive predictive value (PPV) was 41% for the entire screening period; 62% for 2018. The false positive rate (FPR) was 0.036% overall; 0.024% for 2018. The overall prevalence of diseases was 1:3,900; in the historic cohort, the prevalence of the same diseases was 1:8,300; 7.3% had symptoms at the time of screening. At follow-up, 93% of the children had no clinically significant sequelae. Among 82,930 unscreened newborns, 27 (1:3,000) had eNBS panel diseases, some with severe manifestations.This update of eNBS in Denmark confirms that eNBS is a successful preventive public health programme. Early treatment in a latent phase of disease is effective and screening should be extended to other diseases not currently in the programme.The work was supported by grants from The Ronald McDonald Børnefond, Danmarks Sundhedsfond, Direktør Ib Henriksens Fond, Ragnhild Ibsens Legat til Medicinsk Forskning, Gerda og Aage Haenschs Fond, Dronning Louises Børnehospitals Forskningsfond, Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis's Legat, Aase and Ejnar Danielsens Fond, Oda og Hans Svenningsens Fond, Fonden af 1870, Vanførefonden, Fonden til Lægevidenskabens Fremme and Danish Medical Research Council.not relevant.

The preparation of single-and entangled photon pairs (EPPs) is a critical component in the field of quantum information networks. Quantum Dots (QDs)embedded in micro-cavities are a promising realization of such non-classical light However, in most implementations of coupled QD-cavities, the spontaneous emission is only enhanced within a small bandwidth, which compromises the efficient extraction of photon pairs. Here, we discuss the fabrication and functionality of a photonic Bier-Glas cavity. By design, this device architecture combines the Purcell enhancement of a photonic micropillar structure with broadband photonic mode shaping of a vertical, tapered waveguide [1]: The low Q-factor microcavity supports broadband optical resonances, and therefore has the potential to can support the efficient extraction of entangled photon pairs. The cavity, which is characterized by a small mode volume, also promises significant spontaneous emission enhancement of the quantum dots due to the Purcell effect. The combination of the tapered waveguide puts extraction efficiencies larger than ε = 0,70 within reach. Our device is based on a MBE grown GaAs/AlGaAs heterostructure containing a low density layer of InAs QDs grown with the partial capping and annealing technique. Careful optimization of the subsequent reactive ion etching step allows us to implement its characteristic Bier-Glas shape. Initial optical characterization verifies the presence of optical resonances, as well as pronounced, bright QD emission signals.

Semiconductor quantum dots are inevitably coupled to the vibrational modes of their host lattice. This interaction reduces the efficiency and the indistinguishability of single-photons emitted from semiconductor quantum dots. While the adverse effects of phonons can be significantly reduced by embedding the quantum dot in a photonic cavity, phonon-induced signatures in the emitted photons cannot be completely suppressed and constitute a fundamental limit to the ultimate performance of single-photon sources based on quantum dots. In this paper, we present a self-consistent theoretical description of phonon effects in such sources and describe their influence on the figures of merit.

We perform numerical optimization of micropillar single-photon source. We present calculations of achievable efficiency and indistinguishability with phonon-induced decoherence, and identify the design parameters providing the best performance.

© 2022 Optica Publishing Group. Users may use, reuse, and build upon the article, or use the article for text or data mining, so long as such uses are for non-commercial purposes and appropriate attribution is maintained. All other rights are reserved. We report on the design of nanohole/nanobeam cavities in ridge waveguides for on-chip, quantum-dot-based single-photon generation. Our design overcomes limitations of a low-refractive-index-contrast material platform in terms of emitter-mode coupling efficiency and yields an outcoupling efficiency of 0.73 to the output ridge waveguide. Importantly, this high coupling efficiency is combined with broadband operation of 9 nm full-width half-maximum. We provide an explicit design procedure for identifying the optimum geometrical parameters according to the developed design. Besides, we fabricate and optically characterize a proof-of-concept waveguide structure. The results of the microphotoluminescence measurements provide evidence for cavity-enhanced spontaneous emission from the quantum dot, thus supporting the potential of our design for on-chip single-photon sources applications.

Congenital nephrogenic diabetes insipidus (CNDI) is characterized by the reduced ability of renal collecting duct cells to reabsorb water in response to the antidiuretic effect of vasopressin. Chronic polyuria and polydipsia are the hallmarks of the disease. Approximately 90% of all patients with CNDI have X-linked inherited disease caused by variants in the arginine vasopressin receptor 2 (AVPR2) gene. We present genetic findings in 34 individuals from 19 kindreds including one or more family members with CNDI. Coding regions of AVPR2 were sequenced bi-directionally. We identified eight novel disease-causing variants in AVPR2, p.Arg68Alafs*124, p.Ser171Arg, p.Gln174Pro, p.Trp200Arg, p.Gly201Cys, p.Gly220Arg, p.Val226Glu, and p.Gln291Pro in nine kindreds. In all three families with more than one affected individual, the novel variants segregated with the disease. We also identified eight recurrent disease-causing variants, p.Val88Met, p.Leu111Valfs*80, p.Arg113Trp, p.Tyr124*, p.Ser167Leu, p.Thr207Asn, p.Arg247Alafs*12, and p.Arg337* in ten kindreds. Our findings contribute to the growing list of AVPR2 variants causing X-linked CNDI.CONCLUSION: Being a rapid diagnostic tool for CNDI, direct sequencing of AVPR2 should be encouraged in newborns with familial predisposition to CNDI. What is Known: • Disease-causing variants in AVPR2 cause X-linked congenital nephrogenic diabetes insipidus (CNDI). • DNA sequencing of AVPR2 is rapid, facilitates differential diagnosis, early intervention, and genetic diagnosis thus reducing morbidity in CNDI. What is New: • We identified eight novel disease-causing variants in AVPR2: p.Arg68Alafs*124, p.Ser171Arg, p.Gln174Pro, p.Trp200Arg, p.Gly201Cys, p.Gly220Arg, p.Val226Glu, and p.Gln291Pro, thereby adding to the growing list of AVPR2 disease-causing variants and emphasizing the importance of genetic testing in CNDI.

Background: Biomarkers may qualify diagnosis, treatment allocation, and prognostication in neonatal encephalopathy. Biomarker development is challenged by competing etiologies, inter-individual genetic variability, and a lack of specific neonatal markers. To address these challenges, we used a standardized neonatal hypoxic-ischemic (HI) encephalopathy model with pre- and post-HI sampling of cerebrospinal fluid (CSF) and plasma. Objectives: The study aimed to identify novel candidate protein biomarkers of HI encephalopathy in a newborn piglet model in CSF and plasma. Methods: FiO2 was lowered to 4% in 6 newborn piglets, then adjusted over a 45-min period keeping the amplitude integrated-EEG < 7 µV to induce HI encephalopathy. CSF and plasma was sampled pre-HI and 2 h after HI, protein levels were then analyzed by mass spectrometry. Results: Protein levels after HI changed significantly for 18 CSF proteins and 37 plasma proteins. CSF and plasma data showed distinct information, although peptidyl-prolyl cis-trans isomerase A had elevated levels in both fluids. HI regulation involved functional groups such as the antioxidant system, cell proliferation, cell structure, and apoptosis. S100-A8, which increased the most in CSF (9.5 fold), is known to be involved in inflammatory and immune response and to be highly regulated during injury. In plasma, increased proteins included FABP1 (31.8 fold) and proteins with antioxidant (SOD1, GPX3) and lectin function (REG3A, LGALS3). Conclusions: In this exploratory study, we have identified candidate biomarkers for HI in CSF and plasma, many not previously associated with HI. Identified proteins are promising candidates for further validation in time series experiments and clinical studies.

Objective: Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is characterized by severe polyuria and polydipsia and is caused by variations in the gene encoding the AVP prohormone. This study aimed to ascertain a correct diagnosis, to identify the underlying genetic cause of adFNDI in a Swedish family, and to test the hypothesis that the identified synonymous exonic variant in the AVP gene (c.324G>A) causes missplicing and endoplasmic reticulum (ER) retention of the prohormone. Design/Patients: Three affected family members were admitted for fluid deprivation test and dDAVP (1-deamino-8-d-arginine-vasopressin) challenge test. Direct sequencing of the AVP gene was performed in the affected subjects, and genotyping of the identified variant was performed in family members. The variant was examined by expression of AVP minigenes containing the entire coding regions as well as intron 2 of AVP. Methods/Results: Clinical tests revealed significant phenotypical variation with both complete and partial adFNDI phenotype. DNA analysis revealed a synonymous c.324G>A substitution in one allele of the AVP gene in affected family members only. Cellular studies revealed both normally spliced and misspliced pre-mRNA in cells transfected with the AVP c.324G>A minigene. Confocal laser scanning microscopy showed collective localization of the variant prohormone to ER and vesicular structures at the tip of cellular processes. Conclusion: We identified a synonymous variant affecting the second nucleotide of exon 3 in the AVP gene (c.324G>A) in a family in which adFNDI segregates. Notably, we showed that this variant causes partial missplicing of pre-mRNA, resulting in accumulation of the variant prohormone in ER. Our study suggests that even a small amount of aberrant mRNA might be sufficient to disturb cellular function, resulting in adFNDI.

Light propagation in systems of optical cavities coupled to waveguides can be conveniently described by a general rate equation model known as (temporal) coupled mode theory (CMT). We present an alternative derivation of the CMT for optical cavity-waveguide structures, which explicitly relies on the treatment of the cavity modes as quasinormal modes with properties that are distinctly different from those of the modes in the waveguides. The two families of modes are coupled via the field equivalence principle to provide a physically appealing yet surprisingly accurate description of light propagation in the coupled systems. Practical application of the theory is illustrated using example calculations in one and two dimensions., Comment: 14 pages, 9 figures

Background/Aim: Variability in the severity and age at onset of autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) may be associated with certain types of variants in the arginine vasopressin (AVP) gene. In this study, we aimed to describe a large family with an apparent predominant female occurrence of polyuria and polydipsia and to determine the underlying cause. Methods: The family members reported their family demography and symptoms. Two subjects were diagnosed by fluid deprivation and dDAVP challenge tests. Eight subjects were tested genetically. The identified variant along with 3 previously identified variants in the AVP gene were investigated by heterologous expression in a human neuronal cell line (SH-SY5Y). Results: Both subjects investigated clinically had a partial neurohypophyseal diabetes insipidus phenotype. A g.276_278delTCC variant in the AVP gene causing a Ser18del deletion in the signal peptide (SP) of the AVP preprohormone was perfectly co-segregating with the disease. When expressed in SH-SY5Y cells, the Ser18del variant along with 3 other SP variants (g.227G>A, Ser17Phe, and Ala19Thr) resulted in reduced AVP mRNA, impaired AVP secretion, and partial AVP prohormone degradation and retention in the endoplasmic reticulum. Impaired SP cleavage was demonstrated directly in cells expressing the Ser18del, g.227G>A, and Ala19Thr variants, using state-of-the-art mass spectrometry. Conclusion: Variants affecting the SP of the AVP preprohormone cause adFNDI with variable phenotypes by a mechanism that may involve impaired SP cleavage combined with effects at the mRNA, protein, and cellular level.

Nuclear reprogramming efficiency has been shown to be highly variable among different types of somatic cells and different individuals, yet the underlying mechanism remains largely unknown. Several studies have shown that reprogramming of fibroblasts into induced pluripotent stem cells (iPSCs) requires remodeling of mitochondria and a metabolic shift from an oxidative state to a more glycolytic state. In this study, we evaluated the nuclear reprogramming efficiency in relation to mitochondrial bioenergetic parameters of fibroblasts from seven different human individuals. Using the Seahorse extracellular energy flux analyzer, we measured oxygen consumption rate (OCR) profiles of the cells, along with their nuclear reprogramming efficiency into iPSCs. Our results showed that fibroblasts with the lowest mitochondrial spare respiratory capacity (SRC) had highest nuclear reprogramming efficiency, opposed to fibroblasts with highest mitochondrial SRC, which showed lowest reprogramming efficiency. Furthermore, we found that targeted fluorescent tagging of endogenous genes (MYH6 and COL2A1) by CRISPR/Cas9-mediated homologous recombination was accompanied by an increase in the SRC level of the modified fibroblasts and impaired reprogramming efficiency. Our findings indicate a negative correlation between high mitochondrial SRC in somatic cells and low reprogramming efficiencies. This type of analysis potentially allows screening and predicting reprogramming efficiency prior to reprogramming, and further suggests that nuclear reprogramming might be improved by approaches that modulate the SRC.

Scalable quantum photonic architectures demand highly efficient, high-purity single-photon sources, which can be frequency matched via external tuning. We demonstrate a single-photon source based on an InAs quantum dot embedded in a micropillar resonator, which is frequency tunable via externally-applied stress. Our platform combines the advantages of a Bragg micropillar cavity and the piezo-strain-tuning technique enabling single photon spontaneous emission enhancement via the Purcell effect and quantum dot (QD) with tunable wavelength. Our optomechanical platform has been implemented by integration of semiconductor-based QD-micropillars on a piezoelectric substrate. The fabricated device exhibits spontaneous emission enhancement with a Purcell factor of 4.4$\pm$0.7 and allows for a pure triggered single-photon generation with $g^{(2)}(0)$ < 0.07 under resonant excitation. A quantum dot emission energy tuning range of 0.75 meV for 27 kV/cm applied to the piezo substrate has been achieved. Our results pave the way towards the scalable implementation of single-photon quantum photonic technologies using optoelectronic devices., 16 pages, 4 figures

In this review, we present clinical studies on mindfulness-based therapy (MBT) with a focus on mediating mechanisms for its health promoting effects. These constitute awareness, self-compassion, regulation of dysfunctional patterns of thoughts and emotions, neural network and cellular processes. Among cellular processes are inflammation, oxidative stress, mitochondrial dysfunction and telomere shortening, which all contribute to the molecular pathophysiology of several of today's lifestyle diseases. Finally, we address applications, where strong evidence exists for the clinical impact of MBT.

An optimal single-photon source should deterministically deliver one and only one photon at a time, with no trade-off between the source's efficiency and the photon indistinguishability. However, all reported solid-state sources of indistinguishable single photons had to rely on polarization filtering which reduced the efficiency by 50%, which fundamentally limited the scaling of photonic quantum technologies. Here, we overcome this final long-standing challenge by coherently driving quantum dots deterministically coupled to polarization-selective Purcell microcavities--two examples are narrowband, elliptical micropillars and broadband, elliptical Bragg gratings. A polarization-orthogonal excitation-collection scheme is designed to minimize the polarization-filtering loss under resonant excitation. We demonstrate a polarized single-photon efficiency of 0.60+/-0.02 (0.56+/-0.02), a single-photon purity of 0.975+/-0.005 (0.991+/-0.003), and an indistinguishability of 0.975+/-0.006 (0.951+/-0.005) for the micropillar (Bragg grating) device. Our work provides promising solutions for truly optimal single-photon sources combining near-unity indistinguishability and near-unity system efficiency simultaneously., 28 pages, 16 figures. partial overlap with arXiv:1809.10992 which was unpublished