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Neurodevelopmental diseases are often associated with other comorbidities, especially inflammatory processes. The disease may affect the trace element (TE) status, which in turn may affect disease severity and progression. Selenium (Se) is an essential TE required for the biosynthesis of selenoproteins including the transporter selenoprotein P (SELENOP) and extracellular glutathione peroxidase (GPX3). SELENOP deficiency in transgenic mice resulted in a Se status-dependent phenotype characterized by impaired growth and disturbed neuronal development, with epileptic seizures on a Se-deficient diet. Therefore, we hypothesized that Se and SELENOP deficiencies may be prevalent in paediatric patients with a neurodevelopmental disease. In an exploratory cross-sectional study, serum samples from children with neurodevelopmental diseases (n = 147) were analysed for total serum Se, copper (Cu), and zinc (Zn) concentrations as well as for the TE biomarkers SELENOP, ceruloplasmin (CP), and GPX3 activity. Children with epilepsy displayed elevated Cu and Zn concentrations but no dysregulation of serum Se status. Significantly reduced SELENOP concentrations were found in association with intellectual disability (mean ± SD (standard deviation); 3.9 ± 0.9 mg/L vs. 4.4 ± 1.2 mg/L, p = 0.015). A particularly low GPX3 activity (mean ± SD; 172.4 ± 36.5 vs. 192.6 ± 46.8 U/L, p = 0.012) was observed in phacomatoses. Autoantibodies to SELENOP, known to impair Se transport, were not detected in any of the children. In conclusion, there was no general association between Se deficiency and epilepsy in this observational analysis, which does not exclude its relevance to individual cases. Sufficiently high SELENOP concentrations seem to be of relevance to the support of normal mental development. Decreased GPX3 activity in phacomatoses may be relevant to the characteristic skin lesions and merits further analysis. Longitudinal studies are needed to determine whether the observed differences are relevant to disease progression and whether correcting a diagnosed TE deficiency may confer health benefits to affected children.

The essential trace element selenium (Se) is needed for the biosynthesis of selenocysteine-containing selenoproteins, including the secreted enzyme glutathione peroxidase 3 (GPX3) and the Se-transporter selenoprotein P (SELENOP). Both are found in blood and thyroid colloid, where they serve protective functions. Serum SELENOP derives mainly from hepatocytes, whereas the kidney contributes most serum GPX3. Studies using transgenic mice indicated that renal GPX3 biosynthesis depends on Se supply by hepatic SELENOP, which is produced in protein variants with varying Se contents. Low Se status is an established risk factor for autoimmune thyroid disease, and thyroid autoimmunity generates novel autoantigens. We hypothesized that natural autoantibodies to SELENOP are prevalent in thyroid patients, impair Se transport, and negatively affect GPX3 biosynthesis. Using a newly established quantitative immunoassay, SELENOP autoantibodies were particularly prevalent in Hashimoto’s thyroiditis as compared with healthy control subjects (6.6% versus 0.3%). Serum samples rich in SELENOP autoantibodies displayed relatively high total Se and SELENOP concentrations in comparison with autoantibody-negative samples ([Se]; 85.3 vs. 77.1 µg/L, p = 0.0178, and [SELENOP]; 5.1 vs. 3.5 mg/L, p = 0.001), while GPX3 activity was low and correlated inversely to SELENOP autoantibody concentrations. In renal cells in culture, antibodies to SELENOP inhibited Se uptake. Our results indicate an impairment of SELENOP-dependent Se transport by natural SELENOP autoantibodies, suggesting that the characterization of health risk from Se deficiency may need to include autoimmunity to SELENOP as additional biomarker of Se status.

Objective Iodide transport across thyrocytes constitutes a critical step for thyroid hormone biosynthesis, mediated mainly by the basolateral sodium-iodide-symporter (NIS (SLC5A5)) and the apical anion exchanger pendrin (PDS (SLC26A4)). Both transmembrane proteins have been described as autoantigens in thyroid disease, yet the reports on autoantibody (aAb) prevalence and diagnostic usefulness are conflicting. Reasons for the inconclusive findings may be small study groups and principle differences in the technologies used. Design We decided to re-evaluate this important issue by establishing novel non-radioactive tests using full-length antigens and comparable protocols, and analyzing a large cohort of thyroid patients (n = 323) and control samples (n = 400). Methods NIS and PDS were recombinantly expressed as fusion protein with firefly luciferase (Luc). Stably transfected HEK293 cells were used as reproducible source of the autoantigens. Results Recombinant NIS-Luc showed iodide transport activity, indicating successful expression and correct processing. Commercial antibodies yielded dose-dependent responses in the newly established assays. Reproducibility of assay signals from patient sera was verified with respect to linearity, stability and absence of matrix effects. Prevalence of PDS-aAb was similar in thyroid patients and controls (7.7% vs 5.0%). NIS-aAb were more prevalent in patients than controls (7.7% vs 1.8%), especially in Graves’ Disease (12.3%). Neither NIS-aAb nor PDS-aAb concentrations were related to TPO-aAb or TSH-receptor-aAb concentrations, or to serum zinc or selenium status. Conclusions Our data highlight a potential relevance of autoimmunity against NIS for thyroid disease, whereas an assessment of PDS-aAb in thyroid patients seems not to be of diagnostic value (yet).

The synthesis of thyroid hormone depends on a set of trace elements, most importantly selenium and iodine. The dietary supply with certain micronutrients is limited in many areas of the world, including central Europe and large parts of Asia and Africa. Moreover, both thyroid disease risk and therapy effects are modulated by trace element supply and status.Assessment of trace element status in thyroid patients in a European metropolis.Adult patients visiting a medical praxis in Berlin, Germany, were enrolled into a cross-sectional analysis, and serum samples were obtained from thyroid patients (n = 323) with different conditions including goitre, hypothyroidism, malignancy or autoimmune thyroid disease. Trace elements (iodine, selenium, copper and zinc) were assessed by ICP-MS/MS or total reflection X-ray analysis, along with two protein biomarkers of selenium status (selenoprotein P, glutathione peroxidase), and compared to the clinical phenotype.The patients displayed relatively low serum zinc and selenium concentrations as compared to a set (n = 200) of healthy subjects (zinc; 1025+/-233 vs. 1068+/-230 μg/L, p 0.01, selenium; 76.9+/18.8 vs. 85.1+/-17.4 μg/L, p 0.0001). A high fraction of patients (37.5%) was classified as selenium-deficient (serum selenium concentrations70 μg/L), in particular the patients with thyroid malignancy (59%). Serum copper was not different between the groups, and total serum iodine concentrations were unrelated to thyroid disease. Explorative statistical analyses yielded no significant interactions between the trace elements and disease parameters, except for free thyroxine inversely correlating to the copper/selenium ratio.In adult thyroid patients, there is no relation of circulating copper, iodine, selenium or zinc concentrations to thyroid hormone. However, a large fraction of German thyroid patients displays a considerable selenium deficit, known to constitute a disease risk potentially impairing convalescence and aggravating autoimmune disease processes. It appears advisable to testing thyroid patients for selenium deficiency, and once diagnosed, an increased supply via dietary counselling or active supplementation should be considered.

The ability to tune qubits to flat points in their energy dispersions ("sweet spots") is an important tool for mitigating the effects of charge noise and dephasing in solid-state devices. However, the number of derivatives that must be simultaneously set to zero grows exponentially with the number of coupled qubits, making the task untenable for as few as two qubits. This is a particular problem for adiabatic gates, due to their slower speeds. Here, we propose an adiabatic two-qubit gate for quantum dot hybrid qubits, based on the tunable, electrostatic coupling between distinct charge configurations. We confirm the absence of a conventional sweet spot, but show that controlled-Z (CZ) gates can nonetheless be optimized to have fidelities of $\sim$99% for a typical level of quasistatic charge noise ($\sigma_\varepsilon$$\simeq$1 $\mu$eV). We then develop the concept of a dynamical sweet spot (DSS), for which the time-averaged energy derivatives are set to zero, and identify a simple pulse sequence that achieves an approximate DSS for a CZ gate, with a 5$\times$ improvement in the fidelity. We observe that the results depend on the number of tunable parameters in the pulse sequence, and speculate that a more elaborate sequence could potentially attain a true DSS., Comment: 14 pages, 9 figures

AIM Somatostatin receptor scintigraphy (SRS) is well-established in neuroendocrine tumour (NET) imaging. This study evaluated the impact of attenuation correction (AC) on SRS SPECT data in patients examined by SPECT-CT. METHODS Planar scintigraphy and SPECT-CT of 17 patients (10 men, seven women; age, 40-74 years; mean, 62 years) suffering from NET were included. For the visual assessment of AC, the intensity and contrast of foci classified as pathological were rated in both the non-attenuation corrected (NAC) and the attenuation corrected (AC) SPECT images using a 5-point score. The change in signal intensity after AC was semiquantified two-fold for each focus in both SPECT(AC) and SPECT(NAC): firstly by using tumour-to-background (TB) ratios (defined as T(max)/B(mean)) for the determination of a TB(AC)/TB(NAC) ratio. Secondly, by a T(max,AC)/T(max,NAC) ratio. Both ratios were correlated to the focus depth. RESULTS A total of 46 pathological foci were found. Focus contrast and intensity significantly increased in 14/46 foci (30%) after AC (mean, 3.7-4.0) in the visual analysis (P

We construct an optimal set of single-particle states for few-electron quantum dots (QDs) using the method of natural orbitals (NOs). The NOs include also the effects of the Coulomb repulsion between electrons. We find that they agree well with the noniteracting orbitals for GaAs QDs of realistic parameters, while the Coulomb interactions only rescale the radius of the NOs compared to the noninteracting case. We use NOs to show that four-electron QDs are less susceptible to charge noise than their two-electron counterparts., 11+ pages, 5 figures

Efficient operation sequences to couple and interchange quantum information between quantum dot spin qubits of different kinds are derived using exchange interactions. In the qubit encoding of a single-spin qubit, a singlet-triplet qubit, and an exchange-only (triple-dot) qubit, some of the single-qubit interactions remain on during the entangling operation; this greatly simplifies the operation sequences that construct entangling operations. In the ideal setup, the gate operations use the intra-qubit exchange interactions only once. The limitations of the entangling sequences are discussed, and it is shown how quantum information can be converted between different kinds of quantum dot spin qubits., Comment: 9 pages, 4 figures

We describe and analyze leakage errors of singlet-triplet qubits. Even though leakage errors are a natural problem for spin qubits encoded using quantum dot arrays, they have obtained little attention in previous studies. We describe the realization of leakage correction protocols that can be implemented together with the quantum error correction protocol of the surface code. Furthermore we construct explicit leakage reduction units that need, in the ideal setup, as few as three manipulation steps. Our study shows that leakage errors can be corrected without the need of measurements and at the cost of only a few additional ancilla qubits and gate operations compared to standard quantum error correction codes., 7+ pages, 5 figures

In the semi-conductor double quantum dot singlet-triplet qubit architecture, the decoherence caused by the qubit's charge environment poses a serious obstacle in the way towards large scale quantum computing. The effects of the charge decoherence can be mitigated by operating the qubit in the so called sweet spot regions where it is insensitive to electrical noise. In this paper, we propose singlet-triplet qubits based on two quantum dots of different sizes. Such asymmetric double dot systems allow the implementation of exchange gates with controllable exchange splitting $J$ operated in the doubly occupied charge region of the larger dot, where the qubit has high resilience to charge noise. In the larger dot, $J$ can be quenched to a value smaller than the intra-dot tunneling using magnetic fields, while the smaller dot and its larger splitting can be used in the projective readout of the qubit.

The three-electron configuration of gate-defined double quantum dots encodes a promising qubit for quantum information processing. I propose a two-qubit entangling gate using a pulse-gated manipulation procedure. The requirements for high-fidelity entangling operations are equivalent to the requirements for the pulse-gated single-qubit manipulations that have been successfully realized for Si QDs. This two-qubit gate completes the universal set of all-pulse-gated operations for the three-electron double-dot qubit and paves the way for a scalable setup to achieve quantum computation., 8 pages, 4 figures

The $s_z=0$ spin configuration of two electrons confined at a double quantum dot (DQD) encodes the singlet-triplet qubit (STQ). We introduce the inverted STQ (ISTQ) that emerges from the setup of two quantum dots (QDs) differing significantly in size and out-of-plane magnetic fields. The strongly confined QD has a two-electron singlet ground state, but the weakly confined QD has a two-electron triplet ground state in the $s_z=0$ subspace. Spin-orbit interactions act nontrivially on the $s_z=0$ subspace and provide universal control of the ISTQ together with electrostatic manipulations of the charge configuration. GaAs and InAs DQDs can be operated as ISTQs under realistic noise conditions., 10 pages, 4 figures

We analyze the influence of noise for qubits implemented using a triple quantum dot spin system. We give a detailed description of the physical realization and develop error models for the dominant external noise sources. We use a Davies master equation approach to describe their influence on the qubit. The triple dot system contains two meaningful realizations of a qubit: We consider a subspace and a subsystem of the full Hilbert space to implement the qubit. We test the robustness of these two implementations with respect to the qubit stability. When performing the noise analysis, we extract the initial time evolution of the qubit using a Nakajima-Zwanzig approach. We find that the initial time evolution, which is essential for qubit applications, decouples from the long time dynamics of the system. We extract probabilities for the qubit errors of dephasing, relaxation and leakage. Using the Davies model to describe the environment simplifies the noise analysis. It allows us to construct simple toy models, which closely describe the error probabilities., Comment: 30 pages, 18 figures

Singlet-triplet spin qubits in six-electron double quantum dots, in moderate magnetic fields, can show superior immunity to charge noise. This immunity results from the symmetry of orbitals in the second energy shell of circular quantum dots: singlet and triplet states in this shell have identical charge distributions. Our phase-gate simulations, which include $1/f$ charge noise from fluctuating traps, show that this symmetry is most effectively exploited if the gate operation switches rapidly between sweet spots deep in the (3,3) and (4,2) charge stability regions; fidelities very close to one are predicted if subnanosecond switching can be performed., 7 pages, 3 figures

AIM Somatostatin receptor scintigraphy (SRS) is an established imaging modality for neuroendocrine tumors (NET). Additional single photon emission computed tomography (SPECT-CT) not only permits image fusion but also attenuation correction (AC) of SPECT data. This study evaluated whether attenuation corrected SPECT-images (SPECT[AC]) are more sensitive than nonattenuation corrected SPECT-reconstructions (SPECT[NAC]) for the detection of NET lesions. METHODS The imaging data (planar In-111-octreotide scintigraphy and SPECT-CT) of 50 consecutive patients (28 male; 22 female; age, 34-80; mean, 65 years) with NET were included in this retrospective analysis. SPECT data were reconstructed with and without integrated CT-based AC and then analyzed by 2 experienced readers for the presence of pathologic uptake in a blinded consensus reading. Fused SPECT-CT, contemporary CT/MRI, and clinical as well as imaging follow-up served as a reference standard. All foci were rated in both the SPECT(NAC)- and SPECT(AC)-reconstructions for intensity and contrast using a 6-point-score ("0 = no uptake/no delineation from surrounding tissue" to "5 = very high uptake/very strong delineation from surrounding tissue"). The scores were analyzed in a 6 x 6 contingency table using the McNemar Bowker test. RESULTS A total of 222 pathologic foci were detected by SPECT(NAC) and 227 foci by SPECT(AC), respectively. In 67 of 227 foci (29.5%), focus intensity/contrast increased after AC, whereas only 5 foci showed a decrease (P < 0.001). Sensitivity increased by 2.2% (P = 0.025; 95% CI: 0.02%-4.1%) as 5 foci were detected only by SPECT(AC). However, as these 3 patients were already diagnosed with systemic disease, there was no influence on the therapeutic strategy chosen. CONCLUSION Attenuation correction of somatostatin receptor scintigraphy-SPECT significantly improves focus visualization and, albeit slightly, also significantly increases sensitivity.