Optical Properties of Neutral F Centers in Bulk MgO with Density Matrix Embedding.

The optical spectra of neutral oxygen vacancies (F0 centers) in the bulk MgO lattice are investigated using density matrix embedding theory. The impurity Hamiltonian is solved with the complete active space self-consistent field and second-order n-electron valence state perturbation theory (NEVPT2-DMET) multireference methods. To estimate defect-localized vertical excitation energies at the nonembedding and thermodynamic limits, a double extrapolation scheme is employed. The extrapolated NEVPT2-DMET vertical excitation energy value of 5.24 eV agrees well with the experimental absorption maxima at 5.03 eV, whereas the excitation energy value of 2.89 eV at the relaxed triplet defect-localized state geometry overestimates the experimental emission at 2.4 eV by only nearly 0.5 eV, indicating the involvement of the triplet-singlet decay pathway.

Green's Function Formulation of Quantum Defect Embedding Theory.

We present a Green's function formulation of the quantum defect embedding theory (QDET) where a double counting scheme is rigorously derived within the G0W0 approximation. We then show the robustness of our methodology by applying the theory with the newly derived scheme to several defects in diamond. Additionally, we discuss a strategy to obtain converged results as a function of the size and composition of the active space. Our results show that QDET is a promising approach to investigate strongly correlated states of defects in solids.

All-electron many-body approach to resonant inelastic X-ray scattering.

We present a formalism for the resonant inelastic X-ray scattering (RIXS) cross section. The resulting compact expression in terms of polarizability matrix elements, particularly lends itself to the implementation in an all-electron many-body perturbation theory (MBPT) framework, which is realized in the full-potential package exciting. With the carbon K edge RIXS of diamond and the oxygen K edge RIXS of ß-Ga2O3, respectively, we demonstrate the importance of electron-hole correlation and atomic coherence in the RIXS spectra.

Five-second coherence of a single spin with single-shot readout in silicon carbide.

An outstanding hurdle for defect spin qubits in silicon carbide (SiC) is single-shot readout, a deterministic measurement of the quantum state. Here, we demonstrate single-shot readout of single defects in SiC via spin-to-charge conversion, whereby the defect's spin state is mapped onto a long-lived charge state. With this technique, we achieve over 80% readout fidelity without pre- or postselection, resulting in a high signal-to-noise ratio that enables us to measure long spin coherence times. Combined with pulsed dynamical decoupling sequences in an isotopically purified host material, we report single-spin T2 > 5 seconds, over two orders of magnitude greater than previously reported in this system. The mapping of these coherent spin states onto single charges unlocks both single-shot readout for scalable quantum nodes and opportunities for electrical readout via integration with semiconductor devices.

Quantum embedding theories to simulate condensed systems on quantum computers.

Quantum computers hold promise to improve the efficiency of quantum simulations of materials and to enable the investigation of systems and properties that are more complex than tractable at present on classical architectures. Here, we discuss computational frameworks to carry out electronic structure calculations of solids on noisy intermediate-scale quantum computers using embedding theories, and we give examples for a specific class of materials, that is, solid materials hosting spin defects. These are promising systems to build future quantum technologies, such as quantum computers, quantum sensors and quantum communication devices. Although quantum simulations on quantum architectures are in their infancy, promising results for realistic systems appear to be within reach.

Exciton-Dominated Core-Level Absorption Spectra of Hybrid Organic-Inorganic Lead Halide Perovskites.

In a combined theoretical and experimental work, we investigate X-ray absorption near-edge structure spectroscopy of the I L3 and the Pb M5 edges of the methylammonium lead iodide (MAPbI3) hybrid inorganic-organic perovskite and its binary phase PbI2. The absorption onsets are dominated by bound excitons with sizable binding energies of a few hundred millielectronvolts and pronounced anisotropy. The spectra of both materials exhibit remarkable similarities, suggesting that the fingerprints of core excitations in MAPbI3 are essentially given by its inorganic component, with negligible influence from the organic groups. The theoretical analysis complementing experimental observations provides the conceptual insights required for a full characterization of this complex material.

Calpeptin, not calpain, directly inhibits an ion channel of the inner mitochondrial membrane.

The permeability transition pore (PTP) of inner mitochondrial membranes is a large conductance pathway for ions up to 1500 Da which opening is responsible for ion equilibration and loss of membrane potential in apoptosis and thus in several neurodegenerative diseases. The PTP can be regulated by the Ca(2+)-activated mitochondrial K channel (BK). Calpains are Ca(2+)-activated cystein proteases; calpeptin is an inhibitor of calpains. We wondered whether calpain or calpeptin can modulate activity of PTP or BK. Patch clamp experiments were performed on mitoplasts of rat liver (PTP) and of an astrocytoma cell line (BK). Channel-independent open probability (P(o)) was determined (PTP) and, taking into account the number of open levels, NP(o) by single channel analysis (BK). We find that PTP in the presence of Ca(2+) (200 µM) is uninfluenced by calpain (13 nM) and shows insignificant decrease by the calpain inhibitor calpeptin (1 µM). The NP(o) of the BK is insensitive to calpain (54 nM), too. However, it is significantly and reversibly inhibited by the calpain inhibitor calpeptin (IC50 = 42 µM). The results agree with calpeptin-induced activation of the PTP via inhibition of the BK. Screening experiments with respirometry show calpeptin effects, fitting to inhibition of the BK by calpeptin, and strong inhibition of state 3 respiration.

Real-space multiple-scattering Hubbard model calculations for d- and f-state materials.

Calculations are presented of the electronic structure and X-ray spectra of materials with correlated d- and f-electron states based on the Hubbard model, a real-space multiple-scattering formalism and a rotationally invariant local density approximation. Values of the Hubbard parameter are calculated ab initio using the constrained random-phase approximation. The combination of the real-space Green's function with Hubbard model corrections provides an efficient approach to describe localized correlated electron states in these systems, and their effect on core-level X-ray spectra. Results are presented for the projected density of states and X-ray absorption spectra for transition metal- and lanthanide-oxides. Results are found to be in good agreement with experiment.

Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on 24-hour blood and ocular perfusion pressures: the results of a randomized trial.

BACKGROUND: To compare the effect of bimatoprost and the fixed combination latanoprost-timolol (LTFC) on 24-hour systolic (SBP) and diastolic (DBP) blood pressure and on 24-hour ocular perfusion pressure (OPP). METHODS: 200 patients with glaucoma or ocular hypertension, controlled on the unfixed combination of latanoprost and timolol or eligible for dual therapy being not being fully controlled on monotherapy were enrolled in a randomized, double-masked, placebo-controlled, multicentre clinical trial. They were randomized to LTFC (8 a.m.) or bimatoprost (8 p.m.) and received 24-hour IOP curve at baseline, 6 and 12 weeks (supine and sitting position IOPs were recorded at 8 p.m., midnight, 5 a.m., 8a.m., noon and 4 p.m.). Holter 24-hour blood pressure curve was obtained between weeks 2 and 12. SBP, DBP, OPP were calculated and compared with ANOVA. Rates of diastolic OPP (DPP)≤50, ≤40, ≤30 mmHg in the 2 groups were calculated and compared using Fisher's test. RESULTS: Mean baseline SBP and DBP were 136.5±18.3 vs 134.2±20.1 mmHg (p=0.1) and 79.1±10.2 vs 78.2±10.1 mmHg (p=0.4) in the bimatoprost and LTFC groups respectively. Holter SBP was significantly higher for bimatoprost (135.1 mmHg vs 128.1 mmHg, p=0.04), while no statistically significant difference in DBP was found. DPP was similar in the 2 groups, and proportions of patients with at least one value of the 24-hour curve≤50, ≤40, ≤30 mmHg were 94%, 86%, 41% respectively. CONCLUSIONS: Bimatoprost and LTFC had similar DBPs and OPPs; SBP was significantly lower with LTFC. In this study, the percentage of "dippers" was considerably higher than the one described in previous studies on the role of perfusion pressure in glaucoma. TRIAL REGISTRATION: NCT02154217, May 21, 2014.

Aqueous humor concentrations of topically administered caspofungin in rabbits.

BACKGROUND: The echinocandin caspofungin (CAS) is a novel antifungal drug with fungicidal in vitro activity against all Candida spp., which are the most frequent cause of fungal keratitis. Penetration of CAS through the cornea into the aqueous humor after topical administration was investigated. METHODS: A CAS solution with a concentration of 7 mg/ml was applied onto each rabbit's cornea. Drug application after corneal epithelium abrasion was processed in different time intervals: single application with aqueous humor sampling after 1 and 2 h. In addition, after continuous application of CAS every 30 min, aqueous humor concentrations of CAS after 1, 2 and 5 h were analyzed by liquid-chromatography tandem mass spectrometry. RESULTS: Topical administration of CAS without corneal epithelium abrasion resulted in no detectable amounts of the drug in the aqueous humor. However, with corneal abrasion, after a single application, levels of 2.16 +/- 1.57 microg/ml (n = 6) were reached after 1 h and then decreased to 1.76 +/- 0.88 microg/ml (n = 2) after 2 h. After serial application every 30 min, the following intracameral levels of CAS were detected: after 1 h, 2.11 +/- 1.09 microg/ml (n = 6); after 2 h, 4.94 +/- 1.80 microg/ml (n = 5), and after 5 h, 3.45 +/- 2.11 microg/ml (n = 6). CONCLUSION: In the aqueous humor, therapeutic drug levels can be reached that cover the MICs of most fungi after epithelial abrasion. To achieve a sustained high level of CAS as an effective antifungal therapy for corneal keratitis, CAS should be administered topically every 30 min after removal of the corneal epithelium.

Aqueous humor concentration of voriconazole after topical administration in rabbits.

OBJECTIVES: Voriconazol is a triazole antifungal drug with in vitro fungicidal activity against all Candida spp., Fusarium spp. and Aspergillus spp. which are frequent causes of fungal keratitis depending on geographic location. We investigated the penetration of voriconazole through the cornea into the aqueous humor (AH) after topical administration. METHODS: A 1% voriconazole solution was applied onto each rabbit's cornea. Topical drug application was processed at different time intervals: single drug application with AH sampling after 30 min, 1 h, 2 h, 3 h and 6 h. In addition, we evaluated AH samples after repeated topical application of voriconazole every 30 min after 1, 2, 4 and 6 h. Furthermore, after repeated drug application every hour, we analyzed voriconazole concentration after 2, 3, 4 and 6 h. All samples were analyzed by high-performance liquid chromatography (HPLC)-UV. RESULTS: A single application showed a maximum peak in AH of 3.58 microg/ml (N = 9) after 30 min. Within 3 h the concentration decreased to 0.04 microg/ml (N = 11). Application of voriconazole every half an hour revealed a peak value of 6.73 microg/ml (N = 10) after 2 h; after 4 h the value decreased to 6.19 microg/ml (N = 10) and was constant after 6 h (6.12 microg/ml, N = 6). When administrated every hour, only lower AH concentrations of voriconazole were reached with a maximum level of 2,06 microg/ml (N = 8) after four hours. CONCLUSION: In AH, therapeutic drug levels that cover the minimum inhibitory concentrations (MIC) of most fungi can be reached. To achieve a sustained high level of voriconazole as an effective antifungal therapy for corneal keratitis, voriconazole should be topically administered every 30 min.

Treatment of glaucoma patients with insufficient intraocular pressure control: a survey of German ophthalmologists in private practice.

OBJECTIVE: To assess the degree to which glaucoma treatment guidelines have been incorporated into daily practices and to describe the therapeutic practices chosen for patients with insufficient intraocular pressure (IOP) control. METHODS: Ophthalmologists in private practice in Germany were surveyed to obtain information about patients who exhibited unsatisfactory progress with IOP-lowering pharmacotherapy. Using a questionnaire, physicians provided data concerning treatment difficulty, target IOP, number and type of medications used, two most recent IOP readings, and optic nerve head and visual field observations. RESULTS: Of the 853 patients analyzed, primary open-angle glaucoma was the diagnosis for 67.1%, and other diagnoses included ocular hypertension, normal tension glaucoma, and pseudoexfoliation glaucoma. Target IOP levels had been determined for 95.5% of patients, and not achieving the target pressure was identified as a treatment difficulty for 81.0% of patients. Of patients on monotherapy, beta-blockers were prescribed most often (42.3%). Of all patients, 53.3% were treated with two or more agents as either fixed or non-fixed combinations. The non-fixed combination of a prostaglandin and carbonic anhydrase inhibitor was the most frequently prescribed dual therapy (19.2%). Non-fixed prostaglandin plus beta-blocker was used by 18.0% of dual therapy patients, whereas the available fixed combination was used by 10.5%. Non-compliance was identified as a cause of unsatisfactory IOP-lowering in 26.8% of all patients. This study is limited by its descriptive, non-interventional design. CONCLUSIONS: Treatment alterations are necessary to achieve sufficient IOP control in some patients. If these patients were to take advantage of more aggressive therapies as outlined by treatment guidelines, including newer formulations and fixed combination preparations, both efficacy and compliance may be improved.

The prevalence rates of refractive errors among children, adolescents, and adults in Germany.

PURPOSE: The prevalence rates of myopia vary between 5% in Australian Aborigines to 84% in Hong Kong and Taiwan, 30% in Norwegian adults, and 49.5% in Swedish schoolchildren. The aim of this study was to determine the prevalence of refractive errors in German children, adolescents, and adults. METHODS: The parents (aged 24-65 years) and their children (516 subjects aged 2-35 years) were asked to fill out a questionnaire about their refractive error and spectacle use. Emmetropia was defined as refractive status between +0.25D and -0.25D. Myopia was characterized as /=+0.5D. All information concerning refractive error were controlled by asking their opticians. RESULTS: The prevalence rates of myopia differed significantly between all investigated age groups: it was 0% in children aged 2-6 years, 5.5% in children aged 7-11 years, 21.0% in adolescents (aged 12-17 years) and 41.3% in adults aged 18-35 years (Pearson's Chi-square, p = 0.000). Furthermore, 9.8% of children aged 2-6 years were hyperopic, 6.4% of children aged 7-11 years, 3.7% of adolescents, and 2.9% of adults (p = 0.380). The prevalence of myopia in females (23.6%) was significantly higher than in males (14.6%, p = 0.018). The difference between the self-reported and the refractive error reported by their opticians was very small and was not significant (p = 0.850). CONCLUSION: In Germany, the prevalence of myopia seems to be somewhat lower than in Asia and Europe. There are few comparable studies concerning the prevalence rates of hyperopia.

Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on circadian intraocular pressure.

OBJECTIVE: To compare the effect of bimatoprost and the fixed combination of latanoprost and timolol (LTFC) on 24-hour mean intraocular pressure (IOP) after patients are switched from a nonfixed combination of latanoprost and timolol. DESIGN: Randomized, double-masked, multicenter clinical trial. PARTICIPANTS: Two hundred patients with glaucoma or ocular hypertension. METHODS: Included were patients who were controlled (IOP < 21 mmHg) on the nonfixed combination of latanoprost and timolol for at least 3 months before the baseline visit or patients on monotherapy with either latanoprost or timolol who were eligible for dual therapy not being fully controlled on monotherapy. The latter group of patients underwent a 6-week wash-in phase with the nonfixed combination of latanoprost and timolol before baseline IOP determination and study inclusion. Supine and sitting position IOPs were recorded at 8 pm, midnight, 5 am, 8 am, noon, and 4 pm at baseline, week 6, and week 12 visits. MAIN OUTCOME MEASURE: An analysis of covariance model was used for a noninferiority test of the primary efficacy variable, with mean area under the 24-hour IOP curve after 12 weeks of treatment as response variable and treatment, center, and baseline IOP as factors. A secondary analysis was performed on the within-treatment change from baseline. RESULTS: Mean baseline IOPs were 16.3+/-3.3 mmHg and 15.5+/-2.9.mmHg in the bimatoprost and LTFC groups, respectively. At week 12, mean IOPs were 16.1+/-2.5 mmHg for the bimatoprost group and 16.3+/-3.7 mmHg for the LTFC group, and no significant difference between the 2 treatment groups could be found. As compared with baseline, mean IOP increased by 0.3+/-3.6 mmHg during the day and decreased by 0.8+/-3.8 mmHg during the night in the bimatoprost group, whereas there were increases of 1.43+/-2.6 mmHg and 0.14+/-3.2 mmHg in the LTFC group, respectively. CONCLUSIONS: Bimatoprost is not inferior to the LTFC in maintaining IOP at a controlled level during a 24-hour period in patients switched from the nonfixed combination of latanoprost and timolol.

Absence of blood and lymphatic vessels in the developing human cornea.

PURPOSE: The normal human cornea is devoid of both blood and lymphatic vessels and actively maintains this avascularity (corneal angiogenic privilege). Whether and when corneal angiogenic privilege is achieved during development is unknown. METHODS: This study analyzed whether the cornea is primarily devoid of both blood and lymphatic vessels during intrauterine development or whether secondary regression of pre-existing vessels occurs before delivery. Indirect double immunohistochemistry was performed on 4-microm serial pupil-optic disc sections of paraffin-embedded human eyes stillborn at gestational ages of 17 to 41 weeks with antibodies against von Willebrand factor (vWF; factor VIII-associated antigen) as a panendothelial marker and with antibodies against lymphatic vessel endothelial hyaluronate receptor 1 (LYVE1) as a marker specific for lymphatic vascular endothelium. RESULTS: Human corneas were devoid of both vWF+++/LYVE-1(-) blood vessels and vWF+/LYVE-1+++ lymphatic vessels at all time-points analyzed. In contrast, there were numerous blood and lymphatic vessels detectable in the adjacent conjunctiva. CONCLUSION: The normal human cornea is primarily avascular and devoid of both blood and lymphatic vessels. Corneal angiogenic privilege is already achieved very early during fetal intrauterine development. This suggests early and strong expression of both antiangiogenic and antilymphangiogenic factors in the human cornea during development.

Trypan-blue-assisted anterior continuous curvilinear capsulorhexis in a case of ocular pemphigoid.

PURPOSE: To report on trypan-blue-assisted anterior continuous curvilinear capsulorhexis (ACCC) in a case of ocular pemphigoid. METHODS: Interventional case report. RESULTS: Due to the reduced visibility especially in the corneal periphery caused by the ocular pemphigoid, trypan blue 0,06% (Acri.Blue) was used to stain the anterior capsule of the lens. Then anterior continuous curvilinear capsulorhexis was performed. Due to the blue staining, the visualization of the margin of the rhexis was always good and phacoemulsification procedure was successfully performed afterwards. During the follow-up period of 12-months-postsurgically, no exacerbation of the ocular pemphigoid occurred. CONCLUSIONS: The use of trypan blue staining of the anterior capsule enabled the surgeon to perform a safe anterior continuous curvilinear capsulorhexis and a subsequent phacoemulsification in ocular pemphigoid. No progression of the ocular pemphigoid was seen within the 12-months-post-surgery period.

Analysis of a single nucleotide polymorphism in codon 388 of the FGFR4 gene in malignant gliomas.

The FGFR4 codon 388 polymorphism (Arg(388), Arg/Gly(388) or Gly(388)) was determined in glioblastoma multiforme (GBM), anaplastic astrocytomas (AA), diffuse astrocytomas (DA), and control muscles. Arg(388) was rare in AA, GBM, muscles, and was absent in DA. The Arg/Gly(388) and the Gly(388) frequency was equal among GBM and controls. FGFR4 expression was not related to codon 388 in GBM, and no survival differences between Arg/Gly(388) and Gly(388) tumors were found. U87 cells (Arg/Gly(388)) did not show higher invasion than U138 cells (Gly(388)). This suggests that the FGFR4 codon 388 status does not play a major role in malignant gliomas.

Expression and function of somatostatin receptors in peripheral nerve sheath tumors.

Although somatostatin receptors have been detected in many normal and neoplastic tissues, little is known of their expression and function in peripheral nerve tumors. In the present study, we examined the expression of all 5 somatostatin receptor subtypes (sst1-5) in 3 normal peripheral nerves, 3 traumatic neuromas, 27 schwannomas, 18 neurofibromas, and 177 malignant peripheral nerve sheath tumors (MPNSTs) by immunohistochemistry as well as by Western blot and reverse transcriptase-polymerase chain reaction investigations in 2 normal peripheral nerves, one neurofibroma, 5 schwannomas, and 5 MPNSTs. Immunoreactive somatostatin receptors were not detectable in normal peripheral nerve and in nonneoplastic Schwann cell proliferations. In contrast, sst2A mRNA and protein was present in 89% of schwannomas. This receptor subtype was less frequently detected in neurofibromas (22%) and MPNSTs (15%). Interestingly, sst4 was seen in 32% of MPNSTs and was almost exclusively expressed in this malignant tumor type. In support of a role in Schwann cell tumor growth control by somatostatin was the observation of induced internalization of sst2A and inhibition of cell proliferation in an NF1-associated MPNST cell line. Moreover, administration of an sst2A-selective agonist resulted in induction of MPNST cell apoptosis. We conclude that peripheral nerve sheath tumors often express at least one functional somatostatin receptor. Furthermore, our findings suggest a potential clinical role for somatostatin receptor agonists in tumor imaging and/or treatment of schwannomas and MPNSTs.

Alterations of cell cycle regulators in gliomatosis cerebri.

Gliomatosis cerebri (GC) is regarded as a rare glial neoplasm of unknown origin, and a detailed analysis of molecular alterations underlying this disease has started only recently. However, because GC characteristically affects large parts of the brain and spinal cord, the distribution of genetic alterations may be highly variable between different tumor areas. Additionally, tumor areas with varying degrees of differentiation may be present, raising the possibility to model the genetic events associated with astrocytoma progression. Here we analyzed various tumor regions with features of low-grade and high-grade astrocytomas from 9 autopsy-proven GC cases for the immunoexpression of the cell cycle-controlling proteins mdm2, p21, p27/kip1, p16, and Rb. The samples were also screened for EGFR expression, and for amplification of the EGFR and MDM2 genes. Furthermore, allelic losses of the CDKN2A gene and of a PTEN flanking region of chromosome 10 were determined. We detected tumor regions with immunoexpression of p21 only rarely in our series, without association to the tumor grade. No MDM2 gene amplification was detected. In contrast, three cases demonstrated maintained Rb expression. The expression of p27(kip1) showed a clear reduction with increasing astrocytoma malignancy in 7 cases. Allelic loss of the CDKN2A gene occurred in 5 patients but was not related to the tumor grading, nor to the intensity of p16 immunoexpression. No homozygous CDKN2Adeletions were detected. EGFR amplification was also absent in our series, but one case demonstrated EGFR expression only in the high-grade tumor area. Allelic losses on chromosome 10 were found in one out of six informative cases. However, marked differences in the immunoexpression, as well as in the distribution of genetic aberrations were seen between different tumor samples within a given case. The distribution of the alterations suggests that these molecular genetic changes represent secondary events, which may develop within tumor clones derived from a common founder tumor clone characterized by extraordinary spreading through the brain. Moreover, the detected aberrations in gliomatosis cerebri can reflect the tumor progression associated with secondary malignant astrocytoma formation even within a single case.