A low-rank solution method for Riccati equations with indefinite quadratic terms

Algebraic Riccati equations with indefinite quadratic terms play an important role in applications related to robust controller design. While there are many established approaches to solve these in case of small-scale dense coefficients, there is no approach available to compute solutions in the large-scale sparse setting. In this paper, we develop an iterative method to compute low-rank approximations of stabilizing solutions of large-scale sparse continuous-time algebraic Riccati equations with indefinite quadratic terms. We test the developed approach for dense examples in comparison to other established matrix equation solvers, and investigate the applicability and performance in large-scale sparse examples.Comment: 19 pages, 2 figures, 5 table

Electronic structure of the muonium center as a shallow donor in ZnO

The electronic structure and the location of muonium centers (Mu) in single-crystalline ZnO were determined for the first time. Two species of Mu centers with extremely small hyperfine parameters have been observed below 40 K. Both Mu centers have an axial-symmetric hyperfine structure along with a [0001] axis, indicating that they are located at the AB_{O,//} and BC_{//} sites. It is inferred from their small ionization energy (~6 meV and 50 meV) and hyperfine parameters (~10^{-4} times the vacuum value) that these centers behave as shallow donors, strongly suggesting that hydrogen is one of the primary origins of n type conductivity in as-grown ZnO.Comment: 4 pages, 4 figures, submitted to PR

The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear.

The vestibular maculae of the inner ear contain sensory receptor hair cells that detect linear acceleration and contribute to equilibrioception to coordinate posture and ambulatory movements. These hair cells are divided between two groups, separated by a line of polarity reversal (LPR), with oppositely oriented planar-polarized stereociliary bundles that detect motion in opposite directions. The transcription factor EMX2 is known to establish this planar polarized organization in mouse by regulating the distribution of the transmembrane receptor GPR156 at hair cell boundaries in one group of cells. However, the genes regulated by EMX2 in this context were previously not known. Using mouse as a model, we have identified the serine threonine kinase STK32A as a downstream effector negatively regulated by EMX2

Evidence for treatment with estradiol for women with SARS-CoV-2 infection

Background: Given that an individual’s age and gender are strongly predictive of coronavirus disease 2019 (COVID-19) outcomes, do such factors imply anything about preferable therapeutic options? Methods: An analysis of electronic health records for a large (68,466-case), international COVID-19 cohort, in 5-year age strata, revealed age-dependent sex differences. In particular, we surveyed the effects of systemic hormone administration in women. The primary outcome for estradiol therapy was death. Odds ratios (ORs) and Kaplan-Meier survival curves were analyzed for 37,086 COVID-19 women in two age groups: pre- (15–49 years) and peri-/post-menopausal (> 50 years). Results: The incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is higher in women than men (by about + 15%) and, in contrast, the fatality rate is higher in men (about + 50%). Interestingly, the relationships between these quantities are linked to age: pre-adolescent girls and boys had the same risk of infection and fatality rate, while adult premenopausal women had a significantly higher risk of infection than men in the same 5-year age stratum (about 16,000 vs. 12,000 cases). This ratio changed again in peri- and postmenopausal women, with infection susceptibility converging with men. While fatality rates increased continuously with age for both sexes, at 50 years, there was a steeper increase for men. Thus far, these types of intricacies have been largely neglected. Because the hormone 17ß-estradiol influences expression of the human angiotensin-converting enzyme 2 (ACE2) protein, which plays a role in SARS-CoV-2 cellular entry, propensity score matching was performed for the women’s sub-cohort, comparing users vs. non-users of estradiol. This retrospective study of hormone therapy in female COVID-19 patients shows that the fatality risk for women > 50 years receiving estradiol therapy (user group) is reduced by more than 50%; the OR was 0.33, 95% CI [0.18, 0.62] and the hazard ratio (HR) was 0.29, 95% CI [0.11,0.76]. For younger, pre-menopausal women (15–49 years), the risk of COVID-19 fatality is the same irrespective of estradiol treatment, probably because of higher endogenous estradiol levels. Conclusions: As of this writing, still no effective drug treatment is available for COVID-19; since estradiol shows such a strong improvement regarding fatality in COVID-19, we suggest prospective studies on the potentially more broadly protective roles of this naturally occurring hormone

Hypoxia Routes Tryptophan Homeostasis Towards Increased Tryptamine Production

The liver is the central hub for processing and maintaining homeostatic levels of dietary nutrients especially essential amino acids such as tryptophan (Trp). Trp is required not only to sustain protein synthesis but also as a precursor for the production of NAD, neurotransmitters and immunosuppressive metabolites. In light of these roles of Trp and its metabolic products, maintaining homeostatic levels of Trp is essential for health and well-being. The liver regulates global Trp supply by the immunosuppressive enzyme tryptophan-2,3-dioxygenase (TDO2), which degrades Trp down the kynurenine pathway (KP). In the current study, we show that isolated primary hepatocytes when exposed to hypoxic environments, extensively rewire their Trp metabolism by reducing constitutive Tdo2 expression and differentially regulating other Trp pathway enzymes and transporters. Mathematical modelling of Trp metabolism in liver cells under hypoxia predicted decreased flux through the KP while metabolic flux through the tryptamine branch significantly increased. In line, the model also revealed an increased accumulation of tryptamines under hypoxia, at the expense of kynurenines. Metabolic measurements in hypoxic hepatocytes confirmed the predicted reduction in KP metabolites as well as accumulation of tryptamine. Tdo2 expression in cultured primary hepatocytes was reduced upon hypoxia inducible factor (HIF) stabilisation by dimethyloxalylglycine (DMOG), demonstrating that HIFs are involved in the hypoxic downregulation of hepatic Tdo2. DMOG abrogated hepatic luciferase signals in Tdo2 reporter mice, indicating that HIF stability also recapitulates hypoxic rewiring of Trp metabolism in vivo. Also in WT mice HIF stabilization drove homeostatic Trp metabolism away from the KP towards enhanced tryptamine production, leading to enhanced levels of tryptamine in liver, serum and brain. As tryptamines are the most potent hallucinogens known, the observed upregulation of tryptamine in response to hypoxic exposure of hepatocytes may be involved in the generation of hallucinations occurring at high altitude. KP metabolites are known to activate the aryl hydrocarbon receptor (AHR). The AHR-activating properties of tryptamines may explain why immunosuppressive AHR activity is maintained under hypoxia despite downregulation of the KP. In summary our results identify hypoxia as an important factor controlling Trp metabolism in the liver with possible implications for immunosuppressive AHR activation and mental disturbances

Combined Perfusion and Permeability Imaging Reveals Different Pathophysiologic Tissue Responses After Successful Thrombectomy.

Despite successful recanalization of large-vessel occlusions in acute ischemic stroke, individual patients profit to a varying degree. Dynamic susceptibility-weighted perfusion and dynamic T1-weighted contrast-enhanced blood-brain barrier permeability imaging may help to determine secondary stroke injury and predict clinical outcome. We prospectively performed perfusion and permeability imaging in 38 patients within 24 h after successful mechanical thrombectomy of an occlusion of the middle cerebral artery M1 segment. Perfusion alterations were evaluated on cerebral blood flow maps, blood-brain barrier disruption (BBBD) visually and quantitatively on ktrans maps and hemorrhagic transformation on susceptibility-weighted images. Visual BBBD within the DWI lesion corresponded to a median ktrans elevation (IQR) of 0.77 (0.41-1.4) min-1 and was found in all 7 cases of hypoperfusion (100%), in 10 of 16 cases of hyperperfusion (63%), and in only three of 13 cases with unaffected perfusion (23%). BBBD was significantly associated with hemorrhagic transformation (p < 0.001). While BBBD alone was not a predictor of clinical outcome at 3 months (positive predictive value (PPV) = 0.8 [0.56-0.94]), hypoperfusion occurred more often in patients with unfavorable clinical outcome (PPV = 0.43 [0.10-0.82]) compared to hyperperfusion (PPV = 0.93 [0.68-1.0]) or unaffected perfusion (PPV = 1.0 [0.75-1.0]). We show that combined perfusion and permeability imaging reveals distinct infarct signatures after recanalization, indicating the severity of prior ischemic damage. It assists in predicting clinical outcome and may identify patients at risk of stroke progression

Diagnosis and Management of Pseudoguttata: A Literature Review

Corneal pseudoguttata (PG), also known as pseudoguttae or secondary guttata, is a transient, reversible endothelial edema commonly associated with anterior segment pathology. While considered rare, PG presents on slit-lamp examination more commonly than originally thought. We have clinically observed PG after refractive surgeries, in association with infectious keratitis, and following medication use. PG presents as dark lesions on slit-lamp exam with specular illumination, similar to primary corneal guttata. PG is distinct from guttata because PG resolves over time and does not involve Descemet’s membrane. Other ocular findings that may be confused with guttata include endothelial blebs (EB) and endothelial denudation (ED). EB are possibly a type of PG that present after contact lens use or hypoxia. ED is a distinct entity that is characterized by loss of endothelial cells without involvement of Descemet’s membrane. Confocal microscopy may be useful in differentiating these four endothelial lesions, with differences in border definition and the presence of hyperreflective areas two main distinctions. PG presents as a hyporeflective, elevated shape without clear borders on confocal microscopy. PG, EB, and ED can resolve with time without the need for surgical intervention, unlike corneal guttata. Treatment of the underlying condition will lead to resolution of both PG and EB

Development of a Deep Learning Algorithm for Periapical Disease Detection in Dental Radiographs

Periapical radiolucencies, which can be detected on panoramic radiographs, are one of the most common radiographic findings in dentistry and have a differential diagnosis including infections, granuloma, cysts and tumors. In this study, we seek to investigate the ability with which 24 oral and maxillofacial (OMF) surgeons assess the presence of periapical lucencies on panoramic radiographs, and we compare these findings to the performance of a predictive deep learning algorithm that we have developed using a curated data set of 2902 de-identified panoramic radiographs. The mean diagnostic positive predictive value (PPV) of OMF surgeons based on their assessment of panoramic radiographic images was 0.69(± 0.13), indicating that dentists on average falsely diagnose 31% of cases as radiolucencies. However, the mean diagnostic true positive rate (TPR) was 0.51(± 0.14), indicating that on average 49% of all radiolucencies were missed. We demonstrate that the deep learning algorithm achieves a better performance than 14 of 24 OMF surgeons within the cohort, exhibiting an average precision of 0.60(± 0.04), and an F1 score of 0.58(± 0.04) corresponding to a PPV of 0.67(± 0.05) and TPR of 0.51(± 0.05). The algorithm, trained on limited data and evaluated on clinically validated ground truth, has potential to assist OMF surgeons in detecting periapical lucencies on panoramic radiographs