Failure detection and isolation investigation for strapdown skew redundant tetrad laser gyro inertial sensor arrays

The degree to which flight-critical failures in a strapdown laser gyro tetrad sensor assembly can be isolated in short-haul aircraft after a failure occurrence has been detected by the skewed sensor failure-detection voting logic is investigated along with the degree to which a failure in the tetrad computer can be detected and isolated at the computer level, assuming a dual-redundant computer configuration. The tetrad system was mechanized with two two-axis inertial navigation channels (INCs), each containing two gyro/accelerometer axes, computer, control circuitry, and input/output circuitry. Gyro/accelerometer data is crossfed between the two INCs to enable each computer to independently perform the navigation task. Computer calculations are synchronized between the computers so that calculated quantities are identical and may be compared. Fail-safe performance (identification of the first failure) is accomplished with a probability approaching 100 percent of the time, while fail-operational performance (identification and isolation of the first failure) is achieved 93 to 96 percent of the time

Emerging role of angiogenesis in adaptive and maladaptive right ventricular remodeling in pulmonary hypertension

Right ventricular (RV) function is the primary prognostic factor for both morbidity and mortality in pulmonary hypertension (PH). RV hypertrophy is initially an adaptive physiological response to increased overload; however, with persistent and/or progressive afterload increase, this response frequently transitions to more pathological maladaptive remodeling. The mechanisms and disease processes underlying this transition are mostly unknown. Angiogenesis has recently emerged as a major modifier of RV adaptation in the setting of pressure overload. A novel paradigm has emerged that suggests that angiogenesis and angiogenic signaling are required for RV adaptation to afterload increases and that impaired and/or insufficient angiogenesis is a major driver of RV decompensation. Here, we summarize our current understanding of the concepts of maladaptive and adaptive RV remodeling, discuss the current literature on angiogenesis in the adapted and failing RV, and identify potential therapeutic approaches targeting angiogenesis in RV failure

A case report of hepatopulmonary syndrome in hereditary hemorrhagic telangiectasia (HHT): Not all right-to-left shunting in HHT is due to pulmonary arteriovenous malformations

RATIONALE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by abnormal vessel growth that results in telangiectasias and arteriovenous malformations (AVMs) in the skin, mucosa, and viscera. Up to 30% of patients with HHT exhibit pulmonary AVMs (PAVMs), clinically manifesting as right-to-left shunting and hypoxemia. PATIENT CONCERNS: We report an unusual and novel case of a patient with HHT who lacked clinical sequelae of portal hypertension but presented to clinic with hypoxemia without dyspnea. DIAGNOSES: Diagnostic workup revealed noncardiac right-to-left shunting due to hepatopulmonary syndrome (HPS) from HHT-induced portal hypertension rather than PAVMs. The diagnosis was confirmed by the absence of PAVMs on chest computed tomography and evidence of elevated portal pressures as noted by the presence of small esophageal varices on upper endoscopy and histologic findings on liver biopsy. INTERVENTION: Due to the patient's mild symptoms, no further intervention was required. He was closely followed up in the outpatient setting for changes in symptoms and underwent annual screening for development of PAVMs. OUTCOMES: The patient continues to do well clinically. He has not experienced worsening hypoxemia or dyspnea and has not developed PAVMs. LESSONS: Given that management of hypoxemia in HPS drastically differs from that of hypoxemia due to PAVMs, this case demonstrates the importance of evaluating HHT patients for HPS if they exhibit impaired oxygenation and noncardiac right-to-leftshunting in the setting of hepatic arteriovenous shunting

PatentMatrix: an automated tool to survey patents related to large sets of genes or proteins

<p>Abstract</p> <p>Background</p> <p>The number of patents associated with genes and proteins and the amount of information contained in each patent often present a real obstacle to the rapid evaluation of the novelty of findings associated to genes from an intellectual property (IP) perspective. This assessment, normally carried out by expert patent professionals, can therefore become cumbersome and time consuming. Here we present PatentMatrix, a novel software tool for the automated analysis of patent sequence text entries.</p> <p>Methods and Results</p> <p>PatentMatrix is written in the Awk language and requires installation of the Derwent GENESEQ™ patent sequence database under the sequence retrieval system SRS.</p> <p>The software works by taking as input two files: i) a list of genes or proteins with the associated GENESEQ™ patent sequence accession numbers ii) a list of keywords describing the research context of interest (e.g. 'lung', 'cancer', 'therapeutics', 'diagnostics'). The GENESEQ™ database is interrogated through the SRS system and each patent entry of interest is screened for the occurrence of user-defined keywords. Moreover, the software extracts the basic information useful for a preliminary assessment of the IP coverage of each patent from the GENESEQ™ database. As output, two tab-delimited files are generated which provide the user with a detailed and an aggregated view of the results.</p> <p>An example is given where the IP position of five genes is evaluated in the context of 'development of antibodies for cancer treatment'</p> <p>Conclusion</p> <p>PatentMatrix allows a rapid survey of patents associated with genes or proteins in a particular area of interest as defined by keywords. It can be efficiently used to evaluate the IP-related novelty of scientific findings and to rank genes or proteins according to their IP position.</p

Hypoxia Upregulates Estrogen Receptor β in Pulmonary Artery Endothelial Cells in a HIF-1α-Dependent Manner

17β-Estradiol (E2) attenuates hypoxia-induced pulmonary hypertension (HPH) through estrogen receptor (ER)-dependent effects, including inhibition of hypoxia-induced endothelial cell proliferation; however, the mechanisms responsible for this remain unknown. We hypothesized that the protective effects of E2 in HPH are mediated through hypoxia-inducible factor 1α (HIF-1α)-dependent increases in ERβ expression. Sprague-Dawley rats and ERα or ERβ knockout mice were exposed to hypobaric hypoxia for 2-3 weeks. The effects of hypoxia were also studied in primary rat or human pulmonary artery endothelial cells (PAECs). Hypoxia increased expression of ERβ, but not ERα, in lungs from HPH rats as well as in rat and human PAECs. ERβ mRNA time dependently increased in PAECs exposed to hypoxia. Normoxic HIF-1α/HIF-2α stabilization increased PAEC ERβ, whereas HIF-1α knockdown decreased ERβ abundance in hypoxic PAECs. In turn, ERβ knockdown in hypoxic PAECs increased HIF-2α expression, suggesting a hypoxia-sensitive feedback mechanism. ERβ knockdown in hypoxic PAECs also decreased expression of the HIF inhibitor prolyl hydroxylase 2 (PHD2), whereas ERβ activation increased PHD2 and decreased both HIF-1α and HIF-2α, suggesting that ERβ regulates the PHD2/HIF-1α/HIF-2α axis during hypoxia. Whereas hypoxic wild-type or ERα knockout mice treated with E2 demonstrated less pulmonary vascular remodeling and decreased HIF-1α after hypoxia compared with untreated hypoxic mice, ERβ knockout mice exhibited increased HIF-2α and an attenuated response to E2 during hypoxia. Taken together, our results demonstrate a novel and potentially therapeutically targetable mechanism whereby hypoxia, via HIF-1α, increases ERβ expression and the E2-ERβ axis targets PHD2, HIF-1α, and HIF-2α to attenuate HPH development

Sex, Gender, and Sex Hormones in Pulmonary Hypertension and Right Ventricular Failure

Pulmonary hypertension (PH) encompasses a syndrome of diseases that are characterized by elevated pulmonary artery pressure and pulmonary vascular remodeling and that frequently lead to right ventricular (RV) failure and death. Several types of PH exhibit sexually dimorphic features in disease penetrance, presentation, and progression. Most sexually dimorphic features in PH have been described in pulmonary arterial hypertension (PAH), a devastating and progressive pulmonary vasculopathy with a 3-year survival rate <60%. While patient registries show that women are more susceptible to development of PAH, female PAH patients display better RV function and increased survival compared to their male counterparts, a phenomenon referred to as the “estrogen paradox” or “estrogen puzzle” of PAH. Recent advances in the field have demonstrated that multiple sex hormones, receptors, and metabolites play a role in the estrogen puzzle and that the effects of hormone signaling may be time and compartment specific. While the underlying physiological mechanisms are complex, unraveling the estrogen puzzle may reveal novel therapeutic strategies to treat and reverse the effects of PAH/PH. In this article, we (i) review PH classification and pathophysiology; (ii) discuss sex/gender differences observed in patients and animal models; (iii) review sex hormone synthesis and metabolism; (iv) review in detail the scientific literature of sex hormone signaling in PAH/PH, particularly estrogen-, testosterone-, progesterone-, and dehydroepiandrosterone (DHEA)-mediated effects in the pulmonary vasculature and RV; (v) discuss hormone-independent variables contributing to sexually dimorphic disease presentation; and (vi) identify knowledge gaps and pathways forward

Propagation of the surface plasmon polaritons through gradient index and periodic structures

We study the propagation of surface electromagnetic waves along the metallic surface covered by various layered dielectric structures. We show that strong radiative losses typical for the scattering of the surface wave can be considerably suppressed when single dielectric step is substituted by gradient index or periodic layered structure

High Rate Of Right Ventricular Dysfunction After Negative Computed Tomographic Pulmonary Angiography

Background: Prior work found that 20% of patients with persistent dyspnea have right ventricular (RV) dysfunction. Many patients with suspected pulmonary embolism (PE) who have a negative CTPA have persistent yet unexplained dyspnea. We hypothesized that a substantial proportion of these patients have unrecognized RV dysfunction. We sought to estimate this proportion and develop criteria to predict RV dysfunction on echocardiography after CTPA negative for PE. Methods: This was a four-center, prospective study of patients with ≥one symptom or sign and ≥one risk factor for PE, and CTPA scan performed. To assess potential predictors of RV dysfunction, we recorded 82 clinical predictors in real time. These included clinical findings, 12-lead electrocardiography (ECG), exhaled volumetric CO2/O2, plasma D-dimer and fibrinogen measurements. Patients underwent echocardiography within one week. Isolated RV dysfunction was defined as normal LV function with either moderate-severe RV hypokinesis, or estimated RV systolic pressure >35 mmHg. To assess if RV dysfunction led to symptoms that prompted reevaluation, we compared the frequency of repeat CTPA within 90 days. CTPA scans were interpreted by two independent radiologists. Predictors of RV dysfunction were assessed using a univariate (P<0.1)-multivariate (P<0.05) statistical approach. Results: 647 patients were enrolled; 120 with CPTA positive for PE were excluded, and 97 were excluded because of lack of persistent dyspnea. Of the 430 remaining patients, 184 underwent echocardiography, which demonstrated isolated RV dysfunction in 34% (95% CI: 30-41%). 27% of patients with isolated RV dysfunction had repeat CTPA within 90 days, a significantly higher rate than in patients without echocardiography (4%, P=0.03, Chi Square) or a normal echocardiogram (5%, P=0.02). No repeat CTPA scan showed PE. Of 82 candidate predictors of examined, univariate analysis found only 6 significant: active malignancy, normal CTPA, right bundle branch block on ECG, T-wave inversion in V1-V2 on ECG, history of COPD, and fibrinogen concentration. Of these six, multivariate logistic regression analysis found only normal CTPA as a significant predictor of isolated RV dysfunction. Conclusion: Patients with persistent dyspnea who have a normal CTPA performed for suspected PE have a high rate of unexplained isolated RV dysfunction on echocardiography. These patients are more likely to have persistent symptoms leading to unnecessary repeat CTPA in the short term. These findings form the starting point for a screening protocol to select patients with negative CTPA scanning for formal echocardiography and specialist referral to evaluate for pulmonary hypertension or other treatable causes of RV dysfunction

Allergy approach to a dog population from a veterinary dermatology consultation at the tropical inland city of Londrina, Paraná, Brazil

Background: Prevalence of allergy in dogs is also increasing associated with better living conditions and medical care. Indoor life is more often related to mite and mold sensitization and allergy, while an outdoor environment would favor a pollinic response with seasonal worsening. On the other hand, food allergy tends to present as a perennial condition. The particular frame of a tropical climate may in turn introduce environmental factors associated either with the concentration of available airborne allergens or skin barrier conditions. This study aimed to characterize the allergy frame of a dog population attending the State University of Londrina and Veterinary Clinics Life Space dermatology outpatient consultation, situated in the tropical inland region of Paraná, Brazil. Methods: A 111 allergic patient population (60 males and 51 females) was selected by clinical evaluation and submitted to food allergy restriction measures from 2015 to 2018. Thirty five patients (33.3%) belonged to predisposed breeds, 74.8% were indoor and 25.2% outdoor. Results: First signs started between 1-3 years of age in 55% of the patients and after the 3 years in 45%. Several comorbidities were found in 47.5% of the 1-3 years group and in 60% of the above group. Atopic dermatitis (AD) was diagnosed in 90.9% and food allergy (FA) in 23.7%, with 12.6% of simultaneous AD+FA. Malassezia overgrowth (MO) was diagnosed in 49.6% of the patients, mostly in the AD group. Flea allergy dermatitis was simultaneously diagnosed in 14.4% of the patients and otitis and conjunctivitis in 36% and 18.9%, respectively. Skin barrier disruption with seborrhea was diagnosed in 59% of the patients. The fourth version of the Canine Atopic Dermatitis Extent and Severity Index (CADESI-4) showed 13.5%, 33.3% and 53.2% of Light, Moderate and Severe scores, respectively, and pretty similar in the group of predisposed-breeds. Positive correlation was found between CADESI-4 scores and FA (p=0.03), seborrhea (p<0.00001), MO (p=0.00003) and otitis (p=0.01). Malassezia overgrowth correlated positively with indoor living (p=0.02) and otitis (p<0.00001) despite 29% of MO without otitis. Simultaneous flea allergy correlated negatively with MO (p=0.0079), otitis (p=0.001) and conjunctivitis (p<0.00001). Conclusion: A clear clinical worsening trend was found associated with seborrhea, FA, indoor living and otitis and MO in this tropical population. Malassezia overgrowth is probably more severe in this wet tropical environment