•Progressive collapse response of an actual steel building is investigated.•Experiment included physical removal of four first story columns.•Linear static and nonlinear dynamic analyses of 2-D and ...3-D models are performed.•Current progressive collapse design methodologies are evaluated.
A field experiment and numerical simulations were performed to investigate the progressive collapse potential of an existing steel frame building. Four first-story columns were physically removed from the building to understand the subsequent load redistribution within the building. Experimental data from the field tests were used to compare and verify the computational models and simulations. Due to the scarcity of data from full-scale tests, the experimental data produced during this research is a valuable addition to the state of knowledge on progressive collapse of buildings. The progressive collapse design guidelines typically recommend simplified analysis procedures involving instantaneous removal of specified critical columns in a building. This paper investigates the effectiveness of such commonly used progressive collapse evaluation and design methodologies through numerical simulation and experimental data.
Adenosine deaminase acting on RNA (ADAR) catalyzes the posttranscriptional conversion of adenosine to inosine in double‐stranded RNA (dsRNA), which can lead to the creation of missense mutations in ...coding sequences. Recent studies show that editing‐dependent functions of ADAR1 protect dsRNA from dsRNA‐sensing molecules and inhibit innate immunity and the interferon‐mediated response. Deficiency in these ADAR1 functions underlie the pathogenesis of autoinflammatory diseases such as the type I interferonopathies Aicardi‐Goutieres syndrome and dyschromatosis symmetrica hereditaria. ADAR1‐mediated editing of endogenous coding and noncoding RNA as well as ADAR1 editing‐independent interactions with DICER can also have oncogenic or tumor suppressive effects that affect tumor proliferation, invasion, and response to immunotherapy. The combination of proviral and antiviral roles played by ADAR1 in repressing the interferon response and editing viral RNAs alters viral morphogenesis and cell susceptibility to infection. This review analyzes the structure and function of ADAR1 with a focus on its position in human disease pathways and the mechanisms of its disease‐associated effects.
This article is categorized under:
RNA in Disease and Development > RNA in Disease
RNA Processing > RNA Editing and Modification
RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications
ADAR1 plays an important role in human diseases including immune system disorders, cancer, and viral infections.
Diabetes mellitus represents a growing international public health issue with a near quadrupling in its worldwide prevalence since 1980. Though it has many known microvascular complications, vision ...loss from diabetic retinopathy is one of the most devastating for affected individuals. In addition, there is increasing evidence to suggest that diabetic patients have a greater risk for glaucoma as well. Though the pathophysiology of glaucoma is not completely understood, both diabetes and glaucoma appear to share some common risk factors and pathophysiologic similarities with studies also reporting that the presence of diabetes and elevated fasting glucose levels are associated with elevated intraocular pressure—the primary risk factor for glaucomatous optic neuropathy. While no study has completely addressed the possibility of detection bias, most recent epidemiologic evidence suggests that diabetic populations are likely enriched with glaucoma patients. As the association between diabetes and glaucoma becomes better defined, routine evaluation for glaucoma in diabetic patients, particularly in the telemedicine setting, may become a reasonable consideration to reduce the risk of vision loss in these patients.
Abstract Objective The present study reports the presence of several carotenoids and flavonoids in human milk samples. Methods Samples were collected from 17 women who delivered healthy term babies ...(≥37 wk of gestation) at 1-, 4-, and 13-wk postpartum intervals. Results Epicatechin (63.7–828.5 nmol/L), epicatechin gallate (55.7–645.6 nmol/L), epigallocatechin gallate (215.1–2364.7 nmol/L), naringenin (64.1–722.0 nmol/L), kaempferol (7.8–71.4 nmol/L), hesperetin (74.8–1603.1 nmol/L), and quercetin (32.5–108.6 nmol/L) were present in human milk samples with high inter-/intraindividual variability. With the exception of kaempferol, the mean flavonoid content in human milk was not statistically different among lactation stages. In contrast, carotenoids α-carotene (59.0–23.2 nmol/L), β-carotene (164.3–88.0 nmol/L), α-cryptoxanthin (30.6–13.5 nmol/L), β-cryptoxanthin (57.4–24.8 nmol/L), zeaxanthin (46.3–21.4 nmol/L), lutein (121.2–56.4 nmol/L), and lycopene (119.9–49.5 nmol/L) significantly decreased from weeks 1 to 13 of lactation. Conclusion The observed differences in the relative concentrations of the two phytochemical classes in human milk may be a result of several factors, including dietary exposure, stability in the milk matrix, efficiency of absorption/metabolism, and transfer from plasma to human milk. These data support the notion that flavonoids, as with carotenoids, are dietary phytochemicals present in human milk and potentially available to breast-fed infants.
A steel frame building was tested by physically removing four first story columns from one of the perimeter frames prior to building's scheduled demolition. The purpose of the field experiment was to ...simulate sudden column loss in buildings that may cause progressive collapse. Another objective was to investigate the load redistribution within the building after each column removal. The measured experimental data and observed performance of the building was valuable because it is very difficult and cost-prohibitive to build and test three-dimensional full-scale building specimens in the laboratory. Generally, the design code requirements prescribe simplified analysis procedures involving instantaneous removal of certain critical columns in a building. Design methodologies and simplified analysis procedures recommended in the design guidelines were also evaluated using the experimental data. In this study, two and three-dimensional models of the building were developed and analyzed to simulate the progressive collapse response. The effectiveness of the analysis procedures was evaluated by comparing with the experimental data.
•A steel frame building was tested by physically removing four first story columns.•2-D and 3-D models of the building were analyzed.•Calculated demand-to-capacity ratios exceeded the specified limits.•Although analytically collapse was predicted, test building did not collapse.
Glaucoma is a progressive optic neuropathy that causes characteristic changes of the optic nerve and visual field in relation to intraocular pressure (IOP). It is now known that glaucoma can occur at ...statistically normal IOPs and prevalence studies have shown that normal tension glaucoma (NTG) is more common than previously thought. While IOP is believed to be the predominant risk factor in primary open angle glaucoma (POAG), IOP-independent risk factors, such as vascular dysregulation, are believed to play an important part in the pathogenesis of NTG. Though certain distinguishing phenotypic features of NTG have been reported, such as an increased frequency of disc hemorrhages, acquired pits of the optic nerve and characteristic patterns of disc cupping and visual field loss, there is much overlap of the clinical findings in NTG with POAG, suggesting that NTG is likely part of a continuum of open angle glaucomas. However, IOP modification is still the mainstay of treatment in NTG. As in traditional POAG, reduction of IOP can be achieved with the use of medications, laser trabeculoplasty or surgery. Studies now show that the choice of medication may also be important in determining the outcomes of these patients. Though it is likely that future treatment of NTG will involve modification of both IOP and IOP-independent risk factors, current efforts to develop IOP-independent neuroprotective treatments have not yet proven to be effective in humans.
Objective To evaluate the voice outcomes of adults diagnosed with vocal fold nodules (VFNs) as children and to assess the impact of speech therapy on long-term voice outcomes. Study Design ...Prospective cohort study. Setting Large health care system. Subjects and Methods Subjects diagnosed with VFNs as children between the years 1996 and 2008 were identified within a medical record database of a large health care system. Included subjects were 3 to 12 years old at the time of diagnosis, had a documented laryngeal examination within 90 days of diagnosis, and were ≥18 years as of December 31, 2014. Qualified subjects were contacted by telephone and administered the Vocal Handicap Index-10 (VHI-10) and a 15-item questionnaire inquiring for confounding factors. Results A total of 155 subjects were included, with a mean age of 21.4 years (range, 18-29). The male:female ratio was 2.3:1. Mean VHI-10 score for the entire cohort was 5.4. Mean VHI-10 scores did not differ between those who received speech therapy (6.1) and those who did not (4.5; P = .08). Both groups were similar with respect to confounding risk factors that can contribute to dysphonia, although the no-therapy group had a disproportionately higher number of subjects who consumed >10 alcoholic drinks per week ( P = .01). Conclusion The majority of adults with VFNs as children will achieve a close-to-normal voice quality when they reach adulthood. In our cohort, speech therapy did not appear to have an impact on the long-term voice outcomes.
Objective: The ocular vascular system plays an important role in preserving the visual function. Alterations in either anatomy or hemodynamics of the eye may have adverse effects on vision. Thus, an ...imaging approach that can monitor alterations of ocular blood flow of the deep eye vasculature ranging from capillary-level vessels to large supporting vessels would be advantageous for detection of early stage retinal and optic nerve diseases. Methods: We propose a super-resolution ultrasound localization microscopy (ULM) technique that can assess both the microvessel and flow velocity of the deep eye with high resolution. Ultrafast plane wave imaging was acquired using an L22-14v linear array on a high frequency Verasonics Vantage system. A robust microbubble localization and tracking technique was applied to reconstruct ULM images. The experiment was first performed on pre-designed flow phantoms in vitro and then tested on a New Zealand white rabbit eye in vivo calibrated to various intraocular pressures (IOP) - 10 mmHg, 30 mmHg and 50 mmHg. Results: We demonstrated that retinal/choroidal vessels, central retinal artery, posterior ciliary artery, and vortex vein were all visible at high resolution. In addition, reduction of vascular density and flow velocity were observed with elevated IOPs. Conclusion: These results indicate that super-resolution ULM is able to image the deep ocular tissue while maintaining high resolution that is comparable with optical coherence tomography angiography. Significance: Capability to detect subtle changes of blood flow may be clinically important in detecting and monitoring eye diseases such as glaucoma.
To compare intrasession repeatability versus intersession reproducibility of the peripapillary vessel parameters using optical microangiography-based optical coherence tomography angiography (OCTA) ...in non-glaucomatous and glaucomatous eyes.
In an observational, longitudinal study, peripapillary OCTA scans were collected to evaluate intrasession repeatability and intersession reproducibility using within-eye coefficient of variation (CV
) and intraclass correlation coefficient (ICC). Images were quantified using a custom research-oriented quantification software calculating vessel area density (VAD) and flux and a commercially developed, clinic-oriented quantification software (Cirrus 11.0, Carl Zeiss Meditec) calculating perfusion density (PD) and flux index (FI). Effect of signal strength on the reliability of OCTA parameters was also evaluated.
Among 120 non-glaucomatous eyes, intrasession CV
were 4.2% for VAD, 5.3% for flux, 1.5% for PD and 2.0% for FI. The intersession CV
were 6.5% for VAD, 8.0% for flux, 2.0% for PD and 3.2% for FI. The intrasession ICC ranged from 0.928 to 0.945, and intersession ICC ranged from 0.811 to 0.866. From 118 glaucomatous eyes, intrasession CV
was 9.0% for VAD, 10.3% for flux, 1.7% for PD and 2.3% for FI. The intersession CV
was 12.1% for VAD, 14.2% for flux, 2.3% for PD and 3.5% for FI. The intrasession ICC ranged from 0.904 to 0.972, and intersession ICC ranged from 0.855 to 0.955. Signal strength was significantly positively associated with OCTA vessel parameters (p<0.0001) for both groups.
Peripapillary OCTA vessel parameters had greater intrasession repeatability compared to intersession reproducibility in both non-glaucomatous and glaucomatous eyes. The built-in commercially developed quantification software demonstrated greater agreement than the custom research-oriented quantification software.
Purpose To describe a surgical method of bleb revision for hypotony maculopathy, to evaluate its long-term efficacy, and to define the relationship between the duration of hypotony maculopathy and ...visual acuity (VA) outcomes. Design Noncomparative retrospective case series. Methods Medical records of 33 patients with hypotony maculopathy who underwent primary bleb revision between June 1999 and September 2012 by a single surgeon at an academic medical center were reviewed. Hypotony maculopathy was characterized by the presence of a decrease in VA, retinal striae, and macular edema in the setting of decreased intraocular pressure (IOP) after glaucoma filtering surgery. The main outcome measure was final logMAR VA after bleb revision at 6 and 12 months. Results Thirty-three eyes of 33 patients were followed for 4.68 ± 3.56 years (range 0.55–12.69 years). Mean duration of hypotony maculopathy was 4.98 ± 8.93 months. LogMAR VA improved from 0.78 ± 0.40 at baseline to 0.34 ± 0.34 ( P < .001) 6 months after bleb revision and to 0.45 ± 0.55 ( P < .001) 12 months after bleb revision. Spearman rank coefficient (rs ) correlating duration of hypotony and BCVA at both 6 and 12 months was significant ( P = .015 and rs = 0.426, P = .028 and rs = 0.416, respectively). Mean IOP increased from 3.51 ± 2.27 mm Hg to 12.06 ± 4.06 mm Hg ( P < .001) at 12 months. Fifty-two percent were on no antiglaucoma medications at last follow-up. Five eyes (15%) required a second bleb revision to correct persistent hypotony maculopathy. Conclusion Surgical repair for hypotony maculopathy provided a significant improvement in VA at 6 and 12 months. Surgical bleb revision is associated with good long-term control of IOP and improved VA in eyes with hypotony maculopathy after previous glaucoma filtering surgery.
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