288 research outputs found
Overview of Planned Ultrasonic Imaging System with Automatic ALN Data Interpretation
This presentation discusses a new program designed to investigate the effectiveness with which adaptive learning network (ALNJ analysis can be combined with linear array, phase steered, ultrasonic imaging techniques to provide an enhanced means for automatic data interpretations. The DARPA-sponsored program is being performed as a team effort between Adaptronics, Inc. and Battelle-Northwest. Battelle, under a subcontract from Adaptronics, is adapting the linear array imaging system being developed for the Electric Power Research Institute of Palo Alto, California, for use on this project. A special ultrasonic array will be developed to operate with the high-speed imaging system to acquire and record both specular and nonspecular signal information in both the time and frequency domains. Signal information from a multitude of simple and complex reflectors and defects wilI be recorded on the PDP 11 disk pack incorporated into the ultrasonic imaging system. Adaptronics will utilize the time·domain and frequency spectral data recorded from several thousand data points to develop algorithms and train networks which may describe uniquely the pattern of the reflections. The objective of the program is to provide a high-speed and automatic means for detecting, locating, sizing and displaying flaws in solid materials
Computational Based Investigation of Lattice Cell Optimization under Uniaxial Compression Load
Structural optimization is a methodology used to generate novel structures within a design space by finding a maximum or minimum point within a set of constraints. Topology optimization, as a subset of structural optimization, is often used as a means for light-weighting a structure while maintaining mechanical performance. This article presents the mathematical basis for topology optimization, focused primarily on the Bi-directional Evolutionary Structural Optimization (BESO) and Solid Isotropic Material with Penalization (SIMP) methodologies, then applying the SIMP methodology to a case study of additively manufactured lattice cells. Three lattice designs were used: the Diamond, I-WP, and Primitive cells. These designs are all based on Triply Periodic Minimal Surfaces (TPMS). Individual lattice cells were subjected to a uniaxial compression load, then optimized for these load conditions. The optimized cells were then compared to the base cell designs, noting changes in the stress field response, and the maximum and minimum stress values. Overall, topology optimization proved its utility under this loading condition, with each cell seeing a net gain in performance when considering the volume reduction. The I-WP lattice saw a significant stress reduction in conjunction with the mass and volume reduction, marking a notable increase in cell performance
Ranking ligand affinity for the DNA minor groove by experiment and simulation
The structural and thermodynamic basis for the strength and selectivity of the interactions of minor-groove binders (MGBs) with DNA is not fully understood. In 2003 we reported the first example of a thiazole containing MGB that bound in a phase shifted pattern that spanned 6 base-pairs rather than the usual 4 (for tricyclic distamycin-like compounds). Since then, using DNA footprinting, nuclear magnetic resonance spectroscopy, isothermal titration calorimetry and molecular dynamics, we have established that the flanking bases around the central 4 being read by the ligand have subtle effects on recognition. We have investigated the effect of these flanking sequences on binding and the reasons for the differences and established a computational method to rank ligand affinity against varying DNA sequences
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Rates of asymptomatic respiratory virus infection across age groups.
Respiratory viral infections are a leading cause of disease worldwide. A variety of respiratory viruses produce infections in humans with effects ranging from asymptomatic to life-treathening. Standard surveillance systems typically only target severe infections (ED outpatients, hospitalisations, deaths) and fail to track asymptomatic or mild infections. Here we performed a large-scale community study across multiple age groups to assess the pathogenicity of 18 respiratory viruses. We enrolled 214 individuals at multiple New York City locations and tested weekly for respiratory viral pathogens, irrespective of symptom status, from fall 2016 to spring 2018. We combined these test results with participant-provided daily records of cold and flu symptoms and used this information to characterise symptom severity by virus and age category. Asymptomatic infection rates exceeded 70% for most viruses, excepting influenza and human metapneumovirus, which produced significantly more severe outcomes. Symptoms were negatively associated with infection frequency, with children displaying the lowest score among age groups. Upper respiratory manifestations were most common for all viruses, whereas systemic effects were less typical. These findings indicate a high burden of asymptomatic respiratory virus infection exists in the general population
Fat, syn and disordered eating: The dangers and powers of excess
This is an accepted manuscript of an article published by Taylor & Francis in Fat Studies on 8 April 2015 available online: http://wwww.tandfonline.com/10.1080/21604851.2015.1016777This article draws on qualitative research inside one UK secular commercial weight loss group to show how ancient Christian suspicions of appetite and pleasure resurface in this group’s language of “Syn.” Following ancient Christian representations of sin, members assume that Syn depicts disorder and that fat is a visible sign of a body which has fallen out of place. Syn, though, is ambiguous, utilizing ancient theological meanings to discipline fat while containing within it the power to resist the very borders which hold women’s bodies and fat in place. Syn thus signals both the dangers and powers of disordered eating.This article draws on qualitative research inside one UK secular commercial weight loss group to show how ancient Christian suspicions of appetite and pleasure resurface in this group’s language of “Syn.” Following ancient Christian representations of sin, members assume that Syn depicts disorder and that fat is a visible sign of a body which has fallen out of place. Syn, though, is ambiguous, utilizing ancient theological meanings to discipline fat while containing within it the power to resist the very borders which hold women’s bodies and fat in place. Syn thus signals both the dangers and powers of disordered eating
Identification of Significant \u3cem\u3eE\u3c/em\u3e0 Strength in the 2\u3csub\u3e2\u3c/sub\u3e\u3csup\u3e+\u3c/sup\u3e → 2\u3csub\u3e1\u3c/sub\u3e\u3csup\u3e+\u3c/sup\u3e Transitions of \u3csup\u3e58,60,62\u3c/sup\u3eNi
The E0 transition strength in the 22+ → 21+ transitions of 58,60,62Ni have been determined for the first time following a series of measurements at the Australian National University (ANU) and the University of Kentucky (UK). The CAESAR Compton-suppressed HPGe array and the Super-e solenoid at ANU were used to measure the δ(E2/M1) mixing ratio and internal conversion coefficient of each transition following inelastic proton scattering. Level half-lives, δ(E2/M1) mixing ratios and γ-ray branching ratios were measured at UK following inelastic neutron scattering. The new spectroscopic information was used to determine the E0 strengths. These are the first 2+ → 2+ E0 transition strengths measured in nuclei with spherical ground states and the E0 component is found to be unexpectedly large; in fact, these are amongst the largest E0 transition strengths in medium and heavy nuclei reported to date
Meniscal T1rho and T2 measured with 3.0T MRI increases directly after running a marathon
PURPOSE: To prospectively evaluate changes in T1rho and T2 relaxation time in the meniscus using 3.0 T MRI in asymptomatic knees of marathon runners and to compare these findings with those of age-matched healthy subjects. MATERIAL AND METHODS: Thirteen marathon runners underwent 3.0 T MRI including T1rho and T2 mapping sequences before, 48-72 h after, and 3 months after competition. Ten controls were examined at baseline and after 3 months. All images were analyzed by two musculoskeletal radiologists identifying and grading cartilage, meniscal, ligamentous. and other knee abnormalities with WORMS scores. Meniscal segmentation was performed to generate T1rho and T2 maps in six compartments. RESULTS: No differences in morphological knee abnormalities were found before and after the marathon. However, all marathon runners showed a significant increase in T1rho and T2 values after competition in all meniscus compartments (p < 0.0001), which may indicate changes in the biochemical composition of meniscal tissue. While T2 values decreased after 3 months T1rho values remained at a high level, indicating persisting changes in the meniscal matrix composition after a marathon. CONCLUSION: T2 values in menisci have the potential to be used as biomarkers for identifying reversible meniscus matrix changes indicating potential tissue damage. T1rho values need further study, but may be a valuable marker for diagnosing early, degenerative changes in the menisci following exercise
Risk of chronic kidney disease after cancer nephrectomy.
The incidence of early stage renal cell carcinoma (RCC) is increasing and observational studies have shown equivalent oncological outcomes of partial versus radical nephrectomy for stage I tumours. Population studies suggest that compared with radical nephrectomy, partial nephrectomy is associated with decreased mortality and a lower rate of postoperative decline in kidney function. However, rates of chronic kidney disease (CKD) in patients who have undergone nephrectomy might be higher than in the general population. The risks of new-onset or accelerated CKD and worsened survival after nephrectomy might be linked, as kidney insufficiency is a risk factor for cardiovascular disease and mortality. Nephron-sparing approaches have, therefore, been proposed as the standard of care for patients with type 1a tumours and as a viable option for those with type 1b tumours. However, prospective data on the incidence of de novo and accelerated CKD after cancer nephrectomy is lacking, and the only randomized trial to date was closed prematurely. Intrinsic abnormalities in non-neoplastic kidney parenchyma and comorbid conditions (including diabetes mellitus and hypertension) might increase the risks of CKD and RCC. More research is needed to better understand the risk of CKD post-nephrectomy, to develop and validate predictive scores for risk-stratification, and to optimize patient management
Assessment of p.Phe508del-CFTR functional restoration in pediatric primary cystic fibrosis airway epithelial cells
© 2018 Sutanto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene can reduce function of the CFTR ion channel activity and impair cellular chloride secretion. The gold standard method to assess CFTR function of ion transport using the Ussing chamber requires a high number of airway epithelial cells grown at air-liquid interface, limiting the application of this method for high throughput screening of potential therapeutic compounds in primary airway epithelial cells (pAECs) featuring less common CFTR mutations. This study assessed an alternative approach, using a small scale halide assay that can be adapted for a personalized high throughput setting to analyze CFTR function of pAEC. Methods Pediatric pAECs derived from children with CF (pAEC CF ) were established and expanded as monolayer cultures, before seeding into 96-well plates for the halide assay. Cells were then transduced with an adenoviral construct containing yellow fluorescent protein (eYFP) reporter gene, alone or in combination with either wild-type CFTR (WT-CFTR) or p.Phe508-del CFTR. Four days post transduction, cells were stimulated with forskolin and genistein, and assessed for quenching of the eYFP signal following injection of iodide solution into the assay media. Results Data showed that pAEC CF can express eYFP at high efficiency following transduction with the eYFP construct. The halide assay was able to discriminate functional restoration of CFTR in pAEC CF treated with either WT-CFTR construct or the positive controls syntaxin 8 and B-cell receptor-associated protein 31 shRNAs. Significance The current study demonstrates that the halide assay can be adapted for pediatric pAEC CF to evaluate restoration of CFTR function. With the ongoing development of small molecules to modulate the folding and/or activity of various mutated CFTR proteins, this halide assay presents a small-scale personalized screening platform that could assess therapeutic potential of molecules across a broad range of CFTR mutations
A Protective Role for ELR+ Chemokines during Acute Viral Encephalomyelitis
The functional role of ELR-positive CXC chemokines in host defense during acute viral-induced encephalomyelitis was determined. Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of mice resulted in the rapid mobilization of PMNs expressing the chemokine receptor CXCR2 into the blood. Migration of PMNs to the CNS coincided with increased expression of transcripts specific for the CXCR2 ELR-positive chemokine ligands CXCL1, CXCL2, and CXCL5 within the brain. Treatment of JHMV-infected mice with anti-CXCR2 blocking antibody reduced PMN trafficking into the CNS by >95%, dampened MMP-9 activity, and abrogated blood-brain-barrier (BBB) breakdown. Correspondingly, CXCR2 neutralization resulted in diminished infiltration of virus-specific T cells, an inability to control viral replication within the brain, and 100% mortality. Blocking CXCR2 signaling did not impair the generation of virus-specific T cells, indicating that CXCR2 is not required to tailor anti-JHMV T cell responses. Evaluation of mice in which CXCR2 is genetically silenced (CXCR2−/− mice) confirmed that PMNs neither expressed CXCR2 nor migrated in response to ligands CXCL1, CXCL2, or CXCL5 in an in vitro chemotaxis assay. Moreover, JHMV infection of CXCR2−/− mice resulted in an approximate 60% reduction of PMN migration into the CNS, yet these mice survived infection and controlled viral replication within the brain. Treatment of JHMV-infected CXCR2−/− mice with anti-CXCR2 antibody did not modulate PMN migration nor alter viral clearance or mortality, indicating the existence of compensatory mechanisms that facilitate sufficient migration of PMNs into the CNS in the absence of CXCR2. Collectively, these findings highlight a previously unappreciated role for ELR-positive chemokines in enhancing host defense during acute viral infections of the CNS
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