Subsurface Inclusion Quantification Using Multi-Frequency Ultrasonic Surface Waves

Rolling contact fatigue (RCF) is one of the major sources of subsurface-initiated spalling in bearing components. These types of spalls initiate in regions where microcracks are formed due to a localized increase in stress from inclusions near the surface. Ultrasonic bulk inspection is a powerful method to detect defects in a large volume of steel. However, inclusions near the surface of a sample can elude detection because reflections from the inclusion can be masked by reflections from the sample surface. This limitation can be eliminated if ultrasonic surface wave methods are used for inspection. Surface waves have material displacements localized near the sample surface but decay with depth giving an effective inspection of depth on the order of the wavelength. Ultrasonic scattering from inclusions also is wavelength dependent and these two aspects can complicate the interpretation of ultrasonic experimental data. In this presentation, a model is described for the scattering of a surface wave by a subsurface spherical inclusion. The amplitude-versus-depth profile of a surface wave is combined with the solution for the scattering of a shear wave from a spherical scatterer in order to approximate the problem of interest. Trends of reflected amplitude with respect to inspection frequency, inclusion depth, and inclusion diameter are discussed first. Then a necessary calibration experiment is described that uses subsurface defects of known size created using femtosecond laser machining. A model of the calibration sample allows measurements on unknown samples to be interpreted quantitatively. The final analysis shows that the reflected amplitude from multiple frequency measurements can be used to characterize the size and depth of the subsurface inclusions

Ethical and social implications of using predictive modeling for Alzheimer´s disease prevention:a systematic literature review

BACKGROUND: The therapeutic paradigm in Alzheimer's disease (AD) is shifting from symptoms management toward prevention goals. Secondary prevention requires the identification of individuals without clinical symptoms, yet "at-risk" of developing AD dementia in the future, and thus, the use of predictive modeling. OBJECTIVE: The objective of this study was to review the ethical concerns and social implications generated by this new approach. METHODS: We conducted a systematic literature review in Medline, Embase, PsycInfo, and Scopus, and complemented it with a gray literature search between March and July 2018. Then we analyzed data qualitatively using a thematic analysis technique. RESULTS: We identified thirty-one ethical issues and social concerns corresponding to eight ethical principles: (i) respect for autonomy, (ii) beneficence, (iii) non-maleficence, (iv) equality, justice, and diversity, (v) identity and stigma, (vi) privacy, (vii) accountability, transparency, and professionalism, and (viii) uncertainty avoidance. Much of the literature sees the discovery of disease-modifying treatment as a necessary and sufficient condition to justify AD risk assessment, overlooking future challenges in providing equitable access to it, establishing long-term treatment outcomes and social consequences of this approach, e.g., medicalization. The ethical/social issues associated specifically with predictive models, such as the adequate predictive power and reliability, infrastructural requirements, data privacy, potential for personalized medicine in AD, and limiting access to future AD treatment based on risk stratification, were covered scarcely. CONCLUSION: The ethical discussion needs to advance to reflect recent scientific developments and guide clinical practice now and in the future, so that necessary safeguards are implemented for large-scale AD secondary prevention.</p

Cloud optical depth retrievals from the Aerosol Robotic Network (AERONET) cloud mode observations

Cloud optical depth is one of the most poorly observed climate variables. The new “cloud mode” capability in the Aerosol Robotic Network (AERONET) will inexpensively yet dramatically increase cloud optical depth observations in both number and accuracy. Cloud mode optical depth retrievals from AERONET were evaluated at the Atmospheric Radiation Measurement program’s Oklahoma site in sky conditions ranging from broken clouds to overcast. For overcast cases, the 1.5 min average AERONET cloud mode optical depths agreed to within 15% of those from a standard ground‐based flux method. For broken cloud cases, AERONET retrievals also captured rapid variations detected by the microwave radiometer. For 3 year climatology derived from all nonprecipitating clouds, AERONET monthly mean cloud optical depths are generally larger than cloud radar retrievals because of the current cloud mode observation strategy that is biased toward measurements of optically thick clouds. This study has demonstrated a new way to enhance the existing AERONET infrastructure to observe cloud optical properties on a global scale

Genome-wide changes in genetic diversity in a population of Myotis lucifugus affected by white-nose syndrome

Novel pathogens can cause massive declines in populations, and even extirpation of hosts. But disease can also act as a selective pressure on survivors, driving the evolution of resistance or tolerance. Bat white-nose syndrome (WNS) is a rapidly spreading wildlife disease in North America. The fungus causing the disease invades skin tissues of hibernating bats, resulting in disruption of hibernation behavior, premature energy depletion, and subsequent death. We used whole-genome sequencing to investigate changes in allele frequencies within a population of Myotis lucifugus in eastern North America to search for genetic resistance to WNS. Our results show low F-ST values within the population across time, i.e., prior to WNS (Pre-WNS) compared to the population that has survived WNS (Post-WNS). However, when dividing the population with a geographical cut-off between the states of Pennsylvania and New York, a sharp increase in values on scaffold GL429776 is evident in the Post-WNS samples. Genes present in the diverged area are associated with thermoregulation and promotion of brown fat production. Thus, although WNS may not have subjected the entire M. lucifugus population to selective pressure, it may have selected for specific alleles in Pennsylvania through decreased gene flow within the population. However, the persistence of remnant sub-populations in the aftermath of WNS is likely due to multiple factors in bat life history.Peer reviewe

Thermodynamic characterization of RNA triloops

ABSTRACT: Relatively few thermodynamic parameters are available for RNA triloops. Therefore, 24 stemloop sequences containing naturally occurring triloops were optically melted, and the thermodynamic parameters ΔH°, ΔS°, ΔG°3 7 , and T M for each stem-loop were determined. These new experimental values, on average, are 0.5 kcal/mol different from the values predicted for these triloops using the model proposed by Mathews et al. [Mathews, D. H., Disney, M. D., Childs, J. L., Schroeder, S. J., Zuker, M., and Turner, D. H. (2004) Proc. Natl. Acad. Sci. U.S. A. 101, 7287-7292]. The data for the 24 triloops reported here were then combined with the data for five triloops that were published previously. A new model was derived to predict the free energy contribution of previously unmeasured triloops. The average absolute difference between the measured values and the values predicted using this proposed model is 0.3 kcal/mol. These new experimental data and updated predictive model allow for more accurate calculations of the free energy of RNA stemloops containing triloops and, furthermore, should allow for improved prediction of secondary structure from sequence. RNA stem-loops containing three nucleotides in the loop, triloops, are common secondary structure motifs found in naturally occurring RNA. For example, bacterial 16S rRNAs strongly favor tetraloops; however, the UUU triloop is the most common replacement (1). In the 16S-like rRNA variable regions, triloops account for 7% of the loops in bacteria and 16% of the loops in eukaryotes (2). Triloops are also found in large subunit rRNAs (3, 4), 5S rRNAs (5), signal recognition particles (6), RNase P RNAs (7), and group I introns (8, 9). More specifically, triloops are found in Brome mosaic virus (þ) strand RNA (10), human rhinovirus isotype 14 (11), iron responsive element RNA (12), and an RNA aptamer for bacteriophage MS2 coat protein (13), to name a few. Although relatively unstable due to the strain in the loop, triloops may be an important structural feature due to the accessibility of the loop nucleotides for recognition by proteins, other nucleic acids, or small molecules. It has been shown that triloops play a role in various biological processes, including virus replication The current model used by secondary structure prediction algorithms to predict the thermodynamic contribution of RNA triloops to stem-loop stability is sequence independent; all triloops contribute 5.4 kcal/mol to stem-loop stability, with the exception of 5 0 CCC3 0 which contributes 6.9 kcal/mol (21). In addition, there are two unstable triloop sequences (5 0 CAACG3 0 and 5 0 GUUAC3 0 ) for which this predictive model is not used; instead, the ΔG°3 7,loop values (6.8 and 6.9 kcal/mol, respectively) for these two triloops are provided in a lookup table (21). An interesting study by the Bevilacqua laboratory (19) used a combinatorial approach and temperature gradient gel electrophoresis to identify stable and unstable RNA triloops. It was discovered that sequence preferences for exceptionally stable triloops included a U-rich loop and C-G as the closing base pair. Although they used 10 mM NaCl during their melting experiments, they suggested that the rules for predicting triloop stability at 1 M NaCl should be modified; however, this has yet to be done. Here, we report the thermodynamic parameters for 24 previously unmeasured RNA triloops in 1 M NaCl and propose a new algorithm for predicting the contribution of triloops to stem-loop stability, which includes two bonuses for stabilizing sequence features. MATERIALS AND METHODS Compiling and Searching a Database for RNA Triloops. The initial aim of this project was to identify the most frequently occurring RNA triloops in nature and to thermodynamically characterize these hairpin triloop sequences. Therefore, a database of 1349 RNA secondary structures containing 123 small subunit rRNAs (22), 223 large subunit rRNAs (3, 4), 309 5S rRNAs (5), 484 tRNAs (23), 91 signal recognition particles (6), 16 RNase P RNAs (7), 100 group I introns (8, 9), and 3 group II introns (24) was compiled. This database was searched for triloops, and the number of occurrences for each type of triloop was tabulated. In this work, G-U pairs are considered to be canonical base pairs. Design of Sequences for Optical Melting Studies. Since most thermodynamic parameters for RNA secondary structure motifs are reported for RNA solutions containing 1 M NaCl, the melting buffer used in this work also contained 1 M NaCl. A major limitation of a thermodynamic analysis of RNA hairpins using this high salt concentration is the possible bimolecular

Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study

Purpose To determine treatment and aging-related effects on longitudinal cognitive function in older breast cancer survivors. Methods Newly diagnosed nonmetastatic breast cancer survivors (n = 344) and matched controls without cancer (n = 347) 60 years of age and older without dementia or neurologic disease were recruited between August 2010 and December 2015. Data collection occurred during presystemic treatment/control enrollment and at 12 and 24 months through biospecimens; surveys; self-reported Functional Assessment of Cancer Therapy-Cognitive Function; and neuropsychological tests that measured attention, processing speed, and executive function (APE) and learning and memory (LM). Linear mixed-effects models tested two-way interactions of treatment group (control, chemotherapy with or without hormonal therapy, and hormonal therapy) and time and explored three-way interactions of ApoE (ε4+ v not) by group by time; covariates included baseline age, frailty, race, and cognitive reserve. Results Survivors and controls were 60 to 98 years of age, were well educated, and had similar baseline cognitive scores. Treatment was related to longitudinal cognition scores, with survivors who received chemotherapy having increasingly worse APE scores (P = .05) and those initiating hormonal therapy having lower LM scores at 12 months (P = .03) than other groups. These group-by-time differences varied by ApoE genotype, where only ε4+ survivors receiving hormone therapy had short-term decreases in adjusted LM scores (three-way interaction P = .03). For APE, the three-way interaction was not significant (P = .14), but scores were significantly lower for ε4+ survivors exposed to chemotherapy (−0.40; 95% CI, −0.79 to −0.01) at 24 months than ε4+ controls (0.01; 95% CI, 0.16 to 0.18; P < .05). Increasing age was associated with lower baseline scores on all cognitive measures (P < .001); frailty was associated with baseline APE and self-reported decline (P < .001). Conclusion Breast cancer systemic treatment and aging-related phenotypes and genotypes are associated with longitudinal decreases in cognitive function scores in older survivors. These data could inform treatment decision making and survivorship care planning

Genome-Wide Changes in Genetic Diversity in a Population of Myotis lucifugus Affected by White-Nose Syndrome

Novel pathogens can cause massive declines in populations, and even extirpation of hosts. But disease can also act as a selective pressure on survivors, driving the evolution of resistance or tolerance. Bat white-nose syndrome (WNS) is a rapidly spreading wildlife disease in North America. The fungus causing the disease invades skin tissues of hibernating bats, resulting in disruption of hibernation behavior, premature energy depletion, and subsequent death. We used whole-genome sequencing to investigate changes in allele frequencies within a population of Myotis lucifugus in eastern North America to search for genetic resistance to WNS. Our results show low F-ST values within the population across time, i.e., prior to WNS (Pre-WNS) compared to the population that has survived WNS (Post-WNS). However, when dividing the population with a geographical cut-off between the states of Pennsylvania and New York, a sharp increase in values on scaffold GL429776 is evident in the Post-WNS samples. Genes present in the diverged area are associated with thermoregulation and promotion of brown fat production. Thus, although WNS may not have subjected the entire M. lucifugus population to selective pressure, it may have selected for specific alleles in Pennsylvania through decreased gene flow within the population. However, the persistence of remnant sub-populations in the aftermath of WNS is likely due to multiple factors in bat life history