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At least 55 records · Page 3

YAP1 Dysfunction Promotes Molecular Properties Linked to Breast Cancer Susceptibility

YAP1 is a cotranscription factor that promotes malignant and stem cell properties in cancer. We previously found that YAP1 dysregulation is associated with aging in human mammary epithelia. With increased age, YAP1 expression changes in luminal epithelial cells, the prospective breast cancer cell of origin. Because age is a significant risk factor for breast cancer, we tested whether YAP1 dysregulation acted early in cancer progression by conferring cellular states associated with increased cancer susceptibility. In this study, we find that with increased age and genetic risk for developing cancer, human breast tissues showed significantly increased YAP1 expression, and cultured primary human mammary epithelial cells (HMEC) showed significantly increased expression of both YAP1 and its transcriptional targets. Increased YAP1 expression in cultured HMEC induced gene expression changes associated with increased cancer susceptibility, such as genes associated with stem cell states, increased telomerase activity, breast cancer progression, and increased age and genetic breast cancer risk. Furthermore, overexpression of YAP1 in post-stasis HMEC—finite lifespan cells that have bypassed a retinoblastoma-mediated senescence barrier—promoted properties related to increased growth potential. We found that YAP1 dysregulation in finite epithelial cells allows for access to gene programs and functions that are typically thought to be restricted to stem cells. We hypothesize that YAP1 acts early in breast cancer progression, long before the development of a tumor, to impose cancer-susceptible molecular states.

YAP1

Landslides Across the USA: Occurrence, Susceptibility, and Data Limitations

Detailed information about landslide occurrence is the foundation for advancing process understanding, susceptibility mapping, and risk reduction. Despite the recent revolution in digital elevation data and remote sensing technologies, landslide mapping remains resource intensive. Consequently, a modern, comprehensive map of landslide occurrence across the United States (USA) has not been compiled. As a first step toward this goal, we present a national-scale compilation of existing, publicly available landslide inventories. This geodatabase can be downloaded in its entirety or viewed through an online, searchable map, with parsimonious attributes and direct links to the contributing sources with additional details. The mapped spatial pattern and concentration of landslides are consistent with prior characterization of susceptibility within the conterminous USA, with some notable exceptions on the West Coast. Although the database is evolving and known to be incomplete in many regions, it confirms that landslides do occur across the country, thus highlighting the importance of our national-scale assessment. The map illustrates regions where high-quality mapping has occurred and, in contrast, where additional resources could improve confidence in landslide characterization. For example, borders between states and other jurisdictions are quite apparent, indicating the variation in approaches to data collection by different agencies and disparity between the resources dedicated to landslide characterization. Further investigations are needed to better assess susceptibility and to determine whether regions with high relief and steep topography, but without mapped landslides, require further landslide inventory mapping. Overall, this map provides a new resource for accessing information about known landslides across the USA.

Landslide mapping

Chrono-Validation of Near-Real-Time Landslide Susceptibility Models via Plugin Statistical Simulations

The idea behind any validation scheme in landslide susceptibility studies is to test whether a model calibrated on a certain data can predict an unknown dataset of the same nature (landslide presences/absences and covariates). Almost the entirety of landslide susceptibility studies are validated by subsetting a single dataset into a training and test sets. This dataset usually corresponds either to event-specific or to historical inventories. Very rarely, a multi-temporal inventory is available and, in the few cases where this condition is met, the validation practices involve training a model on a specific landslide inventory, deriving a single predictive equation and validating it on a subsequent landslide inventory. This commonly leads landslide predictive studies, even those with a strong statistical rigor, to neglect the uncertainty estimation in their modeling scheme. In statistics, validation can also be performed via statistical simulations. This means that after fitting a given model, one can generate any number of predictive functions and test their predictive skills on any type and number of unknown datasets. In this work, we take a similar direction and we apply it to model and validate three separate co-seismic inventories, including an uncertainty estimation phase. We mapped these inventories within the same area in Indonesia, for three earthquakes occurred in 2012, 2017 and 2018. Specifically, we build three event-specific Bayesian Generalize Additive Models of the binomial family. From each model we then simulate 1000 predictive realizations over the remaining two inventories, by using a plug-in scheme where all the morphometric covariates are kept fixed and only the ground motion is replaced according to the prediction target. By doing so, we introduce a new analytical tool for near-real-time landslide predictive purposes, which is able to produce a probabilistic model which stands in between the definitions of susceptibility and hazard. In fact, our model is able to accurately estimate “where” and “when” - although not “how frequently” - landslide have occurred by featuring the multitemporal information of the trigger. In our findings, the simulations are quite similar to the fitted models; and the nine combinations we analyse produce excellent performance. This result confirms the assumption that “the past is the key to the future”, as we show that the relative contribution of each variable and their interactions in each probabilistic model remains practically the same across temporal replicates. This information is not trivial because it supports the routines implemented in global near-real-time applications.

Temporal validation

Ion diffusion retarded by diverging chemical susceptibility

Abstract For first-order phase transitions, the second derivatives of Gibbs free energy (specific heat and compressibility) diverge at the transition point, resulting in an effect known as super-elasticity along the pressure axis, or super-thermicity along the temperature axis. Here we report a chemical analogy of these singularity effects along the atomic doping axis, where the second derivative of Gibbs free energy (chemical susceptibility) diverges at the transition point, leading to an anomalously high energy barrier for dopant diffusion in co-existing phases, an effect we coin as super-susceptibility. The effect is realized in hydrogen diffusion in vanadium dioxide (VO 2 ) with a metal-insulator transition (MIT). We show that hydrogen faces three times higher energy barrier and over one order of magnitude lower diffusivity when it diffuses across a metal-insulator domain wall in VO 2 . The additional energy barrier is attributed to a volumetric energy penalty that the diffusers need to pay for the reduction of latent heat. The super-susceptibility and resultant retarded atomic diffusion are expected to exist universally in all phase transformations where the transformation temperature is coupled to chemical composition, and inspires new ways to engineer dopant diffusion in phase-coexisting material systems.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH

Theory of nonlinear terahertz susceptibility in ferroelectrics

An analytical theory is developed for predicting the nonlinear susceptibility of ionic polarization to continuous electromagnetic waves in both bulk and strained thin film ferroelectrics. Using a perturbation method for solving the nonlinear equation of motion for ionic polarization within the framework of Landau-Ginzburg-Devonshire theory, the full second-order nonlinear susceptibility tensor is derived as a function of frequency, temperature, and strain. Here, the theory predicts the coexistence of a significantly enhanced second-order dielectric susceptibility and a relatively low dielectric loss in BaTiO 3 films with a strain-stabilized monoclinic ferroelectric phase and in a strained SrTiO 3 film near its temperature-driven second-order ferroelectric-to-paraelectric phase transition. In this paper, we establish a theoretical framework for predicting and exploiting nonlinear interactions between terahertz waves and ferroelectric materials and, more generally, suggest exciting opportunities to strain-engineer nonlinear dynamical properties of ferroelectrics beyond the static and quasistatic limits.

36 MATERIALS SCIENCE

Relative susceptibility of titanium alloys to hot-salt stress-corrosion

Susceptibility of titanium alloys to hot-salt stress-corrosion cracking increased as follows: Ti-2Al-11Sn-5Zr-0.2Si(679), Ti-6Al-2Sn-4Zr-2Mo(6242), Ti-6Al-4V(64), Ti-6Al-4V-3Co(643), Ti-8Al-1Mo-1V(811), and Ti-13V-11Cr-3A1(13-11-3). The Ti-5Al-6Sn-2Zr-1Mo-0.25Si(5621S) alloy was both the least and most susceptible depending on heat treatment. Such rankings can be drastically altered by heat-to-heat and processing variations. Residual compressive stresses and cyclic exposures also reduce susceptibility to stress-corrosion. Simulated turbine-engine compressor environmental variables such as air velocity, pressure, dewpoint, salt concentration, and salt deposition temperature have only minor effects. Detection of substantial concentrations of hydrogen in all corroded alloys confirmed the existence of a hydrogen embrittlement mechanism.

Gray, H. R.

Altered susceptibility to motion sickness as a function of subgravity level.

Large interindividual differences among 74 normal subjects in the change in susceptibility to motion sickness with effective lifting of the normal g-load by parabolic flight maneuvers were recorded with high test-retest reliability. Most subjects, who were required to make standardized head movements while seated in a chair rotating at a constant speed, demonstrated either a substantial increase or a decrease in susceptibility, in confirmation of a previous study, while a few appeared to be more or less unaffected by the 1 g to 0 g gravitational change. A similar test procedure conducted with eighteen of the subjects at lunar- and Martian-gravity levels revealed further interindividual differences in susceptibility as a function of g-level.

Miller, E. F., II

Stress corrosion cracking susceptibility of 18 Ni maraging steel

The stress corrosion cracking (SCC) resistance of 18Ni maraging steel (grades 200, 250, 300, and 350) was determined in 3.5 percent salt (NaCl) solution, synthetic sea water, high humidity, and outside MSFC atmosphere. All grades of the maraging steel were found to be susceptible to SCC in varying degrees according to their strengths, with the lowest strength steel (grade 200) being the least susceptible and the highest strength steel (grade 350), the most susceptible to SCC. The SCC resistance of 250 grade maraging steel was also evaluated in salt and salt-chromate solutions using fracture mechanics techniques. The threshold value, K sub SCC, was found to be approximately 44 MN/sq m square root m, (40 ksi square root in.) or 40 percent of the K sub Q value.

Humphries, T. S.

Comparison of five levels of motion sickness severity as the basis for grading susceptibility

The motion sickness susceptibility of 275 healthy male subjects was measured quantitatively by a standardized laboratory procedure using a Stille rotational chair. The results, in terms of velocity of the chair and the number of active head movements, were combined into a single numerical score that represented the total stressor stimulus sustained in reaching, in turn, each of five specific criteria for diagnosing the severity of motion sickness. The stressor value (E factor) of a single head movement at each test rpm was adjusted to yield an equivalent susceptibility score (Coriolis Sickness Susceptibility Index, or CSSI) independent of the endpoint selected. Close agreement among the CSSI scores obtained at each endpoint was found in intercorrelations, test-retest reliability coefficients, and frequency distributions, which reflected the orderliness and stability in the appearance, ramification, and intensification of the acute symptomatology evoked in progressing from mild malaise to frank sickness.

Miller, E. F., II

Individual differences in susceptibility to motion sickness among six Skylab astronauts

Motion sickness was studied in Skylab crewmen. By mission-day 8 (MD 8), astronauts were virtually free of motion sickness symptoms after rotation and linear acceleration tests. None of the Skylab-II astronauts (crewmen 1-3) was motion sick aloft, but astronaut 6 of the Skylab-III crew experienced motion sickness within an hour after transition into orbit. All three astronauts (4-6) of Skylab-III experienced motion sickness in the workshop, where astronaut 6 was most susceptible and astronaut 4 least susceptible. The higher susceptibility of SL-III crewmen in the workshop, as compared with SL-II crewmen, may be attributable to the fact that they were based in the command module (CM) less than one-third as long as were SL-II astronauts. I.e., the unnatural movements permitted in the open spaces of the workshop entrained more complex interactions of unusual vestibular and visual stimuli than did those in the CM. The observed reduced liability to kinetosis relative to earth may be due to absence of the gravity stimulus to the otolith organs.

Graybiel, A.

Magnetization and magnetic susceptibilities of GdH3, HoH3, ErH3 and YbH3

The magnetic susceptibility of powdered samples of HoH3, ErH3, GdH3 and YbH3 have been measured in the temperature range from 4.2 to 1.2 K. Two broad, local maxima are observed in the variation of chi versus T for GdH3, with maxima in (delta chi delta T) versus T at 1.8 K and 3.3 K. The inverse susceptibilities for HoH3 and ErH3 both obey a Curies-Weiss law over a limited range (4.2 to 2.6K and 4.2 to 2 K respectively) with values for the Weiss constant of -4.25 K and -1.11 K, and effective moments of 8.6 and 7.7 Bohr magnetons respectively. The susceptibility of YbH3 is independent of temperature over the range investigated. High-field magnetization measurements yield extrapolated saturation moments of 7.0 + or - 0.25 Bohr magnetons/ion for GdH3, 6.1 + or - 0.2 Bohr magnetons/ion for HoH3 and 3.74 + or - 0.11 Bohr magnetons/ion for ErH3. In addition, ErH3 exhibits a van Vleck paramagnetism in the high field region.

Flood, D. J.

Observed differences in learning ability of heart rate self-regulation as a function of hypnotic susceptibility

Three groups of eight male and female subjects (aged 20-27 yr) categorized by low and high hypnotic susceptibility were taught to control their heart rates by means of an appropriate autogenic therapy/biofeedback technique. The experimental groups were trained by autogenic therapy and biofeedback, while the control group received only biofeedback. Significant differences are observed in all psychological test scores between subjects of high and low hypnotic susceptibility. The results confirm that (1) there are qualitative and quantitative differences between the performance of individuals with high and low hypnotic susceptibility; (2) interindividual-variability tests yield data relevant to individual performance in visceral learning tasks; (3) the combined autogenic therapy/biofeedback/verbal feedback technique is suitable for conditioning large stable autonomic responses in humans; and (4) this kind of conditioning is effective in eliminating or alleviating physiological reactions to some environmental stressors.

Cowings, P. S.

Susceptibility measurements on the superconducting properties of Nb-Ge alloys

A susceptibility apparatus to measure superconducting properties of samples made in the MSFC Drop Tube was used to measure the transition temperature (Tc) and susceptibilities of Nb and Nb Ge Alloys prepared in bulk spherical (2-4 mm diameter) form using a 32 m drop tube in which containerless low gravity solidification could take place. Results indicate that a drop tube processing environment was beneficial for increasing the Tc of the superconducting phase of the material over that of arc melted material. The increase in Tc is found to be related to the amount of solidification of the total sample that took place before reaching the bottom of the drop tube. In phase and quadrature phase measurements of the specimen's susceptibility indicated that some improvement in homogeneity takes place in drop tube processing. These phase measurements also indicated little or no shielding of a lower Tc phase by a higher Tc filamentary structure.

Rathz, T. J.

ac susceptibility of thermally annealed and neutron irradiated Cu-Ni alloys

Thermal annealing and high-flux neutron irradiation are used to vary the degree of short-range atomic order in Cu-Ni alloys of composition 40, 50, and 60 at. pct Ni. The magnetic state is measured by ac magnetic susceptibility measurements. It is shown that annealing at 350 C causes significant changes in the susceptibility of all the samples. In the 50 and 60 at. pct Ni samples, the transition is broadened and extended to higher temperatures, while the 40 at. pct Ni sample changes from a paramagnetic system to a weakly ferromagnetic system. The neutron irradiation, in contrast to the thermal treatment, causes the development of smaller size cluster formations. The irradiated 60 at. pct Ni sample exhibits no change in the shape of its susceptibility curve from that of the quenched sample, whereas, the 40 pct alloy is changed, by irradiation, from a paramagnetic system to a spin-glass system.

Catchings, R. M., III

Theoretical study relating the two-photon absorption cross section to the susceptibility controlling four-wave mixing

A theory that it is necessary to extract a two-photon absorption cross section from a mixing signal is developed. The dependence of the cross section on the third-order susceptibility is shown and both the mixing signal and reference signal dependences on the susceptibility are given. Techniques to process the measured value of the susceptibility and relate it to the cross section are developed and limits of validity are established. Finally, a comparison is made between the expression for the cross section presently reported and values given elsewhere.

Burris, J.

Endocrine correlates of susceptibility to motion sickness

Motion sickness releases ACTH, epinerphrine, and norepinephrine. The endocrine responses to motion sickness, adaptive responses leading to the resolution of the syndrome, and the way in which antimotion-sickness drugs influence the endocrine responses were studied. Susceptible or insusceptible subjects were administered antimotion-sickness drugs prior to stressful stimulation. Insusceptible subjects displayed more pronounced elevations of ACTH, epinephrine, and norepinephrine after stressful motion. Predrug levels of ACTH were higher in insusceptible subjects (p less than 0.01). Acute blockade of hormone responses to stressful motion or alteration of levels of ACTH by drugs were not correlated with individual susceptibility. No correlation was apparent between epinephrine and ACTH release. These endocrine differences may represent neurochemical markers for susceptibility to motion, stress, or general adaptability, and it may be that the chronic modulation of their levels might be more effective in preventing motion sickness than the acute blockage or stimulation of specific receptors.

Kohl, R. L.

Oculomotor function during space flight and susceptibility to space motion sickness

Horizontal vestibulo-ocular reflex (VOR) and saccadic eye movements (SEM) were studied in 18 subjects before and during five Space Shuttle missions to evaluate the effects of weightlessness and correlations between results and susceptibility to and actual presence of space motion sickness (SMS). Active sinusoidal head oscillation was the stimulus for VOR tests with vision (VVOR), with eyes shaded (VOR-ES), and VOR suppression (VOR-S). Eye movements were recorded by electrooculography and head position by a potentiometer. No pathological nystagmus or other abnormal eye movements were seen. No significant in-flight changes were seen in the gain, phase shift or waveform of VVOR, VOR-ES or VOR-S. Statistically significant increases in saccadic latency and decreases in saccadic velocity were seen, with no change in saccadic accuracy. Preflight differences between SMS susceptible and nonsusceptible subjects were noted only in VOR-S, with less complete suppression in susceptible subjects, a finding also seen in flight. During flight, VVOR gain was significantly increased in three nonaffected subjects. Saccades of SMS-affected subjects showed increased latency and velocity and decreased accuracy compared to saccades of unaffected subjects.

Thornton, William E.

Development of an Antimicrobial Susceptibility Testing Method Suitable for Performing During Space Flight

Very little is known regarding the affects of the microgravity environment of space flight upon the action of antimicrobial agents on bacterial pathogens. This study was undertaken to develop a simple method for conducting antibacterial susceptibility tests during a Space Shuttle mission. Specially prepared susceptibility test research cards (bioMerieux Vitek, Hazelwood, MO) were designed to include 6-11 serial two-fold dilutions of 14 antimicrobial agents, including penicillins, cephalosporins, a Beta-lactamase inhibitor, vancomycin, erythromycin, tetracycline, gentamicin, ciprofloxacin, and trimethoprim/sulfamethoxazole. Minimal inhibitory concentrations (MICS) of the drugs were determined by visual reading of color endpoints in the Vitek research cards made possible by incorporation of a colorimetric growth indicator (alamarBlue(Trademark), Accumed International, Westlake, OH). This study has demonstrated reproducible susceptibility results when testing isolates of Staphylococcus aurezis, Group A Streptococcus, Enterococcusfaecalis, Escherichia coli (beta-lactamase positive and negative strains), Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomoiias aeruginosa. In some instances, the MICs were comparable to those determined using a standard broth microdilution method, while in some cases the unique test media and format yielded slightly different values, that were themselves reproducible. The proposed in-flight experiment will include inoculation of the Vitek cards on the ground prior to launch of the Space Shuttle, storage of inoculated cards at refrigeration temperature aboard the Space Shuttle until experiment initiation, then incubation of the cards for 18-48 h prior to visual interpretation of MICs by the mission's astronauts. Ground-based studies have shown reproducible MICs following storage of inoculated cards for 7 days at 4-8 C to accommodate the mission's time schedule and the astronauts' activities. For comparison, ground-based control (normal gravity) MIC values will be generated by simultaneous inoculation and incubation of a second set of test cards in a laboratory at the launch site. This procedure can provide a safe and compact experiment that should yield new information on the affects of microgravity on the biological activities of various classes of antibiotics.

Jorgensen, James H.