Hot Spot Size Research Articles

Prognostic potential of automated Ki67 evaluation in breast cancer: different hot spot definitions versus true global score

PurposeThe proliferation-associated biomarker Ki67 has potential utility in breast cancer, including aiding decisions based on prognosis, but has unacceptable inter- and intralaboratory variability. The aim of this study was to compare the prognostic potential for Ki67 hot spot scoring and global scoring using different digital image analysis (DIA) platforms.MethodsAn ER+/HER2− breast cancer cohort (n = 139) with whole slide images of sequential sections stained for hematoxylin–eosin, pancytokeratin and Ki67, was analyzed using two DIA platforms. For hot spot analysis virtual dual staining was applied, aligning pancytokeratin and Ki67 images and 22 hot spot algorithms with different features were designed. For global Ki67 scoring an automated QuPath algorithm was applied on Ki67-stained whole slide images. Clinicopathological data included overall survival (OS) and recurrence-free survival (RFS) along with PAM50 molecular subtypes.ResultsWe show significant variations in Ki67 hot spot scoring depending on number of included tumor cells, hot spot size, shape and location. The higher the number of scored tumor cells, the higher the reproducibility of Ki67 proliferation values. Hot spot scoring had greater prognostic potential for RFS in high versus low Ki67 subgroups (hazard ratio (HR) 6.88, CI 2.07–22.87, p = 0.002), compared to global scoring (HR 3.13, CI 1.41–6.96, p = 0.005). Regarding OS, global scoring (HR 7.46, CI 2.46–22.58, p < 0.001) was slightly better than hot spot scoring (HR 6.93, CI 1.61–29.91, p = 0.009). In adjusted multivariate analysis, only global scoring was an independent prognostic marker for both RFS and OS. In addition, global Ki67-based surrogate subtypes reached higher concordance with PAM50 molecular subtype for luminal A and B tumors (66.3% concordance rate, κ = 0.345), than using hot spot scoring (55.8% concordance rate, κ = 0.250).ConclusionsWe conclude that the automated global Ki67 scoring is feasible and shows clinical validity, which, however, needs to be confirmed in a larger cohort before clinical implementation.

Impact of Void Structure on Initiation Sensitivity

AbstractThe influence of microstructural variation on the initiation of octahydro‐1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocine (HMX) has been evaluated. These evaluations encompass two classes of fine‐grain HMX, Class 5 and Fluid Energy Milled (FEM). Initiation data of HMX using thick Polyimide flyers (203 μm) near the power flux (Πc) limiting condition (2.26 GPa to 4.63 GPa) as a function of density are presented. The initiation results depict decreasing threshold velocities as density decreases for both materials. The Class 5 has a lower threshold velocity value than the FEM at comparable density values. Microstructure evaluations based solely on the total specific interface area (SIA) are inconsistent with the initiation results. Further evaluation resulted in the requirement of calculating cumulative SIA as a function of feature size to match the trends observed in threshold behavior. The results support the concept of an activated hot spot size as a function of pressure as formulated by Khasainov et al. [1]. Analysis of the microstructure indicates the distinguishing features between Class 5 and FEM are the large particle size tails of the distributions.

Combustion Hotspots of Energetic Condensed Systems

The conditions of occurrence, nature, size, and shape of combustion hotspots of energetic condensed systems and the spatial dynamics of the hotspot combustion wave are discussed. A model for the propagation of hotspot combustion waves in condensed systems is briefly described based on the cellular automata method. A possible explanation for the occurrence of unsteady effects in the combustion of solid rocket propellants is proposed.

Numerical studies on autoignition and detonation development from a hot spot in hydrogen/air mixtures

Detonation development inside spark ignition engines can result in the so called super-knock with extremely high pressure oscillation above 200 atm. In this study, numerical simulations of autoignitive reaction front propagation in hydrogen/air mixtures are conducted and the detonation development regime is investigated. A hot spot with linear temperature distribution is used to induce autoignitive reaction front propagation. With the change of temperature gradient or hot spot size, three typical autoignition reaction front modes are identified: supersonic reaction front; detonation development and subsonic reaction front. The effects of initial pressure, initial temperature, fuel type and equivalence ratio on detonation development regime are examined. It is found that the detonation development regime strongly depends on mixture composition (fuel and equivalence ratio) and thermal conditions (initial pressure and temperature). Therefore, to achieve the quantitative prediction of super-knock in engines, we need use the detonation development regime for specific fuel at specific initial temperature, initial pressure, and equivalence ratio.

Hot spots analysis of a sample of 98 Fanaroff-Riley II radio sources

This paper reports our final results related to the study of hot spots (HSs) in a sample of 98 Fanaroff-Riley class II (FR II) radio sources using the VLA at 8.4 GHz. The sample contains 52 radio galaxies (RGs) and 46 quasars (QSRs). We discuss the properties of these HSs, i.e., location (edged or recessed), morphology, and size. The main result is that the number of edged (and recessed) HSs is more for the RGs than for the QSRs. Regarding the compactness of these HSs, QSRs tend to have more compact HSs than RGs. We also found a significant correlation between the hot spot size and the source linear size for the RGs, but not for the QSRs. We discuss the overall properties of the HSs in light of the current models of radio sources.

Detection of overtone and combined peaks using Mn/Cu helical star-shaped (pine-tree-like) sculptured thin films in surface-enhanced Raman spectroscopy

Mn helical star-shaped (pine-tree-like) nano-sculptured thin films with three-, four-and fivefold symmetry on copper substrates were produced using oblique angle deposition method in conjunction with rotation of sample holder at certain angles. Raman spectroscopy of the samples which were subjected to impregnation by 4,4′-bipyridine (C10H8N2) solution was carried out by 632.8 nm wavelength laser. The analysis of the Raman spectra showed enhancement for the 4,4′-bipyridine main bands (1592 and 1297 cm−1) belonging to the C=C stretching mode, aromatic ring stretching ring and in-plane ring mode of 4,4′-bipyridine, same as results obtained for Ag nano-structures. In addition, overtone and combined peaks are detected that may be related to the particular sculptured structure of the thin films fabricated in this work and the laser wavelength used for Raman spectroscopy. UV–Vis (absorption mode) spectra showed consistent observations with the SERS results leading to important role of surface electromagnetic selection rule in intensification of SERS, in addition pointing out the importance of the effect of the size of hot spots on the frequency of the localized surface plasmonic oscillations.

Slow Coarsening in Jammed Athermal Soft Particle Suspensions.

We simulate a densely jammed, athermal assembly of repulsive soft particles immersed in a solvent. Starting from an initial condition corresponding to a quench from a high temperature, we find nontrivial slow dynamics driven by a gradual release of stored elastic energy, with the root mean squared particle speed decaying as a power law in time with a fractional exponent. This decay is accompanied by the presence within the assembly of spatially localized and temporally intermittent "hot spots" of nonaffine deformation, connected by long-ranged swirls in the velocity field, reminiscent of the local plastic events and long-ranged elastic propagation that have been intensively studied in sheared amorphous materials. The pattern of hot spots progressively coarsens, with the hot-spot size and separation slowly growing over time, and the associated correlation length in particle speed increasing as a sublinear power law. Each individual spot, however, exists only transiently within an overall picture of strongly intermittent dynamics.

Finite size effects on the light curves of slowly-rotating neutron stars

An important question when studying the light curves produced by hot spots on the surface of rotating neutron stars is, how might the shape of the light curve be affected by relaxing some of the simplifying assumptions that one would adopt on a first treatment of the problem, such as that of a point-like spot. In this work we explore the dependence of light curves on the size and shape of a single hot spot on the surface of slowly-rotating neutron stars. More specifically, we consider two different shapes for the hot spots (circular and annular) and examine the resulting light curves as functions of the opening angle of the hot spot (for both) and width (for the latter). We find that the point-like approximation can describe light curves reasonably well, if the opening angle of the hot spot is less than $\sim 5^\circ$. Furthermore, we find that light curves from annular spots are almost the same as those of the full circular spot if the opening angle is less than $\sim 35^\circ$ independently of the hot spot's width.

How Do Ocean Warm Anomalies Favor the Aggregation of Deep Convective Clouds?

AbstractWe investigate the role of a warm sea surface temperature (SST) anomaly (hot spot of typically 3 to 5 K) on the aggregation of convection using cloud-resolving simulations in a nonrotating framework. It is well known that SST gradients can spatially organize convection. Even with uniform SST, the spontaneous self-aggregation of convection is possible above a critical SST (here 295 K), arising mainly from radiative feedbacks. We investigate how a circular hot spot helps organize convection, and how self-aggregation feedbacks modulate this organization. The hot spot significantly accelerates aggregation, particularly for warmer/larger hot spots, and extends the range of SSTs for which aggregation occurs; however, at cold SST (290 K) the aggregated cluster disaggregates if we remove the hot spot. A large convective instability over the hot spot leads to stronger convection and generates a large-scale circulation which forces the subsidence drying outside the hot spot. Indeed, convection over the hot spot brings the atmosphere toward a warmer temperature. The warmer temperatures are imprinted over the whole domain by gravity waves and subsidence warming. The initial transient warming and concomitant subsidence drying suppress convection outside the hot spot, thus driving the aggregation. The hot-spot-induced large-scale circulation can enforce the aggregation even without radiative feedbacks for hot spots sufficiently large/warm. The strength of the large-scale circulation, which defines the speed of aggregation, is a function of the hot spot fractional area. At equilibrium, once the aggregation is well established, the moist convective region with upward midtropospheric motion, centered over the hot spot, has an area surprisingly independent of the hot spot size.

Burn regimes in the hydrodynamic scaling of perturbed inertial confinement fusion hotspots

We present simulations of ignition and burn based on the Highfoot and high-density carbon indirect drive designs of the National Ignition Facility for three regimes of alpha-heating—self-heating, robust ignition and propagating burn—exploring hotspot power balance, perturbations and hydrodynamic scaling. A Monte-Carlo particle-in-cell charged particle transport package for the radiation-magnetohydrodynamics code Chimera was developed for this purpose, using a linked-list type data structure.The hotspot power balance between alpha-heating, electron thermal conduction and radiation was investigated in 1D for the three burn regimes. Stronger alpha-heating levels alter the hydrodynamics: sharper temperature and density gradients at hotspot edge; and increased hotspot pressures which further compress the shell, increase hotspot size and induce faster re-expansion. The impact of perturbations on this power balance is explored in 3D using a single Rayleigh–Taylor spike. Heat flow into the perturbation from thermal conduction and alpha-heating increases by factors of , due to sharper temperature gradients and increased proximity of the cold, dense material to the main fusion regions respectively. The radiative contribution remains largely unaffected in magnitude.Hydrodynamic scaling with capsule size and laser energy of different perturbation scenarios (a short-wavelength multi-mode and a long-wavelength radiation asymmetry) is explored in 3D, demonstrating the differing hydrodynamic evolution of the three alpha-heating regimes. The multi-mode yield increases faster with scale factor due to more synchronous compression producing higher temperatures and densities, and therefore stronger bootstrapping of alpha-heating. The perturbed implosions exhibit differences in hydrodynamic evolution due to alpha-heating in addition to the 1D effects, including: reduced perturbation growth due to ablation from both fire-polishing and stronger thermal conduction; and faster re-expansion into regions of weak confinement, which can result in loss of confinement.

Temperature gradient induced detonation development inside and outside a hotspot for different fuels

With the dimensionless parameters obtained for syngas/air mixture, Bradley detonation peninsula is often used to determine the detonation development for hotspot autoignition (AI) in reactive flows. In this work, similar numerical simulations were carried out in order to identify the characteristics of detonation peninsula when considering other fuels. Three alternative C0-1 fuels with detailed chemistry and transport were employed in a 1-D reaction wave propagation induced by temperature gradients, and different critical temperature gradients and hotspot sizes were considered. Meanwhile, the role of detonation parameters in the detonation development outside hotspot was addressed. First, the results show that different AI propagation modes can be well depicted using the dimensionless parameters for individual fuel at various critical temperature gradients. However, the quantitative difference in detonation development regime is significantly observed between different fuels with distinct physical–chemical properties even though similar regime distribution is observed. Second, the evolutions of AI reaction wave propagation outside hotspot were further studied, and combustion mode transitions involving detonation termination and formation were observed. The evolutions of the thermodynamic state of different flow particles show that detonation development is found to switch from constant-pressure to constant-volume combustion. Meanwhile, scaling analysis on combustion mode transitions indicates that besides the early-stage propagation controlled by reactivity gradient in hotspot interior, the reactivity of the mixture outside hotspot also plays an important role in detonation development. This can provide great insights into proposing integrated dimensionless parameters for determining detonation development in the whole reactive flows.

Thermonuclear ignition and the onset of propagating burn in inertial fusion implosions.

Separating ignition of the central hot spot from propagating burn in the surrounding dense fuel is crucial to conclusively assess the achievement of ignition in inertial confinement fusion (ICF). We show that the transition from hot spot ignition to the onset of propagating burn occurs when the alpha heating within the hot spot has amplified the fusion yield by 15× to 25× with respect to the compression-only case without alpha energy deposition. This yield amplification corresponds to a value of the fractional alpha energy f_{α}≈1.4 (f_{α}=0.5 alpha energy/hot spot energy). The parameter f_{α} can be inferred in ICF experiments by measuring the neutron yield, hot spot size, temperature, and burn width. This ignition threshold is measurable and applicable to all ICF implosions of deuterium and tritium targets both direct and indirect drive. The results of this Rapid Communication can be used to set the goals of the ICF effort with respect to the first demonstration of thermonuclear ignition.

Estimating nucleon substructure properties in a unified model of p-Pb and Pb-Pb collisions

We apply a well tested hybrid transport model, which couples viscous hydrodynamics to a hadronic afterburner, to describe bulk observables in proton-lead and lead-lead collisions at sNN=5.02TeV. The quark-gluon plasma (QGP) initial conditions are modeled using the parametric TRENTo model with additional nucleon substructure parameters to vary the number and size of hot spots inside each nucleon, followed by a pre-equilibrium free streaming stage to match the full energy-momentum tensor of the initial state onto viscous hydrodynamics. Initial condition and QGP medium parameters, such as the temperature dependence of the QGP shear and bulk viscosities, are then calibrated using Bayesian parameter estimation to describe charged particle yields, mean pT and anisotropic flow harmonics of both collision systems in a single self-consistent framework. We find that the hybrid model provides a compelling, simultaneous description of both collision systems using appropriately chosen model parameters, and present new posterior estimates for the size and shape of the nucleon and temperature dependence of QGP shear and bulk viscosities.

Probing the transverse size of initial inhomogeneities with flow observables

Disentangling the effect of initial conditions and medium properties is an open question in the field of relativistic heavy-ion collisions. We argue that, while one can study the impact of initial inhomogeneities by varying their size, it is important to maintain the global properties fixed. We present a method to do this. We show that many observables are insensitive to the the hot spot sizes, including integrated vn, scaled distributions of vn, symmetric cumulants, event-plane correlations, and differential vn(pT). We find however that the factorization breaking ratio rn and sub-leading component in a Principal Component Analysis are more sensitive to the initial granularity and can be used to probe short-scale features of the initial density.

Imaging assessment of cardioprotection mediated by a dodecafluoropentane oxygen-carrier administered during myocardial infarction

IntroductionThe objective of this study was to investigate the cardioprotective effects of a dodecafluoropentane (DDFP)-based perfluorocarbon emulsion (DDFPe) as an artificial carrier for oxygen delivery to ischemic myocardium, using 99mTc-duramycin SPECT imaging. MethodsRat hearts with Ischemia-reperfusion (I/R) was prepared by coronary ligation for 45-min followed by reperfusion. The feasibility of 99mTc-duramycin in detecting myocardial I/R injury and its kinetic profile were first verified in the ischemic hearts with 2-h reperfusion (n = 6). DDFPe (0.6 mL/kg) was intravenously administered at 10 min after coronary ligation in fifteen rats and saline was given in thirteen rats as controls. 99mTc-duramycin SPECT images were acquired in the DDFPe-treated hearts and saline controls at 2-h (DDFPe-2 h, n = 7 and Saline-2 h, n = 6) or 24-h (DDFPe-24 h, n = 8 and Saline-24 h, n = 7) of reperfusion. ResultsSPECT images, showing “hot-spot” 99mTc-duramycin uptake in the ischemic myocardium, exhibited significantly lower radioactive retention and smaller hot-spot size in the DDFPe-2 h and DDFPe-24 h hearts compared to controls. The infarcts in the Saline-24 h hearts extended significantly relative to measurements in the Saline-2 h. The extension of infarct size did not reach a statistical difference between the DDFPe-2 h and DDFPe-24 h hearts. Ex vivo measurement of 99mTc-duramycin activity (%ID/g) was lower in the ischemic area of DDFPe-2 h and DDFPe-24 h than that of the Saline-2 h and Saline-24 h hearts (P < 0.05). The area of injured myocardium, delineated by the uptake of 99mTc-duramycin, extended more substantially outside the infarct zone in the controls. ConclusionsSignificant reduction in myocardial I/R injury, as assessed by 99mTc-duramycin cell death imaging and histopathological analysis, was induced by DDFPe treatment after acute myocardial ischemia. 99mTc-duramycin imaging can reveal myocardial cell death in ischemic hearts and may provide a tool for the non-invasive assessment of cardioprotective interventions.

Insemination or phosphatidic acid induces an outwardly spiraling disk of elevated Ca2+ to produce the Ca2+ wave during Xenopus laevis fertilization

During Xenopus fertilization, the initial intracellular calcium ((Ca2+)i) release at the sperm-egg binding site (hot spot) has not been described without the use of inhibitors, nor related to underlying ER structure. Without inhibitors, we now report that sperm induce an initial hot spot after sperm addition to Xenopus eggs that was ~25 µm. This area is consistent with the size of ER patches and clusters of IP3 receptors that have enhanced activity. Furthermore, we find a new mechanism for the fertilization (Ca2+)i wave; instead of outward diffusion of inositol 1,4,5-trisphosphate (IP3), we find that the wave was generated by an outward, clockwise rotation of a ~63 µm disk of elevated (Ca2+)i moving very rapidly at ~65 µm/s. We also suggest a new mechanism for the acceleration of the fertilization (Ca2+)i wave as the disk accelerated and was joined by other rotating disks (some rotating counterclockwise) at a time when the speed of the (Ca2+)i wave increases. To examine the role of phosphatidic acid (PA) in the release of (Ca2+)i during Xenopus fertilization, we find that two inhibitors of PA production delayed the appearance of fertilization hot spots by ~9–12 min but did not reduce the size of hot spots and actually accelerated the later (Ca2+)i wave. Surprisingly, global addition of PA to Xenopus eggs induced localized hot spots at a time and size that was similar to those induced after sperm addition. In contrast, sperm induce a rapid (Ca2+)i wave (~4 µm/s) within ~30 s after hot spot appearance, whereas hot spots induced by PA required an ~32 min to induce a very slow (~1 µm/s) (Ca2+)i wave with a lower peak of (Ca2+)i. Thus, PA may not be required for the initial release of (Ca2+)i at the sperm-egg binding site, but mimics sperm by inducing a similarly sized localized (Ca2+)i release. As compared with sperm, PA may induce a weak, slow (Ca2+)i wave by slowly increasing IP3 receptor clustering. Addition of PA to Xenopus oocytes, or Ca2+ ionophore to either Xenopus oocytes or eggs, did not induce hot spots but a global (Ca2+)i wave that rapidly moved at ~12 µm/s.

Starspots in contact and semi-detached binary systems

AbstractWe investigated the statistical properties of both cool and hot starspots in eclipsing binary stars. The starspot and binary parameters for contact and semi-detached systems were collected from literature, determined on the basis of synthetic light-curve analysis. We examined associations between these parameters. It was found that the cool spots in W-type binaries show properties similar to those of sunspots and starspots generated by dynamos, which differs from those of the cool spots in A-type binaries.The properties of hotspots also differ between the W- and A-type samples. From the physical properties of A- and W-type binaries, we infer that mass transfer is a dominant process for forming the hotspots in A-type binaries, and that both mass transfer and magnetic activity can contribute to the formation of the hotspots in W-type binaries. Our results also indicate that the hotspot size in the A-type sample is correlated with the temperature of spotted stars, orbital period, mass ratio, and fill-out factor.

Influence of chemical kinetics on spontaneous waves and detonation initiation in highly reactive and low reactive mixtures

Understanding the mechanisms of explosions is important for minimising devastating hazards. Due to the complexity of real chemistry, a single-step reaction mechanism is usually used for theoretical and numerical studies. The purpose of this study is to look more deeply into the influence of chemistry on detonation initiated by a spontaneous wave. The results of high-resolution simulations performed for one-step models are compared with simulations for detailed chemical models for highly reactive and low reactive mixtures. The calculated induction times for H2/air and for CH4/air are validated against experimental measurements for a wide range of temperatures and pressures. It is found that the requirements in terms of temperature and size of the hot spots, which can produce a spontaneous wave capable to initiate detonation, are quantitatively and qualitatively different for one-step models compared to detailed chemical models. The time and locations when the exothermic reaction affects the coupling between the pressure wave and spontaneous wave are considerably different for a one-step and detailed models. The temperature gradients capable to produce detonation and the corresponding size of hot spots are much shallower and, correspondingly, larger than those predicted using one-step models. The impact of the detailed chemical model is particularly pronounced for the methane-air mixture. In this case, not only the hot spot size is much greater than that predicted by a one-step model, but even at the elevated pressure, the initiation of detonation by a temperature gradient is possible only if the temperature outside the gradient is rather high, so that can ignite a thermal explosion. The obtained results suggest that the one-step models do not reproduce correctly the transient and ignition processes, so that interpretation of the simulations performed using a one-step model for understanding mechanisms of flame acceleration, DDT and the origin of explosions must be considered with great caution.

A fast and accurate temperature prediction method for microfluidic cooling with multiple distributed hotspots

As the feature size decreases and integration degree increases, integrated circuits face a serious thermal challenge. Microfluidic cooling (i.e., forced convection of coolant inside micrometer-sized channels) has been regarded as a promising solution for the growing challenge of heat dissipation inside electronic devices. However, to the best of authors’ knowledge, the cooling performance of fluids inside microchannels is usually formulated under a uniform heat source, which is not the case in real applications where hotspots are distributed. The effect of the size of multiple distributed hotspots on microfluidic cooling has not previously been investigated. By implementing micro/nanofabrication technologies, hotspots with feature sizes of 50 µm, 100 µm, and 200 µm, were designed and fabricated on an 80-µm-thick Si substrate to mimic multiple distributed hotspots. Parallel microchannels, which were 60 µm deep, 50 µm wide, and 3440 µm long, were prepared for microfluidic cooling. In each single-hotspot heating experiment, a fitting parameter of the normalized heat transfer coefficient (h) was extracted from the power input and the local temperature excess based on the thermal spreading resistance model. The results indicated that h, i.e. the cooling performance on the hotspot, decreased with hotspot size. Therefore, in cases with varied hotspot sizes on a single chip, separate thermal analysis for each hotspot may be required to correctly predict microfluidic cooling performance. A simplified model based on the superposition principle was proposed to predict the temperature excess of multiple distributed hotspots with microfluidic cooling. The method was experimentally verified to attain a deviation less than 15%. Computation time was noticeably reduced from more than four hours (for a full-scale numerical simulation) to several minutes after implementing the simplified model.

Computational Study of Thermal Transport in Nanowire-Graphene Thin Films

Metal nanowires-doped polycrystalline graphene is recently shown to be very promising as transparent conducting material for many applications including solar cells, touchscreens, and light-emitting diodes. However, the thermal reliability of these thin-film materials can be a concern and is not well understood yet. In this study, we develop and utilize a coupled electrothermal model to examine self-heating in the nanowire-polygraphene thin-film hybrid material. We study the effects of various key material/topological parameters such as nanowire density and alignment, and interfacial thermal resistances at nanowire junctions, and nanowire-graphene interfaces on the temperature distribution of both nanowire network and polygraphene. The analysis provides useful insights about the size, location, and number of hotspots in the nanowires and polygraphene. The peak and average temperature variation in the thin-film material are explored and analyzed for varied nanowire density and percentage of high-resistance grain boundaries, and, in this respect, we observe that the variation of both peak and average temperature of the nanowire network deviates from the classical behavior expected from an electrical conductor, and rather it follows the trend according to the copercolating charge transport within the nanowire-polygraphene hybrid material. We find that the temperature profile of nanowires follows the Weibull distribution for various current values in the network for both below and above percolation threshold of nanowire networks. We systematically study the effect of nanowire orientation on the temperature profile in the material, and find that aligned nanowires along the main transport direction is likely to experience higher temperature rise due to the enhanced current. The developed framework can help us to provide design guidelines to mitigate the bottlenecks and accelerate the advent of these types of hybrid materials as transparent conducting electrodes.