Hot Spot Position Research Articles

Pulsed and Polarized X‐Ray Emission From Neutron Star Surfaces

ABSTRACTThe intense magnetic fields of neutron stars naturally lead to strong anisotropy and polarization of radiation emanating from their surfaces, both being sensitive to the hot spot position on the surface. Accordingly, pulse phase‐resolved intensities and polarizations depend on the angle between the magnetic and spin axes and the observer's viewing direction. In this paper, results are presented from a Monte Carlo simulation of neutron star atmospheres that uses a complex electric field vector formalism to treat polarized radiative transfer due to magnetic Thomson scattering. General relativistic influences on the propagation of light from the stellar surface to a distant observer are taken into account. The paper outlines a range of theoretical predictions for pulse profiles at different X‐ray energies, focusing on magnetars and also neutron stars of lower magnetization. By comparing these models with observed intensity and polarization pulse profiles for the magnetar 1RXS J1708‐40, and the light curve for the pulsar PSR J0821‐4300, constraints on the stellar geometry angles and the size of putative polar cap hot spots are obtained.

Investigation of Coupling Effect for Adjacent Orthopedic Implants on MRI Radio-Frequency Heating

This paper investigates the mechanism of radio-frequency (RF) heating that occurs when two adjacent orthopedic implants are present together under magnetic resonance imaging (MRI) at 1.5 Tesla and 3.0 Tesla. When a patient has multiple implants close to each other, interactions between the implants may increase RF heating. Typical generic interlocking plate and antibiotic nail implants are adopted as examples. To analyze the effect of adjacent implants, the amplitude and direction of incident and scattering vector electric fields at the hot spot position are calculated and extracted using numerical simulation based on Huygens principle. It is shown that a strong coupling effect occurs due to the existence of both the incident field and a strong scattering field. Huygens principle can be used to obtain the first and second order scattering fields generated between implants. If the first- and second-order electric field terms are summed within a certain region, the RF-induced heating of this dual-implant system increases.

Hot spot localization in the field of view of the Kirkpatrick–Baez microscope

The Kirkpatrick–Baez (KB) microscope is an effective instrument for x-ray imaging of hot spot. However, the non-uniform distribution of response efficiency in the field of view is a drawback of the KB microscope. A more accurate hot spot image requires the correction of the measured image by combining the hot spot position and the response efficiency distribution. Here, we describe a method to locate the position of the hot spot in the field of view during hot spot imaging with a KB microscope. The position of the hot spot in the field of view can be obtained by measuring the grazing incidence angle change during hot spot imaging. In the experiment of hot spot self-emission imaging with a four-channel KB microscope, the location of the hot spot with an accuracy of 15 μm was realized, and the intensity corrected hot spot image was obtained. This will solve the problem of the non-uniform distribution of the response efficiency of the KB microscope and enable quantitative measurement of hot spot radiation intensity.

Investigation on Accelerated Initiation of Oblique Detonation Wave Induced by Laser-Heating Hot-Spot

A reliable initiation of oblique detonation is critical in oblique detonation engines, especially for oblique detonation engines under extreme conditions such as a high altitude and low Mach number, which may lead to excessive length of the induction zone and even the phenomenon of extinction. In this paper, surface ignition was applied to the initiation of oblique detonation, and a high-temperature region was set on the wedge to simulate the presence of a hot-spot induced by the laser heating. The two-dimensional multi-component Navier–Stokes equations considering a detailed H2 combustion mechanism are solved, and the oblique detonation wave accelerated by a hot-spot is studied. In this paper, hot-spots in the induction zone on the wedge, are introduced to explore the possibility of hot-spot initiation, providing a potential method for initiation control. Results show that these methods can effectively promote the accelerated initiation of the oblique detonation. Furthermore, the hot-spot temperature, size and position are varied to analyze their effects on the initiation position. Increasing the temperature and size of the hot-spot both can accelerate initiation, but from the perspective of energy consumption, a small hot-spot at a high temperature is preferable for accelerating ODW initiation than a large hot-spot at a low temperature. The initiated position of the oblique detonation is sensitive to the position of the hot-spots; if a 2000 K hotspot is at the beginning of the wedge, then the ODW’s initiation distance will be reduced to about 30% of that without hotspot acceleration.

Cold Spot SCANNER: Colab Notebook for predicting cold spots in protein–protein interfaces

BackgroundProtein–protein interactions (PPIs) are conveyed through binding interfaces or surface patches on proteins that become buried upon binding. Structural and biophysical analysis of many protein–protein interfaces revealed certain unique features of these surfaces that determine the energetics of interactions and play a critical role in protein evolution. One of the significant aspects of binding interfaces is the presence of binding hot spots, where mutations are highly deleterious for binding. Conversely, binding cold spots are positions occupied by suboptimal amino acids and several mutations in such positions could lead to affinity enhancement. While there are many software programs for identification of hot spot positions, there is currently a lack of software for cold spot detection.ResultsIn this paper, we present Cold Spot SCANNER, a Colab Notebook, which scans a PPI binding interface and identifies cold spots resulting from cavities, unfavorable charge-charge, and unfavorable charge-hydrophobic interactions. The software offers a Py3DMOL-based interface that allows users to visualize cold spots in the context of the protein structure and generates a zip file containing the results for easy download.ConclusionsCold spot identification is of great importance to protein engineering studies and provides a useful insight into protein evolution. Cold Spot SCANNER is open to all users without login requirements and can be accessible at: https://colab.research.google.com/github/sagagugit/Cold-Spot-Scanner/blob/main/Cold_Spot_Scanner.ipynb.

Precise regulation of surface plasmonic hotspots in an Au split nanoring coupled system

The signal enhancement in plasmon-enhanced spectroscopy is primarily contributed by hotspots generated through the surface plasmon resonance effect. Precise control of hotspot positions within nanostructures is of great significance in surface-enhanced Raman spectroscopy (SERS) and high spatial resolution imaging. However, predicting the positions of hotspots is challenging due to the small nanogaps and complex plasmonic interactions. In this study, we theoretically investigate the localized surface plasmonic properties of split ring nanostructure. The effects of variations in the inner radius, gap distance and thickness of the split ring on the hotspot distribution at the nanogaps are systematically analyzed using a three-dimensional finite element method. The results demonstrate that precise control over the positions and quantities of hotspots can be achieved by choosing the excitation wavelength and the gap size of the split rings. The calculated maximum Raman enhancement obtained at the hotspots can reach nine orders of magnitude. Our findings not only contribute to a deeper understanding of the SERS enhancement mechanism, but also provide theoretical insights for further development of surface-enhanced fluorescence, plasmonic sensors, and super-resolution imaging in the field of interface spectroscopy.

Numerical study on the critical characteristics of internal short-circuit hot spot in lithium-ion batteries

High current density resulting from internal short circuit (ISC) in lithium-ion batteries leads to rapid local temperature rise, forming a hot spot. This study quantitatively characterized the critical properties of ISC hot spot in batteries. ISC hot spot in batteries exhibit two different evolution patterns. When the short circuit resistance approaches the internal resistance of the battery, the hot spot temperature reaches its peak at 1165 K. The thermal runaway characteristics of batteries vary depending on the short circuit resistance, with the hot spot growing and spreading rapidly when the resistance value is 30 mΩ. In addition, a modeling study was conducted to examine the critical characteristics of short circuit resistance. At a hot spot radius of 2 mm, the critical resistance was determined to be 281 mΩ, accompanied by a critical hot spot temperature of 562 K. Under subcritical conditions, the SEI film decomposes completely, while the electrolyte undergoes minimal decomposition. Interestingly, it was observed that the critical resistance and critical hot spot temperature decrease as the hot spot radius increases. Finally, the study quantified the effects of hot spot thermal conductivity, convective heat transfer coefficient, and hot spot position on the critical threshold of hot spots. These findings provide valuable references for the design of batteries with high critical thresholds.

Exploiting the flow maldistribution characteristics in parallel microchannel heat sinks of I, U, and Z configurations to tackle the nonuniform heat loads

This study aims to analyze the cooling performance of parallel microchannel heat sinks (PMCHS) under uneven heat flux distributions, taking into account different flow configurations including I, U, and Z. The objective is to demonstrate the potential of utilizing the flow maldistribution inherent in each configuration to effectively manage and mitigate the effects of uneven heat flux distributions. Four different heating arrangements have been considered, namely uniform, non-streamline, streamline, and across-streamline to generate the uneven heat flux distributions. A three-dimensional numerical simulation has been performed to analyze the combined effect of uneven heat flux distributions and flow maldistribution characteristics on the thermal performance of PMCHS. To assess the thermal performances; thermal resistance (Rth), Nusselt number (Nu), temperature nonuniformity (Ψ), and fin efficiency (ηfin) have been employed. The results show that all three flow configurations exhibit similar thermal performances for uniform heat load conditions (0.1 K/W for Rth, 5.5 kW for Nu, 0.3 for Ψ, and 0.98 for ηfin). However, in the case of uneven heat flux distributions, the thermal performance of each configuration is observed to be varying with respect to hotspot positions. This study reveals that each configuration has a huge discrepancy in terms of thermal performance with respect to uneven heat flux distributions. Also, the study concludes that a single flow configuration alone is insufficient to address the cooling challenges that arise due to uneven heat flux distributions. The cooling capability of any configuration to handle uneven heat distributions mainly depends upon the flow maldistribution characteristics of the respective configurations.

Whole exome sequencing identifies novel variants of PIK3CA and validation of hotspot mutation by droplet digital PCR in breast cancer among Indian population

BackgroundBreast cancer (BC) is the most common malignancy with very high incidence and relatively high mortality in women. The PIK3CA gene plays a pivotal role in the pathogenicity of breast cancer. Despite this, the mutational status of all exons except exons 9 and 20 still remains unknown.MethodsThis study uses the whole exome sequencing (WES) based approach to identify somatic PIK3CA mutations in Indian BC cohorts. The resultant hotspot mutations were validated by droplet digital PCR (ddPCR). Further, molecular dynamics (MD) simulation was applied to elucidate the conformational and functional effects of hotspot position on PIK3CA protein.ResultsIn our cohort, PIK3CA showed a 44.4% somatic mutation rate and was among the top mutated genes. The mutations of PIK3CA were confined in Exons 5, 9, 11, 18, and 20, whereas the maximum number of mutations lies within exons 9 and 20. A total of 9 variants were found in our study, of which 2 were novel mutations observed on exons 9 (p.H554L) and 11 (p.S629P). However, H1047R was the hotspot mutation at exon 20 (20%). In tumor tissues, there was a considerable difference between copy number of wild-type and H1047R mutant was detected by ddPCR. Significant structural and conformational changes were observed during MD simulation, induced due to point mutation at H1047R/L position.ConclusionsThe current study provides a comprehensive view of novel as well as reported single nucleotide variants (SNVs) in PIK3CA gene associated with Indian breast cancer cases. The mutation status of H1047R/L could serve as a prognostic value in terms of selecting targeted therapy in BC.

The temperature and drift law of hot spots of oil-immersed air-cooled power transformers

This paper carries out three-dimensional transient simulation calculation of hot spot distribution of oil immersed air-cooled transformer under different working conditions based on the finite element method, couples the electromagnetic loss calculation result unit to the temperature field, and takes it as the heat source to establish the mapping relationship of magnetic heat flow multi physical field. Taking SFZ11-30000/110 transformer as an example, the temperature distribution and hotspot position under different working conditions are obtained. By comparing the results of the heating test, the effectiveness of the simulation model is verified. Studies have shown that as the load increases, the position of the hotspot shifts along the wind axis. After the fan is turned on, there is also an axial upward drift of about 3% at the hot spot, which provides a method basis for the winding insulation and heat dissipation design of oil immersed air-cooled power transformer.

Stress spectrum compilation method and residual life prediction for hot spot position of metro bogie frame under resonance condition

Metro bogie frames occasionally suffer from fatigue failure during the operation. Through fatigue fractography, it is determined that the fusion defect of the weld root at the frame’s hot spot is the internal cause of fatigue failure. According to the field test, the modal frequency of the frame coincides with the wheel-rail coupling vibration frequency when running under some specific track structures, which is the external cause of the frame’s fatigue failure. In addition, the wheel out-of-roundness (OOR) and the curved track with a radius below 600 m significantly affect the fatigue life. Based on this, the tailoring principle of the stress spectrum is studied and the whole life cycle stress spectrum is compiled. Finally, the residual life of the frame evaluated by the damage tolerance method is 1.208 × 105 km. The evaluation of the residual life provides a reference for optimizing the maintenance strategy of the bogie frame.

Thermal analysis and optimization on a transformer winding based on non-uniform loss distribution

Generally, thermal analyses and optimizations on the transformer winding were carried out under an assumption of uniform heat losses. But in fact, winding heat losses are distributed unevenly, which may intensify local hot-spots and result in winding performance deterioration. This work was to investigate the difference of winding temperature distributions under the two loss conditions. To realize it, first, an electromagnetic-thermo-flow bidirectional coupling numerical model was developed for a converter transformer winding to calculate actual winding losses and temperature. Then, the winding temperature distribution was compared with that under the assumed uniform loss condition, and their differences were quantitatively analyzed. The results showed that for most winding structures studied in this work, the winding hot-spot temperature rises (ΔTmax) under the non-uniform loss condition was greater than that under the assumed uniform loss condition, and their difference was greater than 5%. This difference was more obvious at a less flow rate. This suggested that ΔTmax would be underestimated based on the assumption of uniform heat losses, which posed a threat to the transformer reliability. Therefore, it was necessary to consider non-uniform loss distribution to calculate the winding temperature, so as to improve the safety margin of the transformer and thus improve its reliability. Furthermore, to eliminate the uncertainty of multi-response optimization results caused by the uniform loss assumption, a multi-response optimization on the winding structural parameters was conducted based on the non-uniform loss distribution. The optimization results under the two loss conditions were compared. The results showed that the optimum winding structural parameters under the two loss conditions were consistent. However, the hot-spot positions of the optimum winding structure under the two loss conditions were different. This meant that it was feasible to adopt the general assumption to conduct multi-response optimizations to improve efficiency, but to predict the hot-spot of the optimum winding structure more accurately, it was necessary to consider the non-uniform loss distribution.

Numerical estimation of the hotspot positions of floating plastic debris in the Tsushima Strait using the adjoint marginal sensitivity method

Marine plastic has become a global problem and the situation is also very serious in the Sea of Japan. Tsushima Island, Japan is one of the areas encountering severe problems with beach plastics, followed by many other beaches facing the Sea of Japan. The total cost of beach cleanup is nontrivial for municipalities facing the sea. Offshore recovery of floating large debris at its concentrated areas, or hotspots, could be less burdensome and more economical than the beach cleanup. For this purpose, it is necessary to confirm the presence of hotspots in a target sea, and identifying offshore hotspots using a suitable numerical method can aid in the recovery of large floating plastics. In this study, we estimated the hotspot position of floating plastic bags in the Tsushima Strait using the adjoint marginal sensitivity method and measurement data in the Sea of Japan. The numerical results were found to be moderately comparable with satellite images using indices of large floating plastics.

De novo mutation hotspots in homologous protein domains identify function-altering mutations in neurodevelopmental disorders

Variant interpretation remains a major challenge in medical genetics. We developed Meta-Domain HotSpot (MDHS) to identify mutational hotspots across homologous protein domains. We applied MDHS to a dataset of 45,221 de novo mutations (DNMs) from 31,058 individuals with neurodevelopmental disorders (NDDs) and identified three significantly enriched missense DNM hotspots in the ion transport protein domain family (PF00520). The 37 unique missense DNMs that drive enrichment affect 25 genes, 19 of which were previously associated with NDDs. 3D protein structure modeling supports the hypothesis of function-altering effects of these mutations. Hotspot genes have a unique expression pattern in tissue, and we used this pattern alongside in silico predictors and population constraint information to identify candidate NDD-associated genes. We also propose a lenient version of our method, which identifies 32 hotspot positions across 16 different protein domains. These positions are enriched for likely pathogenic variation in clinical databases and DNMs in other genetic disorders.

Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRASG12C Inhibitor.

Activating mutations in KRAS are the most frequent oncogenic alterations in cancer. The oncogenic hotspot position 12, located at the lip of the switch II pocket, offers a covalent attachment point for KRASG12C inhibitors. To date, KRASG12C inhibitors have been discovered by first covalently binding to the cysteine at position 12 and then optimizing pocket binding. We report on the discovery of the in vivo active KRASG12C inhibitor BI-0474 using a different approach, in which small molecules that bind reversibly to the switch II pocket were identified and then optimized for non-covalent binding using structure-based design. Finally, the Michael acceptor containing warhead was attached. Our approach offers not only an alternative approach to discovering KRASG12C inhibitors but also provides a starting point for the discovery of inhibitors against other oncogenic KRAS mutants.

Rational Design of a Thermostable 2'-Deoxyribosyltransferase for Nelarabine Production by Prediction of Disulfide Bond Engineering Sites.

One of the major drawbacks of the industrial implementation of enzymatic processes is the low operational stability of the enzymes under tough industrial conditions. In this respect, the use of thermostable enzymes in the industry is gaining ground during the last decades. Herein, we report a structure-guided approach for the development of novel and thermostable 2′-deoxyribosyltransferases (NDTs) based on the computational design of disulfide bonds on hot spot positions. To this end, a small library of NDT variants from Lactobacillus delbrueckii (LdNDT) with introduced cysteine pairs was created. Among them, LdNDTS104C (100% retained activity) was chosen as the most thermostable variant, displaying a six- and two-fold enhanced long-term stability when stored at 55 °C (t1/255 °C ≈ 24 h) and 60 °C (t1/260 °C ≈ 4 h), respectively. Moreover, the biochemical characterization revealed that LdNDTS104C showed >60% relative activity across a broad range of temperature (30–90 °C) and pH (5–7). Finally, to study the potential application of LdNDTS104C as an industrial catalyst, the enzymatic synthesis of nelarabine was successfully carried out under different substrate conditions (1:1 and 3:1) at different reaction times. Under these experimental conditions, the production of nelarabine was increased up to 2.8-fold (72% conversion) compared with wild-type LdNDT.

Numerical investigation of plasmonic bowtie nanorings with embedded nanoantennas for achieving high SEIRA enhancement factors

This paper presents the numerical investigation of several complex plasmonic nanostructures — bowtie nanoring and crossed-bowtie nanoring nanoantennas with embedded bowtie nanoantennas and crossed-bowtie nanoantennas — for surface enhanced infrared absorption (SEIRA) spectroscopy-based substrates. The proposed nanostructures exhibit substantially large SEIRA enhancement factor (∼8.1 × 105) compared to previously reported enhancement factor values for bowtie nanoantennas or nanoring antennas. The plasmonic properties of the proposed nanostructures have been studied by the numerical evaluation of the near-field electromagnetic enhancement at resonant plasmon mode excitation wavelengths in the mid-IR spectral regime. The highest SEIRA enhancement of ∼8.1 × 105 occurs at a wavelength of ∼6800 nm (6.8 μm). A substantial electric field enhancement as large as ∼375, corresponding to SEIRA EF of ∼1.4 × 105 is noted even when the minimum gaps between the plasmonic nanostructures is as large as 10 nm, which can easily be fabricated using the conventional nanolithography techniques. The occurrence of several electric field hotspots due to the presence of plasmonic nanoantennas embedded inside the nanorings was observed, as the electric fields are enhanced in the vicinity of the plasmonic nanostructures being proposed. The multiple electric field hotspots in the proposed nanostructures can lead to larger average electric field enhancement as well as the average SEIRA enhancement for these substrates. Moreover, by embedding plasmonic nanoantenna structures inside the bowtie nanorings and crossed-bowtie nanorings, large spectral tunability of plasmon resonance wavelengths is achieved in the spectral regime from 4 μm to 8 μm. This is done by varying a larger number of spectral parameters that are present in these complex nanostructures. This paper also reports a novel configuration of crossed-bowtie nanoring plasmonic structure exhibiting less polarization dependence of the SEIRA enhancement factor. This structure also exhibits tunability of hotspot positions when the direction of the polarization of the incident light is rotated. The proposed structures in this paper can be fabricated by the state-of-the-art nanofabrication technologies. The proposed structures could find potential applications in chemical and biological sensing and biochemical detection of analyte molecules.

Hotspot Detection with Machine Learning Based on Pixel-Based Feature Extraction

The complexity of physical verification increases rapidly with fast shrinking technology nodes. Considering only design rule checking (DRC) constraints or lithography models cannot capture the side physical effects in the fabrication process well. Thus, it is desirable to consider a more general physical verification problem with various types of hotspots. In this paper, we apply machine learning which is based on pixel-based feature extraction to deal with the generalized hotspot detection problem. First, a two-dimensional discrete Fourier transformation-based pixel extraction method is proposed to alleviate the shifting effect and produce stable hotspot features. Then, a pattern-based layout scanning approach is developed to enhance the program efficiency while preserving good detection accuracy. Finally, we design two false alarm reduction strategies to effectively reduce the number of detected nonhotspots and further improve the accuracy of hotspot position. Experimental results based on the industrial benchmarks show that our algorithm outperforms three competitive works in terms of accuracy, false alarm rate, efficiency, and time.

Evolution of intra-tumoral heterogeneity across different pathological stages in papillary thyroid carcinoma

BackgroundIntra-tumor heterogeneity (ITH) results from the continuous accumulation of mutations during disease progression, thus impacting patients’ clinical outcome. How the ITH evolves across papillary thyroid carcinoma (PTC) different tumor stages is lacking.MethodsWe used the whole-exome sequencing data from The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) cohort to track the ITH and assessed its relationship with clinical features through different stages of the PTC progression. We further assayed the expression levels of the specific genes in papillary thyroid cancer cell lines compared to an immortalized normal thyroid epithelial cell line by qRT-PCR.ResultsWe revealed the timing of mutational processes and the dynamics of the temporal acquisition of somatic events during the lifetime of the PTC. ITH significantly influences the PTC patient’s survival rate and, as genetic heterogeneity increases, the prognosis gets worse in advanced tumor stages. ITH also affects the mutational architecture of each clinical stage which is subject to periodic fluctuations. Different mutational processes may cooperate to shape a stage-specific mutational spectrum during the progression from early to advanced tumor stages. Moreover, different evolutionary paths characterize PTC progression across pathological stages due to both mutations recurrently occurring in all stages in hotspot positions and distinct codon changes dominating in different stages. A different expression level of specific genes also exists in different thyroid cancer cell lines.ConclusionsOur findings suggest ITH as a potential unfavorable prognostic factor in PTC and highlight the dynamic changes in different clinical stages of PTC, providing some clues for the precision medicine and suggesting different diagnostic decisions depending on the clinical stages of patients. Finally, complete clear guidelines to define risk stratification of PTC patients are lacking; thus, this work could contribute to defining patients who need more aggressive treatments and, in turn, could reduce the social burden of this cancer.

Structural insight and engineering of a plastic degrading hydrolase Ple629

Polyethylene terephthalate (PET) is one of the most abundantly produced synthetic polyesters. The vast number of waste plastics including PET has challenged the waste management sector while also posing a serious threat to the environment due to improper littering. Recently, enzymatic PET degradation has been shown to be a viable option for a circular plastic economy, which can mitigate the plastic pollution. While protein engineering studies on specific PET degradation enzymes such as leaf-branch compost cutinase (LCC), Thermobifida sp. cutinases and Ideonella sakaiensis PETase (IsPETase) have been extensively published, other homologous PET degrading enzymes have received less attention. Ple629 is a polyester hydrolase identified from marine microbial consortium having activity on PET and the bioplastic polybutylene adipate terephthalate (PBAT). In order to explore its catalytic mechanism and improve its potential for PET hydrolysis, we solved its crystal structure in complex with a PET monomer analogue, and validated its structural and mechanistic similarity to known PET hydrolases. By structural comparisons, we identified some hot spot positions described in previous research on protein engineering of PET hydrolases. We substitute these amino acid residues in Ple629, and obtained variants with improved activity and thermo-stability. The most promising variant D226A/S279A exhibited a more than 5.5-fold improved activity on PET nanoparticles than the wild-type enzyme, suggesting its potential applicability in the biotechnological plastic recycling.