bluuebunny/crossref_metadata_2025 huggingface dataset:
An IGBT coupling structure with a smart service life reliability predictor using active learning
Authors: Feng Shizhe , Guo Yicheng , Li Weihua , Du Haiping , Krolczyk Grzegorz , Li Z
Published: September 2024

An effective approach is proposed to evaluate the service life reliability of a multi-physics coupling structure of an insulated gate bipolar transistor (IGBT) module. The node-based smoothed finite element method with stabilization terms is firstly employed to construct an electrical-thermal-mechanical (ETM) coupling structure of the IGBT module, based on which the multi-physics responses can be accurately calculated to predict the service life of the IGBT module. By using the high-quality sample data obtained through the ETM coupling model, a Monte Carlo based active learning Kriging metamodel (AK-MCS) is developed to assess the service life reliability of the IGBT module, which can greatly reduce the computational cost needed by the surrogate model construction and reliability analysis. Numerical results show that the proposed ETM coupling structure can produce high-quality sample data of the IGBT dynamics and the AK-MCS machine learning technique can accurately estimate the service life reliability of the IGBT module.
Dynamic stability and response of morphing wing structure with time-varying stiffness
Authors: Prabhakar Manoj , Murugan Senthil
Published: September 2024

Morphing, adaptable or smart structures are being used in mechanical and aerospace applications in recent years. These structures often have the property of time-varying stiffness or inertial properties, which can cause parametric instability issues that are not well understood. This paper examines the dynamic stability and response of a morphing aircraft wing with periodically time-varying structural stiffness. The wing is modeled as a beam with coupled bending-torsion motion, and parametrically excited stiffness. Aerodynamic loads introduce aerodynamic damping and aerodynamic stiffness to the wing structure. The dynamic and aeroelastic equation of motion resembles a coupled, damped Mathieu-type equation but differs with asymmetric damping and stiffness matrices, and symmetric inertial matrix. Further, these equations are functions of airspeed, magnitude and frequency of parametric excitation. Initially, dynamic stability of the wing is analyzed using Floquet theory, and the instability regions are numerically quantified by stability charts. Subsequently, dynamic responses in the stable and unstable regions are investigated with a Floquet-based Harmonic balance method. The findings reveal that, at zero airspeed, the combination instabilities are eliminated by varying the bending and torsional stiffness with equal magnitudes and frequency. However, as airspeed increases, instability regions shift unevenly, leading to the emergence of new instabilities. Furthermore, the response analysis within stable regions uncovers several unfavorable zones for operating the variable stiffness, where response decay is slower. The results clearly show that parametric excitation can cause unusual phenomena that significantly impact the operation of morphing wings with variable stiffness, which needs to be thoroughly investigated for successful implementation.
Multifunctional 1D/2D silver nanowires/MXene-based fabric strain sensors for emergency rescue
Authors: Xie Jiayu , Zhang Ying , Wang Huajun , Liu Qingqing , He Jingqiang , Guo Ronghui
Published: September 2024

Monitoring the vital signs of the injured in accidents is crucial in emergency rescue process. Fabric-based sensing devices show a vast range of potential applications in wearable healthcare monitoring, human motion and thermal management due to their wearable flexibility and high sensitivity. Nevertheless, flexible electronic devices for both precise monitoring of health under low strain and motion under large strain are still a challenge in extremely harsh environment. Therefore, development of sensors with both high sensitivity and wide strain range remains a formidable challenge. Herein, a wearable flexible strain sensor with a one-dimensional/two-dimensional (1D/2D) composite conductive network was developed for healthcare and motion monitoring and thermal management by coating 1D silver nanowires (AgNWs) and 2D Ti3C2T
x
MXene composite films on nylon/spandex blended knitted fabric (MANS). The MANS strain sensor can simultaneously achieve high sensitivity (gauge factor for up to 267), a wide range of detection (1%–115%), excellent repeatability and cycling stability (1000 cycles). The sensor can be utilized for human health monitoring including heartbeat, pulse detection, breathing and various human motion. Moreover, the MANS sensor also has the electrical heating properties and voltage control temperature between 20 °C–110 °C can achieved at low voltage. In addition, the MANS shows hydrophobicity with water contact angle of 137.1°. The MXene/AgNWs composite conductive layer with high sensitivity under low and large strains, electrical thermal conversion, and hydrophobicity has great potential for precisely monitoring health and motion of the injured in emergency rescue in harsh environment.
Research on a frequency-increasing piezoelectric wave energy harvester based on gear mechanism and magnetic rotor
Authors: Liu Renwen , Yang Bowen , Fan Wei , Liu Zheming , Wang Chensheng , He Lipeng
Published: September 2024

Wave energy is a widespread clean energy source, but harvesting low-frequency wave energy efficiently remains a challenge. In this paper, a frequency-increasing piezoelectric wave energy harvester (FPWEH) based on gear mechanism and magnetic rotor is proposed. The gear mechanism transforms the vertical motion of the wave into the higher-frequency rotational motion of the magnetic rotor. The magnetic rotor is equipped with several rotating magnets and one revolution of the magnetic rotor enables multiple excitations of the piezoelectric cantilevers. Therefore, the wave excitation frequency is increased, so that the FPWEH can obtain better output performance. The major factors influencing output performance are determined through theoretical and simulation analysis, and a test system to simulate the wave environment is established. According to experimental findings, the FPWEH can generate an output voltage of 69.82 V and a maximum power of 28.33 mW when the external resistance is 20 kΩ. It can also successfully power thermohygrometer and light-emitting diodes. These results validate the feasibility of the FPWEH for providing electricity to electronics with low power requirements. This research also offers a novel approach to harvesting low-frequency wave energy.
A high throughput facility for the RF characterisation of planar superconducting thin films
Authors: Seal D , Malyshev O B , Goudket P , Sian T , Gurran L , Valizadeh R , Marks H , Pattalwar S , Pattalwar N , Pira C , Chyhyrynets E , Burt G
Published: September 2024

Accelerator laboratories worldwide are researching copper radio frequency (RF) cavities coated with superconducting thin films to exceed the limits of bulk niobium. The development and RF testing of thin films on small planar samples is vital before cavity depositions. A team at Daresbury Laboratory have developed a cost-effective facility using a novel 7.8 GHz Choke Cavity for the RF characterisation of planar samples. RF chokes ensure that no electrical contact is required between the sample and the cavity. The main advantages are: a simple sample design (90–130 mm diameter disk with no sample-cavity welding) and easy operation using a LHe-free cryostat. This enables high sample throughput, with up to 3 sample tests per week, making the facility suitable for quick, systematic scanning of deposition parameters. With the sample thermally and physically isolated from the test cavity, it is possible to measure the average surface resistance,

R

s

, directly using an RF-DC compensation method. Facility commissioning has been performed with bulk and thin film niobium samples. These tests have demonstrated the ability to measure

R

s

at temperatures in the range 4–20 K and sample peak magnetic fields up to 3 mT. At present, the minimum resolvable

R

s

is 0.5 

μ
Ω

with typical uncertainties of 9%–15%. The design, operation and commissioning of this facility is reported in this paper.
Large-angle analytical solution of magnetization precession in ferromagnetic resonance
Authors: Jia Zhen-Lin , Wang Shu-Chen , Li Tong , Jin Xiao-Wei , Xue De-Sheng
Published: September 2024

Dynamics of magnetization M driven by microwave are derived analytically from the nonlinear Landau–Lifshitz–Gilbert equation. Analytical M and susceptibility are obtained self-consistently under a positive circularly polarized microwave field,

h

=

(
h
cos
⁡
ω
t
,
h
sin
⁡
ω
t
,
0
)

, with frequency

ω

, which is perpendicular to a static field,

H

=

(
0
,
0
,
H
)

. It is found that the orbital of M is always a cone along H. However, with increasing h the polar angle

θ

of M initially increases, then keeps 90° when

h

⩾

h

0

=
α
ω

/

γ

in ferromagnetic resonance (FMR) mode, where

α

is Gilbert damping constant and

γ

is gyromagnetic ratio. These effects result in a nonlinear variation of FMR signal as h increases to

h
⩾

h

0

, where the maximum of resonance peak decreases from a steady value, linewidth increases from a decreasing trend. These analytical solutions provide a complete picture of the dynamics of M with different h and H.
Space-time structures, light trajectories and shadows for Kerr-Newman-AdS black hole with surrounding perfect fluid matter in Rastall gravity
Authors: Ma Ju , Wang Jian-cheng , Qin Long-hua , Gao Quan-gui
Published: September 2024

We present the horizon structures and the shadows for Kerr-Newman-AdS black hole located in perfect fluid matter field in Rastall gravity. By considering the Hamilton-Jacobi equation and Carter constant separable method, we obtain the null geodesic equations of the black hole space-time as well as the unstable circular photon orbits in terms of the impact parameters. The horizon structures of the space-time are calculated numerically. The results show that there are four roots for a general case of the horizon equation (the Cauchy horizon

r

−

h

, the event horizon

r

+

h

, the cosmological horizon r

q
of Rastall gravity and the cosmological horizon r

c
of cosmological constant), which lead to a specific characteristic with the subregions of the space-time. The influences of the cosmological horizons r

q
and r

c
on the light trajectories around the black hole are also investigated. Furthermore, we study the effects of the parameters, including the perfect fluid matter intensity N

s
, the Rastall parameter k
λ, the cosmological constant Λ, the black hole spin a and the black hole charge Q on black hole shadows in detail.
Radiation shielding properties of gold nanoparticle-dispersed bismuth borate glasses using Phy-X/PSD software
Authors: Abhishek  , Mahendru Nancy , Gupta Indu , Bansal Naveen , Singla Shivani
Published: September 2024

With the increasing use of radioactive materials in various sectors, effective radiation shielding has become a critical concern. The present study explores the potential of bismuth borate glasses doped with gold nanoparticles for gamma-ray shielding applications. Glass samples with a base composition of 30Bi2O3:70B2O3, containing varying concentrations of 10 nm gold nanoparticles, were synthesized using the melt quenching technique. The physical and morphological properties of the samples were characterized, confirming the presence of uniformly dispersed gold nanoparticles of size (4 nm) smaller than the size of precursor nanoparticles. Shielding parameters, including mass attenuation coefficient (MAC), half value layer (HVL), ten value layer (TVL), mean free path (MFP), and effective atomic number (Zeff), were analyzed using the Phy-X/PSD program. Results showed that the obtained highest MAC value is 155.864 cm2/g which is superior to other reported materials. The HVL and TVL values increased with the increase in energy range, indicating effective gamma-ray shielding potential. These findings suggest that optimizing the dispersion and concentration of gold nanoparticles in bismuth borate glasses could enhance their performance as radiation shielding materials, making them promising candidates for various applications.
Gamma rays from dark matter spikes in EAGLE simulations
Authors: Aschersleben J. , Bertone G. , Horns D. , Moulin E. , Peletier R.F. , Vecchi M.
Published: September 2024

Intermediate Mass Black Holes (IMBHs) with a mass range between 100 M⊙ and 106 M⊙ are expected to be surrounded by high dark matter densities, so-called dark matter spikes.
The high density of self-annihilating Weakly Interacting Massive Particles (WIMPs) in these spikes leads to copious gamma-ray production. Sufficiently nearby IMBHs could therefore appear as unidentified gamma-ray sources.
However, the number of IMBHs and their distribution within our own Milky Way is currently unknown. In this work, we provide a mock catalogue of IMBHs and their dark matter spikes obtained from the EAGLE simulations, in which black holes with a mass of 105 M⊙/h are seeded into the centre of halos greater than 1010 M⊙/h to model black hole feedback influencing the formation of galaxies.
The catalogue contains the coordinates and dark matter spike parameters for about 2500 IMBHs present in about 150 Milky Way-like galaxies. We expect about 15+9
-6 IMBHs within our own galaxy, mainly distributed in the Galactic Centre and the Galactic Plane. In the most optimistic scenario, we find that current and future gamma-ray observatories, such as Fermi-LAT, H.E.S.S. and CTAO, would be sensitive enough to probe the cross section of dark matter self-annihilation around IMBHs down to many orders of magnitude below the thermal relic cross section for dark matter particles with masses from GeV to TeV.
We have made the IMBH mock catalogue and the source code for our analysis publicly available, providing the resources to study dark matter self-annihilation around IMBHs with current and upcoming gamma-ray observatories.
Gauss-Bonnet Cosmology: large-temperature behaviour and bounds from Gravitational Waves
Authors: Biswas Anirban , Kar Arpan , Lee Bum-Hoon , Lee Hocheol , Lee Wonwoo , Scopel Stefano , Velasco-Sevilla Liliana , Yin Lu
Published: September 2024

We provide a transparent discussion of the high temperature asymptotic behaviour of Cosmology in a dilaton-Einstein-Gauss-Bonnet (dEGB) scenario of modified gravity with vanishing scalar potential. In particular, we show that it has a clear interpretation in terms of only three attractors (stable critical points) of a set of autonomous differential equations: w = -1/3, w = 1 and 1 < w < 7/3, where w ≡ p/ρ is the equation of state, defined as the ratio of the total pressure and the total energy density. All the possible different high-temperature evolution histories of the model are exhausted by only eight paths in the flow of the set of the autonomous differential equations. Our discussion clearly explains why five out of them are characterized by a swift transition of the system toward the attractor, while the remaining three show a more convoluted evolution, where the system follows a meta-stable equation of state at intermediate temperatures before eventually jumping to the real attractor at higher temperatures. Compared to standard Cosmology, the regions of the dEGB parameter space with w = -1/3 show a strong enhancement of the expected Gravitational Wave stochastic background produced by the primordial plasma of relativistic particles of the Standard Model. This is due to the very peculiar fact that dEGB allows to have an epoch when the energy density ρ
rad of the relativistic plasma dominates the energy of the Universe while at the same time the rate of dilution with T of the total energy density is slower than what usually expected during radiation dominance. This allows to use the bound from Big Bang Nucleosynthesis (BBN) to put in dEGB a constraint T
RH ≲ (108 – 109) GeV on the reheating temperature of the Universe T
RH. Such BBN bound is complementary to late-time constraints from compact binary mergers.
The Simons Observatory: impact of bandpass, polarization angle and calibration uncertainties on small-scale power spectrum analysis
Authors: Giardiello S. , Gerbino M. , Pagano L. , Alonso D. , Beringue B. , Bolliet B. , Calabrese E. , Coppi G. , Errard J. , Fabbian G. , Harrison I. , Hill J.C. , Jense H.T. , Keating B. , La Posta A. , Lattanzi M. , Lonappan A.I. , Puglisi G. , Reichardt C.L. , Simon S.M.
Published: September 2024

We study the effects due to mismatches in passbands, polarization angles, and temperature and polarization calibrations in the context of the upcoming cosmic microwave background experiment Simons Observatory (SO). Using the SO multi-frequency likelihood, we estimate the bias and the degradation of constraining power in cosmological and astrophysical foreground parameters assuming different levels of knowledge of the instrumental effects. We find that incorrect but reasonable assumptions about the values of
all the systematics examined here can have significant effects on cosmological
analyses, hence requiring marginalization approaches at the likelihood level.
When doing so, we find that the most relevant effect is due to bandpass shifts. When marginalizing over them, the posteriors of parameters describing astrophysical microwave foregrounds (such as radio point sources or dust) get degraded, while cosmological parameters constraints are not significantly affected.
Marginalization over polarization angles with up to 0.25° uncertainty causes an irrelevant bias ≲ 0.05 σ in all parameters.
Marginalization over calibration factors in polarization broadens the constraints on the effective number of relativistic degrees of freedom Neff by a factor 1.2, interpreted here as a proxy parameter for non standard model physics targeted by high-resolution CMB measurements.
PINN for solving forward and inverse problems involving integrable two-dimensional nonlocal equations
Authors: Chen Xi , Peng Wei-Qi
Published: September 2024

In this paper, the physics informed neural network (PINN) deep learning method is applied to solve two-dimensional nonlocal equations, including the partial reverse space y-nonlocal Mel’nikov equation, the partial reverse space-time nonlocal Mel’nikov equation and the nonlocal two-dimensional nonlinear Schrödinger (NLS) equation. By the PINN method, we successfully derive a data-driven two soliton solution, lump solution and rogue wave solution. Numerical simulation results indicate that the error range between the data-driven solution and the exact solution is relatively small, which verifies the effectiveness of the PINN deep learning method for solving high dimensional nonlocal equations. Moreover, the parameter discovery of the partial reverse space-time nonlocal Mel’nikov equation is analysed in terms of its soliton solution for the first time.
A robust time scale for space applications using the student’s t-distribution
Authors: McPhee Hamish , Tourneret Jean-Yves , Valat David , Delporte Jérôme , Grégoire Yoan , Paimblanc Philippe
Published: September 2024

In this article, the principles of robust estimation are applied to the standard basic time scale equation to obtain a new method of assigning weights to clocks. Specifically, the Student’s t-distribution is introduced as a new statistical model for an ensemble of clocks that are experiencing phase jumps, frequency jumps or anomalies in their measurement links. The proposed robust time scale is designed to mitigate the effects of these anomalies without necessarily identifying them, but through applying a method of robust estimation for the parameters of a Student’s t-distribution. The proposed time scale algorithm using the Student’s t-distribution (ATST) is shown to achieve comparable robustness to phase jumps, frequency jumps, and anomalies in the measurements with respect to the AT1 oracle time scale. The AT1 oracle is a special realization of the AT1 time scale which corrects all anomalies by having prior knowledge of their occurrences. The similar performance of ATST and AT1 oracle suggests that the ATST algorithm is efficient for obtaining robustness with no prior knowledge or detection of the occurrences of anomalies.
Time division interferometer setups
Authors: Fernandez-Guasti M
Published: September 2024

A time division interferometer (TDI) in the optical regime is presented, where a wavetrain is temporally split into two distinct parts that are superimposed at a subsequent stage. At any one time, the photons have no alternatives, only one possible path is possible. There is no path bifurcation in the setup, i.e. no ‘Y’ where the photons can take left or right. The photons choice, if any, is to arrive/collapse before or after the time t
1 when the time modulated medium changes its state. In time-varying media, as energy can be exchanged between the wave and medium, the wave frequency is modified. Thus, the diverted photons become doubly tagged, in their wave vector direction as well as their frequency. A streak camera detector array resolves both, the fringe pattern as well as the frequency beats, in a space versus time interferogram. This apparatus has

0.66

ns

temporal resolution and

70

μ
m

spatial resolution. Several TDI configurations are described, two of them are implemented: a spatio-temporal interferometer where the ‘which path’ criterion is readily observed and an all temporal TDI where only temporal interference is present. Novel possibilities of TDI schemes are discussed.
Investigation of machining performance of waspaloy using copper-graphite composite electrodes in electric discharge machining
Authors: Putta Priyanka , V Jayakumar , PK Giridharan
Published: September 2024

This study endeavoured to investigate the machining of Waspaloy using Electric Discharge Machining (EDM), utilizing copper-graphite composites as the tool material. Given the limited existing research on machining Waspaloy with composite tools, this study aims to address this gap by employing a copper-graphite composite tool. In this work, pure copper electrode and three composite electrodes with varying graphite percentages in copper, viz. copper containing 5%, 10%, and 15% graphite (CuGr-5, CuGr-10, and CuGr-15), are utilized for experimentation. Composite electrodes are fabricated by the stir-casting process. The scanning electron microscope reveals that the graphite specks are homogeneously disseminated over the matrix material. The Taguchi mixed orthogonal array was used for developing experimental runs. By varying the current, polarity, pulse on and off times, tool materials, and gap, machining performance was measured in terms of Material Removal Rate (MRR), Tool Wear Rate (TWR), and Surface Roughness (Ra). It was observed that CuGr-5 provides an enhancement in MRR due to the improved electric conductivity, bridging effect, and increased energy concentration at the spark gap. Diverse characteristics witnessed on the surface morphology include black dots, globules, remelted layers, micro-cracks, and scratches. When machined with a CuGr5 electrode, the surface quality improved owing to the completed flushing and uniform distribution of generated heat as confirmed through worn surface morphology. The parameters were optimized utilizing the PROMETHEE optimization technique; it was found that the CuGr-5 electrode with the assessment value 0.02458 was optimal for machining of Waspaloy.
Defect prediction and performance optimization of A413 vertical centrifugal castings through FEA-based simulation
Authors: Mazloum Kamar , Al Njjar Ameen , Sata Amit
Published: September 2024

This study benefits from advanced simulation based on finite element analysis, where finite element analysis possesses robust numerical algorithms to confront critical industrial challenges, including prediction and optimization techniques. The primary goal is to predict the location and quantity of shrinkage porosity and air entrainment, and to mitigate them by optimizing key casting process factors while considering the geometric effects. Virtual experiments designed through the Taguchi method, with three parameters (aspect ratio, pouring temperature, and mold rotation speed) at five levels each, were conducted using the finite element analysis software ProCAST. Post-experimentation, comprehensive data analyses, including signal-to-noise ratio and response surface methods, were employed to determine optimal conditions. Additionally, a sophisticated regression model was developed to clarify the complex relationship between key parameters and defect aspects. Optimal conditions to reduce shrinkage porosity were identified within parameter ranges of (50–75) rpm, (750–800) °C, and (1.75–2) aspect ratio. Similarly, optimal parameters to reduce air entrainment were identified as 150 rpm, 800 °C, and (1) aspect ratio.
Effects of an Intervention on Black Family Incomes on Self-Rated Health and Obesity in Black and White Adolescents and Young Adults
Authors: Polos Jessica , Alexandria Shaina , Hargrove Taylor , Koning Stephanie , McDade Thomas W , Kershaw Kiarri N
Published: September 2024

Structural racism contributes to health disparities between U.S. non-Hispanic Black and non-Hispanic white populations by differentially distributing resources used to maintain health. Policies that equitably redistribute resources may mitigate racialized health disparities. Using National Longitudinal Study of Adolescent to Adult Health data and time-to-event parametric g-formula methods, we investigate a hypothetical intervention to reduce Black-white family income inequities on racialized differences in self-rated health (N=11,312) and obesity (N=10,547). We first intervene to increase individual Black family incomes by $11,000, creating Black-white equity in median incomes in 1995. Then, we measure social multiplier effects by additionally increasing county-level Black median household incomes by $11,000. By Wave 4, individual, direct effects models comparing Black intervention to Black control groups show no risk differences in self-rated health (RD=-0.009; 95% CI: -0.026, 0.008) or obesity (RD=0.003; 95% CI: -0.017, 0.023). Social multiplier effects models suggestively reduce Black-white inequalities in obesity by increasing obesity in white intervention versus white control groups (RD=0.050=; 95% CI: -0.011, 0.110), but exacerbate Black-white disparities in self-rated health by reducing self-rated health in Black intervention versus white control groups (RD=0.184; 95% CI: 0.018, 0.351). In this cohort, income transfers may not reduce racialized disparities in obesity and self-rated health.
Can algorithms Replace Expert Knowledge for Causal Inference? A Case Study on Novice Use of Causal Discovery
Authors: Gururaghavendran Rajesh , Murray Eleanor J
Published: September 2024

Background

With growing interest in causal inference and machine learning among epidemiologists, there is increasing discussion of causal discovery algorithms for guiding covariate selection. We present a case study of novice application of causal discovery tools and attempt to validate the results against a well-established causal relationship.

Methods

As a case study, we attempted causal discovery of relationships relevant to the effect of adherence on mortality in the placebo arm of the Coronary Drug Project (CDP) dataset. We used four algorithms available as existing software implementations and varied several model inputs.

Results

We identified 15 adjustment sets from 17 model parameterizations. When applied to a baseline covariate adjustment analysis, these 15 adjustment sets returned effect estimates with similar magnitude and direction of bias as prior published results. When using methods to control for time-varying confounding, there was generally more residual bias than compared to expert-selected adjustment sets.

Conclusion

Although causal discovery algorithms can perform on par with expert knowledge, we do not recommend novice use of causal discovery without the input of experts in causal discovery. Expert support is recommended to aid in choosing the algorithm, selecting input parameters, assessing underlying assumptions, and finalizing selection of the adjustment variables.
The role of imagination in making water from moon rocks: How scientists use imagination to break constraints on imagination
Authors: Stuart Michael T , Sargeant Hannah
Published: September 2024

Scientists recognize the necessity of imagination for solving tough problems. But how does the cognitive faculty responsible for daydreaming also help in solving scientific problems? Philosophers claim that imagination is informative only when it is constrained to be maximally realistic. However, using a case study from space science, we show that scientists use imagination intentionally to break reality-oriented constraints. To do this well, they first target low-confidence constraints, and then progressively higher-confidence constraints until a plausible solution is found. This paper exemplifies a new approach to epistemology of imagination that focuses on sets of imaginings (rather than individual imaginings), and responsible (rather than reliable) imaginings.
SnapHiC-G: identifying long-range enhancer–promoter interactions from single-cell Hi-C data via a global background model
Authors: Liu Weifang , Zhong Wujuan , Giusti-Rodríguez Paola , Jiang Zhiyun , Wang Geoffery W , Sun Huaigu , Hu Ming , Li Yun
Published: September 2024

Harnessing the power of single-cell genomics technologies, single-cell Hi-C (scHi-C) and its derived technologies provide powerful tools to measure spatial proximity between regulatory elements and their target genes in individual cells. Using a global background model, we propose SnapHiC-G, a computational method, to identify long-range enhancer–promoter interactions from scHi-C data. We applied SnapHiC-G to scHi-C datasets generated from mouse embryonic stem cells and human brain cortical cells. SnapHiC-G achieved high sensitivity in identifying long-range enhancer–promoter interactions. Moreover, SnapHiC-G can identify putative target genes for noncoding genome-wide association study (GWAS) variants, and the genetic heritability of neuropsychiatric diseases is enriched for single-nucleotide polymorphisms (SNPs) within SnapHiC-G-identified interactions in a cell-type-specific manner. In sum, SnapHiC-G is a powerful tool for characterizing cell-type-specific enhancer–promoter interactions from complex tissues and can facilitate the discovery of chromatin interactions important for gene regulation in biologically relevant cell types.
Large language model produces high accurate diagnosis of cancer from end-motif profiles of cell-free DNA
Authors: Liu Jilei , Shen Hongru , Chen Kexin , Li Xiangchun
Published: September 2024

Instruction-tuned large language models (LLMs) demonstrate exceptional ability to align with human intentions. We present an LLM-based model—instruction-tuned LLM for assessment of cancer (iLLMAC)—that can detect cancer using cell-free deoxyribonucleic acid (cfDNA) end-motif profiles. Developed on plasma cfDNA sequencing data from 1135 cancer patients and 1106 controls across three datasets, iLLMAC achieved area under the receiver operating curve (AUROC) of 0.866 [95% confidence interval (CI), 0.773–0.959] for cancer diagnosis and 0.924 (95% CI, 0.841–1.0) for hepatocellular carcinoma (HCC) detection using 16 end-motifs. Performance increased with more motifs, reaching 0.886 (95% CI, 0.794–0.977) and 0.956 (95% CI, 0.89–1.0) for cancer diagnosis and HCC detection, respectively, with 64 end-motifs. On an external-testing set, iLLMAC achieved AUROC of 0.912 (95% CI, 0.849–0.976) for cancer diagnosis and 0.938 (95% CI, 0.885–0.992) for HCC detection with 64 end-motifs, significantly outperforming benchmarked methods. Furthermore, iLLMAC achieved high classification performance on datasets with bisulfite and 5-hydroxymethylcytosine sequencing. Our study highlights the effectiveness of LLM-based instruction-tuning for cfDNA-based cancer detection.
COFFEE: consensus single cell-type specific inference for gene regulatory networks
Authors: K Lodi Musaddiq , Chernikov Anna , Ghosh Preetam
Published: September 2024

The inference of gene regulatory networks (GRNs) is crucial to understanding the regulatory mechanisms that govern biological processes. GRNs may be represented as edges in a graph, and hence, it have been inferred computationally for scRNA-seq data. A wisdom of crowds approach to integrate edges from several GRNs to create one composite GRN has demonstrated improved performance when compared with individual algorithm implementations on bulk RNA-seq and microarray data. In an effort to extend this approach to scRNA-seq data, we present COFFEE (COnsensus single cell-type speciFic inFerence for gEnE regulatory networks), a Borda voting-based consensus algorithm that integrates information from 10 established GRN inference methods. We conclude that COFFEE has improved performance across synthetic, curated, and experimental datasets when compared with baseline methods. Additionally, we show that a modified version of COFFEE can be leveraged to improve performance on newer cell-type specific GRN inference methods. Overall, our results demonstrate that consensus-based methods with pertinent modifications continue to be valuable for GRN inference at the single cell level. While COFFEE is benchmarked on 10 algorithms, it is a flexible strategy that can incorporate any set of GRN inference algorithms according to user preference. A Python implementation of COFFEE may be found on GitHub: https://github.com/lodimk2/coffee
Summary statistics knockoffs inference with family-wise error rate control
Authors: Yu Catherine Xinrui , Gu Jiaqi , Chen Zhaomeng , He Zihuai
Published: September 2024

Testing multiple hypotheses of conditional independence with provable error rate control is a fundamental problem with various applications. To infer conditional independence with family-wise error rate (FWER) control when only summary statistics of marginal dependence are accessible, we adopt GhostKnockoff to directly generate knockoff copies of summary statistics and propose a new filter to select features conditionally dependent on the response. In addition, we develop a computationally efficient algorithm to greatly reduce the computational cost of knockoff copies generation without sacrificing power and FWER control. Experiments on simulated data and a real dataset of Alzheimer’s disease genetics demonstrate the advantage of the proposed method over existing alternatives in both statistical power and computational efficiency.
Design of cyborg proteins by loop region replacement with oligo(ethylene glycol): exploring suitable mutations for cyborg protein construction using machine learning
Authors: Yospanya Wijak , Matsumura Akari , Imasato Yukihiro , Itou Tomoyuki , Aoki Yusuke , Nakazawa Hikaru , Matsui Takashi , Yokoyama Takeshi , Ui Mihoko , Umetsu Mitsuo , Nagatoishi Satoru , Tsumoto Kouhei , Tanaka Yoshikazu , Kinbara Kazushi
Published: September 2024

We synthesized a “cyborg protein,” wherein a synthetic molecule partially substitutes the main peptide chain by linking 2 protein domains with a synthetic oligomer. Green fluorescent protein (GFP) served as the model for constructing the cyborg proteins. We prepared circularly permuted GFP (cpGFP) with new termini between β10 and β11, where the original N- and C-termini were linked by a cleavable peptide loop. The cyborg GFP was constructed from cpGFP by linking the β10 and β11 with oligo(ethylene glycol) (OEG) using maleimide–cysteine couplings, followed by the enzymatic cleavage of the N- and C-termini linking loop by thrombin. With the help of machine learning, we were able to obtain the cpGFP mutants that significantly alter the fluorescence intensity (53% increase) by thrombin treatment, which splits cpGFP into 2 fragments (fragmented GFP), and by heat shock. When the cyborg GFP was constructed using this mutant, the fluorescence intensity increased by 13% after heat treatment, similar to cpGFP (33% increase), and the behavior was significantly different from that of the fragmented GFP. This result suggests the possibility that the OEG chain in the cyborg protein plays a similar role to the peptide in the main chain of the protein.
Neural network potential calculations for melamine adsorption onto Pt (111) compared with density functional theory
Authors: Tada Kohei
Published: September 2024

The investigation of Pt-adsorbed melamine is important in elucidating the effect of molecular decoration on the enhancement of catalytic performance for fuel cells, and is an interesting system in which covalent stabilization between the surface and the molecule competes with resonance destabilization by the coordination. The present work discusses whether graph neural network potentials can predict the adsorption structure with the competition. The most stable structure predicted by preferred potential was consistent with that by density functional theory but underestimated resonance destabilization.
Lipid and Glucose Profiles in Pregnant Women With Human Immunodeficiency Virus (HIV) on Tenofovir-based Antiretroviral Therapy
Authors: Eke Ahizechukwu C , Brummel Sean S , Aliyu Muktar H , Stranix-Chibanda Lynda , Eleje George U , Ezebialu Ifeanyichukwu U , Korutaro Violet , Wabwire Deo , Matubu Allen , Mbengeranwa Tapiwa , Chakhtoura Nahida , Chinula Lameck , McCarthy Katie , Knowles Kevin , Krotje Chelsea , Linton Macrae F , Dooley Kelly E , Sax Paul E , Brown Todd , Lockman Shahin
Published: September 2024

Background

Tenofovir alafenamide (TAF)-based antiretroviral therapy (ART) regimens have been associated with adverse changes in lipid and glucose profiles compared with tenofovir disoproxil fumarate (TDF)-based ART, but data in pregnancy are limited. We evaluated metabolic markers in pregnant women with human immunodeficiency virus (HIV) after starting TAF- versus TDF-based ART.

Methods

We analyzed data within the IMPAACT 2010/VESTED trial, which demonstrated better pregnancy outcomes in pregnant women randomized to initiate TAF/Emtricitabine/Dolutegravir (TAF/FTC + DTG; n = 217) or TDF/FTC + DTG (n = 215). We measured non-fasting plasma concentrations of glucose, total-cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), lipoprotein (a), and triglycerides from samples collected 8 weeks after enrollment. We employed linear regression models to estimate by-arm mean differences.

Results

In total, 219 participants enrolled in the DTG arms in Zimbabwe and Uganda: 109 in the TAF/FTC + DTG and 110 in the TDF/FTC + DTG arms. At study entry, mean gestational age was 22.6 weeks, median HIV-1 RNA was 711 copies/mL, and mean age was 25.8 years. By 8 weeks, mean total cholesterol was 12 mg/dL higher in women randomized to TAF/ FTC + DTG versus TDF/FTC + DTG (95% confidence interval [CI]: 3.8, 21.1). Pregnant women in the TAF/FTC + DTG arm had higher mean LDL-C (7.1 mg/dL, 95% CI: .2, 14.0), triglycerides (12.3 mg/dL, 95% CI: 1.8, 22.7), lipoprotein (a) (7.3 mg/dL, 95% CI: 1.1, 13.6), and lower mean HDL-C (2.8 mg/dL, 95% CI: .1, 5.6) compared to the TDF/FTC + DTG arm.

Conclusions

Pregnant women randomized to start TAF/FTC + DTG had higher lipids than those randomized to TDF/FTC + DTG within 8 weeks of ART initiation. However, lipid levels were within normal reference ranges.
An attempt to generate panoramic radiographs including jaw cysts using StyleGAN3
Authors: Fukuda Motoki , Kotaki Shinya , Nozawa Michihito , Tsuji Kaname , Watanabe Masahiro , Akiyama Hironori , Ariji Yoshiko
Published: September 2024

Objectives

The purpose of this study was to generate radiographs including dentigerous cysts by applying the latest generative adversarial network (GAN; StyleGAN3) to panoramic radiography.

Methods

A total of 459 cystic lesions were selected, and 409 images were randomly assigned as training data and 50 images as test data. StyleGAN3 training was performed for 500 000 images. Fifty generated images were objectively evaluated by comparing them with 50 real images according to four metrics: Fréchet inception distance (FID), kernel inception distance (KID), precision and recall, and inception score (IS). A subjective evaluation of the generated images was performed by three specialists who compared them with the real images in a visual Turing test.

Results

The results of the metrics were as follows: FID, 199.28; KID, 0.14; precision, 0.0047; recall, 0.00; and IS, 2.48. The overall results of the visual Turing test were 82.3%. No significant difference was found in the human scoring of root resorption.

Conclusions

The images generated by StyleGAN3 were of such high quality that specialists could not distinguish them from the real images.
265. INITIAL RESULTS FROM RESOLVE, A PHASE 1B DOSE-ESCALATION STUDY OF EP-104GI (EXTENDED-RELEASE FLUTICASONE PROPIONATE INTRA-ESOPHAGEAL INJECTION) FOR EOSINOPHILIC ESOPHAGITIS
Authors: Helliwell James , Malone Amanda , Bredenoord Arjan J , Nguyen Nam , Ko Hin Hin , Dobek Christine , Peck Vik , Dellon Evan S
Published: September 2024

Background

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by inflammation, influx of eosinophils and esophageal remodeling. Therapy for EoE includes swallowed/topical corticosteroids, dupilumab, and dietary elimination; but these are not always effective.

EP-104GI is an extended-release fluticasone propionate (FP) intra-esophageal injection being developed as a novel treatment for EoE. EP-104GI consists of coated FP crystals that release locally via diffusion at a pre-defined rate to reduce peak concentrations and prolong therapeutic window.

RESOLVE (NCT05608681) is a Phase 1b, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of EP-104GI in patients with EoE.

Methods

The conservative starting dose of EP-104GI consisted of 1 mg injected at each of 4 sites in 4 quadrants over two ‘rings’ in the esophagus. Dose escalations increase the dose per site and/or number of sites; the second cohort received 1 mg at each of 8 sites.

After a single administration of EP-104GI, participants are assessed for up to 24 weeks including adverse events (AEs) and laboratory tests. Efficacy assessments include histological endpoints and patient-reported symptom outcomes including the Straumann Dysphagia Index (SDI). Esophageal biopsies are collected at baseline, Week 4 and Week 12.

Results

All subjects demonstrated decreased symptom scores compared to baseline, with generally greater responses at the higher EP-104GI dose in Cohort 2 (Fig 1). Histologically, all Cohort 2 patients showed decreases in EoEHSS scores with 2/3 having ≈50% decrease in total grade score and ≈35% decrease in total stage score at Week 4, also, eosinophil counts were reduced by ≈35% at Week 4 and ≈40% at Week 12.

Findings from Cohorts 1 and 2 of the ongoing trial include mild-moderate treatment-emergent AEs, the majority occurring on the day of treatment. No AEs were related to EP-104GI.

Conclusions

The initial results presented here indicate that the novel diffusion-based localized delivery of FP via EP-104GI injection into the esophagus is feasible and safe in patients with EoE and could avoid the side-effects typically associated with swallowed/topical corticosteroids. Efficacy data from the doses studied, although limited at this point, suggest a dose-response relationship with symptom outcomes and also show histologic improvements. These findings support the potential for an interval of at least 6 months between inter-esophageal injections, which may be further extended at the higher doses to be investigated in this study. Recruitment is ongoing.
266. NSQIP 5-FACTOR MODIFIED FRAILTY INDEX PREDICTS MORBIDITY BUT NOT MORTALITY AFTER ESOPHAGECTOMY
Authors: Qu Linda Chang , Vogt Kelly , Malthaner Richard
Published: September 2024

Background

Frailty is a source of morbidity in esophagectomy patients. To aid clinical decision making, it is important to determine if the simplified 5-factor modified frailty index (mFI-5) retains the same associations between frailty and adverse outcomes as its 11-factor predecessor.

Methods

Patients undergoing esophagectomy for esophageal cancer or dysplasia from 2016-2018 were identified using National Surgical Quality Improvement Program (NSQIP). The mFI-5 was used to determine association between frailty and post-esophagectomy morbidity and mortality.

Results

In total, 2,567 patients were included. No patients had a mFI-5 score higher than 3/5 and the score distribution was wide: mFI0 = 1103 (43%), mFI1 = 982 (38.3%), mFI2 = 435 (16.9%), mFI3 = 47 (1.8%). Clavien-Dindo grade IV complications increased with mFI score: mFI0 (11.2%), mFI1 (15.6%), mFI2 (19.8%), mFI3 (25.5%), as did mortality: mFI0 (1.9%), mFI1 (3%), mFI2 (3.4%), mFI3 (4.3%). Multivariate logistic regression analyses controlling for age, sex, body mass index, American Society of Anesthesiology classification, operative duration, emergency surgery status, and neoadjuvant therapy status showed increasing frailty score was associated with Clavien-Dindo grade IV complications (p=0.01), but not mortality (p=0.13).

Conclusions

The mFI-5 is associated with morbidity but not mortality in patients who have undergone esophagectomy for esophageal cancer. Compared to the mFI-11, the mFI-5 may not be nuanced enough in the assessment of frailty specific to this patient population.
273. PERIOPERATIVE BLOOD TRANSFUSIONS AND SURVIVAL IN GASTROESOPHAGEAL CANCERS – A SWEDISH POPULATION-BASED STUDY
Authors: Edholm David , Lagergren Jesper , Hedberg Jakob , Rouvelas Ioannis , Johansson Jan , Lindblad Mats , Linder Gustav
Published: September 2024

Background

Blood transfusions have been associated with decreased long-term survival in cancer patients, possibly due to immunological factors. This cohort study aimed to investigate associations, if any, between perioperative transfusions and survival in gastroesophageal cancer patients.

Methods

A population-based cohort study was conducted based on the National Registry for Esophageal and Gastric cancer (NREV), which harbors clinical data including given transfusions. All patients resected for esophageal or gastric cancer in Sweden, between 2017 and 2022, were included and their survival was acquired from the Swedish Cause of Death Registry. Multivariable Cox regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI), adjusted for confounders (age, American Society of Anesthesiologist class, access of surgery and pathological TNM stage)

Results

Of 1,368 patients, 227 patients (17%) received perioperative transfusions. Transfusion was associated with an increased risk of all-cause mortality within 3 years of surgery (HR 1.48 95% CI 1.17-1.91). Kaplan-Meier curves depicted worse crude survival in patients having received peroperative transfusion (Figure 1).

To exclude the effects of surgery-related postoperative complications on short-term mortality, a sensitivity analysis was performed, excluding patients who died within 30 days of resection, and found that the impact of transfusions on survival remained.

Conclusion

Perioperative blood transfusions might have a negative impact on survival in patients who undergo gastroesophageal cancer surgery.