bluuebunny/crossref_metadata_2025 huggingface dataset:
INDIDO: A novel low-power approach for domino logic circuits
Authors: Mushtaq Umayia , Akram Md Waseem , Prasad Dinesh , Islam Aminul
Published: May 2024

Power dissipation in Nanoelectronic circuits at advanced technology nodes is dominated by leakage power dissipation. This is due to an increase in short channel effects in the scaled transistors.The VLSI industry is seeking alternative options to enhance the performance of portable electronic systems by ensuring higher speed and reduced power dissipation. In the ultra-deep submicron (DSM) regime, a new device called the fin-shaped field effect transistor (FinFET) was developed to replace CMOS technology. FinFET, a multi-gate device, significantly reduces power dissipation compared to planer MOS (Metal Oxide Semiconductor ) transistor, but it doesn’t entirely resolve the issue. To further reduce power dissipation in the ultra DSM regime, low power approaches are required. Domino logic, a widely-used dynamic logic, is commonly utilized in high-speed VLSI architectures. In this research work, a novel INput Dependent Inverter DOmino (INDIDO) logic approach for low-power domino logic circuits using FinFET devices is proposed. A comparative analysis between the proposed INDIDO method and the existing approaches is performed for domino logic circuits for various performance metrics at the 16 nm technology node. In this research, various circuits like domino buffer, domino OR, domino AND, domino XOR and domino half adder are designed using the proposed INDIDO approach.The proposed INDIDO FinFET buffer circuit offers significant improvement in energy efficiency and FOM (Figure of Merit) by 53.18% and 82% respectively as compared to conventional FinFET footed domino buffer circuit. Beside this, proposed circuits like INDIDO OR, INDIDO AND, INDIDO XOR and INDIDO Half adder circuit follow the same trend as INDIDO buffer circuit and show better performance parametres in comparison to the existing low power domino approaches as well. In addition to this, the proposed INDIDO buffer circuits are also analyzed for PVT(process voltage and temperature) variability.This whole analysis makes us to conclude that proposed INDIDO approach reduces power dissipation and delay penalty, have high noise tolerance capacity, more immunity against PVT variations and high energy efficiency in comparison to the already existing techniques.
Computational analysis of a four-flap valveless micropump (FFVM) for low reynolds number applications in microfluidic systems
Authors: Gavali Sachin R , Pawar Dr. Prashant M
Published: May 2024

Microfluidic systems are crucial in various fields including biological fluid handling and microelectronic cooling. Micropumps play a vital role in microfluidics. Valveless micropumps are the preferred choice in microfluidics because of their ability to minimize the risk of clogging and gently handle biological materials. In this comprehensive Four-Flap Valveless Micropump (FFVM) simulation, the fluid flow and associated deformation in the valveless micropump are analyzed. The oscillatory fluid motion generated by a straightforward reciprocating pumping mechanism is transformed into a unidirectional net flow by the micropump. This pump eliminates the need for intricate actuation mechanisms found in valve-based pumps while offering precise direction control. The input is given in terms of the Reynolds number or inflow velocity. In this study, the Reynolds numbers were changed from 16 to 50, which resulted in a positive correlation with the net flow rates, yielding a maximum net flow rate of 20.81 μl min−1 at a Reynolds number of 50. The influence of the average flow velocity is evident, with a peak net flow rate of 29.16 μl min−1 at 50 cm s−1. The FFVM showcases adaptability by delivering fluid within microfluidic pathways, holding promising applications in precision drug delivery systems.
Investigating the nonlinear optical response of virgin cherry kernel oil and its application to detecting adulteration
Authors: Hassan Amir Namiq , Haddad Mohammad Ali , Golestanifar Moein , Behjat Abbas
Published: May 2024

The nonlinear optical (NLO) response of materials is the basis for their use in various applications including optical switching, optical data storage, and optical limiting. Additionally, it can be used as an innovative authentication method. In this study, the NLO properties of virgin cherry kernel oil (VCKO) were investigated by observing of spatial self-phase modulation (SSPM) diffraction rings using a

532

nm

continuous-wave laser beam. Based on the intensity-dependent number of symmetric diffraction rings, the nonlinear refraction coefficient and thermo-optical coefficient of VCKO were estimated to be

3.81
×

10

−
6

cm

2

/
W

and

5.34
×

10

−
4

K

−
1

,

respectively, for the first time, according to the authors’ knowledge. Furthermore, we employed the SSPM technique for adulteration detection in the VCKO sample by analyzing its NLO properties. To accomplish this, we prepared different adulterated samples by mixing VCKO with cheaper commercial oils, such as virgin sunflower oil (VSFO) and virgin canola oil (VCO) at various concentration ratios. In the mixed VCKO adulterated samples, the measured NLO parameters were highly correlated with the amount of adulteration. The results confirmed the ability of the SSPM technique to determine the degree of adulteration in oil samples by measuring and comparing their NLO properties. In addition, our results indicate that cherry kernel oil can be a viable candidate as a nonlinear medium for optical applications.
Large teleportation of two-qubit state between non-neighboring nodes based on the utilization of multiple cluster states within quantum networks
Authors: El Hadfi Hanane , El Kirdi Meryem , Drissi Lalla Btissam , Ahl Laamara Rachid
Published: May 2024

The transmission of quantum states over extended distances is constrained by photon losses, ruling out direct amplification akin to classical telecommunications due to the non-cloning theorem. Overcoming this challenge involves implementing quantum repeater protocols that leverage entanglement swapping to create long-distance entanglement from shorter distances. A novel multi-hop quantum teleportation scheme, blending concepts from quantum repeaters and teleportation, is under exploration. It aims to transfer arbitrary two-qubit states between two distant parties, even in the absence of a direct quantum channel. Intermediate nodes, connected via a four-qubit entangled cluster state as quantum channels, are introduced based on a more general routing protocol. Bell measurements are independently conducted by the source node (Alice) and all intermediate nodes, with simultaneous transmission of measurement results, significantly reducing time consumption. Determining the quantum state from Bell measurement results requires only the destination node (Bob) for a simple unitary transformation. Moreover, this protocol holds promise for implementation on the IBM Quantum Experience platform once the requisite quantum circuits are designed. This overview encompasses both the theoretical and simulated status of the proposed scheme, with simulated findings incorporated into quantum state tomography to verify the accuracy of the transmitted quantum state.
A comparative study on ReLU Implementation using TMDFETs
Authors: Hanamashetti Sanket , Vadde Venkatesh , Muralidharan Bhaskaran
Published: May 2024

In this study, we compare the implementation of the rectified linear (ReLU) activation function using transition metal dichalcogenide field-effect transistors (TMDFETs) and metal-oxide-semiconductor FETs (MOSFETs). Five TMDs - MoS
2, MoSe
2, MoTe
2, WS
2, WSe
2 along with three variants (low-power, high-performance, and multi-gate) of the MOSFETs are simulated. Three ReLU circuits utilizing these FETs are employed for the comparison. The power consumption, speed, and accuracy of the ReLU implementation are measured and compared for each circuit and each FET. Our simulation results show that the MOSFETs consume much less power than the TMDFETs and deliver more accurate ReLU functionality. However, the TMDFETs are much faster than the MOSFETs. Among the TMDFETs, the WS
2 FET stands out, as it has higher accuracy, consumes the least power and its power consumption is comparable to the MOSFETs. Additionally, WS
2 is faster compared to MOSFETs, resulting in a trade-off between power efficiency and speed. This makes WS
2 an attractive option for implementing the ReLU activation function.
Black holes in degenerate Einstein Gauss-Bonnet gravity: can QNMs distinguish them from GR?
Authors: Gera Suvikranth , Roy Poulami Dutta
Published: May 2024

For the first time, we study the quasi-normal modes(QNMs) of massless scale fields propagating in spacetimes with zero metric determinant. In this context, we work with asymptotically flat solutions to degenerate Einstein-Gauss-Bonnet (EGB) theory introduced in [JCAP
02 (2022) 020]. This solution has two distinct branches akin to Einstein Gauss-Bonnet(EBG) gravity. However, unlike the EBG solutions, both the branches of dEGB are well-defined asymptotically. The negative branch solutions from both theories are equivalent under the identification of certain parameters. We provide constraints on the Gauss-Bonnet coupling parameters, which result in black hole spacetimes, and study the behaviour of a propagating scalar field through the computation of QNMs. Finally, we compare the time domain evolution of the scalar field in the background of these black holes with their GR counterparts.
Mode coupling with Fabry–Perot modes in photonic crystal slabs
Authors: Qin 秦 Ken 恳 , Hu 胡 Peng 鹏 , Liu 刘 Jie 杰 , Xiang 向 Hong 红 , Han 韩 De-Zhuan 德专
Published: May 2024

Fabry–Perot (FP) modes are a class of fundamental resonances in photonic crystal (PhC) slabs. Owing to their low quality factors, FP modes are frequently considered as background fields with their resonance nature being neglected. Nevertheless, FP modes can play important roles in some phenomena, as exemplified by their coupling with guided resonance (GR) modes to achieve bound states in the continuum (BIC). Here, we further demonstrate the genuine resonance mode capability of FP modes PhC slabs. Firstly, we utilize temporal coupled-mode theory to obtain the transmittance of a PhC slab based on the FP modes. Secondly, we construct exceptional points (EPs) in both momentum and parameter spaces through the coupling of FP and GR modes. Furthermore, we identify a Fermi arc connecting two EPs and discuss the far-field polarization topology. This work elucidates that the widespread FPs in PhC slabs can serve as genuine resonant modes, facilitating the realization of desired functionalities through mode coupling.
Adherence of p-Terphenyl (PTP) film on the dichroic filter used for the X-ARAPUCA device
Authors: Mendonça A.P.A. , Machado A.A. , Marques F.C. , Bazetto M.C.Q. , Merlo R.B. , Pierobão C. , Figueroa C.A. , Perotti B.L. , Segreto E.
Published: May 2024

The adherence of the p-Terphenyl film to the substrate in the X-ARAPUCA dichroic filter is directly correlated with the long-term efficiency and durability of this device. This study presents the results of different cleaning methods established to analyze their contributions to the film's adherence to the substrate. The samples underwent analysis of their crystalline and morphological structure using XRD and AFM techniques. Three distinct techniques were employed in the adherence tests: ultrasonic bath, scratch test, and cryogenic immersion method with turbulence, as these devices will be submerged in liquid argon in the DUNE experiment.
Results suggest that the deposited PTP layer exhibits a monoclinic crystalline structure, with topography revealing percolated planar grains and roughness ranging from 13 nm to 18 nm. The various adherence techniques employed yielded consistent results, highlighting the standard cleaning process involving Soap + H2O + N2 + Kiln as the preferred method.
Correlation between charge and current gain in LGADs treated with IR lasers
Authors: Ristić Aleksandar , Kramberger Gregor , Debevc Jernej , Hiti Bojan , Mandić Igor , Skomina Petja , Ristić Goran
Published: May 2024

This study investigates the correlation between the gain,
defined as the increase of measured charge generated from the
absorption of incident radiation, and the gain measured as the
increase of sensor leakage current in Low Gain Avalanche Detectors
(LGAD) before and after neutron irradiations. LGADs exhibit high
signal-to-noise ratios for minimum ionizing particles and will be
used in high-energy physics experiments, mainly related to timing
applications. Transient Current Technique (TCT) measurements were
conducted with LGADs and PIN diodes. The electric field screening
effect, caused by free and trapped carriers, is identified as the
main reason for the differences measured in gain determined from the
increase in leakage current and collected charge. These effects are
more significant in irradiated LGAD sensors. The experimental
results confirm expectations, demonstrating a growing spread between
the two measured gains with fluence. The study enables the
prediction of charge gain from the leakage current measurements,
which are easier to conduct.
Distinct intraseasonal periodicity of Siberian high as modulated by ENSO: dominance of Madden–Julian oscillation
Authors: Zhou Fang , Huang Min , Liu Minghong , Qian Yitian , Zhu Yan
Published: May 2024

While previous studies have demonstrated that the El Niño-Southern Oscillation (ENSO) can impact global climate systems on the intraseasonal timescale, how ENSO affects the intraseasonal variability of the Siberian high (SH) still remains unclear. Based on spectral analysis, the SH exhibits evident intraseasonal periodicity (ISP) differences, with 25–50 d during El Niño winters and 50–90 d during La Niña winters. The northward propagation of the Rossby wave from the tropics during the phase transition of the SH leads to the Madden–Julian oscillation (MJO) dominating the difference in the ISP of the SH. The faster eastward propagation of the MJO in El Niño winters leads to a quicker evolution of the SH. Accompanied by the eastward propagation of the MJO, when the tropical westerly in the lower troposphere is located over the Indian Ocean, it can deflect to the north and involved the Eurasian cyclonic circulation, which contributes to the negative phase of the SH. When the tropical westerly moves eastward and the easterly is occupied the Indian Ocean, the middle-to-high latitude northerly completely dominates the East Asia region, penetrates southward to the South China Sea, deflects westward, and involved the tropical easterly, acting as the positive peak stage of the SH. The upper-level tropical zonal wind overrides the low-level tropical zonal wind, forming a coupled circulation and air temperature pattern together with the low level. The faster propagation of the MJO in El Niño winters leads to the intraseasonal evolution of the El Niño-related SH to change from lagging behind the La Niña-related SH to exceeding it, thereby contributing to the ISP of the SH being much shorter during El Niño winters.
Recent shift from energy- to moisture-limitation over global croplands
Authors: Coffel Ethan D , Lesk Corey
Published: May 2024

Hot and dry conditions pose a substantial risk to global crops. The frequency of co-occurring heat and drought depends on land–atmosphere coupling, which can be quantified by the correlation between temperature and evapotranspiration (r(T, ET)). We find that the majority of global croplands have experienced declines in r(T, ET) over the past ∼40 years, indicating a shift to a more moisture-limited state. In some regions, especially Europe, the sign of r(T, ET) has flipped from positive to negative, indicating a transition from energy-limitation to moisture-limitation and suggesting a qualitative shift in the local climate regime. We associate stronger declines in r(T, ET) with faster increases in annual maximum temperatures and larger declines in soil moisture and ET during hot days. Our results suggest that shifts towards stronger land–atmosphere coupling have already increased the sensitivity of crop yields to temperature in much of the world by 12%–37%, as hot days are not only hotter, but also more likely to be concurrently dry.
An effective Hamiltonian for the simulation of open quantum molecular systems
Authors: Site Luigi Delle , Djurdjevac Ana
Published: May 2024

We discuss the derivation of an effective Hamiltonian for open quantum many-particle systems. The aim is to define an operator that can be used for (molecular) simulations where, through the exchange of energy and matter with the surrounding environment (reservoir), the number of particles, n, becomes a variable of the problem. The Hamiltonian is formally derived from the Von Neumann equation; specifically, we derive an n-hierarchy of equations for the density matrix,

ρ
^

n

, for near equilibrium situations. Such a hierarchy, in case of stationary equilibrium, delivers the standard grand canonical density matrix as it would be expected. We report that a similar Hamiltonian was conjectured, from empirical considerations, in the field of superconductivity. Thus our result also provide a formal basis for this long-standing hypothesis. Finally, an application is discussed for Path Integral simulations of molecular systems.
A non-enzymatic sensor obtained by direct writing of a AuNP-based ink for monitoring ascorbic acid in sweat
Authors: Nga Dau Thi Ngoc , Thu Vu Thi , Noël Vincent , Mattana Giorgio , Piro Benoît
Published: May 2024

Recently, there has been an increasing interest in the development of wearable sensors for monitoring vitamin C (ascorbic acid) in sweat. These sensors can help assess personal nutritional status, prevent vitamin imbalances, and determine the effectiveness of certain medical treatments. This study presents the first example of non-enzymatic ascorbic acid sensor based on the catalytic activity of printed AuNPs. The three-electrode electrochemical system sensor was fabricated by printing a working and counter-electrode from an AuNP-based ink and a pseudo-reference electrode from a silver ink, on a flexible Kapton® substrate. SEM examination of the printed gold layer revealed a highly divided material, which facilitates electron transfer and accelerates the oxidation of ascorbic acid. In vitro amperometry demonstrated a proportional increase in current with ascorbic acid concentration ranging from 10 to 390 μM, with a sensitivity of 14 μA·mM−1·cm−2. The low oxidation potential of +0.2 V vs Ag/AgCl effectively avoided most interfering oxidations. These results pave the way toward evaluation on the body of healthy volunteers, by placing the sensor directly on their skin, for example for tracking the changes in ascorbic acid concentration in sweat when eating Vitamin C tablets or Vitamin C-containing food such as orange juice. The very first results demonstrated good real-time performance in testing in such experimental conditions. This has potential applications in healthcare, not only on skin but also on therapeutic bandages applied to chronic wounds.
Impact of electric and clean-fuel vehicles on future PM2.5 and ozone pollution over Delhi
Authors: Mogno Caterina , Wallington Timothy J , Palmer Paul I , Hakkim Haseeb , Sinha Baerbel , Sinha Vinayak , Steiner Allison L , Sharma Sumit
Published: May 2024

We investigate the impact of adoption of electric vehicles and cleaner fuels on future surface levels of PM2.5 and ozone over Delhi for two contrasting seasons, pre-monsoon and post-monsoon. We run the WRF-Chem atmospheric transport model at high resolution (4 km) with two transport emission scenarios for year 2030: (1) a scenario with electrification of two- and three-wheelers and light commercial vehicles, and (2) a scenario which also includes conversion of diesel vehicles to compressed natural gas (CNG). Compared to the baseline values in 2019, the scenario with both electrification and conversion of diesel vehicles to CNG has a greater reduction in PM2.5 concentrations (up to 5%) than the electrification of two- and three-wheelers and light commercial vehicles alone (within 1%), mainly due to the the greater reduction in primary emissions of PM2.5 and black carbon from diesel conversion to CNG. Vehicles electrification could result in an increase in the daily maximum 8-hours ozone concentrations, which are partially offset by additionally converting to CNG—by −1.9% and +2.4% during pre-monsoon and post-monsoon seasons. This reflects higher NOx emissions from the CNG vehicle scenario compared to electrification-alone scenario, which limits the increase of surface ozone in the VOC-limited chemical environment over Delhi. Our findings highlight the importance of a coordinated strategy for PM2.5 and ozone when considering traffic emission controls, and highlight that the transition to electric vehicles should be accompanied by the conversion of diesel vehicles to CNG to limit surface ozone increase and achieve greater reduction in PM2.5 concentrations over Delhi. However, the small changes in PM2.5 and in ozone compared to the baseline scenario highlight the importance of joint emissions reduction from other sectors to achieve substantial progress in PM2.5 and ozone air quality in Delhi.
Adaptive protection coordination in microgrid based on nature inspired meta-heuristic optimization algorithm
Authors: Kumari Rani , Naick Bhukya Krishna
Published: May 2024

Ensuring a robust protection system is crucial for safeguarding the integrity of the overall system against abnormalities. Incorporating distributed generation (DG) into the distribution network can introduce fluctuations in fault current levels and directions, potentially causing mismatches in the response of the existing coordination system. This study proposes an adaptive protection coordination scheme designed to accommodate both grid-connected and standalone modes, addressing various fault scenarios. Utilizing a hybrid WCMFO algorithm, optimal relay settings are determined to facilitate effective coordination within a microgrid setup. The proposed method has been analyzed on 9 bus Canadian benchmark system integrated with four DGs. The performance of the proposed method is compared to other optimization techniques to demonstrate its effectiveness. System modelling is conducted using MATLAB/Simulink, and validation is further carried out using industrial ETAP software on a test microgrid system. The analysis extends to evaluating the enhancement in overall system reliability, quantified in terms of energy not supplied (ENS).
Implementation of dual-axis solar tracker using smart battery protection system
Authors: Mohammed Azaharahmed , Battina N Malleswararao , Majahar Hussain , Gottapu Kusuma
Published: May 2024

Solar energy plays a vital role in power generation as a part of renewable energy source. Due to the intermittent nature of solar input and to increase the power output a dual-axis solar tracker is considered initially, and the power output is stored in the battery. The power extracted from the solar is enhanced with a dual tracker compared with other techniques. Moreover, the stored power in the battery is effected by cycles of charging and discharge. To aid and improve the performance of batteries a novel smart battery protection scheme is introduced. This scheme considers the battery parameters such as voltage, current, and temperature within the prescribed limit. Also, during fault conditions, this scheme provides safe operation of the battery which enhances the battery life.
DDoS Attack Detection in Edge-IIoT Network Using Ensemble Learning
Authors: Laiq Fariba , Al-Obeidat Feras , Amin Adnan , Moreira Fernando
Published: May 2024

As the number of IoT devices increases daily due to the rapid growth in technology, every device and network is vulnerable to attacks because it is exposed to the internet. Denial of Service (DoS) is a prevalent type of intrusion on the Internet of Things (IoT) network in which the server becomes down due to flooding requests. Distributed Denial of Service (DDoS) is a special type of DoS attack where the network of malicious computers called botnet consumes the target’s system resources by flooding the requests. Edge computing is closely related to Industrial Internet of Things (IIoT), and industry 4.0. Both of them are relatively emerging technologies so security is a crucial part of them. By incorporating our contributions to the current and innovative dataset Edge-IIoT, the proposed study presents a novel approach to detect DDoS attacks in an IIoT network in the domain of edge computing, whether the traffic is normal or malicious (DDoS traffic). This study explores various Ensemble Learning (EL) techniques to predict normal and malicious DDoS traffic along with the type of DDoS attack. The study applies various preprocessing techniques like Synthetic Minority Over Sampling Technique (SMOTE), label encoding, etc. to enhance the model’s performance and reveals how EL techniques performs better in terms of accuracy than the individual classifiers. Further, the performance of all EL techniques has been investigated in terms of all evaluation measures, including the elapsed time. This important addition not only broadens the focus of study in this area but also offers insightful comparisons of the efficiency and precision of various ensemble approaches as well as individual classifiers. The study achieved a maximum of 99.99% in all evaluation measures.
Machine-learning strategies for the accurate and efficient analysis of x-ray spectroscopy
Authors: Penfold Thomas , Watson Luke , Middleton Clelia , David Tudur , Verma Sneha , Pope Thomas , Kaczmarek Julia , Rankine Conor
Published: May 2024

Computational spectroscopy has emerged as a critical tool for researchers looking to achieve both qualitative and quantitative interpretations of experimental spectra. Over the past decade, increased interactions between experiment and theory have created a positive feedback loop that has stimulated developments in both domains. In particular, the increased accuracy of calculations has led to them becoming an indispensable tool for the analysis of spectroscopies across the electromagnetic spectrum. This progress is especially well demonstrated for short-wavelength techniques, e.g. core-hole (x-ray) spectroscopies, whose prevalence has increased following the advent of modern x-ray facilities including third-generation synchrotrons and x-ray free-electron lasers. While calculations based on well-established wavefunction or density-functional methods continue to dominate the greater part of spectral analyses in the literature, emerging developments in machine-learning algorithms are beginning to open up new opportunities to complement these traditional techniques with fast, accurate, and affordable ‘black-box’ approaches. This Topical Review recounts recent progress in data-driven/machine-learning approaches for computational x-ray spectroscopy. We discuss the achievements and limitations of the presently-available approaches and review the potential that these techniques have to expand the scope and reach of computational and experimental x-ray spectroscopic studies.
Machine Learning and Information Theory Concepts towards an AI Mathematician
Authors: Bengio Yoshua , Malkin Nikolay
Published: May 2024

The current state of the art in artificial intelligence is impressive, especially in terms of mastery of language, but not so much in terms of mathematical reasoning. What could be missing? Can we learn something useful about that gap from how the brains of mathematicians go about their craft? This essay builds on the idea that current deep learning mostly succeeds at system 1 abilities—which correspond to our intuition and habitual behaviors—but still lacks something important regarding system 2 abilities—which include reasoning and robust uncertainty estimation. It takes an information-theoretical posture to ask questions about what constitutes an interesting mathematical statement, which could guide future work in crafting an AI mathematician. The focus is not on proving a given theorem but on discovering new and interesting conjectures. The central hypothesis is that a desirable body of theorems better summarizes the set of all provable statements, for example, by having a small description length while at the same time being close (in terms of number of derivation steps) to many provable statements.
Finite measures of maximal entropy for an open set of partially hyperbolic diffeomorphisms
Authors: Mongez Juan , Pacifico Maria
Published: May 2024

We consider partially hyperbolic diffeomorphisms

f
f

with a one-dimensional central direction such that the unstable entropy is different from the stable entropy. Our main result proves that such maps have a finite number of ergodic measures of maximal entropy. Moreover, any

C

1
+

C^{1+}

diffeomorphism near

f
f

in the

C
1

C^1

topology possesses at most the same number of ergodic measures of maximal entropy. These results extend the findings in Buzzi, Crovisier, and Sarig [Ann. of Math. (2) 195 (2022), pp. 421–508] to arbitrary dimensions and provides an open class of non-Axiom A systems of diffeomorphisms exhibiting a finite number of ergodic measures of maximal entropy. We believe our technique, essentially distinct from the one in Buzzi et al., is robust and may find applications in further contexts.
Predicting functional UTR variants by integrating region-specific features
Authors: Li Guangyu , Wu Jiayu , Wang Xiaoyue
Published: May 2024

The untranslated region (UTR) of messenger ribonucleic acid (mRNA), including the 5′UTR and 3′UTR, plays a critical role in regulating gene expression and translation. Variants within the UTR can lead to changes associated with human traits and diseases; however, computational prediction of UTR variant effect is challenging. Current noncoding variant prediction mainly focuses on the promoters and enhancers, neglecting the unique sequence of the UTR and thereby limiting their predictive accuracy. In this study, using consolidated datasets of UTR variants from disease databases and large-scale experimental data, we systematically analyzed more than 50 region-specific features of UTR, including functional elements, secondary structure, sequence composition and site conservation. Our analysis reveals that certain features, such as C/G-related sequence composition in 5′UTR and A/T-related sequence composition in 3′UTR, effectively differentiate between nonfunctional and functional variant sets, unveiling potential sequence determinants of functional UTR variants. Leveraging these insights, we developed two classification models to predict functional UTR variants using machine learning, achieving an area under the curve (AUC) value of 0.94 for 5′UTR and 0.85 for 3′UTR, outperforming all existing methods. Our models will be valuable for enhancing clinical interpretation of genetic variants, facilitating the prediction and management of disease risk.
Mutational signatures of colorectal cancers according to distinct computational workflows
Authors: Battuello Paolo , Corti Giorgio , Bartolini Alice , Lorenzato Annalisa , Sogari Alberto , Russo Mariangela , Di Nicolantonio Federica , Bardelli Alberto , Crisafulli Giovanni
Published: May 2024

Tumor mutational signatures have gained prominence in cancer research, yet the lack of standardized methods hinders reproducibility and robustness. Leveraging colorectal cancer (CRC) as a model, we explored the influence of computational parameters on mutational signature analyses across 230 CRC cell lines and 152 CRC patients. Results were validated in three independent datasets: 483 endometrial cancer patients stratified by mismatch repair (MMR) status, 35 lung cancer patients by smoking status and 12 patient-derived organoids (PDOs) annotated for colibactin exposure. Assessing various bioinformatic tools, reference datasets and input data sizes including whole genome sequencing, whole exome sequencing and a pan-cancer gene panel, we demonstrated significant variability in the results. We report that the use of distinct algorithms and references led to statistically different results, highlighting how arbitrary choices may induce variability in the mutational signature contributions. Furthermore, we found a differential contribution of mutational signatures between coding and intergenic regions and defined the minimum number of somatic variants required for reliable mutational signature assignment. To facilitate the identification of the most suitable workflows, we developed Comparative Mutational Signature analysis on Coding and Extragenic Regions (CoMSCER), a bioinformatic tool which allows researchers to easily perform comparative mutational signature analysis by coupling the results from several tools and public reference datasets and to assess mutational signature contributions in coding and non-coding genomic regions. In conclusion, our study provides a comparative framework to elucidate the impact of distinct computational workflows on mutational signatures.
Klinefelter syndrome: etiology and clinical considerations in male infertility
Authors: Chen Xinyue , Zhang Xueguang , Jiang Ting , Xu Wenming
Published: May 2024

Klinefelter syndrome (KS) is the most prevalent chromosomal disorder occurring in males. It is defined by an additional X chromosome, 47,XXY, resulting from errors in chromosomal segregation during parental gametogenesis. A major phenotype is impaired reproductive function, in the form of low testosterone and infertility. This review comprehensively examines the genetic and physiological factors contributing to infertility in KS, in addition to emergent assisted reproductive technologies, and the unique ethical challenges KS patients face when seeking infertility treatment. The pathology underlying KS is increased susceptibility for meiotic errors during spermatogenesis, resulting in aneuploid or even polyploid gametes. Specific genetic elements potentiating this susceptibility include polymorphisms in checkpoint genes regulating chromosomal synapsis and segregation. Physiologically, the additional sex chromosome also alters testicular endocrinology and metabolism by dysregulating interstitial and Sertoli cell function, collectively impairing normal sperm development. Additionally, epigenetic modifications like aberrant DNA methylation are being increasingly implicated in these disruptions. We also discuss assisted reproductive approaches leveraged in infertility management for KS patients. Application of assisted reproductive approaches, along with deep comprehension of the meiotic and endocrine disturbances precipitated by supernumerary X chromosomes, shows promise in enabling biological parenthood for KS individuals. This will require continued multidisciplinary collaboration between experts with background of genetics, physiology, ethics, and clinical reproductive medicine.
Inference for possibly misspecified generalized linear models with nonpolynomial-dimensional nuisance parameters
Authors: Hong Shaoxin , Jiang Jiancheng , Jiang Xuejun , Wang Haofeng
Published: May 2024

It is routine practice in statistical modelling to first select variables and then make inference for the selected model as in stepwise regression. Such inference is made upon the assumption that the selected model is true. However, without this assumption, one would not know the validity of the inference. Similar problems also exist in high-dimensional regression with regularization. To address these problems, we propose a dimension-reduced generalized likelihood ratio test for generalized linear models with nonpolynomial dimensionality, based on quasilikelihood estimation that allows for misspecification of the conditional variance. The test has nearly oracle performance when using the correct amount of shrinkage and has robust performance against the choice of regularization parameter across a large range. We further develop an adaptive data-driven dimension-reduced generalized likelihood ratio test and prove that, with probability going to one, it is an oracle generalized likelihood ratio test. However, in ultrahigh-dimensional models the penalized estimation may produce spuriously important variables that deteriorate the performance of the test. To tackle this problem, we introduce a cross-fitted dimension-reduced generalized likelihood ratio test, which is not only free of spurious effects, but robust against the choice of regularization parameter. We establish limiting distributions of the proposed tests. Their advantages are highlighted via theoretical and empirical comparisons to some competitive tests. An application to breast cancer data illustrates the use of our proposed methodology.
Spinal cord neurone loss and foot placement changes in a rat knock-in model of amyotrophic lateral sclerosis Type 8
Authors: Murage Brenda , Tan Han , Mashimo Tomoji , Jackson Mandy , Skehel Paul A
Published: May 2024

Amyotrophic lateral sclerosis is an age-dependent cell type–selective degenerative disease. Genetic studies indicate that amyotrophic lateral sclerosis is part of a spectrum of disorders, ranging from spinal muscular atrophy to frontotemporal dementia that share common pathological mechanisms. Amyotrophic lateral sclerosis Type 8 is a familial disease caused by mis-sense mutations in VAPB. VAPB is localized to the cytoplasmic surface of the endoplasmic reticulum, where it serves as a docking point for cytoplasmic proteins and mediates inter-organelle interactions with the endoplasmic reticulum membrane. A gene knock-in model of amyotrophic lateral sclerosis Type 8 based on the VapBP56S mutation and VapB gene deletion has been generated in rats. These animals display a range of age-dependent phenotypes distinct from those previously reported in mouse models of amyotrophic lateral sclerosis Type 8. A loss of motor neurones in VapBP56S/+ and VapBP56S/P56S animals is indicated by a reduction in the number of large choline acetyl transferase–staining cells in the spinal cord. VapB−/− animals exhibit a relative increase in cytoplasmic TDP-43 levels compared with the nucleus, but no large protein aggregates. Concomitant with these spinal cord pathologies VapBP56S/+, VapBP56S/P56S and VapB−/− animals exhibit age-dependent changes in paw placement and exerted pressures when traversing a CatWalk apparatus, consistent with a somatosensory dysfunction. Extramotor dysfunction is reported in half the cases of motor neurone disease, and this is the first indication of an associated sensory dysfunction in a rodent model of amyotrophic lateral sclerosis. Different rodent models may offer complementary experimental platforms with which to understand the human disease.
Low-intensity pulsed ultrasound for ‘no-option’ chronic/critical limb-threatening ischaemia in a patient with Buerger disease: a case report
Authors: Mohamad Yusoff Farina , Kajikawa Masato , Sakamoto Takumi , Tanaka Akio , Higashi Yukihito
Published: May 2024

Background

Buerger disease, also known as Winiwarter–Buerger disease or thromboangiitis obliterans (TAO), is a non-specific inflammation of small- and medium-sized arteries with thrombus obliteration and without atherosclerotic changes. Patients with TAO can develop chronic limb-threatening ischaemia (CLTI) and are at risk of limb amputation despite smoking cessation and exercise therapy recommendations.

Case summary

A 72-year-old Japanese man presented with painful discolouration of toes and renal impairment. He was diagnosed with Rutherford classification Stage 6 CLTI with immunoglobulin A nephropathy. He refused limb amputation. Clinical symptoms reduced after treatment with low-intensity pulsed ultrasound (LIPUS). LIPUS is a non-invasive option to alleviate peripheral arterial disease symptoms. Despite the initiation of conventional therapy measures, there was a worsening of the limb condition. The non-invasive investigational treatment option of LIPUS was initiated after the poor clinical outcomes of the conventional therapy measures. The patient’s symptoms in the bilateral lower limbs, ulcers, and the blue-coloured toes gradually lessened. After 1 year of treatment with LIPUS, he had achieved better walking independence with improved quality of life.

Discussion

Low-intensity pulsed ultrasound is a non-invasive option for therapeutic angiogenesis with the potential to improve ischaemic limb conditions in patients with peripheral arterial disease and to avoid major amputation procedures.
Unmeasurable low vitamin D levels caused by a novel, homozygote loss-of-function variant in the group-specific component gene
Authors: Nygaard Rie Harboe , Lauritzen Esben Stistrup , Sikjær Tanja , Højskov Carsten Schriver , Rejnmark Lars , Møller Holger Jon
Published: May 2024

A 29-year-old female, born to consanguineous parents, was found with unmeasurable levels of vitamin D (<10 nmol/L) after routine biochemical screening during her first pregnancy. She did not respond to either oral or intramuscular vitamin D supplementation and was an otherwise healthy young woman, with no signs of rickets, osteomalacia, osteoporosis, or secondary hyperparathyroidism. Western blot analysis revealed total lack of vitamin D binding protein, and next generation sequencing confirmed a novel, pathogenic homozygote loss-of-function mutation in exon 13 of the group-specific component gene, that encodes the poly A tail for vitamin D binding protein. She was therefore diagnosed with hereditary DBP deficiency, and vitamin D supplementation was diminished to life-long regular vitamin D supplementation (25 μg per day). This case is extremely interesting, as it expands our knowledge of vitamin D physiology and supports the free hormone hypothesis, given that the patient was asymptomatic despite no measurable levels of vitamin D.
Stochastic time series analysis of atrial fibrillatory electrograms in paroxysmal atrial fibrillation
Authors: Leftheriotis D , Giannakakis G , Flevari P , Adamopoulos A , Fiippatos G
Published: May 2024

Background/Introduction

Regional dominant frequency and instantaneous frequency modulation of short fractionated atrial electrograms have been associated with ablation targets and the prognosis of atrial fibrillation (AF). However, inconsistent and not fully comprehensible results have been reported.

Purpose

To construct a simple computational algorithm for the analysis of continuous fibrillatory atrial electrograms and evaluate it in clinical practice, among patients with paroxysmal AF.

Methods

Before the first cryo-balloon ablation, 3-minute continuous local electrogram recordings during pace-induced AF were obtained by the circumferential catheter from the left atrial appendage (LAA) and each pulmonary vein: left superior (LSPV), left inferior (LIPV), right superior (RSPV) and right inferior (RIPV). Following time- and frequency-domain analysis, non-linear detrended fluctuation analysis (DFA α) with analysis for short-term (DFA α1) and long-term fluctuations (DFA α2) was performed. The signals were detrended by subtracting time series polynomial fit and badpass filtered in the MATLAB environment (cut-off voltage 0.1 mV to avoid scar and artifacts).

Results

Fifteen patients were studied. Among different atrial areas, higher mean peak rate (pr) along with lower standard deviation of between peaks intervals (sdpp) and root square of peak-to-peak differences (rmppd) were observed in the LAA and left veins (Fig. 1). In patients with longer AF history (> 2 yrs), lower α, α1 and α2 exponents of DFA were observed (Fig. 2).

Conclusions

This algorithm depicted dissimilar impact on atrial electrical activity between different atrial areas. Patients with longer AF history had less self-similarity in local LAA electrograms. This might indicate possible ablation targets and reveal patients with greater AF burden and worse arrhythmic prognosis.Leftheriotis - Figure 1Leftheriotis - Figure 2
Impact of induced atrial fibrillation during atrioventricular nodal reentrant tachycardia ablation
Authors: Santos A R , Ferreira A , Lousinha A , Cruz M , Portugal G , Osorio P , Valente B , Cunha P , Paulo M , Bras M , Delgado A S , Guerra C , Fonseca H , Oliveira M , Ferreira R
Published: May 2024

Ablation is the treatment of choice for atrioventricular nodal reentrant tachycardia (AV NRT). Atrial fibrillation (AF) can incidentally occur during this procedure, labeling these patients (P) as susceptible for AF in the future. Our aim was to assess the presence of new onset AF in P who presented this arrhythmia during the electrophysiological study (EPS).

Methods

We retrospectively analyzed 580 P that underwent AV NRT ablation between November 2008 and August 2020. Patients with previous AF were excluded. After having AF induced during the EPS, 62 P were identified as susceptible for developing AF. Data were collected by contacting P and consulting medical records.

Results

The studied population had 64.5% (n=40) females, 35.5% (n=22) males, with ages between 15 and 81years old (median 52.3, mean 50.1). At ablation date, 33.9% (n=21) had hypertension, 3.2% (n=2) diabetes, 6.5% (n=4) chronic kidney disease, 3.2% (n=2) obstructive sleep apnea, 6.5% (n=4) coronary artery disease and 6.5% (n=4) structural heart disease. Previously to ablation, 46.8% (n=29) were on beta-blocker, 1.6% (n=1) on amiodarone and 3.2% (n=2) on flecainide. When admitted to the procedure, 98.4% (n=61) were in sinus rhythm and 1.6% (n=1) had a pacemaker. "Slow-fast" was the most common AVNRT type (96.8%). During the EPS, other arrhythmias were induced: in 12.9% (n=8) atrial flutter and in 9.7% (n=6) atrial tachycardia. After AF induction, 12.9% (n=8) needed electrical cardioversion and 3.2% (n=2) needed both electrical and pharmacological. At the time of ablation, transient complete atrioventricular block was noted in 6.5% (n=4) P. When contacted, 100% (n=62) had 1 year of follow-up, 69.4% (n=43) 5 years and 25.8% (n=16) 10 years, with a mean follow-up of 6.6 years. It was not possible to contact 12.9% (n=8) of the P, of those, 6.5% (n=4) died and 6.5% (n=4) did not reply. Recurrence of AV NRT was documented in 6.4% (n=4) P and all underwent a successful second ablation. Almost one third, 32.3% (n=20), were symptomatic, mainly with palpitations, and 27.4% (n=17) maintained follow up with a Cardiologist. New-onset AF was documented in 1 P only (1.6%), diagnosed 9 years after the procedure.

Conclusion

In our cohort, the induction of AF during EPS did not translate into clinical AF during follow-up. Whether this is a nonspecific finding related to catheter manipulation or pacing maneuvers on pharmacological provocation deserves further investigation.