bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Runner Balance for a Family Product of Injection Molding Process
Authors: Budiyantoro C , Sosiati H
Published: April 2024

A family mold is used in the injection molding process to produce components of different sizes that would normally be assembled into a single product assembly. The uniform quality of each injection molded part is strongly influenced by the filling balance of the mold cavity. The filling balance can be controlled by optimizing the dimensions of runners that are directed towards each cavity. In this paper, an optimization method is proposed that aims at balancing the filling time that maximizes the quality of a family mold cavity. There are two steps proposed in this research, namely theoretical calculations and simulation of runner balanced design using the software. The results of this study can be used as a practical reference in designing a mold for family products to avoid design errors as early as possible. The result obtained from an industrial case study highlighted the effectiveness of the proposed approach in finding the optimal runner dimension by a restricted number of simulations.
The Effect Analysis of ZnO Variations on Corn Starch and Cellulose Biocomposites toward Impact Strength
Authors: Widi I K A , Sutrisno T A , Febritasari R , Ariyanto A
Published: April 2024

Biocomposites made from renewable resources make biocomposites a more viable and promising alternative for the manufacture of metal replacement materials. The use of polyester resin as a matrix in composites does have good mechanical properties. However, it needs development to improve the mechanical properties better, namely by adding corn starch to help the polyester resin matrix. The addition of ZnO and cellulose to strengthen the mechanical properties of the biocomposite. This research was conducted using an experimental method, namely by varying the percentage of 100% Polyester Resin, 2.5% ZnO, 5% ZnO, and 7.5% ZnO to determine the difference in the impact value of the biocomposite. From the impact test results, the specimen with the best mechanical properties will be continued with X-Ray Diffraction testing, to determine the crystallinity index and crystal size. Based on data analysis and discussion, the average impact value of biocomposite 100% Polyester Resin, 2.5% ZnO, 5% ZnO, 7.5% ZnO respectively 0.0139 J/mm2 0.0188 J/mm2 0.0241 J/mm2 0.0168 J/mm2. The best impact value was obtained on biocomposite specimens with a percentage of 5% ZnO. The average impact value obtained is 0.0241 J/mm2. The results of the calculation of the crystallinity index on the specimens with a percentage of 2.5% ZnO, 5% ZnO, and 7.5% ZnO respectively 70.58%, 73.43%, 81.16%, with a crystal size of 28.53 nm, 42.80 nm, 52.21 nm. It can be seen that as the percentage of ZnO increases, the crystallinity index and crystal size increase.
Metallurgical Characterization of Micro Friction Stir Spot Welding (μFSSW) Parameters on Similar Materials AA1100
Authors: Membala S B , Sutresman O S , Arsyad H , Syahid M , Widyianto A
Published: April 2024

The Micro Friction Stir Spot Welding (μFSSW) process is a metal plate welding technique with a relatively thin plate thickness. The advantages of this welding are the higher quality of the weld and the relatively low deformation. This study aimed to determine the effect of depth of penetration, dwell time, and tool geometry on the trend of material flow on the macro-structure of the welds produced in μFSSW technique using AA1100 thin aluminum plates. In this study, the parameters that are changed are the depth of the chisel, dwell time, and tool geometry. In this study, the parameters of the penetration depth were divided into 500 microns, dwell time was split into three lengths of time (300 ms, 500 ms, and 700 ms), and tool geometry was divided into two types of tool geometries (tool-1 and tool-2). In addition, the macro test was carried out to determine the depth of the weld, contour profile, and stretch macrostructure. The results of the macro test will be used to analyze the material flow relationship in each weld zone on the welding results of all existing parameters. Based on the results of the study, the effect of depth of penetration, dwell time, and tool geometry on the weld depth and metallography (hook width, hook height, and effective top sheet thickness) of welds using AA1100 thin plates is influential along with various tool geometries and the deeper the weld penetration and the longer stirring time, although the results are not always directly proportional.
The Limit of Incomplete Information in Inverse Analysis for Hidden Corrosion Inference in Reinforced Concrete
Authors: Ibrahim I B M , Fonna S , Kurniawan R , Huzni S
Published: April 2024

One recurring problem in reinforced concrete structures is hidden corrosion. Detection of hidden corrosion is difficult due to incomplete information that can be measured. To overcome this problem, inverse analysis can be employed. Inverse analysis uses incomplete information from field measurement, and employs optimization to infer further information. Previous research has demonstrated the inference capability of inverse analysis for hidden corrosion detection in reinforced concrete. However, question remains on the limit of incompleteness of measurement data. The aim of this study is to simulate and examine the limit of incomplete information that can be allowed for an effective inverse analysis. The inverse analysis of hidden corrosion in reinforced concrete is formulated as a PDE-constrained optimization. The objective function of the optimization is the distance function between measurement data and FEM simulation. The search space is the PDE boundary conditions configuration. A FEM simulation is used to simulate measurement data by half-cell potential mapping on a concrete block of 2 by 1 meters. To simulate incomplete information, the number of measurement points is varied from 2 to 20 points on the surface of the concrete block. Results show that 20 measurement points are needed to successfully infer hidden corrosion profile. However, when the number of measurement points are below this, the effectiveness of inverse analysis varies and does not seem to correlate to the amount of information (i.e., number of measurement points). Further study is needed if this is due to a fluke or choice of measurement point’s location.
Finite Element Analysis of Polyethylene Pipe with Elliptical Hole Supported by Saddle Fusion Patch with Fin
Authors: Hermawan T L , Sriwijaya R
Published: April 2024

Underground pipe installation is one of the crucial components in supporting industrial activities. Damage to the underground pipe is typical and usually done by patching repair. Analysis of the stress distribution on pipe with patch has been done previously. An analysis needs to be done to determine the effectiveness of the patches and the effect of the growth of the damage. The purpose of this paper is to know the effect of the application of fins on the saddle fusion patch with variations in the number of fins, fin angle orientation, and fin height on the stress distribution on the PE 80 pipe. The research was carried out on a polyethylene pipe with elliptical defects that have been repaired with a saddle fusion patch with a fin as a stiffener. The pipe is a medium-density polyethylene pipe (MDPE80), and the patched is high-density polyethylene (HDPE100). The variation in the research is the fin’s height, the fin’s number and orientation of the fin, and the variation of defect dimension as representative of crack growth. The study was carried out using a finite element analysis tool, ANSYS 2020. The simulation results showed that the addition of fins and the difference in given height on the saddle fusion patch could reduce the stress acting on the cracked pipe. The stress drop that occurs in the addition of the number of fins is not only influenced by the number of fins but also influenced by the orientation of the added fins. The results of this study will provide an overview of the optimal patch thickness after being given reinforcement by fins added to the patch. The hole variations carried out aim to simulate so that the damage that occurs does not repeat itself after being given a patch. Information regarding the optimal and efficient patch thickness becomes an input that is used as a consideration in determining effective and economical repair steps.
Railway track vertical irregularities classification based on vehicle response using machine learning method
Authors: Wikaranadhi P , Alfian S D , Handoko Y A , Palar P S
Published: April 2024

The common method of railway track irregularities assessment currently used, based on track geometry measurement data, is expensive to run, disrupts regular train services, and shows poor correlation with the actual vehicle response when running on a given track section. Vehicle response-based track irregularities assessment methods aim to overcome the shortcomings of geometry measurement-based methods. One of the possible methods is to establish the correlation between track geometry and vehicle response statistically using machine learning. Classification algorithms have been used in previous research for categorizing track sections into discrete classes. In this paper, in addition to discrete classification, the probability for which a track section is categorized as a certain class is presented. Testing results of the trained machine learning classification model showed high accuracy, precision, and recall. The results indicated that this method is suitable for classification of the vertical track irregularities. Further testing was performed with shifted classification threshold. The finding showed that the classification model’s precision and recall could be adjusted by shifting the classification threshold. The result of this study highlights the potential of machine learning classification usage for track irregularities assessment.
Exact closed forms for the transmittance of electromagnetic waves in one-dimensional anisotropic periodic media
Authors: Torres-Guzmán J C , Díaz-de-Anda A , Arriaga J
Published: April 2024

In this work, we obtain closed expressions for the transfer matrix and the transmittance of electromagnetic waves propagating in finite one-dimensional anisotropic periodic stratified media with an arbitrary number of cells. By invoking the Cayley–Hamilton theorem on the transfer matrix for the electromagnetic field in a periodic stratified media formed byNcells, we obtain a fourth-order recursive relation for the matrix coefficients that defines the so-called Tetranacci polynomials (TPs). In the symmetric case, corresponding to a unit-cell transfer matrix with a characteristic polynomial where the coefficients of the linear and cubic terms are equal, closed expressions for the solutions to the recursive relation, known as symmetric TPs, have recently been derived, allowing us to write the transfer matrix and transmittance in a closed form. We show as sufficient conditions that the4×4differential propagation matrix of each layer in the binary unit cell,Δ,a)has eigenvalues of the form±p1,±p2, withp1≠p2, andb)its off-diagonal2×2block matrices possess the same symmetric structure in both layers. Otherwise, the recursive relations are still solvable for any4×4matrix and provide an algorithm to compute theNth power of the transfer matrix without carrying out explicitly the matrix multiplication ofNmatrices. We obtain analytical expressions for the dispersion relation and transmittance, in closed form, for two finite periodic systems: the first one consists of two birefringent uniaxial media with their optical axis perpendicular to thez-axis, and the second consists of two isotropic media subject to an external magnetic field oriented along thez-axis and exhibiting the Faraday effect. Our formalism applies also to lossy media, magnetic anisotropy or optical activity.
Performance Enhancement of PV Module with Cooling Effect using Wet Wicks
Authors: Mumu Tazeen Afrin , Smrity Araf Mim Ahmed , Bhuyan Ayesha , Islam A.K.M. Sadrul
Published: April 2024

Solar energy is one of the most potential sources of power production among all the renewable energies which is eco-friendly and can be much cheaper too. The energy conversion efficiency of the PV module decreases even more due to an increase in operating cell temperature over a certain limit. One way of improving the efficiency of the system is to maintain a low operating temperature by cooling it down during its operational period. This study compares the effects of cooling on the performance of photovoltaic systems. Experiments are performed on the solar panel inclined at a fixed 23.45° angle with the horizontal to the south without active cooling initially to have a set of reference performance parameters for comparison. The polycrystalline PV Module was tested with different cooling methods including Normal water Spray over the front surface, wet jute, and wet woolen material over the back surface of the panel. The cooling of the panels combined with the soiling effect enhances solar efficiency. The wet woolen material results in the most significant efficiency improvement, followed closely by wet jute and normal water spray.
Control of linear instabilities in two-dimensional airfoil boundary layers
Authors: Dandelia Harvansh , Kant Ravi , Narayanan Vinod
Published: April 2024

The present study deals with the control of linear, modal and non-modal growth of perturbations in a trapezoidal wing boundary layer. The asymmetric NACA 2515 airfoil is chosen for the analysis. The boundary layer velocity profiles, at different locations on the airfoil, are obtained using the Falkner–Skan equations. The non-modal linear stability theory is used to obtain the amplification of the initial perturbations, for which the state-space approach is adopted. The control is brought about using a Linear Quadratic Regulator (LQR) controller by the means of addition of fluid momentum in the wall-normal direction from the wing surface. Maximum transient energy growth is calculated across a range of wavenumber pairs, and control is applied to the pair with the highest energy growth. In this numerical analysis, we show that the transient growth is higher towards the trailing edge because of the adverse pressure gradient of the flow. Upon control actuation, the reduction in the transient energy growth of perturbations is achieved up to a maximum of 54.6%.
Strategy for transferring van der Waals materials and heterostructures
Authors: Fan Sidi , Li Xianxu , Mondal Ashok , Wang Wenjie , Lee Young Hee
Published: April 2024

Two-dimensional (2D) layered materials and heterostructures have garnered significant attention for their exploration of uncharted scientific phenomena and their versatile applications. The customization of van der Waals heterostructures heavily relies on their transfer assembly techniques. While traditional dry or wet transfer methods show promise in manipulating 2D materials and heterostructures, challenges such as residues from supporting layers, incomplete substrate etching, embedded bubbles at interfaces, and transfer-induced damages like cracks and wrinkles still pose significant hurdles. In this review, we comprehensively examine the state of transfer technology, identifying the origins of these technical challenges and discussing potential solutions. We specifically focus on strategies developed within the last 3–5 years that aim to address these complex transfer issues, facilitating the integration of 2D materials and heterostructures into existing silicon-based technologies. Finally, we offer perspectives to guide the optimization of each transfer method and inspire future industrial applications of 2D materials.
A critical review on polyvinylidene fluoride (PVDF)/zinc oxide (ZnO)-based piezoelectric and triboelectric nanogenerators
Authors: Shee Chirantan , Banerjee Swagata , Bairagi Satyaranjan , Baburaj Aiswarya , Naveen Kumar S K , Aliyana Akshaya Kumar , Mulvihill Daniel M , Alagirusamy R , Ali S Wazed
Published: April 2024

In this current energy crisis era, piezoelectric and triboelectric effects are emerging as promising technologies for energy harvesting. Polyvinylidene fluoride (PVDF) and its copolymers are well-known piezoelectric materials with high piezoelectric coefficients, which are widely used in flexible electronic devices. PVDF is also greatly utilized in the preparation of triboelectric layer due to its higher electronegative nature amongst common polymers. On the other hand, zinc oxide (ZnO) has been widely studied to investigate its multifunctional properties, including piezoelectricity, pyroelectricity and antibacterial activity. This versatile material can be prepared, using low cost and environmentally friendly routes, in various morphologies. Various research has already been performed to capture the synergistic effects of reinforcing ZnO within the PVDF polymeric matrix. This work first describes the basic principles of piezoelectric and triboelectric effects. Thereafter, the piezoelectric and triboelectric performances of PVDF and ZnO-based materials are briefly depicted based on their structures. Finally, the challenges and future scope associated with the mechanical energy harvesting from such materials are highlighted.
Renewable sources with virtual inertia penetration in multi area interconnected AGC using a modified MPC controller
Authors: Vidyarthi Prabhat Kumar , Kumar Ashiwani , Kumari Ankita , Kumar Aaryan
Published: April 2024

The challenge of controlling frequency deviation becomes more difficult as the complexity of a power plant increases. The robustness of the controller has a major impact on the stability of a complex power system (CPS). Due to the hybridization of CPS basic Automatic Generation Control (AGC) controllers (PID, FOPID, and TID), they are insufficient to give optimal performance to a plant. This requires a robust controller. So, a modified MPC controller has been proposed and evaluated by comparing it with several existing controllers, which gives optimal performance in terms of overshoot, undershoot, and settling time and improves its performance approximately 45%. This research discusses a combined AGC model and control for a three-area CPS, where each producing area consists of a thermal plant, a Diesel power plant, and a Solar Thermal Power Plant (STPP). The results of the modified MPC are superior to those of the basic controller compared to several existing controllers. An improved version of Sea-horse Optimization (SHO) has been proposed to optimize the different controller settings. The superiority of the SHO is shown by a comparison with some well-known, current meta-heuristic methods. The higher penetration levels of renewable energy sources (RESs) reduced system inertia which further deteriorate frequency response in CPS. To overcome these challenges, virtual inertia (VI) has been implemented with MPC. VI is applied to improve the performance of the AGC of the interconnected CPS along with emphasizing the nature of intermittent RESs of PV and wind energy. The thorough study findings provide compelling evidence for the effectiveness and efficiency of the recommended control strategies and also point to the possibility of applying them in actual power systems to improve stability and performance.
School racial/ethnic composition, effect modification by caring teacher/staff presence, and mid-/late-life depressive symptoms: findings from the Study of Healthy Aging in African Americans
Authors: Mobley Taylor M , Hayes-Larson Eleanor , Wu Yingyan , Peterson Rachel L , George Kristen M , Gilsanz Paola , Glymour M Maria , Thomas Marilyn D , Barnes Lisa L , Whitmer Rachel A , Mayeda Elizabeth Rose
Published: April 2024

For Black students in the United States, attending schools with a higher proportion of White students is associated with worse mental and physical health outcomes in adolescence/early adulthood. To our knowledge, no prior studies have evaluated the association between school racial/ethnic composition from kindergarten through grade 12 and later-life mental health. In a cohort of Black adults aged ≥50 years in Northern California who retrospectively reported (2017-2020) school racial/ethnic composition for grades 1, 6, 9, and 12, we assessed the association between attending a school with mostly Black students versus not and mid-/late-life depressive symptoms (8-item Patient-Reported Outcomes Measurement Information System (PROMIS) depression score, standardized to the 2000 US adult population) using age-, sex/gender-, southern US birth–, and parental education–adjusted generalized estimating equations, and assessed effect modification by the presence of a caring teacher/staff member. Levels of later-life depressive symptoms were lower among those who attended schools with mostly Black students in grades 1 and 6 (β = −0.12 [95% CI, −0.23 to 0.00] and β = −0.11 [95% CI, −0.22 to 0.00], respectively). In grade 6, this difference was larger for students without an adult at school who cared about them (β = −0.29 [95% CI, −0.51 to −0.07] vs β = −0.04 [95% CI, −0.17 to 0.09]). Among Black Americans, experiencing early schooling with mostly Black students may have later-life mental health benefits; this protective association appears more important for students without the presence of caring teachers/staff.

This article is part of a Special Collection on Mental Health.
GAUSS: a summary-statistics-based R package for accurate estimation of linkage disequilibrium for variants, Gaussian imputation, and TWAS analysis of cosmopolitan cohorts
Authors: Lee Donghyung , Bacanu Silviu-Alin
Published: April 2024

Motivation

As the availability of larger and more ethnically diverse reference panels grows, there is an increase in demand for ancestry-informed imputation of genome-wide association studies (GWAS), and other downstream analyses, e.g. fine-mapping. Performing such analyses at the genotype level is computationally challenging and necessitates, at best, a laborious process to access individual-level genotype and phenotype data. Summary-statistics-based tools, not requiring individual-level data, provide an efficient alternative that streamlines computational requirements and promotes open science by simplifying the re-analysis and downstream analysis of existing GWAS summary data. However, existing tools perform only disparate parts of needed analysis, have only command-line interfaces, and are difficult to extend/link by applied researchers.

Results

To address these challenges, we present Genome Analysis Using Summary Statistics (GAUSS)—a comprehensive and user-friendly R package designed to facilitate the re-analysis/downstream analysis of GWAS summary statistics. GAUSS offers an integrated toolkit for a range of functionalities, including (i) estimating ancestry proportion of study cohorts, (ii) calculating ancestry-informed linkage disequilibrium, (iii) imputing summary statistics of unobserved variants, (iv) conducting transcriptome-wide association studies, and (v) correcting for “Winner’s Curse” biases. Notably, GAUSS utilizes an expansive, multi-ethnic reference panel consisting of 32 953 genomes from 29 ethnic groups. This panel enhances the range and accuracy of imputable variants, including the ability to impute summary statistics of rarer variants. As a result, GAUSS elevates the quality and applicability of existing GWAS analyses without requiring access to subject-level genotypic and phenotypic information.

Availability and implementation

The GAUSS R package, complete with its source code, is readily accessible to the public via our GitHub repository at https://github.com/statsleelab/gauss. To further assist users, we provided illustrative use-case scenarios that are conveniently found at https://statsleelab.github.io/gauss/, along with a comprehensive user guide detailed in Supplementary Text S1.
MEG-PPIS: a fast protein–protein interaction site prediction method based on multi-scale graph information and equivariant graph neural network
Authors: Ding Hongzhen , Li Xue , Han Peifu , Tian Xu , Jing Fengrui , Wang Shuang , Song Tao , Fu Hanjiao , Kang Na
Published: April 2024

Motivation

Protein–protein interaction sites (PPIS) are crucial for deciphering protein action mechanisms and related medical research, which is the key issue in protein action research. Recent studies have shown that graph neural networks have achieved outstanding performance in predicting PPIS. However, these studies often neglect the modeling of information at different scales in the graph and the symmetry of protein molecules within three-dimensional space.

Results

In response to this gap, this article proposes the MEG-PPIS approach, a PPIS prediction method based on multi-scale graph information and E(n) equivariant graph neural network (EGNN). There are two channels in MEG-PPIS: the original graph and the subgraph obtained by graph pooling. The model can iteratively update the features of the original graph and subgraph through the weight-sharing EGNN. Subsequently, the max-pooling operation aggregates the updated features of the original graph and subgraph. Ultimately, the model feeds node features into the prediction layer to obtain prediction results. Comparative assessments against other methods on benchmark datasets reveal that MEG-PPIS achieves optimal performance across all evaluation metrics and gets the fastest runtime. Furthermore, specific case studies demonstrate that our method can predict more true positive and true negative sites than the current best method, proving that our model achieves better performance in the PPIS prediction task.

Availability and implementation

The data and code are available at https://github.com/dhz234/MEG-PPIS.git.
Exact solution for minimization of root mean square deviation with G-RMSD to determine molecular similarity
Authors: Nabika Tomohiro , Iwata Satoru , Satoh Hiroko
Published: April 2024

Generalized root mean square deviation (G-RMSD) is an optimization method for three-dimensional molecular similarity determination. It calculates the minimum value of RMSD among all the possible one-to-one matchings between the atoms and positions of the molecules. The first paper on G-RMSD introduced two approaches called alternating optimization (AO) and tangent space relaxation (TSR) methods, which give local optimum solutions. We propose here a new method of G-RMSD using a branch-and-bound method (BnB) on isometric transformations, called IsometryOpt, which is mathematically proven to give an exact G-RMSD index, i.e. this method can reach the global optimum solution. The performance of IsometryOpt was compared to AO and TSR, as well as the MatchFastOpt method. IsometryOpt shows better performance than MatchFastOpt for molecules with the same number of atoms. AO and TSR fail to reach exact values in some cases. We also have developed two improved methods to search for all possible matches of a substructure in one or more molecules. One is called IsometrySearch, which uses BnB on isometric transformations. The other is a variant version of MatchFPT, called MatchFPT-delta. Computer experiments indicate that MatchFPT-delta performs better than MatchFPT and IsometrySearch.
For Tuberculosis, Not “To Screen or Not to Screen?” but “Who?” and “How?”
Authors: Farhat Maha Reda , Jacobson Karen Rita
Published: April 2024

Active case finding leveraging new molecular diagnostics and chest X-rays with automated interpretation algorithms is increasingly being developed for high-risk populations to drive down tuberculosis incidence. We consider why such an approach did not deliver a decline in tuberculosis prevalence in Brazilian prison populations and what to consider next.
Association Between Causative Pathogen and Occurrence of Infection-Related Glomerulonephritis in Infective Endocarditis
Authors: Shrestha Nabin K , Kanyo Emese C , Nakhoul Georges N , Herlitz Leal C , Gordon Steven M
Published: April 2024

Among patients with pathologically proven infective endocarditis, the association of pathogen with occurrence of infection-related glomerulonephritis (IRGN) was examined in 48 case patients with IRGN and 192 propensity score-matched controls. Bartonella was very strongly associated with IRGN (odds ratio, 38.2 [95% confidence interval, 6.7–718.8]; P < .001); other microorganisms were not.
Genome editing and kidney health
Authors: Tavakolidakhrabadi Nadia , Aulicino Francesco , May Carl J , Saleem Moin A , Berger Imre , Welsh Gavin I
Published: April 2024

Genome editing technologies, clustered regularly interspaced short palindromic repeats (CRISPR)-Cas in particular, have revolutionized the field of genetic engineering, providing promising avenues for treating various genetic diseases. Chronic kidney disease (CKD), a significant health concern affecting millions of individuals worldwide, can arise from either monogenic or polygenic mutations. With recent advancements in genomic sequencing, valuable insights into disease-causing mutations can be obtained, allowing for the development of new treatments for these genetic disorders. CRISPR-based treatments have emerged as potential therapies, especially for monogenic diseases, offering the ability to correct mutations and eliminate disease phenotypes. Innovations in genome editing have led to enhanced efficiency, specificity and ease of use, surpassing earlier editing tools such as zinc-finger nucleases and transcription activator-like effector nucleases (TALENs). Two prominent advancements in CRISPR-based gene editing are prime editing and base editing. Prime editing allows precise and efficient genome modifications without inducing double-stranded DNA breaks (DSBs), while base editing enables targeted changes to individual nucleotides in both RNA and DNA, promising disease correction in the absence of DSBs. These technologies have the potential to treat genetic kidney diseases through specific correction of disease-causing mutations, such as somatic mutations in PKD1 and PKD2 for polycystic kidney disease; NPHS1, NPHS2 and TRPC6 for focal segmental glomerulosclerosis; COL4A3, COL4A4 and COL4A5 for Alport syndrome; SLC3A1 and SLC7A9 for cystinuria and even VHL for renal cell carcinoma. Apart from editing the DNA sequence, CRISPR-mediated epigenome editing offers a cost-effective method for targeted treatment providing new avenues for therapeutic development, given that epigenetic modifications are associated with the development of various kidney disorders. However, there are challenges to overcome, including developing efficient delivery methods, improving safety and reducing off-target effects. Efforts to improve CRISPR-Cas technologies involve optimizing delivery vectors, employing viral and non-viral approaches and minimizing immunogenicity. With research in animal models providing promising results in rescuing the expression of wild-type podocin in mouse models of nephrotic syndrome and successful clinical trials in the early stages of various disorders, including cancer immunotherapy, there is hope for successful translation of genome editing to kidney diseases.
Pericardial agenesis: a case report of a rare congenital heart disease
Authors: Trimarchi Giancarlo , Zito Concetta , Pelaggi Giuseppe , Carerj Scipione , Di Bella Gianluca
Published: April 2024

Background

Pericardial agenesis is a rare congenital heart disease characterized by a variable clinical presentation.

Case summary

A 32-year-old man was sent by an occupational health physician to our health care centre because of pathological electrocardiogram (ECG). On transthoracic echocardiogram, we had some difficulty to obtain a good quality of four-chamber apical view that was shifted upper and laterally towards the left anterior axillary line. Nonetheless, an abnormal diastolic expansion of the apex of the left ventricle (LV) that had an otherwise normal systolic function was detected. A chest X-ray confirmed the leftward shift of the heart, with the elongation of the left border of cardiac silhouette and cardiac MRI, finally revealed the absence of left-sided pericardium associated with a leftward dislocation of the heart and a dysmorphism of the LV apex that appeared rounded and curved. The non-invasive work-up was completed with 48 h long Holter ECG that was unremarkable. The exercise test was also negative for both inducible myocardial ischaemia and arrhythmias. Patient was scheduled for loop-recorder implantation, and a 6-month clinical follow-up was advised.

Discussion

Pericardial agenesis is a rare congenital heart disease associated with an increased risk of cardiac arrhythmias and type A aortic dissection, however its clinical course could be also completely unremarkable. The diagnosis is challenging, and cardiac MRI remains the gold standard imaging modality. In complete left-sided and asymptomatic forms, no treatment is needed. Prognosis is not well established due to both the rarity of disease and extreme variability of clinical presentation.
Glucagon-like peptide-1 receptor agonists use and associations with outcomes in heart failure and type 2 diabetes: data from the Swedish Heart Failure and Swedish National Diabetes Registries
Authors: Wallner Markus , Biber Mattia Emanuele , Stolfo Davide , Sinagra Gianfranco , Benson Lina , Dahlström Ulf , Gudbjörnsdottir Soffia , Cosentino Francesco , Mol Peter G M , Rosano Giuseppe M C , Butler Javed , Metra Marco , Lund Lars H , Ferrannini Giulia , Savarese Gianluigi
Published: April 2024

Aims

To assess the use and associations with outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in a real-world population with heart failure (HF) and type 2 diabetes mellitus (T2DM).

Methods and results

The Swedish HF Registry was linked with the National Diabetes Registry and other national registries. Independent predictors of GLP-1 RA use were assessed by multivariable logistic regressions and associations with outcomes were assessed by Cox regressions in a 1:1 propensity score-matched cohort. Of 8188 patients enrolled in 2017–21, 9% received a GLP-1 RA. Independent predictors of GLP-1 RA use were age <75 years, worse glycaemic control, impaired renal function, obesity, and reduced ejection fraction (EF). GLP-1 RA use was not significantly associated with a composite of HF hospitalization (HHF) or cardiovascular (CV) death regardless of EF, but was associated with a lower risk of major adverse CV events (CV death, non-fatal stroke/transient ischaemic attack, or myocardial infarction), and CV and all-cause death. In patients with body mass index ≥30 kg/m2, GLP-1 RA use was also associated with a lower risk of HHF/CV death and HHF alone.

Conclusions

In patients with HF and T2DM, GLP-1 RA use was independently associated with more severe T2DM, reduced EF, and obesity and was not associated with a higher risk of HHF/CV death but with longer survival and less major CV adverse events. An association with lower HHF/CV death and HHF was observed in obese patients. Our findings provide new insights into GLP-1 RA use and its safety in HF and T2DM.
To block or not: why the British ruling elite enabled the Industrial Revolution during the 18th century
Authors: Gulsunar Emrah
Published: April 2024

This study explores why the ruling elite in 18th-century Britain not only allowed but actively supported industrialization. Economic rents, political power, and international competition are commonly cited as the reasons, but these explanations lack empirical evidence. By conducting a text analysis of parliamentary legislation and debates on the cotton industry, this study demonstrates that the ruling elite was primarily motivated by keeping unemployment low and sustaining the British economy’s international competitiveness. A favorable political system facilitated the realization of the elite’s objectives.
Accurate prediction equations for ventilatory thresholds in cardiometabolic disease when gas exchange analysis is unavailable: development and validation
Authors: Milani Juliana Goulart Prata Oliveira , Milani Mauricio , Machado Felipe Vilaça Cavallari , Wilhelm Matthias , Marcin Thimo , D’Ascenzi Flavio , Cavigli Luna , Keytsman Charly , Falter Maarten , Bonnechere Bruno , Meesen Raf , Braga Fabrício , Cipriano Graziella França Bernardelli , Cornelissen Veronique , Verboven Kenneth , Cipriano Junior Gerson , Hansen Dominique
Published: April 2024

Aims

To develop and validate equations predicting heart rate (HR) at the first and second ventilatory thresholds (VTs) and an optimized range-adjusted prescription for patients with cardiometabolic disease (CMD). To compare their performance against guideline-based exercise intensity domains.

Methods and results

Cross-sectional study involving 2868 CMD patients from nine countries. HR predictive equations for first and second VTs (VT1, VT2) were developed using multivariate linear regression with 975 cycle-ergometer cardiopulmonary exercise tests (CPET). ‘Adjusted’ percentages of peak HR (%HRpeak) and HR reserve (%HRR) were derived from this group. External validation with 1893 CPET (cycle-ergometer or treadmill) assessed accuracy, agreement, and reliability against guideline-based %HRpeak and %HRR prescriptions using mean absolute percentage error (MAPE), Bland–Altman analyses, intraclass correlation coefficients (ICC). HR predictive equations (R²: 0.77 VT1, 0.88 VT2) and adjusted %HRR (VT1: 42%, VT2: 77%) were developed. External validation demonstrated superiority over widely used guideline-directed intensity domains for %HRpeak and %HRR. The new methods showed consistent performance across both VTs with lower MAPE (VT1: 7.1%, VT2: 5.0%), ‘good’ ICC for VT1 (0.81, 0.82) and ‘excellent’ for VT2 (0.93). Guideline-based exercise intensity domains had higher MAPE (VT1: 6.8–21.3%, VT2: 5.1–16.7%), ‘poor’ to ‘good’ ICC for VT1, and ‘poor’ to ‘excellent’ for VT2, indicating inconsistencies related to specific VTs across guidelines.

Conclusion

Developed and validated HR predictive equations and the optimized %HRR for CMD patients for determining VT1 and VT2 outperformed the guideline-based exercise intensity domains and showed ergometer interchangeability. They offer a superior alternative for prescribing moderate intensity exercise when CPET is unavailable.
Phenotypic plasticity in tropical butterflies is linked to climatic seasonality on a macroevolutionary scale
Authors: Halali Sridhar , Brakefield Paul M , Brattström Oskar
Published: April 2024

Phenotypic plasticity can be adaptive in fluctuating environments by providing rapid environment–phenotype matching and this applies particularly in seasonal environments. African Bicyclus butterflies have repeatedly colonized seasonal savannahs from ancestral forests around the late Miocene, and many species now exhibit seasonal polyphenism. On a macroevolutionary scale, it can be expected that savannah species will exhibit higher plasticity because of experiencing stronger environmental seasonality than forest species. We quantified seasonality using environmental niche modeling and surveyed the degree of plasticity in a key wing pattern element (eyespot size) using museum specimens. We showed that species occurring in highly seasonal environments display strong plasticity, while species in less seasonal or aseasonal environments exhibit surprisingly variable degrees of plasticity, including strong to no plasticity. Furthermore, eyespot size plasticity has a moderate phylogenetic signal and the ancestral Bicyclus likely exhibited some degree of plasticity. We propose hypotheses to explain the range of plasticity patterns seen in less seasonal environments and generate testable predictions for the evolution of plasticity in Bicyclus. Our study provides one of the most compelling cases showing links between seasonality and phenotypic plasticity on a macroevolutionary scale and the potential role of plasticity in facilitating the colonization of novel environments.
Quantifying genome-specific carbon fixation in a 750-meter deep subsurface hydrothermal microbial community
Authors: Coskun Ömer K , Gomez-Saez Gonzalo V , Beren Murat , Özcan Doğacan , Günay Suna D , Elkin Viktor , Hoşgörmez Hakan , Einsiedl Florian , Eisenreich Wolfgang , Orsi William D
Published: April 2024

Dissolved inorganic carbon has been hypothesized to stimulate microbial chemoautotrophic activity as a biological sink in the carbon cycle of deep subsurface environments. Here, we tested this hypothesis using quantitative DNA stable isotope probing of metagenome-assembled genomes (MAGs) at multiple 13C-labeled bicarbonate concentrations in hydrothermal fluids from a 750-m deep subsurface aquifer in the Biga Peninsula (Turkey). The diversity of microbial populations assimilating 13C-labeled bicarbonate was significantly different at higher bicarbonate concentrations, and could be linked to four separate carbon-fixation pathways encoded within 13C-labeled MAGs. Microbial populations encoding the Calvin–Benson–Bassham cycle had the highest contribution to carbon fixation across all bicarbonate concentrations tested, spanning 1–10 mM. However, out of all the active carbon-fixation pathways detected, MAGs affiliated with the phylum Aquificae encoding the reverse tricarboxylic acid (rTCA) pathway were the only microbial populations that exhibited an increased 13C-bicarbonate assimilation under increasing bicarbonate concentrations. Our study provides the first experimental data supporting predictions that increased bicarbonate concentrations may promote chemoautotrophy via the rTCA cycle and its biological sink for deep subsurface inorganic carbon.
Genomic insights into Spiroplasma endosymbionts that induce male-killing and protective phenotypes in the pea aphid
Authors: Arai Hiroshi , Legeai Fabrice , Kageyama Daisuke , Sugio Akiko , Simon Jean-Christophe
Published: April 2024

The endosymbiotic bacteria Spiroplasma (Mollicutes) infect diverse plants and arthropods, and some of which induce male killing, where male hosts are killed during development. Male-killing Spiroplasma strains belong to either the phylogenetically distant Citri-Poulsonii or Ixodetis groups. In Drosophila flies, Spiroplasma poulsonii induces male killing via the Spaid toxin. While Spiroplasma ixodetis infects a wide range of insects and arachnids, little is known about the genetic basis of S. ixodetis-induced male killing. Here, we analyzed the genome of S. ixodetis strains in the pea aphid Acyrthosiphon pisum (Aphididae, Hemiptera). Genome sequencing constructed a complete genome of a male-killing strain, sAp269, consisting of a 1.5 Mb circular chromosome and an 80 Kb plasmid. sAp269 encoded putative virulence factors containing either ankyrin repeat, ovarian tumor-like deubiquitinase, or ribosome inactivating protein domains, but lacked the Spaid toxin. Further comparative genomics of Spiroplasma strains in A. pisum biotypes adapted to different host plants revealed their phylogenetic associations and the diversity of putative virulence factors. Although the mechanisms of S. ixodetis-induced male killing in pea aphids remain elusive, this study underlines the dynamic genome evolution of S. ixodetis and proposes independent acquisition events of male-killing mechanisms in insects.
Nicotinic acid availability impacts redox cofactor metabolism in Saccharomyces cerevisiae during alcoholic fermentation
Authors: Duncan James D , Setati Mathabatha E , Divol Benoit
Published: April 2024

Anaerobic alcoholic fermentation, particularly in high-sugar environments, presents metabolic challenges for yeasts. Crabtree-positive yeasts, including Saccharomyces cerevisiae, prefer fermentation even in the presence of oxygen. These yeasts rely on internal NAD+ recycling and extracellular assimilation of its precursor, nicotinic acid (vitamin B3), rather than de novo NAD+ production. Surprisingly, nicotinic acid assimilation is poorly characterized, even in S. cerevisiae. This study elucidated the timing of nicotinic acid uptake during grape juice-like fermentation and its impact on NAD(H) levels, the NAD+/NADH ratio, and metabolites produced. Complete uptake of extracellular nicotinic acid occurred premid-exponential phase, thereafter small amounts of vitamin B3 were exported back into the medium. Suboptimal levels of nicotinic acid were correlated with slower fermentation and reduced biomass, disrupting redox balance and impeding NAD+ regeneration, thereby affecting metabolite production. Metabolic outcomes varied with nicotinic acid concentrations, linking NAD+ availability to fermentation efficiency. A model was proposed encompassing rapid nicotinic acid uptake, accumulation during cell proliferation, and recycling with limited vitamin B3 export. This research enhances the understanding of nicotinic acid uptake dynamics during grape juice-like fermentation. These insights contribute to advancing yeast metabolism research and have profound implications for the enhancement of biotechnological practices and the wine-making industry.
Hydroboration
Authors: Thomas Susan E.
Published: April 2024

This chapter focuses on the characteristics of the hydroboration reaction. It begins with defining hydroboration as the addition of a boron-hydrogen bond to either the carbon-carbon double of an alkene or the carbon-carbon triple bond of an alkyne. The chapter reveals that the first examples of hydroboration were reported in 1956 from the laboratories of H.C Brown. The chapter then proceeds to show how the hydroboration reaction has found many applications in organic chemistry. It elaborates on the simplest boron hydride: borane. It then investigates how borane transforms a wide range of alkenes into trialkylboranes under mild conditions. Finally, the chapter reviews how the trifunctional nature of borane and its trialkylborane products imposes some limitations on its use. It then analyses the role of alkylboranes as hydroborating reagents and how it is used in asymmetric hydroboration.
Alkene synthesis (Peterson olefination)
Authors: Thomas Susan E.
Published: April 2024

This chapter highlights the key compounds in the application of organosicilicon chemistry to the synthesis of alkenes: β-hydroxysilanes. It describes the three methods of generating them starting with the addition of α-metallated silanes to carbonyl compounds. α-Metallated silanes may be generated in several ways including addition of organometallic nucleophiles to vinylsilanes, deprotonation of α to silicon, and metal-halogen exchange. The chapter then investigates another method of generating β-hydroxysilanes: the addition of dialkylcuprates to α, β-epoxysilanes. α, β-epoxysilanes are readily synthesized by epoxidation of vinyl silanes. They react with organocuprate reagents in a regiospecific manner to give β-hydroxysilanes. Finally, the chapter elaborates on the last method of generating β-hydroxysilanes: the addition of hydride sources or organometallic reagents to β-ketosilanes. It also considers the conversion of β-hydroxysilanes into alkenes and some examples of silicon-based alkene synthesis.