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Temperature dependence of the deformation behavior and mechanical properties of a Fe–Mn–Al–C low-density steel for cryogenic application

The temperature dependence of the deformation behavior and mechanical properties of a Fe–20Mn–6Al-0.6C-0.15Si austenitic low-density steel was studied by tensile test and Charpy impact test at −196 °C, −77 °C and room temperature (RT), followed by microstructure analyses. The results indicate that the decreased tensile temperature, which is corresponding to reduced stacking fault energy (SFE), promotes the planar glide of dislocations. This led to larger fraction of low-angle grain boundaries (LAGBs) at lower tensile temperature. Consequently, both the tensile strength and elongation were improved as temperature decreased. At lower impact test temperature, the load and energy of crack initiation were larger, indicating a higher resistance to crack initiation. However, the transition from stable to unstable crack propagation occurred more rapidly at lower temperature, resulting in lower crack propagation energy and reduced resistance to crack propagation. This is because less region experienced planar glide. Due to the rapid unstable crack propagation, the Charpy absorbed energy at −196 °C was the lowest. The smaller fracture surface area, larger fibrous zone and more obvious ductile fracture characteristics in radial zone suggest that the toughness is better at higher temperature. Additionally, the presence of secondary cracks at RT delayed fracture, therefore benefitting toughness.

Parameter analysis and prediction of crack propagation for thermoplastic composite pipes under lateral pressure

ABSTRACT The research investigates the process of crack propagation in thermoplastic composite pipes (TCPs) with initial racks subjected to lateral pressure, through a combination of numerical simulations and experimental studies. In the numerical analysis, a TCP is subjected to lateral pressure, considering parameters such as initial crack length, initial crack angle, and lateral displacement. This analysis employs the extended finite element method (XFEM). The results reveal that crack propagation predominantly occurs perpendicular to the fibre winding angle. Moreover, it is observed that longer initial cracks result in lower crack initiation loads, while the final extent of crack propagation increases with the initial crack length. The experimental study considers three distinct initial crack angles and verifies the conclusions drawn from the numerical simulations. Furthermore, a crack propagation prediction model is developed that combines particle swarm optimization (PSO) with backpropagation (BP) neural networks. The predictive results demonstrate a high level of accuracy.

Computational Modeling of Bone Fracture Healing Under Different Initial Conditions and Mechanical Load.

Computational model of bone healing can replace animal experiments to study the parameters affecting the bone healing process, thus reducing the damage to experimental animals and saving a lot of time. We propose a computational model for continuous simulation of four phases of bone healing to study the effects of mechanical environmental and biological factors, including initial conditions at the fracture site, mechanical stimulus loading, and vascular growth rate. A finite element model of mechanobiological fracture healing containing several pre-determined variables was developed for bone healing after fracture in sheep, which included many relevant parameters and biological effects during fracture healing, such as the effects of mechanical environment, blood supply level in the local fracture area, cell migration and diffusion, and resorption effects of fracture healing. The effects of several parameters on indices such as Young's modulus of the callus during bone healing were obtained by simulation. The initial geometry of the healing tissue and mechanical loading had the greatest effect on fracture healing, and different preset values were likely to cause delayed or non-healing fractures. Changed initial tissue properties of the healing tissue showed a nonlinear effect on fracture healing rather than a linear delay or advancement. Parameters related to angiogenesis had a greater effect on fracture healing compared to those related to cell migration. This paper quantified the effect of fracture healing pre-determined variables on fracture healing to better understand the application of mechanobiology in fracture healing simulation models and optimization of treatment strategies. The importance of initial conditions and loads on fracture healing has been shown to help physicians treat bone nonunion or delayed bone healing after a fracture.

Numerical simulation of the crack propagation effect on the hysteretic behavior of CHS-X joints

The circular hollow section (CHS) X-joint hysteresis behavior significantly affects the seismic behavior of the steel tubular structure using this type of joint. The hysteresis behavior of this type of joint considering crack growth is studied by tests and numerical simulation. Two CHS X-joints were fabricated and tested under axial cyclic loading until the joints were cracked. The hysteresis curves of the joints, considering the influence of damage and fracture, were obtained, and the hysteresis performance of the joints was evaluated according to the curves. The VUSDFLD subroutine based on the ductile fracture model CVGM (cyclic void growth model) was embedded into ABAQUS, and the FE simulation of the test joints considering crack occurrence and growth was carried out. The test results are compared with the results of FE analysis, revealing that the proposed method accurately simulates the hysteresis behavior of these joints and the crack propagation behaviors under cyclic loads. The difference between the test and simulated crack initiation loads for the two joints is 10.8 % and 5.7 %, respectively.

Dynamical Modeling and Qualitative Analysis of a Delayed Model for CD8 T Cells in Response to Viral Antigens.

Although the immune effector CD8 T cells play a crucial role in clearance of viruses, the mechanisms underlying the dynamics of how CD8 T cells respond to viral infection remain largely unexplored. Here, we develop a delayed model that incorporates CD8 T cells and infected cells to investigate the functional role of CD8 T cells in persistent virus infection. Bifurcation analysis reveals that the model has four steady states that can finely divide the progressions of viral infection into four states, and endows the model with bistability that has ability to achieve the switch from one state to another. Furthermore, analytical and numerical methods find that the time delay resulting from incubation period of virus can induce a stable low-infection steady state to be oscillatory, coexisting with a stable high-infection steady state in phase space. In particular, a novel mechanism to achieve the switch between two stable steady states, time-delay-based switch, is proposed, where the initial conditions and other parameters of the model remain unchanged. Moreover, our model predicts that, for a certain range of initial antigen load: 1) under a longer incubation period, the lower the initial antigen load, the easier the virus infection will evolve into severe state; while the higher the initial antigen load, the easier it is for the virus infection to be effectively controlled and 2) only when the incubation period is small, the lower the initial antigen load, the easier it is to effectively control the infection progression. Our results are consistent with multiple experimental observations, which may facilitate the understanding of the dynamical and physiological mechanisms of CD8 T cells in response to viral infections.

Characterization and Determinants of Long-Term Immune Recovery Under Suppressive Antiretroviral Therapy.

We developed a robust characterization of immune recovery trajectories in people living with HIV on antiretroviral treatment (ART) and relate our findings to epidemiological risk factors and bacterial pneumonia. Using data from the Swiss HIV Cohort Study and the Zurich Primary HIV Infection Cohort Study (n = 5907), we analyzed the long-term trajectories of CD4 cell and CD8 cell counts and their ratio in people living with HIV on ART for at least 8 years by fitting nonlinear mixed-effects models. The determinants of long-term immune recovery were investigated using generalized additive models. In addition, prediction accuracy of the modeled trajectories and their impact on the fit of a model for bacterial pneumonia was assessed. Overall, our population showed good immune recovery (median plateau [interquartile range]-CD4: 718 [555-900] cells/μL, CD8: 709 [547-893] cells/μL, CD4/CD8: 1.01 [0.76-1.37]). The following factors were predictive of recovery: age, sex, nadir/zenith value, pre-ART HIV-1 viral load, hepatitis C, ethnicity, acquisition risk, and timing of ART initiation. The fitted models proved to be an accurate and efficient way of predicting future CD4 and CD8 cell recovery dynamics: Compared with carrying forward the last observation, mean squared errors of the fitted values were lower by 1.3%-18.3% across outcomes. When modeling future episodes of bacterial pneumonia, using predictors derived from the recovery dynamics improved most model fits. We described and validated a method to characterize individual immune recovery trajectories of people living with HIV on suppressive ART. These trajectories accurately predict long-term immune recovery and the occurrence of bacterial pneumonia.

Roadway rock burst prediction based on catastrophe theory

In order to quantitatively calculate the critical depth and critical load of mines affected by rock burst, and to achieve effective prevention and control of rock burst in coal mines, this paper proposes a mechanical model for predicting the occurrence of rock burst in coal mine roadways based on catastrophe theory. Additionally, a theoretical calculation formula for initiating rock burst is derived. The first step was to establish a mechanical analysis model, which directly correlated with the in-situ stress, physical and mechanical characteristics of the coal-rock mass, and engineering structural parameters. Following this, a mechanical instability criterion was derived for the key load-bearing circle within the surrounding rock of the roadway. In the final step, the critical depth and load for rock burst initiation were verified for 25 distinct coal mines in China that were prone to rock burst hazards. The research results demonstrate that the discrepancy between the theoretically calculated critical depth and the actual measured statistical values was less than 35%. In addition, the difference between the theoretically determined critical depth and the value calculated by Pan Yishan was less than 32%. Notably, the ratio of the theoretically calculated critical load to the uniaxial compressive strength of the coal-rock mass ranged from 0.38 to 1.93. This aligns with empirical data on rock burst occurrences, as set out in the engineering classification standards for rock masses. These research outcomes substantiated the practical utility of the proposed theory, thereby laying a robust theoretical groundwork for the quantitative control of rock burst.

Density affects rearing performance of juvenile landlocked fall Chinook Salmon

AbstractObjectiveDensity‐related information for landlocked fall Chinook Salmon Oncorhynchus tshawytscha shortly after first feeding is poorly understood. This study was undertaken to determine the effects of a range of rearing densities (low, intermediate, and high) on rearing performance and survival of newly feed‐trained juvenile landlocked fall Chinook Salmon.MethodsThe fish were reared for 66 days in 1.8‐m (diameter) tanks with approximate volume of 2036 L at one of three loadings of approximately 2500, 5000, or 10,000 fish/tank.ResultThe initial and final densities for each of the three loadings were 0.73 and 8.93, 1.45 and 16.41, and 2.90 and 26.86 kg/m3, respectively. At the end of the study, the specific growth rates were significantly lower, total lengths were significantly shorter, and feed conversion ratios were significantly greater in the fish from the highest‐density treatment relative to the fish in the other treatments. Percentage of weight gain, final weights, and condition factor were significantly reduced in fish from the highest‐density treatment relative those at the lowest density. There were no significant differences in any growth metrics between fish that were reared at the lowest and intermediate densities. The intermediate density (5000 fish/tank) produced intermediate results that did not significantly differ from either the highest or lowest densities. Mortality was not significantly different among the density treatments.ConclusionAn initial loading of 5000 fish in 1.8‐m (diameter) circular tanks, corresponding to initial and final densities of 1.45 and 16.41 kg/m3, respectively, is recommended to minimize the detrimental effects of density on newly feeding Chinook Salmon while maximizing their production in often limited hatchery space.

Harnessing RNA Interference for Cholesterol Lowering: The Bench-to-Bedside Story ofInclisiran.

Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone of reducing risk for atherosclerotic cardiovascular disease. Despite the approval of nonstatin therapies for LDL-C lowering over the past 2 decades, these medications are underused, and most patients are still not at guideline-recommended LDL-C goals. Barriers include poor adherence, clinical inertia, concern for side effects, cost, and complex prior authorization processes. With atherosclerotic cardiovascular disease-related mortality increasing globally, there remains a need for additional therapeutic options for lowering LDL-C as part of an atherosclerotic cardiovascular disease prevention strategy. Following the identification of PCSK9 (proprotein convertase subtilisin/kexin type 9) as a promising therapeutic target, inclisiran was developed using the natural process of RNA interference for robust, sustained prevention of hepatic PCSK9 synthesis. Twice-yearly maintenance subcutaneous inclisiran (following initial loading doses at Day 1 and Day 90) reduces circulating LDL-C levels by ≈50% versus placebo when added to maximally tolerated statins. Long-term safety and tolerability of inclisiran have been assessed, with studies underway to evaluate the effects of inclisiran on cardiovascular outcomes and to provide additional safety and effectiveness data. In 2021, <20 years after the discovery of PCSK9, inclisiran became the first RNA interference therapeutic approved in the United States for LDL-C lowering in patients with established atherosclerotic cardiovascular disease or familial hypercholesterolemia and has since been approved for use in patients with primary hyperlipidemia. This article reviews the journey of inclisiran from bench to bedside, including early development, the clinical trial program, key characteristics of inclisiran, and practical points for its use in the clinic.

Epoxy-Printed Circuit Board Interfacial Fracture Reliability Under Three-Point and Four-Point Bend Loading After Sustained Elevated Temperature Exposure

Abstract The survivability and reliability of commercial electronic components under very high thermo-mechanical loads are improved using underfilling and potting methods. Potting protects from operating conditions such as moisture, water, or corrosive agents. Furthermore, potting offers damping against shock and vibrations, heat dissipation, and structural support. Being one of the most cost-efficient methods, potting greatly increases reliability and therefore reduces costs for replacements and repairs. It also addresses trapped hot air issues better than other restraint technologies. In potted electronic assemblies, interfacial delamination at the epoxy and printed circuit board (PCB) interface has been one of the major failure modes. Interfacial delamination happens at the epoxy/PCB interface under dynamic shock loads, which leads to failures at the solder interconnects of the electronic components. Sustained operation and storage at elevated temperatures change the interfacial characteristics at the epoxy/PCB interface. This research is focused on interfacial failure mechanics at epoxy/PCB interfaces with high-temperature isothermal aging. In the selection of the epoxy potting material and the reliability assessments of the supplemental restraint systems, fracture parameters such as steady-state strain energy release rate stress and fracture toughness are critical. Rectangular beam specimens of the epoxy/PCB interface are fabricated for different potting compounds, and the fracture behavior is studied under quasi-static monotonic three-point and four-point bend loads. One of the main differences between three-point and four-point bend loading is that the maximum bending stress occurs at the midpoint under the point of loading of the specimen in three-point bending, whereas the peak stress is distributed over the section of the specimen between the loading points in four-point bending. Four different potting compounds with diverse properties have been studied. The recommended curing schedule from the manufacturer has been chosen and followed for all the potting compounds. The epoxy/PCB interfacial samples are aged at a high temperature of 100 °C for 30–180 days. Damage has been assumed to happen at the epoxy/PCB interface under dynamic loads. The critical load of crack initiation for the epoxy/PCB interface has been determined from the experimental findings, and it is used in the computation of fracture toughness values. The fracture toughness values are compared for the various epoxy/PCB systems based on the number of days of thermal aging and the method of flexure testing. A cohesive zone model has been constructed for predominantly mode-I delamination with four-point bend stress to predict the interfacial delamination behavior at the epoxy/PCB interfaces. It has been assumed that the bulk material is linear elastic during the bending load. The cohesive zone has been modeled at the interface, where the interfacial fracture has been assumed to occur. The fracture behavior in the simulation is predicted based on the fracture parameters determined through the experiment. The computed cohesive zone parameters are unique to the interfaces, and they can be used across various applications with the same epoxy/PCB interface to predict interfacial delamination and to select a more suitable potting material.

Unraveling Reactivity Differences: Room-Temperature Ring-Opening Metathesis Polymerization (ROMP) versus Frontal ROMP.

In this study, we explore the distinct reactivity patterns between frontal ring-opening metathesis polymerization (FROMP) and room-temperature solventless ring-opening metathesis polymerization (ROMP). Despite their shared mechanism, we find that FROMP is less sensitive to inhibitor concentration than room-temperature ROMP. By increasing the initiator-to-monomer ratio for a fixed inhibitor/initiator quantity, we find reduction in the ROMP background reactivity at room temperature (i.e., increased resin pot life). At elevated temperatures where inhibitor dissociation prevails, accelerated frontal polymerization rates are observed because of the concentrated presence of the initiator. Surprisingly, the strategy of employing higher initiator loading enhances both pot life and front speeds, which leads to FROMP rates exceeding prior reported values by over 5 times. This counterintuitive behavior is attributed to an increase in the proximity of the inhibitor to the initiator within the bulk resin and to whether the temperature favors coordination or dissociation of the inhibitor. A rapid method was developed for assessing resin pot life, and a straightforward model for active initiator behavior was established. Modified resin systems enabled direct ink writing of robust thermoset structures at rates much faster than previously possible.

Shear performance of high-strength bolted connections with stainless-clad steel plates in a corrosive environment

Stainless-clad (SC) steel plates offer desirable corrosion resistance at a relatively low cost, but their shear performance in high-strength bolted connections in a corrosive environment has not been fully explored. In this study, monotonic tensile tests were performed on specimens connected by normal and stainless high-strength bolts at different corrosion degrees. The results were used to determine the influence of corrosion on the slip coefficient, bolt pre-tension force, initial slip load, and ultimate bearing capacity, and a simplified method was developed for estimating the slip coefficient and initial slip load.

Numerical study on soil springs stiffnesses of laterally loaded monopiles

Unlike traditional pile foundations, monopiles supporting offshore wind turbines usually have the characteristics of large diameter (D) and relatively low length-to-diameter ratio (L m /D). Accurate evaluation of the soil springs stiffnesses around the monopile is crucial for the design requirements and assessment of the dynamic response of offshore wind turbines. Over the past decade, a large number of initial stiffness models of lateral p-y spring have been proposed. However, limited research has been devoted to additional soil reaction springs, namely the rotational m-θ spring and pile base shear Q b-y b spring. Moreover, the contribution of these additional components is closely related to the pile-soil relative stiffness (K R), and it is a challenge to consider their relationship in the design. In this paper, a three-dimensional finite element analysis of elastic soil is performed to systematically investigate the effects of pile D, L m /D and soil elastic modulus (E s) on soil spring stiffness, and the effect of non-uniform soil is also discussed. The relationship between the initial load contribution ratio of each spring and the K R is clarified, and a new proposal for the soil springs stiffnesses considering the K R is put forward and verified for reasonableness.

Efficacy and safety of caspofungin for the treatment of invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease.

We assessed the efficacy of a 3-week primary or salvage caspofungin regimen in patients with chronic obstructive pulmonary disease (COPD) and concomitant proven or suspected invasive pulmonary aspergillosis (IPA). Forty-four patients were treated with an initial loading caspofungin dose of 70 mg, followed by a daily dose of 50 mg for 20 days. The main efficacy endpoint was clinical effectiveness. Secondary endpoints included the clinical efficacy of caspofungin after 1 week, therapeutic efficacy based on the European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, the sensitivity of different Aspergillus strains to caspofungin in vitro, and the safety of caspofungin. An assessment of 42 patients in the intention-to-treat group revealed efficacy rates of 33.33% within 1 week and 38.10% within 3 weeks. According to the EORTC/MSG criteria, the treatment success rate was 38.10%. The success rate of first-line treatment was 54.76%, whereas salvage treatment had a success rate of 45.24%. No adverse events were reported among the participants. Caspofungin is effective and safe as an initial or salvage treatment for patients with IPA and COPD.

Red Blood Cells in the Cerebrospinal Fluid Compartment After Subarachnoid Haemorrhage: Significance and Emerging Therapeutic Strategies.

Subarachnoid haemorrhage (SAH) is a subtype of stroke that predominantly impacts younger individuals. It is associated with high mortality rates and can cause long-term disabilities. This review examines the contribution of the initial blood load and the dynamics of clot clearance to the pathophysiology of SAH and the risk of adverse outcomes. These outcomes include hydrocephalus and delayed cerebral ischaemia (DCI), with a particular focus on the impact of blood located in the cisternal spaces, as opposed to ventricular blood, in the development of DCI. The literature described underscores the prognostic value of haematoma characteristics, such as volume, density, and anatomical location. The limitations of traditional radiographic grading systems are discussed, compared with the more accurate volumetric quantification techniques for predicting patient prognosis. Further, the significance of red blood cells (RBCs) and their breakdown products in secondary brain injury after SAH is explored. The review presents novel interventions designed to accelerate clot clearance or mitigate the effects of toxic byproducts released from erythrolysis in the cerebrospinal fluid following SAH. In conclusion, this review offers deeper insights into the complex dynamics of SAH and discusses the potential pathways available for advancing its management.

Enzymatic digestion does not compromise sliding-mediated cartilage lubrication

Articular cartilage's remarkable low-friction properties are essential to joint function. In osteoarthritis (OA), cartilage degeneration (e.g., proteoglycan loss and collagen damage) decreases tissue modulus and increases permeability. Although these changes impair lubrication in fully depressurized and slowly slid cartilage, new evidence suggests such relationships may not hold under biofidelic sliding conditions more representative of those encountered in vivo. Our recent studies using the convergent stationary contact area (cSCA) configuration demonstrate that articulation (i.e., sliding) generates interfacial hydrodynamic pressures capable of replenishing cartilage interstitial fluid/pressure lost to compressive loading through a mechanism termed tribological rehydration. This fluid recovery sustains in vivo-like kinetic friction coefficients (µk<0.02 in PBS and <0.005 in synovial fluid) with little sensitivity to mechanical properties in healthy tissue. However, the tribomechanical function of compromised cartilage under biofidelic sliding conditions remains unknown. Here, we investigated the effects of OA-like changes in cartilage mechanical properties, modeled via enzymatic digestion of mature bovine cartilage, on its tribomechanical function during cSCA sliding. We found no differences in sliding-driven tribological rehydration behaviors or µk between naïve and digested cSCA cartilage (in PBS or synovial fluid). This suggests that OA-like cartilage retains sufficient functional properties to support naïve-like fluid recovery and lubrication under biofidelic sliding conditions. However, OA-like cartilage accumulated greater total tissue strains due to elevated strain accrual during initial load application. Together, these results suggest that elevated total tissue strains—as opposed to activity-mediated strains or friction-driven wear—might be the key biomechanical mediator of OA pathology in cartilage. Statement of SignificanceOsteoarthritis (OA) decreases cartilage's modulus and increases its permeability. While these changes compromise frictional performance in benchtop testing under low fluid load support (FLS) conditions, whether such observations hold under sliding conditions that better represent the joints’ dynamic FLS conditions in vivo is unclear. Here, we leveraged biofidelic benchtop sliding experiments—that is, those mimicking joints’ native sliding environment—to examine how OA-like changes in mechanical properties effect cartilage's natural lubrication. We found no differences in sliding-mediated fluid recovery or kinetic friction behaviors between naïve and OA-like cartilage. However, OA-like cartilage experienced greater strain accumulation during load application, suggesting that elevated tissue strains (not friction-driven wear) may be the primary biomechanical mediator of OA pathology.

Shear performance of high-strength bolt-epoxy bonding composite connector in steel-concrete composite structure

To clarify the shear mechanism of high-strength bolt-epoxy bonding composite connectors in prefabricated steel-concrete composite structures, twenty-one direct shear specimens and six double shear specimens were carried out in this study. The pretension force, interface type, epoxy curing time and loading pattern were considered. Results revealed that the main failure mode of high-strength bolt-epoxy bonding composite connectors was that the large area of epoxy matrix was separated from the steel plate, and the bolt was sheared off. The load-slip curve of composite connector specimens included the elastic stage, epoxy failure stage, frictional slip stage, bolt force transmission stage and failure stage. Compared to the specimens with a bolt connector under recommended pretension, the average initial slip load of composite connector specimens was 437.7% higher. Additionally, the average initial slip load of specimens with 1-day epoxy curing time was 24.4% lower than 7-day curing time, but the average ultimate load and ultimate slip were 12.4% and 29.4% higher, respectively. When the pretension ratio decreased from 1.0 to 0.6, the average initial slip load of specimens with a bolt connector was significantly decreased by 33.0% and the average ultimate slip of composite connector specimens was increased by 18.1%. The average initial slip load and ultimate load of composite connector specimens were comparable under cyclic loading compared to monotonic loading. Upon the experimental results and existing formulas, some equations were proposed for predicting the initial slip load and bearing capacity of steel-concrete composite structures with composite connectors.

Topology optimization design of recoverable bistable structures for energy absorption with embedded shape memory alloys

In this work, multistable mechanical metamaterials with recoverable capabilities are designed for high energy absorption and resistance to repetitive impacts. Based on the known curved beam with energy dissipation characteristics, the shape memory alloys (SMAs) curved beam is added and optimized to achieve recoverability of the bi-layer beam structure. To simultaneously achieve bistable characteristics and recoverability in the designed metamaterial, the optimization model is formulated to maximize the energy absorption capacity of the structure while constraining the peak and valley forces. To solve this complex and highly nonlinear topological optimization problem with stringent constraints, the topological design of the SMAs layer is represented using a limited number of design variables along with the material-field series expansion strategy, and the optimization problem is subsequently solved using a non-gradient-based optimization algorithm. Finite element simulation results demonstrated that the optimized design possesses a substantial capacity for energy absorption. Additionally, the design structure can recover to its initial state from buckling induced by the initial load by regulating the external temperature. Different multistable metamaterials, including those designed to prevent repetitive impacts, have been further developed based on the designed recoverable high-energy-absorbing bistable unit cells, utilizing combinations of varying energy absorption capacities.

The genomic landscape of transposable elements in yeast hybrids is shaped by structural variation and genotype-specific modulation of transposition rate.

Transposable elements (TEs) are major contributors to structural genomic variation by creating interspersed duplications of themselves. In return, structural variants (SVs) can affect the genomic distribution of TE copies and shape their load. One long-standing hypothesis states that hybridization could trigger TE mobilization and thus increase TE load in hybrids. We previously tested this hypothesis (Hénault et al., 2020) by performing a large-scale evolution experiment by mutation accumulation (MA) on multiple hybrid genotypes within and between wild populations of the yeasts Saccharomyces paradoxus and Saccharomyces cerevisiae. Using aggregate measures of TE load with short-read sequencing, we found no evidence for TE load increase in hybrid MA lines. Here, we resolve the genomes of the hybrid MA lines with long-read phasing and assembly to precisely characterize the role of SVs in shaping the TE landscape. Highly contiguous phased assemblies of 127 MA lines revealed that SV types like polyploidy, aneuploidy, and loss of heterozygosity have large impacts on the TE load. We characterized 18 de novo TE insertions, indicating that transposition only has a minor role in shaping the TE landscape in MA lines. Because the scarcity of TE mobilization in MA lines provided insufficient resolution to confidently dissect transposition rate variation in hybrids, we adapted an in vivo assay to measure transposition rates in various S. paradoxus hybrid backgrounds. We found that transposition rates are not increased by hybridization, but are modulated by many genotype-specific factors including initial TE load, TE sequence variants, and mitochondrial DNA inheritance. Our results show the multiple scales at which TE load is shaped in hybrid genomes, being highly impacted by SV dynamics and finely modulated by genotype-specific variation in transposition rates.

A 28-year-old male patient with asymptomatic and multi-drug-resistant HBV infection: a case report

Chronic hepatitis B virus (HBV) infection poses a significant global health challenge, impacting millions of individuals and elevating the risk of morbidity and mortality. Antiviral therapies are the primary treatment for chronic HBV infection, but treatment resistance can occur, leading to poor clinical outcomes and an increased risk of liver complications. This case report presents the clinical trajectory of a 28-year-old male diagnosed with asymptomatic HBV infection in 2016 under the auspices of the Hepatitis Control Program, Government of Azad Jammu and Kashmir, Pakistan. Over 6 years, persistent HBsAg, HBV, and HBeAg were observed, with absent acute markers and co-infections. Initial HBV DNA viral load was 1 × 104 copies/mL in 2016, escalating despite entecavir and pegylated interferons therapy, indicating multi-drug resistance. Tenofovir therapy initially reduced viral load but later exacerbated it, reaching 1.86 × 106 copies/mL in 2022. Liver function abnormalities and lipid profile irregularities persisted. Urine examination consistently showed abnormalities. Pending HBV DNA sequencing results may offer insights into treatment resistance. This case underscores the need for an adaptive approach in managing chronic HBV infections within public health programs. Continuous monitoring, integration of virological and biochemical data, and a tailored treatment strategy are essential for optimizing outcomes in similar cases, stressing the importance of refining therapeutic approaches against chronic HBV infection.