Fragmentation Process Research Articles

PARG inhibitor sensitivity correlates with accumulation of single-stranded DNA gaps in preclinical models of ovarian cancer

Poly (ADP-ribose) glycohydrolase (PARG) is a dePARylating enzyme which promotes DNA repair by removal of poly (ADP-ribose) (PAR) from PARylated proteins. Loss or inhibition of PARG results in replication stress and sensitizes cancer cells to DNA-damaging agents. PARG inhibitors are now undergoing clinical development for patients having tumors with homologous recombination deficiency (HRD), such as cancer patients with germline or somatic BRCA1/2-mutations. PARP inhibitors kill BRCA-deficient cancer cells by increasing single-stranded DNA gaps (ssGAPs) during replication. Here, we report that, like PARP inhibitor (PARPi), PARG inhibitor (PARGi) treatment also causes an accumulation of ssGAPs in sensitive cells. PARGi exposure increased accumulation of S-phase-specific PAR, a marker for Okazaki fragment processing (OFP) defects on lagging strands and induced ssGAPs, in sensitive cells but not in resistant cells. PARGi also caused accumulation of PAR at the replication forks and at the ssDNA sites in sensitive cells. Additionally, PARGi exhibited monotherapy activity in specific HR-deficient, as well as HR-proficient, patient-derived, or patient-derived xenograft (PDX)-derived organoids of ovarian cancer, and drug sensitivity directly correlated with the accumulation of ssGAPs. Taken together, PARGi treatment results in toxic accumulation of PAR at replication forks resulting in ssGAPs due to OFP defects during replication. Regardless of the BRCA/HRD-status, the induction of ssGAPs in preclinical models of ovarian cancer cells correlates with PARGi sensitivity. Patient-derived organoids (PDOs) may be a useful model system for testing PARGi sensitivity and functional biomarkers.

Drastic variation in mitochondrial genome organization between two congeneric species of bird lice (Philopteridae: Ibidoecus).

The over 4,100 species of bird lice are classified into 214 genera in the parvorders Amblycera and Ischnocera. Congeneric species of bird lice usually share much similarity in morphology and in mitochondrial (mt) genome organization. Two recent studies, however, reported substantial intra-genus variation in mt genome organization in bird lice. Both the ancestral single-chromosome mt genome and a fragmented mt genome with two or three minichromosomes were observed in the genera Austromenopon and Laemobothrion. To better understand intra-genus variation in mt genome organization, we sequenced the complete mt genome of the white spoonbill louse Ibidoecus plataleae and compared it with that of the glossy ibis feather louse Ibidoecus bisignatus reported previously. We found that I. plataleae had a fragmented mt genome with 12 minichromosomes; each minichromosome was 2,798 to 3,628bp in size and had 2 to 6 genes. This is in stark contrast to the mt genome of I. bisignatus, which has all genes on a single chromosome, 14,909bp in size. This is the most drastic intra-genus variation in mt genome organization observed to date in animals, indicating an unprecedented rapid process of mt genome fragmentation in the genus Ibidoecus. The divergence time between I. plataleae and I. bisignatus is currently unknown but is estimated to be less than 23million years. Either many minichromosal split events occurred after I. plataleae diverged from I. bisignatus, or one minichromosome splits into multiple minichromosomes in a single event. Sequencing and comparing more Ibidoecusi species will help understand the unusual mt genome fragmentation in this genus.

Peridynamics simulations of the damage of reinforced concrete structures under radial blasting

Concrete is prone to damage under explosive loads, which can cause a large number of casualties and property losses. The concrete fragmentation process during explosion is transient and dynamic, and the experimental measurement of such events is difficult and risky to conduct, and the intermediate explosion process is difficult to observe in the experimental tests. Therefore, the numerical simulation is an ideal method to model and simulate the explosion process of concrete. Different from the traditional finite element method, Peridynamics (PD) method uses the spatial integral equation to replace the traditional local differential equation to solve the fragmentation problem with massive and complex discontinuous patterns. In this study, a peridynamics (PD) model is developed to simulate the failure process of reinforced concrete (RC) structures under radial blasting. Concrete PD models with different cavity sizes and reinforcement conditions were established and calibrated with the experimental data. We find that the crack growth and damage pattern obtained in the peridynamics simulation is consistent with the experiment test results, which verifies the feasibility of peridynamics method as a modeling tool for modeling concrete damage under explosive load and for evaluating anti-explosion performance of RC concrete structures.

Molecular dynamics of deformation and fragmentation processes in liquid droplets under pulsed electric field

The deformation and breakup of droplets are widely observed in various aspects of production and daily life. Using molecular dynamics simulations, this study primarily investigated the deformation and breakup of droplets in a nitrogen environment under pulsed electric fields of different frequencies. The results indicate that the droplet deformation undergoes periodic changes under the influence of the pulsed electric field. At equivalent electric field strengths, droplets are more likely to break under a 6.25 GHz pulsed electric field compared to a 25 GHz pulsed electric field, where droplet deformation remains stable without breaking. At every frequency, the bond energy of water molecules consistently decreases. The solvent-accessible surface area changes with the electric field at 6.25 GHz. Furthermore, the minimum value of hydrogen bond quantity reached under high-frequency pulsed fields is higher than that under low-frequency fields. The change in hydrogen bond quantity is inversely proportional to the solvent-accessible surface area. These findings provide insights into the microscopic mechanisms of droplet deformation and breakup, offering a reference for future studies.

Fragmentation behavior and velocity formula for secondary fragments from RC slabs during contact explosions

The failure process of reinforced concrete (RC) slabs under contact explosion is dominated by localized damages, accompanied by numerous flying fragments. These concrete fragments pose a significant threat to personnel and equipment, as well as causing dynamic deformation and failure of the retrofitting materials used to restrain the fragments. The behavior of concrete fragmentation during explosions has been seldom studied experimentally, and few fragment velocity formulas exist that incorporate multiple factors. In this paper, the fragmentation process is recorded using two high-speed cameras, revealing that concrete fragmentation during explosions exhibits notable zoning characteristics, with the maximum velocity observed at the center of the fragment cloud’s front. To predict this maximum velocity, a model is derived from dimensional analysis. Utilizing this model, velocity prediction formulas are proposed and validated by 29 contact explosion tests. The formulas consider the explosive-rebar position, slab thickness, explosive mass and explosive shape, and are further improved by considering the concrete cover. The results indicate that, when the slab is not breached, the deceleration of rebar on fragments is weak. However, once the slab is breached, this deceleration becomes increasingly significant as the defined scaled thickness (TS) decreases. In the limiting case, the fragment velocity when the charge is located above the rebar is 0.636 times that of when the charge avoids the rebar. Fragments when the charge avoids the rebar, should be regarded as the most unfavorable case in secondary fragment hazards assessment and structural design.

Bubble fragmentation in turbulent flow and the potential implications of shear structures for bubbles formed by breaking waves

Large bubbles (1–5 mm radius) are important in a wide range of situations, including air-sea gas transfer, aerosol production as they burst at water surfaces, and the aeration of liquids in bioreactors and other industrial processes. When rising through turbulent flow, these bubbles are commonly distorted and may fragment to form daughter bubbles if their radius exceeds the Hinze scale (at which the restoring force due to surface tension is equal to the forces causing bubble distortion). Here, we present the results of laboratory experiments with fragmentation resulting from bubbles rising through a sheared and turbulent flow. The effects of water temperature, surface tension, local shear rate, and viscous dissipation rate of turbulent kinetic energy were assessed. Passive acoustical methods produce robust measurements of bubble fragmentation processes, allowing for rapid data collection to generate large data sets. In our experiments, even for bubbles very close to the Hinze scale, the dominant fragmentation mechanism is the capillary-driven fragmentation of elongated bubble filaments. The probability distribution of daughter bubble sizes from a single fragmentation event was independent of temperature, surface tension, and rate of viscous dissipation of turbulent kinetic energy. The overwhelming majority of fragmentation events resulted in one very large and one very small bubble, even for Hinze-scale parent bubbles and low Weber numbers (We < 5.3). Our results suggest that in a turbulent flow, there may be a link between the shear induced by large scale structures and the size of the smallest bubbles produced underneath a breaking wave.

Barriers and hurdles delaying governance approval for an ethically approved nationwide clinical trial in pancreatic cancer.

Streamlined, expedited clinical research is fundamental to rapidly test, translate and implement novel treatments into routine care to improve patient outcomes. The National Mutual Acceptance (NMA) scheme was designed to expedite the ethics approval process, however, growing concerns exist about the fragmented time-consuming governance process needed to actually commence clinical research in Australia. This study reports hurdles and barriers encountered while seeking governance approval for the SCANPatient trial. SCANPatient is a nationwide multi-centre trial comparing standard narrative radiological reporting of CT scans for suspected pancreatic ductal adenocarcinoma. with an alternative structured approach. SCANPatient was approved by a national Human Research Ethics Committee under the NMA. The documents, time, costs and platforms required to obtain governance approval and open the trial at 30 participating hospitals were analysed. Wide variation exists in research governance office (RGO) requirements for local approval, resulting in extra costs (>$117 000), delays of up to 4 months in commencing the trial at some participating sites, unplanned adjustment of the study design, and ultimately the loss of several potential sites. There were inconsistencies among RGOs minimum requirements and processes across jurisdictions and sites, with delays in obtaining approval signatures, time-consuming processes, differing platforms used to submit governance reviews and inflexibility of RGO processes all contributing to delays in progressing the trial and obtaining governance approval. The current governance process is time- and cost-consuming and undermines the NMA scheme's efforts to streamline the clinical trials review process.

Information as public good and public service media in Europe: Introduction to this special issue

The right to public life has been one of the most important achievements of modernity. It was a result of long and painful civil struggles for dignity in a democratic public sphere. While de jure we are all welcome in the public sphere, de facto rapid processes of fragmentation and numerous contexts of misinformation insulate the actual chances of meaningful contribution to public life. Platform users are aggressively approached as consumers of goods and services and continuously stimulated to produce large quantities of any content, just to feed the voracious platforms. The sobering truth is that many people on the private high-tech platforms do not act like true democrats, but like private individuals who pursue very personal aims. At the same time, a private person does not have a mandate to act in the public interest of the rest of the citizens. For these reasons, we turn to information as a public good and public responsibility in this special issue. It is about media as a public service that allows democracy to keep centre stage within a polity. When citizens interact with relevant public information, they build the capacity to control their political environment, to form informed opinions and act upon them. When this basic desideratum is not structurally at the core of society, one cannot even start to consider democracy as the first course of action for the generations to come. Information as a public good is not a thing of nature, but a purposeful action. We take this stance when we approach information as a public good, rather than some residual category of market failure. The scope of this special issue is to analyse and explore the resources and institutional settings that allow information to thrive as a public good in the European contemporary informational ecosystem.

A complementary approach for detecting biological signals through a semi-automated feature selection tool.

Untargeted metabolomics is often used in studies that aim to trace the metabolic profile in a broad context, with the data-dependent acquisition (DDA) mode being the most commonly used method. However, this approach has the limitation that not all detected ions are fragmented in the data acquisition process, in addition to the lack of specificity regarding the process of fragmentation of biological signals. The present work aims to extend the detection of biological signals and contribute to overcoming the fragmentation limits of the DDA mode with a dynamic procedure that combines experimental and in silico approaches. Metabolomic analysis was performed on three different species of actinomycetes using liquid chromatography coupled with mass spectrometry. The data obtained were preprocessed by the MZmine software and processed by the custom package RegFilter. RegFilter allowed the coverage of the entire chromatographic run and the selection of precursor ions for fragmentation that were previously missed in DDA mode. Most of the ions selected by the tool could be annotated through three levels of annotation, presenting biologically relevant candidates. In addition, the tool offers the possibility of creating local spectral libraries curated according to the user's interests. Thus, the adoption of a dynamic analysis flow using RegFilter allowed for detection optimization and curation of potential biological signals, previously absent in the DDA mode, being a good complementary approach to the current mode of data acquisition. In addition, this workflow enables the creation and search of in-house tailored custom libraries.

Modelling freckles and spurious grain formation in directionally solidified superalloy castings

Segregation channels with misoriented spurious grains, known as freckles, are an unacceptable casting defect in superalloy turbine blades. A digital-twin method to predict segregation channels was proposed in our previous studies; however, the formation of spurious grains was ignored. Here, we extend the digital twin methodology by incorporating dendrite fragmentation, which is recognized as the predominant mechanism in the formation of spurious grains. The flow-induced fragmentation process has been refined to account for the timing of dendrite pinch-off. A three-phase mixed columnar-equiaxed solidification model was used to track the motion of the crystal fragments. Directional solidification experiments for superalloy casting were conducted in an industrial-scale Bridgman furnace, and the distribution of spurious grains in the freckles was metallographically analysed. Excellent simulation-experiment-agreement was achieved. Based on this study, the formation of spurious grains within the segregation channels is mainly caused by the flow-driven fragmentation mechanism. Experimentally measured freckles can be reproduced only if the timing of the dendrite pinch-off is considered.

A spatially-dependent fragmentation process

A spatially-dependent fragmentation process

Impacts of land use and land cover change on the landscape pattern and ecosystem services in the Poyang Lake Basin, China

ContextDecades of intensifying human activities have led to drastic changes in land use and land cover (LULC) in the Poyang Lake Basin (PLB), resulting in significant changes in landscape pattern and ecosystem service value (ESV), thereby affecting regional sustainability.ObjectivesWe focused on understanding the impact of LULC changes on the landscape pattern and ESV of the PLB and used the Patch-generating Land Use Simulation model (PLUS) to predict LULC changes in 2050.MethodsWe evaluated landscape patterns using landscape metrics and calculated ESV using the ecosystem service equivalent factor method. The Pearson correlation coefficient was used to analyze the correlation between landscape patterns and ESV from 1990 to 2020. Then, we combined the PLUS model and the ecosystem service equivalent factor method to calculate the ESV under multiple scenarios from 2020 to 2050.ResultsFrom 1990 to 2020, the LULC of the PLB changed to varying degrees. The PLB has undergone a rapid process of landscape fragmentation, and the total ESV of the PLB has decreased. The total ESV was positively correlated with the CONTAG index and negatively correlated with the SHDI index. Between 2020 and 2050, the ESV of the PLB is projected to decrease under the NDS (nature development scenario) and EDS (economic development scenario) and increase under the EPS (ecological protection scenario).ConclusionsESV responded to changes in landscape pattern. We recommend that the PLB should increase patch connectivity. Additionally, future development in the PLB should prioritize ecological protection to prevent further declines in ESV.

Advances in Mass Spectrometry Fragmentation Techniques for Peptide and Protein Characterization: CID to ETD

Mass spectrometry (MS) has transformed the field of proteomics by enabling the precise analysis of proteins and peptides at the molecular level. The heart of this analysis is the process of fragmentation, which plays a pivotal role in elucidating amino acid sequence, identifying post-translational modifications (PTMs), and characterizing structural features. Peptides and proteins are first ionized and then subjected to fragmentation techniques such as Collision-Induced Dissociation (CID), Electron-Transfer Dissociation (ETD), and Electron-Capture Dissociation (ECD). These techniques induce fragmentation along the peptide backbone, generating characteristic fragment ions (b and y ions, c and z ions) that reflect the sequence of amino acids. The mass-to-charge (m/z) ratios of these fragment ions provide crucial data for de novo sequencing and PTM identification. Furthermore, fragmentation patterns can reveal insights into protein folding, interactions, and dynamics. This article provides the detailed view of mass fragmentation techniques in peptides and proteins, highlighting its importance in advancing proteomic research and its applications in fields ranging from biomarker discovery to drug development.

(J/ψ,J/ψ), and (ηc,ηc) production through two intermediate photons in electron-positron annihilation at B-factories

We study the processes, e−e+→γ⁎γ⁎→J/ψ+J/ψ, and e−e+→γ⁎γ⁎→ηc+ηc at s=10.6 GeV in the framework of 4×4 Bethe-Salpeter equation. For J/ψ+J/ψ production, the dominant contribution is through fragmentation process, while for ηc+ηc production, the quark rearrangement diagrams contribute. Our results of cross section for J/ψ+J/ψ and ψ(2S)+ψ(2S) are compatible with the experimental upper limits set by Belle Collaboration, while in the absence of experimental data for ηc(1S)+ηc(1S), and ηc(2S)+ηc(2S) production, we have given theoretical prediction of their cross sections, and compared with NRQCD prediction.

Characteristics of Rock Avalanche Deposit in Wangjiapo, Ludian Based on UAV Aerial Image Recognition

Rock avalanche disasters in alpine and gorge regions are frequent and large in scale and cause severe damage. The movement of a rock avalanche is complex and has not been fully studied. The deposits of a rock avalanche can provide valuable insights into its movement process, which is crucial in understanding the rock fragmentation mechanism and predicting disaster-affected areas. Taking the Wangjiapo rock avalanche in Yunnan Province of China as an example, the size, shape and distribution characteristics of the deposit were analyzed based on field surveys, unmanned aerial vehicle (UAV) photography and image recognition technology. Initially, 3062 deposited rock blocks were manually measured in the field. Subsequently, the Particles/Pores and Cracks Analysis System (PCAS) was employed to identify 11,357 rock blocks with an area greater than 0.1 m2 from UAV orthophotos. By comparing the characteristics of the rock blocks obtained through image recognition and manual measurement, the statistical analysis of UAV aerial imagery combined with PACS proved feasible in studying the Wangjiapo rock avalanche. The results showed that the rock block movement was accompanied by fragmentation and sorting processes; furthermore, the roundness increased with the migration distance. Small blocks were more prevalent at the foot of the slope, while irregularly shaped, large blocks dominated in source areas. The movement of huge blocks was characterized by significant potential energy-driven features and inertia advantages, allowing them to travel farther than smaller blocks, and they tended to be concentrated in the central area of the deposit. Additionally, affected by the cementation degree of breccia and the topography, the blocks in the eastern and western deposit areas exhibited different fragmentation and deposition characteristics.

Beyond the Airports Act: Investigating the Privatisation of Airports by Local Governments in Regional Australia

Costs associated with running local airports are spurring some local governments to pursue alternative governance arrangements. Some regional councils are considering privatisation, with four having already gone down this path. Although some of these arrangements broadly follow those specified by the Airports Act 1996, other arrangements have led to fragmented processes and reduced public engagement in local communities. The study reveals that, while long‐term leasing aims to alleviate the council's financial burden, it can negatively impact the broader public interest. The findings suggest the need for more transparent and adaptable governance models to ensure that regional airports serve both commercial interests and public needs.

Theoretical Study on the Dissociation Mechanism of Thiophene in the UV Photoabsorption, Ionization, and Electron Attachment Processes

ABSTRACTA computational study on the intricate mechanism of thiophene ring‐fragmentation (TRF) in the UV photodissociation, dissociative ionization, and dissociative electron attachment process has been performed. The complete fragmentation process is studied using high level G4 composite method for neutral, cationic, and anionic species by elucidating a detailed mechanism for various reaction channels. The study shows that for neutral thiophene, the major pathway is the migration of H atom and subsequent fragmentation through a transition state yielding acetylene (HC≡CH) and H2C=C=S. However, for the thiophene cation, the acetylene (HC≡CH)+H2C=C=S+ channel is a two‐step and barrier less process. The onset of CH3+HC=C=C=S channel has been observed in both the thiophene cation and anion which was absent in the neutral analogue. Similarly, the onset of H2S+HC≡C—C≡CH channel has been found to operate only in the thiophene cation. Others, such as HCS and HS elimination channels have been found in all the species showing similar dissociation mechanism. For the thiophene anion, the TRF process is very much similar to that of thiophene cation. However, the reaction enthalpies of the various elimination channels in the anionic species are lower as compared to that of cationic species. During the study, the ionization energies and electron affinities of various molecules/radicals produced during the fragmentation process of thiophene were also computed.

A Review of the Application of Soot Catalysts: Focus on the Soot Oxidation-Induced Fragmentation Process

A Review of the Application of Soot Catalysts: Focus on the Soot Oxidation-Induced Fragmentation Process

Organisation and management of multi-professional care for cancer patients at end-of-life: state-of-the-art from a survey to community and hospital-based professionals.

Providing timely and satisficing End-of-Life care (EOLC) is a priority for healthcare systems since aging population and chronic diseases are boosting the global demand for care at end-of-life (EOL). In OECD countries the access to EOLC is insufficient. In Italy, the average rate of cancer patients assisted by the palliative care (PC) network at EOL was 28% in 2021, with high variability in the country. Among theItalian regions offering the best coverages, Tuscany has a rate of about 40%, but intraregional variation is marked as well. The study aims to explore the delivery of EOLC to adult cancer patients in public facilities in the Tuscany region through survey data collection among professionals. Two online surveys were delivered to Directors of community-based PC Functional-Units (FUs) and Directors of hospital-based medical-oncology units. All FU Directors responded to the survey (n = 14), and a response rate of 96% was achieved from hospital-unit Directors (n = 27). The results highlight the availability of numerous dedicated services, but reveal heterogeneity among and within organisations, including variations in the professionals involved, pathways, and tools adopted. Care continuity is supported by institutionalized collaboration between hospital and community settings, but hindered by fragmented care processes and heterogeneous transition pathways. Late referral to PC is perceived as a major constraint to EOLC. Developing structured pathways for patient transition to end-stage PC is crucial, and practices/processes should be uniformly implemented to ensure equity. Multi-professional care should be facilitated through tailored supporting tools. Both hospital-unit and FU Directors suggest developing shared pathways between organisations/professionals (82% and 80% respectively) and digital information sharing (61% and 80% respectively). Hospital and community-based professionals have similar perceptions about the concerns and challenges to EOLC provision in the region, but community-based professionals are more sensitive to the importance of improving communication on PC to the public and early discussing EOLC with caregivers. This finding suggests the need of enhancing hospital personnel's awareness about these issues. Professional training and the capacity to assess patients' needs and preferences should be improved. The identified needs can inform future research and interventions to improve the quality and outcomes of EOLC for cancer patients.

ATOMS: ALMA three-millimetre observations of massive star-forming regions–XVII. High-mass star-formation through a large-scale collapse in IRAS 15394-5358

ABSTRACT Hub-filament systems are considered as natural sites for high-mass star formation. Kinematic analysis of the surroundings of hub-filaments is essential to better understand high-mass star formation within such systems. In this work, we present a detailed study of the massive Galactic protocluster IRAS 15394$-$5358, using continuum and molecular line data from the ALMA three-millimetre observations of massive star-forming regions (ATOMS) survey. The 3 mm dust continuum map reveals the fragmentation of the massive ($\rm M=843~{\rm M}_{\odot }$) clump into six cores. The core C-1A is the largest (radius = 0.04 pc), the most massive ($\rm M=157~{\rm M}_{\odot }$), and lies within the dense central region, along with two smaller cores ($\rm M=7~and~3~{\rm M}_{\odot }$). The fragmentation process is consistent with the thermal Jeans fragmentation mechanism and virial analysis shows that all the cores have small virial parameter values ($\rm \alpha _{vir}\lt \lt 2$), suggesting that the cores are gravitationally bound. The mass versus radius relation indicates that three cores can potentially form at least a single massive star. The integrated intensity map of $\rm H^{13}CO^{+}$ shows that the massive clump is associated with a hub-filament system, where the central hub is linked with four filaments. A sharp velocity gradient is observed towards the hub, suggesting a global collapse where the filaments are actively feeding the hub. We discuss the role of global collapse and the possible driving mechanisms for the massive star formation activity in the protocluster.