bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the Nonlinear Reactivity Promoting Effect of n-Heptane Addition on the Binary Mixture From Low to Intermediate Temperature: A Case of Methane/n-Heptane Mixtures
Authors: Mai Zhaoming , Wu Yingtao , Tang Chenglong , Wang Wei , Huang Zuohua
Published: November 2023

To understand the effect of n-heptane (NC7H16) addition on the auto-ignition of methane (CH4) at low to intermediate temperatures, the ignition delay times (IDTs) of stoichiometric CH4/NC7H16 blends with varying NC7H16 concentrations were measured at temperatures from 600 to 1000 K, pressures of 20 and 40 bar. Detailed chemical kinetic mechanisms were validated against the newly measured IDTs. Adding NC7H16 in the binary mixture shows a nonlinear promoting effect on the IDTs: micro-addition of NC7H16 can significantly reduce the IDTs of the binary mixture when the NC7H16 is lower than 20%. However, the decrease of the IDTs becomes much slower when further increasing the NC7H16 addition. Affected by the negative temperature coefficient (NTC) behavior of NC7H16, this nonlinear effect is particularly notable at around 795 K, the low boundary of the NTC region. To reveal the nonlinear reactivity-promoting effect of NC7H16 addition on the binary mixture, reaction flux, ignition sensitivity, rate of production of the key radicals along heat production analyses were conducted. Apart from contributing more O˙H production through the low-temperature chain-branching reaction pathways of NC7H16, adding NC7H16 also promotes the pre-ignition heat release of the binary mixture. The heat release raises the system temperature and further promotes the mixture ignition, enhancing the nonlinear effect at low temperatures.
Numerical Analysis of Hydrogen Diffusion and Distribution at Corrosion Defect on Aged Pipelines for Hydrogen Service
Authors: Guo Shiwen , Dong Shaohua , Cheng Frank
Published: November 2023

Using existing natural gas pipelines to transport hydrogen blended natural gas is an important way to achieve efficient hydrogen transportation. However, the existing pipelines may contain corrosion defects, which can affect the diffusion and distribution behavior of hydrogen atoms, further resulting in hydrogen embrittlement and pipeline failure. This study applied the numerical analysis method to simulate the hydrogen atom redistribution in interstitial lattice sites and in trapping sites of X52 steel pipeline with corrosion defect by coupling stress field and hydrogen diffusion field. It was found that under applied tensile strain, the hydrogen atoms accumulated at corrosion defect due to local stress concentration. The maximum lattice concentration was located on the outer pipe wall, and the maximum trapped concentration occurred at the defect center. And both of them elevated with tensile strain and initial concentration increasing, although there was a difference of several orders of magnitude between them. The increase of temperature reduced the maximum concentration. Besides, the maximum hydrogen concentration in trapping sites also increased with the higher binding energy. The proposed model can be used to determine the hydrogen concentration and distribution behavior at corrosion defect for HE prediction of corroded pipeline.
A Systematic Approach to Solving Problematic Heat Exchanger Joints Through Application of WRC 538 & WRC 510 Principles
Authors: Berry Alex , Tanveer Usman , LoCascio Kevin , Seijas Antonio , Naqvi Aamir
Published: November 2023

Shell and tube heat exchangers are commonplace in many industrial installations. To facilitate cleaning and inspection, exchanger components are made to be unbolted. These custom bolted flanged joints are designed to meet or exceed the applicable code requirements to prevent leakage in service. Plant engineers often inherit “problematic” heat exchanger joints that leak during operation. This may happen during start up, normal operation or during a unit upset condition. Flange re-design is often not an option, and the engineer must analyse the “bad-actor” and seek solutions to prevent future leakage. This paper will explore what makes for a leak free joint based on current industry knowledge and explore tools that can be used to evaluate bolted flanged joints quickly and effectively by the plant engineer. With the publication of WRC 538 and WRC 510, engineers can assess bolted flanged joints based on the limiting design of each component and accurately assess the thermal effects for joints operating at temperature. A step-by-step methodology is provided leading to solutions implemented in two case studies that have resulted in leak free joints between turnaround cycles. These solutions address the root cause of all flange leaks which is insufficient gasket stress. However, loss of gasket stress may result for a variety of reasons which are explored in detail.
Assessment of Coke Drum Bulge Deformation Using Online Thermal Data to Determine Optimal Weld Overlay Repair Design
Authors: Berry Alex , Brown Warren , Brodzinski Richard , Seijas Antonio
Published: November 2023

Studies [1–11] have shown bulging in coke drums occurs due to several factors. One of which, are large thermal gradients that occur during the drum operating cycle. A thermocouple array comprising of 126 temperature indicators, spanning 1.7 m (5.5 ft) high, full circumference, was installed onto a coke drum at the location of a significant bulge in order to monitor the drum skin temperature distribution over a thirty-day period (total of 14 drum cycles). This paper presents the findings of this thermal study, exploring the nature of the hot and cold spots seen during the quench phase and maps out the resulting deformations and plastic strains local to the drum bulge. A reinforcing weld overlay repair is selected after using finite element analysis (FEA) to optimise weld coverage, placement (internal surface ID vs external surface OD), number of weld overlay passes and final thickness. The weld overlay effectiveness was found to be primarily based on the axial extent of overlay applied and not significantly affected by the thickness of the overlay.
Fracture Characterization of Structural Steel S275JR Using Conventional CT Specimens, Mini-CT Specimens and Small Punch Specimens: A Comparison
Authors: Sánchez Marcos , Cicero Sergio , Arroyo Borja
Published: November 2023

Miniaturized specimens, such as mini-CT specimens and Small Punch (SP) specimens, are a solid alternative when characterizing the fracture behavior of structural materials but there are restrictions related to the amount of material available, irradiation issues or material inhomogeneities, among other possible concerns. Moreover, in ferritic-pearlitic steels, fracture characterization is of particular interest within the ductile-to-brittle transition zone (DBTZ), and it is often performed through the definition of the Reference Temperature (T0) and the Master Curve (MC) methodology. The use of mini-CT specimens has been validated in a number of steels used in the nuclear industry, but its application in other types of ferritic-pearlitic steels is very limited. In this regard, this work provides an overview of the fracture characterization results (T0) in structural steel S275JR, which have been obtained by using conventional standardized Compact-Tension (CT) specimens, mini-CT specimens and SP specimens. This steel is a low carbon non-alloyed steel which is widely used in civil engineering structures. Here, it is shown how, for this particular structural steel, the use of miniaturized specimens provides T0 estimations which are comparable to those values obtained from conventional larger specimens, and also that the MC approach accurately reflects the fracture behavior in the DBTZ.
Study on Dynamic Buckling Behavior and Post-Buckling Stability of Thin-Walled Cylinders Subjected to Lateral Vibration
Authors: Ye Yiji , Hasegawa Sho , Kasahara Naoto
Published: November 2023

Severe earthquakes are regarded as Beyond Design Basis Events (BDBEs) in nuclear safety. In the case of buckling of the fast reactor vessel under severe earthquakes, previous research indicated that no immediate collapse occurs due to buckling. Therefore, the objective of safety design of FRV under severe earthquakes is to achieve a stable post-buckling state.

In this paper, dynamic buckling behavior and post-buckling stability of thin-walled cylinders subjected to lateral vibration are studied. It is found that the structural integrity is well maintained after buckling occurrence and thus no threat of major collapse. Firstly, due to phase-inverse phenomenon, the response tends to be stabilized in the out-of-phase region after buckling. In addition, large energy dissipation capacity due to hysteresis behavior prevents the increase of kinematic energy after buckling.

A parametric survey of dominant parameters shows that input acceleration with a low input frequency can cause a more severe destructive effect. Furthermore, the response characteristics under composite sinusoidal excitation and seismic excitation are similar to those of single sinusoidal excitation regarding phase-inverse, acceleration reduction and post-buckling hysteresis behavior.
Effect of Normalizing Temperature on Impact Toughness of ASME SA – 350 LF2 Cl1 Forgings
Authors: Hernández Soto Ricardo , Gómez de Salazar José María
Published: November 2023

Four slabs cut out from a forging ring were normalized at 870°C, 885 °C, 900°C and 915°C for three hours. Cooling from normalizing to room temperature proceeded under forced air. Test specimens were extracted for Charpy impact testing at −46°C and metallographic examination. Furthermore, open-source image analysis software ImageJ was used on SEM micrographs to evaluate the size distribution of pearlite nodules.

The four different normalizing temperatures yielded impact test values above the minimum threshold of SA – 350 for LF2 Cl1 classification. However, the slab normalized at 870 °C showed the best performance, being significantly higher (122 Joules average – 53 Joules minimum) than slab normalized at 915°C (86 Joules average – 33 Joules minimum). Normalizing temperatures of 885°C and 900°C behaved similarly (104 J and 113 J average, respectively).

After the metallographic characterization, it was concluded that higher normalizing temperatures increase the austenite grain size and promote finer pearlites made of single-colony nodules. Lower normalizing temperatures restrict the austenitic grain growth, leading to coarser pearlites made of smaller nodules with multiple colonies. These smaller nodules of coarse pearlite oppose more effectively to brittle crack propagation since colony boundaries function as an additional barrier.
Uncertain Factors in Elastic-Plastic Finite Element Analysis for Elbows and Tees
Authors: Azuma Kisaburo , Fujiwara Keita , Kai Satoru , Otani Akihito , Furuya Osamu
Published: November 2023

Low-cycle fatigue is one of the possible failure modes of piping systems caused by severe earthquakes. Fatigue is a type of cumulative damage during long-term operation; hence, fatigue life evaluation could be critical for the piping systems in existing plants. Considering the fatigue evaluation uncertainty, a considerable margin must be included for the seismic design of the piping systems.

Low-cycle fatigue failure is thought to be associated with the equivalent strain obtained by the elastic-plastic finite element analysis. However, some uncertain factors affect the prediction of the equivalent strain of piping systems, like the actual size and material properties of pipe fittings. These properties are not always readily available in existing plants; therefore, an inevitable uncertainty remains in the analysis. Quantifying the influence of these factors is expected to provide a better understanding of the seismic margin of piping systems.

In this study, we investigate the influence of model assumptions on the equivalent strain range of pipe fittings. We model elbows and equal and reducing tees as the typical pipe fittings used in piping systems. Comparing the results of the elastic-plastic analysis associated with various model assumptions, such as hardening models and structural geometries, we discuss herein how uncertain factors affect the equivalent strain prediction.
Experimental Investigation on Temperature Field Evolution of P280GH Pipeline in Butt Welding Process
Authors: Hu Maiwen , Su Hao , Wang Yanping , Han Zelin , Song Yan
Published: November 2023

It is of great significance to investigate the welding temperature field of pipeline around weld joint during welding process for analyzing the thermal stress and evaluating the performance and service life of welded pipelines. In this work, a pipeline butt welding experiment of P280GH steel was conducted to figure out the evolution of welding temperature field and parameters that affected welding temperature field. 27 effective measuring points were placed at different positions along external and internal surfaces in 3 directions (3, 9, and 12 o’clock directions on the circumference of the cross section). By using the thermocouple temperature measurement method, the welding temperatures for all 37 cycles of the argon arc welding process were monitored and recorded. The results indicate that the most critical parameter of temperature field was the distance from the welding position to measuring point. The temperature rose significantly and then dropped as the welding torch passed by a measuring point. The temperature of the measuring point changed more dramatically as it was closer to the weld joint. With the increase in the number of welding cycles resulting in the superposition of weld metal, the magnitude of temperature evolution at the measuring points on the external surface increased progressively, whereas that on the internal surface decreased gradually.
Hot Spent/Waste Heat Boiler Tube Sheet Reliability Analysis
Authors: Subramanian Kannan , Parker Daniel
Published: November 2023

The tube sheet and several tube-to-tube sheet joints at the flue gas inlet of a hot spent boiler experienced failures in a sulfur processing unit. To address this, plugging of tubes that failed at the joint locations, weld repair on the tube sheet, and post weld heat treatment (PWHT) were performed to bring the boiler back to operation. In addition, a few more tubes were also plugged. In these applications, the selection of tubes to be plugged is based on operator’s historical experience-based information. However, such an approach may not adequately address the mechanical integrity of the unplugged tube-to-tube sheet joints and the tube sheet itself. The repair process adds complexity to the problem that already involves numerous parameters that affect this region of the subject boiler. In this work, a case study of the subject boiler presents a systematic approach involving advanced analytical tools that provided insights into the historical reliability issues and a solution to address tube plugging for continued service. It is demonstrated that such engineering approaches can minimize further failures, repair costs, and loss of production time/costs. It is important to note that many of these boilers were designed to ASME Section I, and may benefit from approaches prescribed in ASME Section VIII, Division I, and design by analysis approaches.
Deterministic Leak-Before-Break Treatment of Uncertainties: Part 2 – Example Application
Authors: Kozluk Michael J. , Al-Dojayli Maher , Pavia Renita , Mileta Ernie
Published: November 2023

The Canadian CANDU® Industry has developed and is implementing a composite analytical approach (CAA) to demonstrate, with high confidence, appropriate safety margins for deterministic nuclear safety analysis of large-break loss-of-coolant accident events in existing CANDU reactors. A key element of the CAA is the deterministic leak-before-break (CAA/DLBB) assessment for postulated through-wall cracks in all butt welds in the large-diameter primary heat transport system piping and reactor headers.

The companion paper proposes an approach to integrate the uncertainties of the key leak-rate parameters into a single metric (a quantitative indicator of the uncertainty in the CAA/DLBB assessment, a.k.a., performance indicator). This approach ensures that the uncertainty in individual key parameters is not taken out of the context of the uncertainty of the other key parameters.

This paper illustrates the application of this systematic approach for quantifying the uncertainty in the CAA/DLBB assessment to a specific postulated break location. The example application illustrates how the bounding values of the key leak-rate factors are quantified and how the uncertainties in the factors are integrated using the analytical and numerical approaches and discuss how the proposed approach provides an unbiased estimate of the leak-rate factor for the postulated break location that is assessed.
Development of a Numerical Framework for Microstructure Sensitive Fatigue Life Investigations
Authors: Henrich Manuel , Dölz Michael , Münstermann Sebastian
Published: November 2023

Modern steel grades with increasingly complex microstructure morphologies demand advanced modeling methods. Especially in terms of geometrical microstructure modeling these steels tend to be very challenging. In this study a framework is presented that tackles the modelling of modern microstructures using a new generator for representative volume elements called DRAGen (Discrete Rve Automation and Generation), and a strategy for the numerical investigation of the influence of the surface roughness and residual stresses on the fatigue life and endurance is proposed. The proposed framework consists mainly of three parts: microstructural characterization, generation of statistical representative volume elements and the investigation of micromechanical behavior under extrinsic loading conditions. The microstructural characterization is supported by neural networks while the generation algorithms of the representative volume elements uses the information generated by those neural networks. The mechanical behavior of these representative volume elements is simulated with Abaqus. Due to the usage of a neural network DRAGen can produce very realistic microstructure models following the statistical behavior of the real world material with a high level of detail. It is also possible to introduce features such as surface roughness and residual stresses into the simulations of DRAGen’s representative volume elements. Therefore, the fatigue life estimations performed with these representative volume elements enable a better understanding of the influences that single microstructural features have on fatigue life. This understanding will help to generate a good basis for numerical optimization of the structural integrity of safety-related components.
Study on the Effect of Local Segregations on the Charpy Impact Toughness Scatter, in RCC-M Code 18 and 20MND5 (SA 508 Gr3) Steel Grade Forgings for Nuclear Components
Authors: Joly Pierre , Roch François , Sun Lingtao , Deneuvillers Elizabeth
Published: November 2023

The microstructure of SA508 Gr3 steel heavy forgings features, in some zones coming from the original ingot where solidification took place with equiaxial grains, local segregations between the solidification grains. These segregations were studied in two different forgings, where the mean local composition is offset from the original heat analysis, at two different levels because of macro-segregation. The local chemical compositions show significant peaks in alloying elements associated with a rather high level of impurity (phosphorus). The resulting structures after forging feature “bands” of segregated material elongated in directions normal to the short direction (perpendicular to the surfaces) of the forging. These structures are analyzed, by metallographical and micro-analytical means. Mechanical testing and fractographic analysis showed that these segregations contribute to brittle fracture initiation in the ductile-brittle transition because of their harder and more brittle character than the surrounding matrix. Because of the relatively large distance between them (several mm) and depending on their random position with respect to the specimen notch tip, significant scatter is observed in the Charpy impact energy. An analysis of the scatter of Charpy impact energy in relation with the position of segregated bands in the ligament and their distance from the specimen notch tip is presented.
A Multi-Scale Creep, Fatigue, and Creep-Fatigue Interaction Model for Estimating Reliability of Steel Components at Elevated Temperatures
Authors: Fong Jeffrey T. , Marcal Pedro V. , Cohn Marvin J. , Heckert N. Alan
Published: November 2023

The American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code (BPVC) Committee has recently developed a new Section XI (Nuclear Components Inspection) Division 2 Code named “Reliability and Integrity Management (RIM).” RIM incorporates a new concept known as “System-Based Code (SBC)” originally due to Asada and his colleagues (2001–2004), where an integrated approach from design to service inspection is introduced using three new types of statistical quantities: (1) “system reliability index,” or “system co-reliability target” for any system consisting of structures and components, (2) “structural co-reliability,” for any structure, and (3) “component co-reliability” for any component, where co-reliability is defined as “1 – reliability” and is equal to failure probability. In a recent paper published in the International Journal of Pressure Vessels and Piping (Vol. 173 (2019), pp. 79–93). Fong, Heckert, Filliben, and Freiman developed a new theory of fatigue and creep rupture life modeling for metal alloys at room and elevated temperatures such that the failure probability upper bound (FPUB) of a smooth component can be estimated from fatigue life and creep rupture time test data with simple loading histories. In this paper, we extend the theory to include a methodology to estimate not only the failure probability upper bound, but also the damage state of metal alloy components undergoing creep and fatigue with creep-fatigue interactions. To illustrate our methodology, we present numerical examples based on high temperature creep rupture time test data of stainless steel 316L(N) and room temperature fatigue life test data of AISI 4340 aircraft-quality steel. The significance and limitations of this new damage-state-based approach to modeling creep and fatigue reliability of steel components at elevated temperatures are presented and discussed.
Study on Molten Zone of Butt Fusion Welding Process With Phased Array Ultrasonic Technology for Polyethylene Pipe
Authors: Tao Yangji , Guo Weican , Shi Yan , Miao Cunjian , Tang Ping
Published: November 2023

Butt fusion welding is one of the main methods of connecting polyethylene pipes, widely used in the construction of large diameter thick wall pipes. However, the butt fusion joints are the weak link in the polyethylene pipeline. The butt fusion welding parameters such as the heat plate temperature, heating time and welding pressure affect the properties of welded joints. Previous studies have shown that the welded joint properties are related to the size and shape of the molten zone. The molten zone characteristics can be used to assess the welding process parameters for butt fusion welding. In this study, during the butt fusion welding, the changing state of the molten zone was recorded to obtain the optimal welding process parameters. The real-time video recording of the whole process for polyethylene butt fusion welding was proposed, using ultrasonic phased array focusing and imaging techniques. The ultrasonic signal was detected at the boundary of the molten zone based on the acoustic impedance contrast between the molten and unmolten zones. According to the change of boundary ultrasonic signal, the changing state in the distance of the molten zone was recorded and compared in real time. This experimental method is provided to evaluate the welding process parameters for polyethylene butt fusion welding.
Seismic Design Method of Crossover Piping Across Building Isolation Boundary
Authors: Shibukuwa Kenichi
Published: November 2023

Base-isolated structures for non-nuclear buildings rapidly spreaded after Great Hanshin Earthquake in 1995 and the needs for adopting the base-isolated structure to nuclear power plants have increased since Great East Japan Earthquake in 2011. In the case that base-isolated structure is installed in nuclear power plants, there are technical issues to be addressed such as extreme large anchor movement, design seismic cycle number and buckling failure of vertical component in seismic design of crossover piping across the building isolation boundary, which are supported at many support points. This paper provides specific design methods for crossover piping across the building isolation boundary, such as low cycle fatigue evaluation method by using detail fatigue evaluation method to develop the rational seismic design methods of piping in the future.
Application of Dynamic RBI and IOW Technology in Crude Distillation Unit
Authors: Liu Juanbo , Li Jun , Liu Chang , Han Zhiyuan , Xie Guoshan , Song Libin , Chen Sheng , Kang Haoyuan
Published: November 2023

Crude distillation unit (CDU) generally exists severe corrosion. Risk-based inspection (RBI) technology can effectively assess risk of stationary equipment in petrochemical industry. Meanwhile, integrity operating window (IOW) can effectively control risk by establishing standard and critical limits. Limited of data integrated analysis and the complexity of interfaces connecting in different systems, current risk assessment of complete sets of equipment mainly adopted static method. API 584-2021describes the IOW parameters of the crude distillation unit, but there are few reports about how to apply the dynamic RBI and IOW in the field engineering to achieve real-time risk assessment and warning control of the safety operation boundary. Combining RBI and IOW technology, we recently developed a dynamic risk assessment and IOW warning system by interacting three types dynamic interface data, i.e., medium composition in laboratory information management system (LIMS), real-time process operation parameters in distributed control system (DCS) and equipment thickness in corrosion monitoring system (CMS). The developed system was further applied to the crude distillation unit. Taking three typical corrosion circuits of crude oil circuit before desalting, atmospheric tower overhead circuit and second-line circuit of vacuum tower as examples, the variation of dynamic indicators and risk were investigated. Firstly, the damage modes were analyzed according to API 581 and GB/T 30579. And then the monitoring points including medium compositions, process operation parameters and wall thickness were respectively established by analyzing the corresponding data in LIMS, DCS and CMS. Thus, the risk results will update dynamically with the variations of abovementioned data. Based on dynamic risk results, the critical IOW operation boundaries in typical circuits were also displayed. This research will facilitate grasping the equipment risk state in real-time with dynamic RBI technology while ensuring the equipment steady operation by IOW warning technology.
Kinesiology’s Passport to Success: Transcending Parallel Trenches, Nurturing Active Open-Mindedness, and Learning From the Octopus
Authors: Wiggins David K.
Published: November 2023

This essay is based on the premise that kinesiology has evolved into a field made up of disparate subdisciplinary areas contributing to fragmentation and lack of common goals and objectives since the publication of Franklin M. Henry’s famous 1964 essay “Physical Education: An Academic Discipline.” As it now stands, there is much evidence of significant disparity between kinesiology’s creed and its practice, with the field failing to fulfill its promise of an integrationist approach to the study of human movement. In order to rectify this situation, steps should be taken to encourage individuals in the field to cross subdisciplinary boundaries, practice what psychologist Jonathan Baron has referred to as “active open-mindedness,” and take seriously the cues provided in the books by Rafe Sagarin, Learning from the Octopus: How Secrets from Nature Can Help Us Fight Terrorist Attacks, Natural Disasters, and Diseases, and Sy Montgomery, The Soul of an Octopus: A Surprising Exploration Into the Wonders of Consciousness. One specific recommendation is for academicians in kinesiology to prepare students to become polymaths, a term describing individuals with a thorough knowledge of one subject and broad understanding of many others.
miRNA cargo in circulating vesicles from neurons is altered in individuals with schizophrenia and associated with severe disease
Authors: Barnett Michelle M. , Reay William R. , Geaghan Michael P. , Kiltschewskij Dylan J. , Green Melissa J. , Weidenhofer Judith , Glatt Stephen J. , Cairns Murray J.
Published: November 2023

While RNA expression appears to be altered in several brain disorders, the constraints of postmortem analysis make it impractical for well-powered population studies and biomarker development. Given that the unique molecular composition of neurons are reflected in their extracellular vesicles (EVs), we hypothesized that the fractionation of neuron derived EVs provides an opportunity to specifically profile their encapsulated contents noninvasively from blood. To investigate this hypothesis, we determined miRNA expression in microtubule associated protein 1B (MAP1B)–enriched serum EVs derived from neurons from a large cohort of individuals with schizophrenia and nonpsychiatric comparison participants. We observed dysregulation of miRNA in schizophrenia subjects, in particular those with treatment-resistance and severe cognitive deficits. These data support the hypothesis that schizophrenia is associated with alterations in posttranscriptional regulation of synaptic gene expression and provides an example of the potential utility of tissue-specific EV analysis in brain disorders.
Intracellular delivery of nitric oxide enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction
Authors: Hao Tian , Ji Guangbo , Qian Meng , Li Qiu Xuan , Huang Haoyan , Deng Shiyu , Liu Pei , Deng Weiliang , Wei Yongzhen , He Ju , Wang Shusen , Gao Wenqing , Li Tong , Cheng Jiansong , Tian Jinwei , Pan Leiting , Gao Fei , Li Zongjin , Zhao Qiang
Published: November 2023

Cell therapy by autologous mesenchymal stem cells (MSCs) is a clinically acceptable strategy for treating various diseases. Unfortunately, the therapeutic efficacy is largely affected by the low quality of MSCs collected from patients. Here, we showed that the gene expression of MSCs from patients with diabetes was differentially regulated compared to that of MSCs from healthy controls. Then, MSCs were genetically engineered to catalyze an NO prodrug to release NO intracellularly. Compared to extracellular NO conversion, intracellular NO delivery effectively prolonged survival and enhanced the paracrine function of MSCs, as demonstrated by in vitro and in vivo assays. The enhanced therapeutic efficacy of engineered MSCs combined with intracellular NO delivery was further confirmed in mouse and rat models of myocardial infarction, and a clinically relevant cell administration paradigm through secondary thoracotomy has been attempted.
Marginated aberrant red blood cells induce pathologic vascular stress fluctuations in a computational model of hematologic disorders
Authors: Cheng Xiaopo , Caruso Christina , Lam Wilbur A. , Graham Michael D.
Published: November 2023

Red blood cell (RBC) disorders such as sickle cell disease affect billions worldwide. While much attention focuses on altered properties of aberrant RBCs and corresponding hemodynamic changes, RBC disorders are also associated with vascular dysfunction, whose origin remains unclear and which provoke severe consequences including stroke. Little research has explored whether biophysical alterations of RBCs affect vascular function. We use a detailed computational model of blood that enables characterization of cell distributions and vascular stresses in blood disorders and compare simulation results with experimental observations. Aberrant RBCs, with their smaller size and higher stiffness, concentrate near vessel walls (marginate) because of contrasts in physical properties relative to normal cells. In a curved channel exemplifying the geometric complexity of the microcirculation, these cells distribute heterogeneously, indicating the importance of geometry. Marginated cells generate large transient stress fluctuations on vessel walls, indicating a mechanism for the observed vascular inflammation.
Biochemically functionalized probes for cell-type–specific targeting and recording in the brain
Authors: Zhang Anqi , Zwang Theodore J. , Lieber Charles M.
Published: November 2023

Selective targeting and modulation of distinct cell types and neuron subtypes is central to understanding complex neural circuitry and could enable electronic treatments that target specific circuits while minimizing off-target effects. However, current brain-implantable electronics have not yet achieved cell-type specificity. We address this challenge by functionalizing flexible mesh electronic probes, which elicit minimal immune response, with antibodies or peptides to target specific cell markers. Histology studies reveal selective association of targeted neurons, astrocytes, and microglia with functionalized probe surfaces without accumulating off-target cells. In vivo chronic electrophysiology further yields recordings consistent with selective targeting of these cell types. Last, probes functionalized to target dopamine receptor 2 expressing neurons show the potential for neuron-subtype–specific targeting and electrophysiology.
Swarming magnetic nanorobots bio-interfaced by heparinoid-polymer brushes for in vivo safe synergistic thrombolysis
Authors: Yang Manyi , Zhang Yaoyu , Mou Fangzhi , Cao Chuan , Yu Lingxia , Li Zhi , Guan Jianguo
Published: November 2023

Biocompatible swarming magnetic nanorobots that work in blood vessels for safe and efficient targeted thrombolytic therapy in vivo are demonstrated. This is achieved by using magnetic beads elaborately grafted with heparinoid-polymer brushes (HPBs) upon the application of an alternating magnetic field
B
(
t
). Because of the dense surface charges bestowed by HPBs, the swarming nanorobots demonstrate reversible agglomeration-free reconfigurations, low hemolysis, anti-bioadhesion, and self-anticoagulation in high-ionic-strength blood environments. They are confirmed in vitro and in vivo to perform synergistic thrombolysis efficiently by “motile-targeting” drug delivery and mechanical destruction. Moreover, upon the completion of thrombolysis and removal of
B
(
t
), the nanorobots disassemble into dispersed particles in blood, allowing them to safely participate in circulation and be phagocytized by immune cells without apparent organ damage or inflammatory lesion. This work provides a rational multifaceted HPB biointerfacing design strategy for biomedical nanorobots and a general motile platform to deliver drugs for targeted therapies.
Life, the genome and everything
Authors: Rosenberg Susan M.
Published: November 2023

In this issue of the
Journal of Bacteriology
, N. J. Bonde, E. A. Wood, K. S. Myers, M. Place, J. L. Keck, and M. M. Cox (J Bacteriol 205:e00184-23, 2023,
https//doi.org/10.1128/jb.00184-23
) used an unbiased transposon-sequencing (Tn-seq) screen to identify proteins required for life when cells lose the RecG branched-DNA helicase (synthetic lethality). The proteins’ identities indicate pathways that prevent endogenous DNA damage, pathways that prevent its homology-directed repair (HDR) “strand-exchange” intermediates between sister chromosomes, and pathways that resolve those intermediates. All avoid intermediate pile-up, which blocks chromosome segregation, causing “death-by-recombination.” DNA damage is managed to regulate crucial but potentially lethal HDR.
The common origin and degenerative evolution of flagella in
Actinobacteria
Authors: Zhu Siqi , Sun Xian , Li Yuqian , Feng Xueyin , Gao Beile
Published: November 2023

Species of the phylum
Actinobacteria
have long time been thought mostly non-motile and non-flagellated, in spite of their extraordinary diversity in morphology, physiology, and ecology. It remains unclear how very few actinobacterial species acquired their flagellar genes and the role of flagellar motility in the evolution of different lineages within this large phylum. Here, we performed a comprehensive phylogenomic analysis of flagellar components in all actinobacterial species, including the deepest branches of this phylum identified recently. Our results provide robust evidence that all actinobacterial flagella shared a common origin and likely evolved from their last common flagellated ancestor by vertical inheritance. Later lineages underwent massive flagellar losses with the ecological switch from aquatic to terrestrial land or host-associated environments. In addition, the actinobacterial flagella also showed degenerative evolution in terms of their composition, leading to the simplest rod known so far. Furthermore, these evolutionary changes of flagella were accompanied by noteworthy variations in the chemosensory system and c-di-GMP mediated signaling network. Overall, we present here a detailed picture of flagellar evolution in
Actinobacteria
, which provides new insights into the evolution of major actinobacterial lineages and previously unobserved links between flagella and other biological features. The simplest flagellar rod as a product of degenerative evolution could possibly serve as a model for future nanomachine reconstruction in synthetic biology.

IMPORTANCE

Flagellar motility plays an important role in the environmental adaptation of bacteria and is found in more than 50% of known bacterial species. However, this important characteristic is sparsely distributed within members of the phylum
Actinobacteria
, which constitutes one of the largest bacterial groups. It is unclear why this important fitness organelle is absent in most actinobacterial species and the origin of flagellar genes in other species. Here, we present detailed analyses of the evolution of flagellar genes in
Actinobacteria
, in conjunction with the ecological distribution and cell biological features of major actinobacterial lineages, and the co-evolution of signal transduction systems. The results presented in addition to clarifying the puzzle of sporadic distribution of flagellar motility in
Actinobacteria
, also provide important insights into the evolution of major lineages within this phylum.
Draft genome sequence of
Lacticaseibacillus rhamnosus
CRL 2244, a strain with strong killing effect on carbapenem-resistant
Acinetobacter baumannii
Authors: Traglia German Matias , Rodriguez Cecilia , Leal Camila , Gasca Briea , Aziz Adiba , Lopez Christina , Petrelli Maria Lucia , Salzameda Nicholas T. , Bonomo Robert A. , Raya Raúl , Ramirez Maria Soledad
Published: November 2023

We report here a draft genome assembly of
Lacticaseibacillus rhamnosus
CRL 2244, recovered from wastewater in Argentina. The genome has a size of 2,898,100 bp, with G + C content of 46.73%. Comparative analysis reveals that its closest relative is
L. rhamnosus
1.0320 (GCF_006151905.1), with an average nucleotide identity of 97.46%.
Natural product biosynthetic potential reflects macroevolutionary diversification within a widely distributed bacterial taxon
Authors: Silva Sandra Godinho , Nabhan Homsi Masun , Keller-Costa Tina , Rocha Ulisses , Costa Rodrigo
Published: November 2023

Flavobacteriaceae
spp. are key players in global biogeochemical cycling and are known for their versatile carbohydrate and peptide catabolism. However, it is currently unknown whether secondary metabolism traits underlie their broad range of occurrence across the earth’s biomes. We examined 2,680 genomes to unveil an unprecedented phylogenetic signal dictating natural product biosynthesis diversification within the
Flavobacteriaceae
family. The distribution of secondary metabolite biosynthetic gene clusters (BGCs) across genomes usually follows macroevolutionary, genus-specific patterns. Noticeably, 88.6% of the observed BGCs were inferred to lead to the biosynthesis of likely novel natural products. We found an unanticipated, large diversity of taxon-specific BGCs encoding carotenoid and flexirubin pigments, the vast majority of which awaiting formal description. In particular,
Aquimarina
and
Kordia
spp. possessed large genomes, versatile catabolic traits, and a repertoire of BGCs possibly encoding drug-inspiring polyketides, non-ribosomal peptides, or post-translationally modified peptides. Using a machine learning approach (feature selection), we reveal that marine and non-marine
Flavobacteriaceae
genomes are differentially enriched in CAZymes and peptidases with distinct functionalities and molecular targets.

IMPORTANCE

This is the most comprehensive study performed thus far on the biosynthetic potential within the
Flavobacteriaceae
family. Our findings reveal intertwined taxonomic and natural product biosynthesis diversification within the family. We posit that the carbohydrate, peptide, and secondary metabolism triad synergistically shaped the evolution of this keystone bacterial taxon, acting as major forces underpinning the broad host range and opportunistic-to-pathogenic behavior encompassed by species in the family. This study further breaks new ground for future research on select
Flavobacteriaceae
spp. as reservoirs of novel drug leads.
TRAF3 gene regulates macrophage migration and activation by lung epithelial cells infected with
Aspergillus fumigatus
Authors: Shang Shumi , He Dan , Liu Cong , Bao Xinyuan , Han Shuaishuai , Wang Li
Published: November 2023

Aspergillus fumigatus
is an opportunistic pathogen that infects immunocompromised patients and imposes a heavy burden on global health. Searching for key genes in host resistance to
A. fumigatus
infection can help us understand the mechanisms of
A. fumigatus
-host interactions and provide new targets for the treatment of fungal infections. TRAF3 is one of the intracellular adapter proteins of the innate immune response that regulates signaling in various cellular processes, including host defense against pathogens. However, the defense mechanism of TRAF3 against
A. fumigatus
infection remains unknown. In this study, we found that TRAF3 overexpression led to the adhesion and internalization of more spores of
A. fumigatus
in lung epithelial cells and thus greater host immune surveillance evasion. Meanwhile, TRAF3 was able to regulate the expression of pro-inflammatory cytokines in lung epithelial cells infected with
A. fumigatus
through the negative regulation of NF-κB and MAPK signaling pathways. In this study, we also examined the effects of TRAF3 in the interaction between lung epithelial cells, macrophages, and
A. fumigatus
spores, and the results showed that TRAF3-overexpressing lung epithelial cells reduced the migration and activation of macrophages after
A. fumigatus
infection.
In vivo
experiments using TRAF3-overexpressing transgenic zebrafish larvae revealed that TRAF3 overexpression increased the fungal load and mortality of zebrafish infected with
A. fumigatus
. In conclusion, the TRAF3 gene can negatively regulate the resistance of lung epithelial cells to
A. fumigatus
, which plays an important role in the early infection processes of
A. fumigatus
.

IMPORTANCE

Aspergillus fumigatus
can infect immunocompromised individuals and cause chronic and fatal invasive fungal infections. A better understanding of the molecular mechanisms of
A. fumigatus
-host interactions may provide new references for disease treatment. In this study, we demonstrated that the TRAF3 gene plays an important role in the early infection of
A. fumigatus
by regulating the resistance of lung epithelial cells to
A. fumigatus
. Macrophages are the most abundant innate immune cells in the alveoli; however, few studies have reported on the interactions between lung epithelial cells and macrophages in response to
A. fumigatus
invasion. In our study, it was demonstrated that the TRAF3 gene reduces migration to macrophages and cytokine production by negatively regulating lung epithelial cell adhesion and internalization of
A. fumigatus
spores. Together, our results provide new insights into lung epithelial cell-macrophage interactions during
A. fumigatus
infection.
Marine snowstorm during the Permian–Triassic mass extinction
Authors: Grasby Stephen E. , Ardakani Omid H. , Liu Xiaojun , Bond David P.G. , Wignall Paul B. , Strachan Lorna J.
Published: November 2023

The Permian–Triassic mass extinction (PTME) interval is marked by major excursions in both inorganic and organic carbon (C) isotopes. Carbon cycle models predict that these trends were driven by large increases in productivity, yet organic C–rich rocks are not recorded in most PTME shelf sedimentary successions. Anomalous C-rich facies have been reported from rare abyssal plains records now exposed in Japan and New Zealand, where black shales at the PTME are extraordinarily organic-rich units. We examined organic matter at the Waiheke, New Zealand, section, and results show that these deposits are dominated by lamalginites composed of unicellar solitary or colonial phytoplankton produced during algal blooms that falls as “marine snow.” We modeled the impact of ash fall from eruptions in the Siberian Traps large igneous province and argue that they fertilized the Panthalassa Ocean with P and Fe, leading to a marine “snowstorm” and significant C drawdown marking this major biobloom during the PTME.
A Bare and Gravitationally Dressed Electron Formed from Kerr–Newman Black Hole
Authors: Burinskii A.
Published: November 2023

The Kerr–Newman (KN) electron model, based on the classical KN black hole solution, is modified by adding a “mirror” sheet of KN metric corresponding to a positron, that creates a heavy electron-positron vacuum core dressed by gravity, and allows us to consider the bare and dressed electron separately. The bare electron is formed as a massless relativistic ring string and is responsible for the wave properties of the electron, while the heavy supersymmetric vacuum core receives the additional mass-energy from two Wilson loops dragged by the KN gravitational field, thus creating a magnetically coupled monopole-antimonopole pair. As a result, the KN electron becomes consistent with wave nature of quantum electron and its gravitational interaction increases dramatically from Planck to Compton scale.
Safeguarding essentials in modern-day paediatrics: inflicted injuries, body maps and section 47 investigations
Authors: Thomas Helen , Cromb Daniel , Alcock Anastasia , Jacob Hannah
Published: November 2023

The second case in the Safeguarding Essentials in Modern-day Paediatrics series, this article focuses on inflicted injuries, body maps and child protection investigations (CPIs). Using the scenario of a 6-year-old presenting to the emergency department having ‘fallen off a swing’, this article focuses on key considerations for history taking and examination in cases where you suspect injuries may have been inflicted, and how to discuss raising these suspicions with the family, as well as the importance of accurate body map completion. Also covered are CPIs, giving consideration to the legal framework surrounding these, and relevant useful resources and guidance are provided for dealing with the challenging circumstances that arise when physical abuse is first suspected.