Breakdown Effects Research Articles

Contribution to the Microstructural Study of a Composite Material Based on Carbon Fibers for Use in Orthopedic Prostheses

The use of a carbon fiber composite material to make external prostheses in the form of a femoral socket was the subject of this laboratory study. According to the prior bibliographical studies, this material adapts well to this type of prosthesis. The objective of this research is to study its microscopic structure, in order to verify the good wetting of the fibers by the resin, the good cohesion and molding by infusion. The morphological study of the facies of the parallelepiped-shaped specimens was carried out after cuts perpendicular to the axis of the fiber strands, parallel according to the width and thickness of the specimen. This study was carried out using a scanning electron microscope (SEM), in order to determine, thanks to the typical microstructure of the composite, the various degradations, which appear as a result of the effect of static tension. The laminate used is based on three layers of carbon taffeta fabric and an orthocrylic resin. Tensile tests have been carried out at a speed of 1mm/min with a Zwick/Roell machine with a load cell of 50 kN. This speed was chosen to allow a comparative study with glass fiber specimens, which have been used previously for the production of prostheses, before those made of carbon. The microscopic study allowed to identify the four types of degradation; Matrix fracture, which manifested itself as fault lines, in preferred directions of different sizes. This contributed to interlaminar delamination. The decohesion that contributes to delamination in a different way from that of matrix breakage is visible at different levels. Interlaminar delamination results from the combined effect of matrix breakdown and decohesion and manifests itself as uneven strata. Fiber breakage was manifested by shearing. This study allowed to observing a degradation of the material imposed by static traction. As for the material used in orthopaedics, it has retained good cohesion and meets the requirements of prostheses, despite the defects detected by the microscopic study.

High sensitive room temperature NO2 gas sensor based on the avalanche breakdown induced by Schottky junction in TiO2-Sn3O4 nanoheterojunctions

A novel sensor based on Schottky junction inducing avalanche breakdown effect in TiO 2 -Sn 3 O 4 nanoheterojunctions is assembled. High sensitivity for NO 2 gas sensing is demonstrated at room temperature. TiO 2 -Sn 3 O 4 nanocompositewas synthesized as the gas sensing layer and Schottky contact was formed by Au electrodes. The Schottky contact functions as a “gate” which can trigger the avalanche breakdown effect in the TiO 2 -Sn 3 O 4 heterojunctions. By tuning the Schottky barrier height through the responsive variation of the surface chemisorbed gas and the bias on the device, NO 2 at a concentration from 5 to 50 ppm can be detected with an average response time of 8 s at room temperature. This nanostructured device is a promising candidate for application in high-sensitivity and high-speed NO 2 gas sensor. The methodology and working principle illustrated in this paper present a new sensing mechanism that can be readily and extensively applied to other gas sensing systems. • TiO 2 -Sn 3 O 4 heterostructure was designed and synthesized in order to detect NO 2 gas in room temperature. • Avalanche breakdown effect was used to obtain 900% responsivity when exposed to 50 ppm NO 2 at room temperature. • High sensitivity and excellent selectivity to NO 2 is obtained at room temperature.

Decoupling Contact and Rotary Triboelectrification vs Materials Property: Toward Understanding the Origin of Direct-Current Generation in TENG.

Direct-current (DC) triboelectric nanogenerators (TENGs) are increasingly recognized as next-generation power sources for widespread applications. Research has recently focused on developing novel materials as active layers for DC TENGs and device configurations to elucidate the working mechanisms. In this work, we report the use of a carbyne (dehydrohalogenated poly(vinylidene fluoride) (PVDF)) film as a positive-type friction layer for DC TENGs for efficient harvesting of rotary energy. The fabricated carbyne-based rotary TENG generates an output voltage (120 V) with excellent mechanical stability and peak power density (500 μW m-2). The mechanism of DC output generation from the carbyne-based rotary TENG is explained based on halogen removal from PVDF and the electrostatic breakdown effect. Additionally, the humidity effects on the fabricated carbyne-based rotary TENG toward a self-powered humidity sensor are studied in detail with the aid of in situ Raman analysis, Fourier transform infrared spectroscopy, and open-circuit potential measurements. Together, our experimental results demonstrate that using carbyne as an active triboelectric layer for DC TENGs would greatly benefit the next generation of power devices.

Synergistic degradation of methylene blue by laser cavitation and activated carbon fiber

Methylene blue is widely used, but highly toxic and difficult to be degraded. In this paper, a new method of synergistic degradation of methylene blue by laser cavitation and activated carbon fiber is proposed. This paper theoretically studies the synergistic degradation effect, including radical oxidation effect, shock wave breakdown effect and activated carbon fiber surface adsorption effect. The deep degradation of methylene blue was studied experimentally, and the key influencing factors were analyzed. The results show that: the reason why methylene blue can be degraded is because of the oxidation effect of hydroxyl radicals, thermal decomposition and adsorption of molecules on the surface of carbon fibers. The main factors affecting the degradation rate of methylene blue solution are laser energy and initial concentration of solution. The degradation rate increased by 37.4% with the increase of laser energy (12–48 mJ) and decreased by 2.6% with the increase of initial concentration (0.01–0.05 mg/ml). The maximum degradation rate (93%) of methylene blue solution was reached at 48 mJ and 0.01 mg/ml for 30 min. Compared with the traditional adsorption degradation of carbon fibers, the degradation rate of the synergistic degradation of methylene blue solution by laser cavitation and activated carbon fibers can be increased by about 80% in a short time (30 min).

Improving and Quantifying Surface Charge Density via Charge Injection Enabled by Air Breakdown

AbstractThe modification of triboelectric materials is an important means to improve the output performance of triboelectric nanogenerator (TENG), and the surface charge or ion implantation is an effective way among many modification methods. However, the output enhancement via optimizing triboelectric materials is still limited. Herein, a fast surface charge injection technique based on air breakdown effect is reported, which utilizes an excitation circuit to realize the directional accumulation of charge. Consequently, the output charge density of the Polyimide (PI) film after charge injection reaches 880 µC m‐2, which is the highest of the series of modified triboelectric materials. Moreover, a novel charge transfer mechanism with electrostatic induction competition is proposed, in which significant difference between surface charge density and output charge density is highlighted clearly. Meanwhile, the method of quantifying surface charge density is further given. This work provides a more effective method for the modification of dielectric materials and also offers an important insight towards the charge transfer mechanism in TENG.

SBS-PCM characteristic of sub-nanosecond laser based on rotating wedge

One major setback in the applications of high-power solid-state lasers in areas like high energy density physics is the beam quality that deteriorates with increasing pump power. To solve this problem, we proposed to develop a high beam quality and stable stimulated Brillouin scattering phase conjugation mirror (SBS-PCM) using a filtration approach and a carefully designed geometry that includes a rotating wedge to operate under a high repetition rate laser. Upon reducing the micro-impurities to 100 nm, the accumulated heat at the focus reduced greatly, resulting in improved beam quality and better phase fidelity. At 6.5 mJ input energy and below 100 Hz repetition rates, there is no observable optical breakdown or obvious thermal effects as opposed to the unfiltered medium that experience optical breakdown at 0.5 mJ and 50 Hz repetition rate. The simulated temperature gradient at the focus shows that the material absorbed the laser within a short distance from the irradiation side, and the temperature probe reveals that the temperature increases with pumping power and time due to heat accumulation at the focus. To disperse the heat accumulation through a large area within the SBS cell, we design and introduce a rotating wedge. The impact of the rotating wedge was much more noticeable when the system works at higher pump power.

Anomalous thermoelectric effects and quantum oscillations in the kagome metal CsV3Sb5

The kagome metal compounds $A{\mathrm{V}}_{3}{\mathrm{Sb}}_{5}$ ($A=\text{K}$, Rb, and Cs) feature a wealth of phenomena including nontrivial band topology, charge density wave (CDW), and superconductivity. One intriguing property is the time-reversal symmetry breaking in the CDW state without local moments, which leads to anomalous transport responses. Here, we report the investigation of magnetothermoelectric effects on high-quality ${\mathrm{CsV}}_{3}{\mathrm{Sb}}_{5}$ single crystals. A large anomalous Nernst effect (ANE) is observed at temperatures below 30 K and can be enhanced by the high mobility. Multiple Fermi surfaces with small effective masses are revealed by quantum oscillations in the Nernst and Seebeck signals. Furthermore, we discover a magnetic breakdown effect across the two smallest Fermi surfaces, with a gap around 20 meV between them. We propose that the two Fermi surfaces are split from a Dirac band by the CDW gap. These results indicate the large ANE originates from the CDW modulated nontrivial band structure as well as the extrinsic contributions. A second phase transition below the CDW transition temperature is also suggested by the strange temperature dependence of the ANE.

Demonstration of Picosecond 4H-SiC Diode Avalanche Shaper With Voltage Rise Rate of 11.14 kV/ns and Peak Power Density of 62 MW/cm$^2$

In this letter, for the first time, a high-performance picosecond 4H-SiC diode avalanche shaper (DAS) with a novel <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">${p^+/p^-/n^+}$</tex-math></inline-formula> multilayer epitaxial structure is experimentally demonstrated and characterized. For fabrication of our 4H-SiC DAS, the multilayer epitaxial stacks have been designed in detail and grown using continuous multilayer epitaxial wafer growth. To excite the delayed avalanche breakdown (DAB) effect, the electric field profile in multilayer epitaxial stacks has been numerically simulated in detail to suppress the surface electric field crowding and premature breakdown during the overvoltage pulse applied. A 2.5-kV, 1-ns pulsed power generator is adopted to drive our fabricated SiC DAS, the output on a 50 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\Omega$</tex-math></inline-formula> load is 1860 V, 100 ps, lead a voltage rise rate of 11.14 kV/ns, and a peak power density of 62 MW/cm <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$^2$</tex-math></inline-formula> . Furthermore, the fabricated SiC DAS operates stably in multipulse mode at 1 MHz. To the best of our knowledge, this is the first experimental result reported for picosecond DAS based on the 4H-SiC. This article is significant for developing 4H-SiC-based ultrafast closing switches.

Indoor air dust removal system based on high-voltage direct current triboelectric nanogenerator

Indoor air pollution has become the "invisible killer" of human health, which may cause respiratory diseases, chronic lung diseases, bronchitis, lung cancer, and other diseases. Here, we propose and demonstrate an indoor dust removal system that utilizes high-voltage electrostatic adsorption without assistance of any air filter material. The triboelectric nanogenerator (TENG) is based on contact electrification and air breakdown effects, with a maximum output open-circuit voltage (Voc) of 27 kV. This indoor dust removal system consists of a rotation mode high voltage TENG with direct current (RH-DC-TENG) and dedusting glass (DG), which can achieve rapid reduction of PM2.5 from 954 μg/m3 to 50 μg/m3 in an 8000 cm3 air chamber in 199 s under TENG rotation speed of 120 rpm. This indoor dust removal system is concise, safe, and effective, providing a potential self-driven and sustainable avenue to contributing to a cleaner indoor air environment and improving human health.

‘‘Kai Chaand Thay Sar e Aasman’’ :The Narration Of The Dilapidation Of Civilization

Shams ur Rahman Farooqi is an Indian poet and one of the leading Urdu critics and theorists. He is regarded as the T.S. Eliot of Urdu criticism and has formulated fresh models of literary appreciation. Farooqi’s novel is a true character sketch of Urdu-Persian poetry and Indo-Islamic culture. Although the novel has extraordinary qualities and is its own example, but the history and civilization of the age which it is talking about, is now ours. Is of no particular importance. Also, the language used in this novel is no longer commonplace, so it will be largely difficult and incomprehensible. One can clearly see the effects of this cultural breakdown mentioned earlier. And what has been said about language is that of the easy going temperament of our time. In addition to gender differences, it also interferes with the fact that the character that the author has established in the middle of the novel, contrary to the myths, is not the character of a famous and great classical poet. Rather, he is a person of our cultural history who is known to the world as Wazir Khanum alias Chhoti Begum. She has the honor of being the mother of Wazir Khanum Nawab Mirza Dag Dehlavi. As far as the fame and popularity of Dagh Dehlavi is concerned, if you look at it, Wazir Khanum will be called an anonymous woman. This is also a fact because our literary history about Wazir Khanum has been generally silent. Now, in this novel, the way in which the main character is presented and the details of facts and events that have been narrated, even if they are not fully historically confirmed, but they tell a lot about the life and personality of Wazir Khanum. Something can be guessed. At the same time in the light of the personality of Wazir Khanum of this eraIf a list of the best Urdu novels is compiled, Shams-ur-Rehman Farooqi's "Kai Chand The Sar Aasman" will surely be counted among the first ten novels

Triglyceride breakdown from lipid droplets regulates the inflammatory response in macrophages

In response to inflammatory activation by pathogens, macrophages accumulate triglycerides in intracellular lipid droplets. The mechanisms underlying triglyceride accumulation and its exact role in the inflammatory response of macrophages are not fully understood. Here, we aim to further elucidate the mechanism and function of triglyceride accumulation in the inflammatory response of activated macrophages. Lipopolysaccharide (LPS)-mediated activation markedly increased triglyceride accumulation in macrophages. This increase could be attributed to up-regulation of the hypoxia-inducible lipid droplet–associated (HILPDA) protein, which down-regulated adipose triglyceride lipase (ATGL) protein levels, in turn leading to decreased ATGL-mediated triglyceride hydrolysis. The reduction in ATGL-mediated lipolysis attenuated the inflammatory response in macrophages after ex vivo and in vitro activation, and was accompanied by decreased production of prostaglandin-E2 (PGE2) and interleukin-6 (IL-6). Overall, we provide evidence that LPS-mediated activation of macrophages suppresses lipolysis via induction of HILPDA, thereby reducing the availability of proinflammatory lipid precursors and suppressing the production of PGE2 and IL-6.

Smart Textile Triboelectric Nanogenerators: Prospective Strategies for Improving Electricity Output Performance

By seamlessly integrating the wearing comfortability of textiles with the biomechanical energy harvesting function of a triboelectric nanogenerator (TENG), an emerging and advanced intelligent textile, i.e., smart textile TENG, is developed with remarkable abilities of autonomous power supply and self-powered sensing, which has great development prospects in the next-generation human-oriented wearable electronics. However, due to inadequate interface contact, insufficient electrification of materials, unavoidable air breakdown effect, output capacitance feature, and special textile structure, there are still several bottlenecks in the road towards the practical application of textile TENGs, including low output, high impedance, low integration, poor working durability, and so on. In this review, on the basis of mastering the existing theory of electricity generation mechanism of TENGs, some prospective strategies for improving the mechanical-to-electrical conversion performance of textile TENGs are systematically summarized and comprehensively discussed, including surface/interface physical treatments, atomic-scale chemical modification, structural optimization design, work environmental control, and integrated energy management. The advantages and disadvantages of each approach in output enhancement are further compared at the end of this review. It is hoped that this review can not only provide useful guidance for the research of textile TENGs to select optimization methods but also accelerate their large-scale practical process.

On the Effect of Dielectric Breakdown in UD CFRPs Subjected to Lightning Strike Using an Experimentally Validated Model

To meet worldwide increases in energy demands Wind Turbine (WT) manufacturers are producing turbines with longer blades to generate more electrical energy. To lightweight these blades, Carbon Fibre Reinforced Polymers (CFRP) have been introduced in load carrying structures such as the WT blade sparcaps. The introduction of CFRPs presents new challenges in integrating protection from lightning strikes. The semi-conductive nature of CFRPs adds an additional electrical path to ground, and the anisotropic nature of the material properties, in particular the thermal and electrical conductivities, creates large amounts of resistive heating. The aim of this paper is to develop and validate a modelling approach to predict lightning damage in unidirectional (UD) CFRP materials. The proposed model uses an approximate approach that includes the electric field dependency to simulate dielectric breakdown. The model predictions are validated against experimental data and observations obtained from simulated direct lightning strike tests conducted on UD CFRP laminates. A comparison between the experimental results and the proposed model shows good ability to accurately predict the shape, volume, and depth of the inflicted damage. Furthermore, the proposed model is benchmarked against conventional damage models reported in literature, and a clear improvement of the predictive capability is demonstrated, especially with respect to the predicted depth of damage.

A Scalable Model for Snapback Characteristics of Circuit-Level ESD Simulation

It is challenging to simulate the snapback behaviors under electrostatic discharge (ESD) stresses due to the limitation of simulation program with integrated circuit emphasis (SPICE) simulation tools. In this paper, a new model is proposed to investigate the avalanche breakdown effect using the voltage-controlled current source (VCCS), which greatly facilitates the calculation of the avalanche multiplication factor M and improves the convergence characteristics. In particular, this new method transfers the exponential relationship of M into the linear relationship of the VCCS gain. The versatility of the model is validated by its operations in various ESD protection circuits with MOS as the discharge device, while the scalability is demonstrated by its applications in varied device sizes.

Joint determination of purchasing and production lot sizes in an unreliable production system

This paper discusses a production-inventory system under random machine breakdown. Holding safety stock is the common way to mitigate the effect of random machine breakdown on shortages that may occur during machine repair time. Since holding safety stock can be costly, especially for expensive products, this paper investigates an alternative strategy in which it is assumed that the production manager can purchase the same products from a supplier in order to meet the demands that may be lost due to the depletion of the inventory after the machine breakdown. The supplier has known lead-time and reliability with the quality assured products. Despite holding safety stock, purchasing occurs only when the machine breakdown happens. The question is about the optimal amount of production and purchasing lot sizes to minimize the total expected costs. The optimality of the model is investigated when failure and repair time follow an exponential distribution, and a computational algorithm for finding the optimal lot sizes is presented. A comparison between the purchasing strategy and holding safety stock is performed through a sensitivity analysis regarding some effective parameters. This study shows using the purchasing strategy when holding or production cost rises is more beneficial than holding safety stock.

Correlation Between Insulation Resistance and Temperature Measurement Error in Type K and Type N Mineral Insulated, Metal Sheathed Thermocouples

Mineral insulated, metal sheathed (MI) Type K and Type N thermocouples are widely used in industry for process monitoring and control. One factor that limits their accuracy is the dramatic decrease in the insulation resistance at temperatures above about 600 °C which results in temperature measurement errors due to electrical shunting. In this work the insulation resistance of a cohort of representative MI thermocouples was characterised at temperatures up to 1160 °C, with simultaneous measurements of the error in indicated temperature by in situ comparison with a reference Type R thermocouple. Intriguingly, there appears to be a systematic relationship between the insulation resistance and the error in the indicated temperature. At a given temperature, as the insulation resistance decreases, there is a corresponding increasingly negative error in the temperature measurement. Although the measurements have a relatively large uncertainty (up to about 1 °C in temperature error and up to about 10 % in insulation resistance measurement), the trend is apparent at all temperatures above 600 °C, which suggests that it is real. Furthermore, the correlation disappears at temperatures below about 600 °C, which is consistent with the well-established diminution of insulation resistance breakdown effects below that temperature. This raises the intriguing possibility of using the as-new MI thermocouple calibration as an indicator of insulation resistance breakdown: large deviations of the electromotive force (emf) in the negative direction could indicate a correspondingly low insulation resistance.

Foxp3+ CD4+ regulatory T cells control dendritic cells in inducing antigen-specific immunity to emerging SARS-CoV-2 antigens.

Regulatory T (Treg) cells, which constitute about 5–10% of CD4+T cells expressing Foxp3 transcription factor and CD25(IL-2 receptor α chain), are key regulators in controlling immunological self-tolerance and various immune responses. However, how Treg cells control antigen-specific immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. In this study, we examined the effect of transient breakdown of the immunological tolerance induced by Treg-cell depletion on adaptive immune responses against administered SARS-CoV-2 antigen, spike protein 1 (S1). Notably, without the use of adjuvants, transient Treg-cell depletion in mice induced anti-S1 antibodies that neutralized authentic SARS-CoV-2, follicular helper T cell formation and S1-binding germinal center B cell responses, but prevented the onset of developing autoimmune diseases. To further clarify the mechanisms, we investigated maturation of dendritic cells (DCs), which is essential to initiate antigen-specific immunity. We found that the transient Treg-cell depletion resulted in maturation of both migratory and resident DCs in draining lymph nodes that captured S1-antigen. Moreover, we observed S1-specific CD4+ T cells and CD8+ T cells with interferon-γ production. Thus, captured S1 was successfully presented by DCs, including cross-presentation to CD8+ T cells. These data indicate that transient Treg-cell depletion in the absence of adjuvants induces maturation of antigen-presenting DCs and succeeds in generating antigen-specific humoral and cellular immunity against emerging SARS-CoV-2 antigens. Finally, we showed that SARS-CoV-2 antigen-specific immune responses induced by transient Treg-cell depletion in the absence of adjuvants were compatible with those induced with an effective adjuvant, polyriboinosinic:polyribocytidyl acid (poly IC) and that the combination of transient Treg-cell depletion with poly IC induced potent responses. These findings highlight the capacity for manipulating Treg cells to induce protective adaptive immunity to SARS-CoV-2 with activating antigen-presenting DCs, which may improve the efficacy of ongoing vaccine therapies and help enhance responses to emerging SARS-CoV-2 variants.

Boron release and transfer induced by phengite breakdown in subducted impure metacarbonates

White mica is an important reservoir of boron (B) in subducted metasedimentary rocks. To quantify the effect of phengite breakdown on B release and transfer, we investigated the replacement processes of phengitic mica and associated element redistribution in exhumed ultra-high pressure (UHP) impure marbles from the Dabie terrane, China. Three types of microstructures, which are related to the liberation, transport, and precipitation of B, are recognized: (1) Type-I is the pseudomorphic replacement of phengite by the assemblage of biotite + plagioclase ± quartz ± epidote. The assemblage maintains a flaky shape of pre-existing phengite, which only rarely occurs as a relict phase in the product assemblages. Phase equilibria modelling indicates that the conditions of replacement reactions are 1.2–1.3 GPa at ~600 °C, with a relatively low XCO2 of 0.04–0.16. (2) Type-II is characterized by the local occurrence of fine-grained tourmaline (Tur-F) along the outer margin of Type-I texture domains, which represents the in situ precipitation of B released by the replacement reactions. (3) Type-III texture involves the irregularly shaped intergrowth of tourmaline (Tur-In) + quartz in the calcite matrix, isolated from the Type-I and Type-II texture domains. The Type-III minerals are in equilibrium with diopside and plagioclase and most likely represent the precipitation from a “transported”, B-bearing fluid.Mineral trace element analyses indicate that relict phengite in Type-I texture has significantly higher B contents (284–464 μg/g) than all of the product minerals (2–26 μg/g). A mass balance estimate indicates that the majority (>90%) of B in the reactants is lost during the process of phengite replacement. The calculations in terms of mineral-fluid partition indicate that the fluid involved in the replacement reactions has B contents of 1893–6858 μg/g. In situ B isotopic analyses indicate that Tur-F and Tur-In have a similar variation range of δ11B (+4 ~ +7‰). Both types of low-pressure tourmaline have lower δ11B values than the previously reported eclogite-facies tourmaline (reaching +15‰) from phengite-bearing marbles in the same study area. This result indicates two episodes of tourmaline growth and B transfer. Thus, a two-stage model of B loss from phengite during slab exhumation is proposed. Our results reveal that the breakdown of white mica in exhumed metasedimentary rocks can cause a strong release of B, which would largely influence the B budget at convergent plate margins.

Transient physical modeling and comprehensive optimal design of air-breakdown direct-current triboelectric nanogenerators

Direct-Current Triboelectric Nanogenerators (DC-TENGs) achieves an direct-current (DC) output instead of traditional alternating-current (AC) output of TENG. Among the various structure designs of DC-TENGs, the air-breakdown DC-TENG has created a record of energy density and an almost constant-current output, which has great potential in practical applications. This paper proposes a transient physical-field model and carries out comprehensive optimal design for air-breakdown DC-TENG. The beneficial breakdown domain (BBD) and harmful breakdown domain (HBD) are introduced to reveal the dynamic mechanism that distinguishes the DC-TENGs from AC-TENGs. Indexes of the breakdown charge ratio (BCR) and leading charge density (LCD) are defined to evaluate the extent to which the high-density surface charge is effectively exploited in electricity generation based on the beneficial breakdown effect. The output characteristics of air-breakdown DC-TENGs are theoretically analyzed, revealing the influence of the load resistance, device structure parameters, and initial charge density. Therefore, the optimal design of air-breakdown DC-TENGs is carried out with a high output power and low matching resistance. Finally, these superior performances are verified by experiments, so that the proposed transient physical model and comprehensive optimization method can be reliably extended to the design of all types of air-breakdown DC-TENG, and promote its application in a wide range of fields.

Effects of Alvelestat, an Oral Neutrophil Elastase Inhibitor, on Elevated Elastase and Collagen Turnover Biomarkers in Patients with Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation

IntroductionBronchiolitis Obliterans Syndrome (BOS) is a rare but devastating complication of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) and is associated with a high morbidity and mortality. There is a dearth of treatment options for BOS and new strategies are needed. Airway neutrophilia is a hallmark of BOS, even in the absence of infection, and neutrophil elastase (NE) is an enzyme that has been implicated in the pathogenesis of BOS. We are conducting a phase 1b study of an oral NE inhibitor, alvelestat, in patients with BOS after HCT . Biomarkers, including the elastin breakdown peptides desmosine/isodesmosine (DES/IDES), and stimulated neutrophil elastase assess direct effect on NE activity. Neo-epitope by-products of collagen type 3 and 6 synthesis (PRO-C3 and PRO-C6) and degradation (C3M and C6M) are measured as biomarkers of fibrosis/tissue modellingMethodsPatients age ≥18 years with BOS and chronic GVHD after HCT were recruited to the National Cancer Institute protocol (NCT02669251). This phase 1 study had 2 parts: 8-week intra-patient dose escalation period, followed by a continuation period that allowed for up to 6 months of treatment. Alvelestat was given orally starting at 60mg twice daily, increased every 2 weeks to 120mg twice daily, 180mg twice daily, and finally 240mg twice daily. Peripheral blood samples were collected at baseline and at the end of each dose-escalation stage.Plasma DES/IDES was measured by isotopic dilution liquid chromatography-tandem mass spectrometry (Huang et al Thorax 2012;67:502-508). Ex vivo zymosan stimulated neutrophil elastase activity was measured by ProteaseTag® immunoassay (ProAxsis Ltd, Northern Ireland). PRO-C3, PRO-C6, C3M and C6M were measured by competitive ELISA. (Nordic Biosciences, Denmark). Results are presented as Mean and Standard Error Mean (SEM).ResultsBetween 2016 and 2018, 7 patients were enrolled (3 men and 4 women). Median FEV 1 after bronchodilator at time of enrollment was 44% predicted (range 38-74). All 7 patients were able to tolerate dose escalation of alvelestat up to the maximum dose 240mg twice daily. Preliminary clinical results were previously presented.DES/IDES was elevated at baseline (mean 0.464 (SEM 0.0508) ng/ml, with 6 of 7 subjects above the Upper Limit of Normal (ULN, 0.280 ng/ml)). Levels progressively declined during the dose escalation period to 0.380 (SEM 0.0419) ng/ml by week 8, representing a mean within subject % change from baseline (CFB) of -16.2% (SEM 6.794, Figure 1a)Ex vivo zymosan stimulated elastase activity also showed progressive decrease over the dose escalation period, with some subjects demonstrating 100% suppression (Figure 1b).Collagen synthesis as measured by PRO-C3 and PRO-C6 was increased above ULN at baseline and declined with alvelestat treatment (Figure 1c and 1d). There was no consistent change in collagen degradation biomarkers (C3M, C6M)There was consistency of a suppressive effect on biomarkers of elastase activity and collagen turnover in 6 of 7 treated patients, all of whom had improved or stable lung disease (ranging from change in FEV1 % predicted at end of treatment from +9% to -6%).ConclusionNE can damage lung tissue due to elastin breakdown, pro-inflammatory and pro-fibrotic effects (Sallenave J-M, J Leuk Biol 2015;98:137-139). This is the first evidence of elevated elastase activity as detected by elastin breakdown in patients with BOS and chronic GVHD.Treatment with the selective NE inhibitor, alvelestat was associated with progressive reduction of plasma desmosine levels over 8 weeks of within-subject dose escalation and reduction stimulated neutrophil elastase activity.The consistent suppression of elastase and of collagen synthesis/turnover biomarkers following alvelestat treatment is encouraging for its potential to impact progressive lung fibrosis in BOS and chronic GVHD. DisclosuresParkin: Mereo BioPharma Group: Current Employment. Moore: Mereo BioPharma Group: Current Employment. Pavletic: Center for Cancer Research: Research Funding; National Cancer Institute: Research Funding; National Institutes of Health: Research Funding; Celgene: Research Funding; Actelion: Research Funding; Eli Lilly: Research Funding; Pharmacyclics: Research Funding; Kadmon: Research Funding.