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EXTH-13. COMBINED ANTI-ANGIOGENIC TREATMENT TO INCREASE INTRATUMORAL PERSISTENCE OF CAR T-CELLS IN LUNG CANCER BRAIN METASTASES

Abstract BACKGROUND Metastatic lung cancer, especially when it spreads to the brain, shows a devastating prognosis. Immunotherapeutic approaches including CAR T-cells show promise in hematologic malignancies. However, the presence of immunosuppressive factors within the tumor microenvironment and physical barriers like elevated interstitial pressure due to dysfunctional tumor vessels are one of the main obstacles especially in solid tumors. Evaluation of the potential synergy between anti-angiogenetic drugs and CAR T-cells in this context are an ongoing investigation. METHODS Here, we set up an immunocompetent syngeneic orthotopic cerebral metastasis model in mice by combining a chronic cranial window with repetitive intracerebral two-photon laser scanning microscopy (TPLSM). This model allows in vivo characterization of fluorescent tumor cells and CAR T-cells on a single cell level over time. Intraparenchymal injection of red fluorescent EpCAM-transduced Lewis Lung carcinoma cells (EpCAM/tdtLL/2 cells) followed by injection of EpCAM-directed or undirected CAR T-cells into the adjacent brain tissue was performed. Additionally, aVEGF-A combined with aVEGF-R2 and the respective isotype control were injected intraperitoneally. RESULTS Compared to undirected CAR T-cells, mice receiving EpCAM-directed CAR T-cells showed higher intratumoral CAR T-cell densities after intraparenchymal injection. This finding was accompanied with reduced tumor growth and eventually translates into a survival benefit. However, intratumoral CAR T-cell numbers diminish over time indicating insufficient persistence inside of the tumor microenvironment. Additional anti-VEGF-A/VEGF-R2 treatment results in reduced tumor growth after EpCAM/GFPCAR T-cell and GFPT-cell treatment, respectively. Interestingly, in vivo imaging reveals higher intratumoral CAR T-cell numbers after anti-angiogenic treatment compared to isotype controls pointing towards enhanced CAR T-cell persistence resulting in a survival benefit. CONCLUSION Collectively, our findings indicate that locally injected CAR T-cells may safely induce relevant anti-tumor effects in brain metastases from lung cancer. Additional anti-angiogenic treatment provides a mechanism to enhance intratumoral CAR T-cell persistence and reduce tumor growth.

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  • Neuro-Oncology
  • Nov 11, 2024
  • Jens Blobner + 15
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PD-1 blockade does not improve efficacy of EpCAM-directed CAR T-cell in lung cancer brain metastasis

BackgroundLung cancer brain metastasis has a devastating prognosis, necessitating innovative treatment strategies. While chimeric antigen receptor (CAR) T-cell show promise in hematologic malignancies, their efficacy in solid tumors, including brain metastasis, is limited by the immunosuppressive tumor environment. The PD-L1/PD-1 pathway inhibits CAR T-cell activity in the tumor microenvironment, presenting a potential target to enhance therapeutic efficacy. This study aims to evaluate the impact of anti-PD-1 antibodies on CAR T-cell in treating lung cancer brain metastasis.MethodsWe utilized a murine immunocompetent, syngeneic orthotopic cerebral metastasis model for repetitive intracerebral two-photon laser scanning microscopy, enabling in vivo characterization of red fluorescent tumor cells and CAR T-cell at a single-cell level over time. Red fluorescent EpCAM-transduced Lewis lung carcinoma cells (EpCAM/tdtLL/2 cells) were implanted intracranially. Following the formation of brain metastasis, EpCAM-directed CAR T-cell were injected into adjacent brain tissue, and animals received either anti-PD-1 or an isotype control.ResultsCompared to controls receiving T-cell lacking a CAR, mice receiving EpCAM-directed CAR T-cell showed higher intratumoral CAR T-cell densities in the beginning after intraparenchymal injection. This finding was accompanied with reduced tumor growth and translated into a survival benefit. Additional anti-PD-1 treatment, however, did not affect intratumoral CAR T-cell persistence nor tumor growth and thereby did not provide an additional therapeutic effect.ConclusionCAR T-cell therapy for brain malignancies appears promising. However, additional anti-PD-1 treatment did not enhance intratumoral CAR T-cell persistence or effector function, highlighting the need for novel strategies to improve CAR T-cell therapy in solid tumors.

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  • Cancer Immunology, Immunotherapy
  • Oct 3, 2024
  • Jens Blobner + 19
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Numerical simulation of heat transfer properties of skin tissue acted on repetitive laser irradiation

Pulsed laser has been widely used in the clinical treatment of various diseases and injuries due to its unique advantages in the process of interaction with skin tissue. In order to ensure the therapeutic effect and patient safety, it is necessary to accurately monitor the time-space response of the whole-field temperature of the target tissue irradiated by pulsed laser. A research strategy to explore the thermal response and incidental thermal damage of skin tissue induced by repeated pulses laser has been proposed in present work. A theoretical model involved variable physical properties was first proposed, in which the dual-phase lag (DPL) equation and Henrique burn equation were employed to evaluate the tissue temperature and thermal damage induced by repeated pulse laser irradiation. With the help of finite difference method, the governing equation with variable physical properties was then numerical solved to obtain the time-space distribution of tissue temperature, and the evolution process of the thermal damage was further calculated. The effects of laser input parameters and variable physical parameters on the laser penetration depth, temperature distribution and burn degree of the irradiated tissue were analyzed.

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  • International Communications in Heat and Mass Transfer
  • Sep 17, 2024
  • Yongjian Zhang + 4
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Impact of laser interaction on morphological and mechanical properties of palladium thin film

This research work investigates surface morphology, plasma plume intensity and the hardness of palladium thin film deposited on silicon substrates under the action of laser light. For this purpose, a pulsed Nd:YAG laser (1064 nm, 10 mJ, 12 ns) was used to irradiate the specimen with repetitive laser pulses. The experiment was repeated under the illumination with UV light. The surface morphology of the specimens was examined through an Optical and Field-Emission Scanning Electron Microscopy showing thermal conduction, exfoliation, crater formation, re-deposition of the material, ripples formation, debris, heat-affected zone, holes formation and the formation of nanoparticles. The diameter and the depth of the crater formed on non-UV illuminated Pd thin film were greater than the crater formed on UV illuminated Pd thin film, because of its higher absorption. The photographs of the plasma plume were captured with a computer-controlled image capture system and examined by image processing software. The intensity of UV-illuminated Pd thin film was higher than non-UV illuminated Pd thin film because UV illumination induces defects in the specimen that have additional electronic states. These defects cause higher absorption and more ionization of the target material and emerge a more luminous plasma plume. A nanoindentation test was applied on the material surface to investigate the mechanical properties such as hardness and elastic modulus of the target specimen. The hardness and elastic modulus of the material were increased by cumulative laser shots.

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  • Radiation Effects and Defects in Solids
  • Aug 31, 2024
  • Zainab Masood + 5
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Numerical simulation of the thermo-mechanical coupling behavior of skin tissue exposed to repetitive pulse laser irradiation

A thorough understanding of the thermo-mechanical coupling behavior during the interaction between pulsed laser and skin tissue is a prerequisite for successful application of pulsed laser technology in the treatment of various skin diseases and injuries. Taking into account the complex physiological structure of skin tissue, a theoretical model is established to characterize the thermo-mechanical response of multi-layer skin tissue with variable physical properties, in which the non-linear governing equations of bio-thermo-mechanics with dual-phase lag mechanism and Henrique burn equation are involved. The finite difference method was employed to obtain the time-space distribution of skin temperature, displacement and stress under repeated pulse laser action, and the incidental thermal damage was further evaluated on this basis. The numerical results stated that: i) repeated pulse laser can significant reduce the peak temperature of skin tissue and further reduce or even eliminate thermal damage under the premise of required energy threshold, ii) the thermo-mechanical coupling response and potential thermal damage will be inhibited when the temperature dependence of physical parameter is considered, in which the thermal stress is more sensitive to the temperature dependence than others, iii) the thermal damage is more sensitive to the input parameters than that of thermo-mechanical response, and the burn time can be effectively delayed or even avoided for appropriate input options.

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  • International Journal of Heat and Mass Transfer
  • Aug 22, 2024
  • Xiaoli Dai + 4
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Bacterial reduction and temperature increase of titanium dental implant models treated with a 445 nm diode laser: an in vitro study

In this in vitro study, the use of a 445 nm diode laser was investigated for the decontamination of titanium dental implants. Different irradiation protocols and the effect of repetitive laser irradiation on temperature increase and decontamination efficacy were evaluated on titanium implant models. An automated setup was developed to realize a scanning procedure for a full surface irradiation to recapitulate a clinical treatment. Three irradiation parameter sets A (continuous wave, power 0.8 W, duty cycle (DC) 100%, and 5 s), B (pulsed mode, DC 50%, power 1.0 W, and 10 s), and C (pulsed mode, DC 10%, power 3.0 W, and 20 s) were used to treat the rods for up to ten consecutive scans. The resulting temperature increase was measured by a thermal imaging camera and the decontamination efficacy of the procedures was evaluated against Escherichia coli and Staphylococcus aureus, and correlated with the applied laser fluence. An implant’s temperature increase of 10 °C was set as the limit accepted in literature to avoid thermal damage to the surrounding tissue in vivo. Repeated irradiation of the specimens resulted in a steady increase in temperature. Parameter sets A and B caused a temperature increase of 11.27 ± 0.81 °C and 9.90 ± 0.37 °C after five consecutive laser scans, respectively, while parameter set C resulted in a temperature increase of only 8.20 ± 0.53 °C after ten surface scans. The microbiological study showed that all irradiation parameter sets achieved a complete bacterial reduction (99.9999% or 6-log10) after ten consecutive scans, however only parameter set C did not exceed the temperature threshold. A 445 nm diode laser can be used to decontaminate dental titanium rods, and repeated laser irradiation of the contaminated areas increases the antimicrobial effect of the treatment; however, the correct choice of parameters is needed to provide adequate laser fluence while preventing an implant’s temperature increase that could cause damage to the surrounding tissue.

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  • Scientific Reports
  • Aug 5, 2024
  • Markus Ahrens + 4
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Nanosecond laser micromachining of graphene nanoplatelets reinforced ZK60 matrix composites

AbstractIn this paper, a nanosecond laser was used to etch the surface of graphene nanoplatelets reinforced ZK60 (GNPs/ZK60) matrix composites, and the effects of different scanning speeds, pulse repetition frequency and laser power on the etched morphology of the machined surface were investigated. The experimental results show that the etched groove width and heat affected zone width of GNPs/ZK60 composites are significantly increased compared with ZK60 material due to the influence of graphene, and the growth rate of the difference in heat affected zone width between GNPs/ZK60 composites and ZK60 materials is most significantly affected by the pulse repetition frequency. In addition, the dross height increases with the increase of laser power, while the scaly dross structure becomes increasingly clear.

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  • Materialwissenschaft und Werkstofftechnik
  • Jul 23, 2024
  • Z Wu + 5
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Research and development of double layer P-doped laser induced graphene thin film electrode for flexible micro-supercapacitor applications

Laser-induced graphene (LIG) has garnered significant attention for its cost-effectiveness and high efficiency in fabricating flexible micro-energy storage devices. In this study, we devised a simple method to fabricate double layer P-doped LIG electrodes through repetitive laser induction technology for high-performance flexible energy storage applications. Instead of utilizing commercial polyimide (PI) thin film, we optimized the formation process of P-doped PI thin film and achieved a highly flexible double layer P-doped LIG thin film electrode with a uniformly porous structure and the high porosity through repeated laser induction processes. Experimental results demonstrated that the developed double layer P-doped LIG thin film electrode exhibits high porosity, high specific areal capacitance of 180 mF cm−2, and high energy density of 0.025 mWh cm−2. Furthermore, an all-solid-state micro-supercapacitor utilizing hydrogel electrolyte was assembled, demonstrating a high areal capacitance of 62 mF cm−2 and excellent cycling stability with 95% capacitance retention after 6000 charging/discharging cycles. Moreover, the developed all-solid-state micro-supercapacitor successfully powered a light-emitting diode, showcasing its significant potential for practical energy storage applications.

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  • International Journal of Electrochemical Science
  • May 16, 2024
  • Xing Liu + 5
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Laser-driven high-energy proton beams from cascaded acceleration regimes

Laser-driven ion accelerators can deliver high-energy, high-peak current beams and are thus attracting attention as a compact alternative to conventional accelerators. However, achieving sufficiently high energy levels suitable for applications such as radiation therapy remains a challenge for laser-driven ion accelerators. Here we generate proton beams with a spectrally separated high-energy component of up to 150 MeV by irradiating solid-density plastic foil targets with ultrashort laser pulses from a repetitive petawatt laser. The preceding laser light heats the target, leading to the onset of relativistically induced transparency upon main pulse arrival. The laser peak then penetrates the initially opaque target and triggers proton acceleration through a cascade of different mechanisms, as revealed by three-dimensional particle-in-cell simulations. The transparency of the target can be used to identify the high-performance domain, making it a suitable feedback parameter for automated laser and target optimization to enhance stability of plasma accelerators in the future.

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  • Nature Physics
  • May 13, 2024
  • Tim Ziegler + 21
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The Use of Spatially Multi-Component Plasma Structures and Combined Energy Deposition for High-Speed Flow Control: A Selective Review

This review examines studies aimed at the organization of energy (non-mechanical) control of high-speed flow/flight using spatially multi-component plasma structures and combined energy deposition. The review covers selected works on the experimental acquisition and numerical modeling of multi-component plasma structures and the use of sets of actuators based on plasma of such a spatial type for the purposes of control of shock wave/bow shock wave–energy source interaction, as well as control of shock wave–boundary layer interaction. A series of works on repetitive multiple laser pulse plasma structures is also analyzed from the point of view of examining shock wave/bow shock wave–boundary layer interaction. Self-sustained theoretical models for laser dual-pulse, multi-mode laser pulses, and self-sustained glow discharge are also considered. Separate sections are devoted to high-speed flow control using combined physical phenomena and numerical prediction of flow control possibilities using thermal longitudinally layered plasma structures. The wide possibilities for organization and applying spatially multi-component structured plasma for the purposes of high-speed flow control are demonstrated.

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  • Energies
  • Mar 28, 2024
  • Olga A Azarova + 1
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EXTH-73. IN VIVO EFFECTS OF EPCAM-DIRECTED CAR T CELLS IN COMBINATION WITH PD-1 CHECKPOINT BLOCKADE IN LUNG CANCER BRAIN METASTASIS

Abstract BACKGROUND Metastatic lung cancer is incurable once it spreads to the brain. Chimeric antigen receptor (CAR) T cells show promise in hematologic malignancies but face challenges in solid tumors, particularly in brain tumors, due to a highly immunosuppressive tumor microenvironment (TME), tumor antigen (TA) heterogeneity and impeded infiltration and persistence at the tumor site. To test the efficacy of CAR T cells and to find strategies for potentially enhancing its efficacy, CAR T cells were applied with and without checkpoint-blockade to treat lung cancer brain metastasis. METHODS We used an immunocompetent syngeneic orthotopic cerebral metastasis model combined with a chronic cranial window and repetitive intracerebral two-photon laser scanning microscopy (TPLSM). This allowed us to observe fluorescent tumor cells and CAR T cells in vivo at a single cell level over time. We injected red fluorescent EpCAM-transduced Lewis Lung carcinoma cells (EpCAM-LL/2tdT) into the brain tissue, followed by injection of EpCAM-directed or mock CAR T cells. Animals received anti-PD-1 and the respective isotype control via intraperitoneal injections. RESULTS EpCAM-directed CAR T cells were generated and showed substantial anti-tumor effects in vitro. Local injection into EpCAM-LL/2 tumor-bearing mice led to intratumoral accumulation of CAR T cells, resulting in reduced tumor growth compared to undirected CAR T cells translating into long-term survival in a fraction of animals. However, intratumoral CAR T cell numbers decrease over time pointing towards insufficient persistence. Interestingly, anti-PD-1 treatment did not enhance intratumoral CAR T accumulation, persistence and anti-tumor efficacy. CONCLUSION Our findings demonstrate the great potential of cell-based treatment approaches for the treatment of lung cancer brain metastases and underlines the necessity of further investigations to enhance infiltration and persistence in solid tumors.

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  • Neuro-Oncology
  • Nov 10, 2023
  • Jens Blobner + 12
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EXTH-25. IN VIVO TWO-PHOTON TUMOR IMAGING IN AN ORTHOTOPIC MEDULLOBLASTOMA MOUSE MODEL

Abstract BACKGROUND Medulloblastoma represents the most common primary brain malignancy in pediatric patients and is associated with neuro-cognitive impairment and frequent relapses after aggressive multimodal therapy. Adoptive immunotherapies such as CAR T-cell therapy are currently being investigated, showing promising results in preclinical models but lacking efficacy in first-in-human trials. Refined in vivo models to investigate reasons for treatment failures are therefore urgently needed. METHODS We developed a xenogeneic orthotopic medulloblastoma (MB) model in mice by combining a chronic cerebellar window with repetitive intravital two-photon laser scanning microscopy. Red tdTomato-fluorescent DAOY (SHH MB) tumor cells expressing B7-H3 were implanted intracranially into the cerebellum of immunodeficient mice (n = 7), and tumor cell formation was followed by in vivo-microscopy. Intravenous fluorescein isothiocyanate (FITC)-dextran was used for intravascular plasma staining. B7-H3-directed CAR T-cells were injected into the adjacent brain parenchyma. RESULTS Chronic cranial window implantation was well tolerated and allowed repetitive visualization of the mouse cerebellum. After intracranial tumor cell implantation, continuous tumor growth could be evaluated with epifluorescence as well as 2-photon laser scanning microscopy. Tumor formation was identified as early as day 5 in every mouse and could continuously be followed up to 35 days until mice succumbed due to tumor burden. Window quality and fluorescence intensity remained high until the end of the experiments. Studies on GFP-expressing CAR T-cell injection directed against B7-H3 are currently ongoing. CONCLUSIONS We herein establish a robust orthotopic medulloblastoma mouse model that allows repetitive in vivo tracking of fluorescence-expressing tumor cells, CAR T-cells and blood vessels over weeks. Such models may be used to study medulloblastoma tumor growth under the influence of different immunotherapies and reveal interactions between tumor cells and CAR T-cell therapies on a single-cell level.

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  • Neuro-Oncology
  • Nov 10, 2023
  • Nico Teske + 17
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A laser-processed micro/nanostructures surface and its photothermal de-icing and self-cleaning performance

Micro/nanostructures have garnered significant attention and widespread applications in areas such as photocatalysis, coated fabrics, microchips, and sensors. However, high-resolution and multifunctional micro/nanostructures fabrication remains a great challenge. In this work, a novel self-assembly-femtosecond laser processing for the regular micro squares and nano bumps surface on steel substrates is proposed, and a great potential in the field of anti-icing/de-icing and self-cleaning is demonstrated. The surface tension gradient-driven liquid–air self-assembly provides a silica microsphere monolayer, while the post-femtosecond laser process can give precise micro/nano decoration. We systematically explore the impact of laser repetition frequency, scanning speed, and laser incident power on the size and shape of micro/nano decorations that have been studied. The different performances of self-cleaning effects, ice adhesion, and the photothermal de-icing capability due to the change in surface wettability have been demonstrated. This research shows a new pathway for the creation of smart micro/nanostructures surface which possess stable super hydrophilic and highly adhesive superhydrophobic properties, as well as high abrasion resistance. The discovery achieves a suitable blend of multiple functions on the surface of a single material, which can be applied to various surface engineering fields.

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  • Journal of Colloid and Interface Science
  • Nov 5, 2023
  • Weiling Wang + 8
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OS09.1.AIN VIVOTWO-PHOTON TUMOR IMAGING IN AN ORTHOTOPIC MEDULLOBLASTOMA MOUSE MODEL

Abstract BACKGROUND Medulloblastoma represents the most common primary brain malignancy in pediatric patients and is associated with neuro-cognitive impairment and frequent relapses after aggressive multimodal therapy. Adoptive immunotherapies such as CAR T-cell therapy are currently being investigated, showing promising results in preclinical models but lacking efficacy in first-in-human trials. Refined in vivo models to investigate reasons for treatment failures are therefore urgently needed. METHODS We developed a xenogeneic orthotopic medulloblastoma (MB) model in mice by combining a chronic cerebellar window with repetitive intravital two-photon laser scanning microscopy. Red tdTomato-fluorescent DAOY (SHH MB) tumor cells expressing EphA2 were implanted intracranially into the cerebellum of immunodeficient mice (n = 7), and tumor cell formation was followed by in vivo-microscopy. Intravenous fluorescein isothiocyanate (FITC)-dextran was used for intravascular plasma staining. EphA-directed CAR T-cells were injected into the adjacent brain parenchyma. RESULTS Chronic cranial window implantation was well tolerated and allowed repetitive visualization of the mouse cerebellum. After intracranial tumor cell implantation, continuous tumor growth could be evaluated with epifluorescence as well as 2-photon laser scanning microscopy. Tumor formation was identified as early as day 5 in every mouse and could continuously be followed up to 35 days until mice succumbed due to tumor burden. Window quality and fluorescence intensity remained high until the end of the experiments. Studies on GFP-expressing CAR T-cell injection directed against EphA2 are currently ongoing. CONCLUSIONS We herein establish a robust orthotopic medulloblastoma mouse model that allows repetitive in vivo tracking of fluorescence-expressing tumor cells, CAR T-cells and blood vessels over weeks. Such models may be used to study medulloblastoma tumor growth under the influence of different immunotherapies and reveal interactions between tumor cells and CAR T-cell therapies on a single-cell level.

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  • Neuro-Oncology
  • Sep 8, 2023
  • N Teske + 17
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Finite-Element Modeling of Laser Shock Forming Technology

Laser shock forming is an innovative technology in which a laser shock wave induces a flexural deformation of a thin plate. Naturally, the technology of laser shock forming cannot increase the curvature of the plates indefinitely and its possibilities have limits, especially for thick plates. This article investigates the maximum convex flexural curvature of a plate that can be achieved using the technology of laser shock forming by successively increasing its main characteristics: the laser spot overlap factor, the number of repetitive laser pulses, and the intensity of laser power density. The resulting flexural torque and bending curvature are calculated from the average residual stresses obtained by the finite element method. The proposed method for predicting the plate curvature can effectively predict the flexural behavior of the plate. This allows one to plan the process of laser shock forming properly.

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  • Проблемы машиностроения и надежности машин
  • Sep 1, 2023
  • G Zh Sakhvadze
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Tuning the functional properties by laser powder bed fusion with partitioned repetitive laser scanning: Toward editable 4D printing of NiTi alloys

NiTi shape-memory alloys (SMAs) are promising materials for smart structures by 4D printing. However, most of the researches related to 4D printed NiTi alloys remain at the conceptual level. In this work, NiTi SMAs were 4D printed using laser powder bed fusion (LPBF) combined with a partitioned repetitive laser scanning (PRS) strategy to tune the phase transformation behavior and mechanical properties. A novel fabrication strategy is proposed to realize the editable 4D printing of NiTi SMAs. The intrinsic influencing mechanism was found that a lower laser power in the remelting stage would act as a thermal treatment, promoting the transformation of the B2 to B19′ phase. A higher repetitive laser power would not only remelt the solidified track to fill the previously formed micropore defects but also refine the grains. The mechanical properties of NiTi alloys are finally enhanced. Different sub-regions under various energy inputs exhibit distinct phase transformation behaviors and mechanical properties. The final 4D-printed NiTi alloy exhibits gradually graded transformation behaviors, with a tensile strength of 450 MPa and an elongation of 7.4 %. It is believed that this work could facilitate the development of NiTi alloys for 4D printing.

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  • Journal of Manufacturing Processes
  • Jul 18, 2023
  • Jianbin Zhan + 5
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Painful Cutaneous Laser Stimulation for Temporal Summation of Pain Assessment

Variability in pain sensitivity arises not only from the differences in peripheral sensory receptors but also from the differences in central nervous system (CNS) pain inhibition and facilitation mechanisms. Temporal summation of pain (TSP) is an experimental protocol commonly used in human studies of pain facilitation but is susceptible to confounding when elicited with the skin-contact thermode, which adds the responses of touch-related Aβ low-threshold mechanoreceptors to nociceptive receptors. In the present study, we evaluate an alternative method involving the use of a contactless cutaneous laser for TSP assessment. We show that repetitive laser stimulations with a one second inter-stimulus interval evoked reliable TSP responses in a significant proportion of healthy subjects (N = 36). Female subjects (N = 18) reported greater TSP responses than male subjects confirming earlier studies of sex differences in central nociceptive excitability. Furthermore, repetitive laser stimulations during TSP induction elicited increased time-frequency electroencephalography (EEG) responses. The present study demonstrates that repetitive laser stimulation may be an alternative to skin-contact methods for TSP assessment in patients and healthy controls. PerspectiveTemporal summation of pain (TSP) is an experimental protocol commonly used in human studies of pain facilitation. We show that contactless cutaneous laser stimulation is a reliable alternative to the skin contact approaches during TSP assessment.

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  • The Journal of Pain
  • Jul 1, 2023
  • Dan Wang + 6
Open Access
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Possible Expansion of Blood Vessels by Means of the Electrostrictive Effect

In cases when it is desirable to transport medication through blood vessels, especially when dealing with brain cancer being confronted with the narrow arteries in the brain, the blood–brain barrier makes medical treatment difficult. There is a need of expanding the diameters of the arteries in order to facilitate the transport of medications. Recent research has pointed to various ways to improve this situation; in particular, the use an ultrasound acting on microbubbles in the blood stream has turned out to be a promising option. Here, a different possibility of enlarging the diameters of arteries is discussed, namely to exploit the electrostrictive pressure produced by internal strong, ultrashort and repetitive laser pulses. Each pulse will at first give rise to inward-directed optical forces, and once the pulse terminates, there will be a hydrodynamical bouncing flow in the outward radial direction, giving an outward impulse to the vessel wall. In the absence of friction, a symmetric oscillation picture emerges. Clearly, a supply of repetitive pulses will be needed (at a parametric resonance) to make the effect appreciable. The effect has, to our knowledge, not been discussed before. We give an approximate optical and hydrodynamical theory of it. The calculations indicate promising results for the wall pressure, although experimental work is desirable to demonstrate whether the idea can be useful in practice. Our calculation is made from a general physical perspective that is not necessarily linked to medical applications.

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  • Symmetry
  • Mar 24, 2023
  • Iver Brevik
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Enhanced ion acceleration from transparency-driven foils demonstrated at two ultraintense laser facilities

Laser-driven ion sources are a rapidly developing technology producing high energy, high peak current beams. Their suitability for applications, such as compact medical accelerators, motivates development of robust acceleration schemes using widely available repetitive ultraintense femtosecond lasers. These applications not only require high beam energy, but also place demanding requirements on the source stability and controllability. This can be seriously affected by the laser temporal contrast, precluding the replication of ion acceleration performance on independent laser systems with otherwise similar parameters. Here, we present the experimental generation of >60 MeV protons and >30 MeV u−1 carbon ions from sub-micrometre thickness Formvar foils irradiated with laser intensities >1021 Wcm2. Ions are accelerated by an extreme localised space charge field ≳30 TVm−1, over a million times higher than used in conventional accelerators. The field is formed by a rapid expulsion of electrons from the target bulk due to relativistically induced transparency, in which relativistic corrections to the refractive index enables laser transmission through normally opaque plasma. We replicate the mechanism on two different laser facilities and show that the optimum target thickness decreases with improved laser contrast due to reduced pre-expansion. Our demonstration that energetic ions can be accelerated by this mechanism at different contrast levels relaxes laser requirements and indicates interaction parameters for realising application-specific beam delivery.

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  • Light: Science & Applications
  • Mar 13, 2023
  • + 32
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Experimental X-ray emission doses from GHz repetitive burst laser irradiation at 100 kHz repetition rate

Experimental X-ray emission doses from GHz repetitive burst laser irradiation at 100 kHz repetition rate

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  • Applied Physics B
  • Feb 16, 2023
  • Vytenis Barkauskas + 4
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