Articles de revues : « Photons migration »

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Chen, Yan Ping, Xiong Ma, Chun Bin Li et Song Qing Chen. « Research on the Near-Infrared (NIR) Photon Migration in the Knee ». Advanced Materials Research 760-762 (septembre 2013) : 388–91. http://dx.doi.org/10.4028/www.scientific.net/amr.760-762.388.

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To study the phenomena of photon migration in the knee joint is very important in the field of non-invasive near-infrared optical early diagnosis of osteoarthritis of the knee (KOA). In this paper, a photon propagation model of the knee layered structure based on Monte Carlo method is proposed. The migration trace and distribution rule of the photons in knee layered structure are simulated by the Monte Carlo modeling. The proportion of photons which collide with bone tissue then migrate out of the muscle tissue and photons directly migrate out of muscle tissue is calculated and analyzed. The conclusion is that the MC method provided in this study is useful to analyze the photon migration in knee layered structure and to place the detector in a suitable position.

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Perelman, Lev T., Joshua Winn, Jun Wu, Ramachandra R. Dasari et Michael S. Feld. « Photon migration of near-diffusive photons in turbid media : a Lagrangian-based approach ». Journal of the Optical Society of America A 14, n^o 1 (1 janvier 1997) : 224. http://dx.doi.org/10.1364/josaa.14.000224.

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Lakowicz, Joseph R., Ignacy Gryczynski et Zygmunt Gryczynski. « High Throughput Screening with Multiphoton Excitation ». Journal of Biomolecular Screening 4, n^o 6 (décembre 1999) : 355–61. http://dx.doi.org/10.1177/108705719900400610.

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Fluorescence detection is extensively used in high throughput screening. In HTS there is a continuous migration toward higher density plates and smaller sample volumes. In the present report we describe the advantages of two-photon or multiphoton excitation for HTS. Multiphoton excitation (MPE) is the simultaneous absorption of two long-wavelength photons to excite the lowest singlet state of the fluorophore. MPE is typically accomplished with short but high-intensity laser pulses, which allows simultaneous absorption of two or more photons. The intensity of the multiphoton-induced fluorescence is proportional to the square, cube, or higher power of the instantneous photon flux. Consequently, two-photon or multiphoton excitation only occurs at the focal point of the incident beam. This property of two-photon excitation allows the excited volume to be very small and to be localized in the center of each well in the HTS plate. We show that two-photon-induced fluorescence of fluorescein can be reliably measured in microwell plates. We also show the use of 6-carboxy fluorescein as a pH probe with two-photon excitation, and measure 4′-6-diamidino-2-phenylindole (DAPI) binding and two-photon-induced fluorescence. In further studies we measure the time-dependent intensity decays of DAPI bound to DNA and of calcium-dependent fluorophores. Finally, we demonstrate the possibility of three-photon excitation of several fluorophores, including indole, in the HTS plate. These results suggest that MPE can be used in high-density multiwell plates.

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Baranyai, László, et Manuela Zude. « Analysis of laser light migration in apple tissue by Monte Carlo simulation ». Progress in Agricultural Engineering Sciences 4, n^o 1 (1 décembre 2008) : 45–59. http://dx.doi.org/10.1556/progress.4.2008.3.

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The distribution of laser light in the tissue of Golden Delicious and Idared apples was measured with backscattering imaging and simulated with Monte Carlo (MC) method. The settings of the vision system (sensitivity and resolution) and the parameters of the laser modules (wavelength, power and beam diameter) were used in a time resolved MC model to optimize the computation. The 1 ns pulse containing 1.42 × 10 7 (at 670 nm) and 2.49 × 10 8 (at 785 nm) photons was selected for the simulation of backscattering on the fruit surface. The statistical effect of the scattering coefficient (µ s ), absorption coefficient (μ a ), and anisotropy factor ( g ) on photon flux and shape of the backscattering profile was evaluated within ±20 % range relative to expected mean values for apple tissue (µ a = 0.63 cm −1 , µ s = 30.0 cm −1 and g = 0.8). The multi-factor ANOVA test pointed out the highest importance (p<0.001) of the anisotropy factor compared to the scattering and absorption coefficients. Decreasing value of anisotropy factor enhanced the maximum intensity and increased the decline of the gradient resulting in a rotation of the intensity profiles. The measured backscattering profiles for Golden Delicious apples responded to bruising (p<0.05) already after one day storage.

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Du, Fei, Wenzhi Chang, Jiangang Bi, Shuai Yuan, Xinghui Zhang et Yanpeng Gong. « Evolution mechanism of ultraviolet and electrical phenomena induced by protrusion discharge in GIS ». Journal of Electrical Engineering 71, n^o 4 (1 août 2020) : 268–73. http://dx.doi.org/10.2478/jee-2020-0036.

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AbstractTo improve the sensitive and reliability of condition monitoring in gas insulated switchgear (GIS), discharge perception system applied to GIS insulators protrusion discharge based on single ultraviolet photon is built. Step method is used to inspire the discharges of different severity, based on which, the regression relationship of ultraviolet (UV) signal and electrical signal are studied, and the perception mechanism of UV signal in different severity of discharges is analyzed. The study indicates that, the development of protrusion discharge in GIS can be divided into four stages, and there is no positive correlation between the number of ultraviolet photons caused by discharge radiation and insulation deterioration level, but related to the diffusion, migration and recombination of charged particles, then UV optical method for quantitative monitoring of discharge in each stage is provided, which provide a new method for quantitative measurement of GIS insulator discharge.

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Gratton, Gabriele, Monica Fabiani, David Friedman, Maria Angela Franceschini, Sergio Fantini, Paul Corballis et Enrico Gratton. « Rapid Changes of Optical Parameters in the Human Brain During a Tapping Task ». Journal of Cognitive Neuroscience 7, n^o 4 (octobre 1995) : 446–56. http://dx.doi.org/10.1162/jocn.1995.7.4.446.

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Measures of parameters of the migration of near-infrared photons through the head (attenuation, or intensity, and time-of-flight, or delay) have been proposed as a way of assessing noninvasively and in a quasicontinuous fashion changes in the scattering and absorption properties of brain tissue. These, in turn, may reflect functional changes associated with behavioral tasks. To test this hypothesis, we measured changes of photon migration parameters from scalp locations proximal to the motor cortex from four human subjects, tapping at a rate of 0.8 Hz with their left or right hand, or with their left or right foot. Tapping produced both slow effects (requiring several seconds) and fast effects (tracking the tapping frequency). Slow effects were characterized by increase and delay of the light passing through the hemisphere contralateral to the tapping hand. Fast effects consisted of changes in the light delay during hand tapping. Monte Carlo simulations based on layer models of the brain indicated that fast effects are consistent with changes in deep layers of the head (presumably in the cortex), and that slow effects are consistent with either a shift of absorbing material toward deeper layers or a reduction in scattering. These results suggest that optical parameters can monitor rapid changes of brain activity, matching the contralateral organization of the motor cortex.

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Raja-Mogan, Tharishinny, Bunsho Ohtani et Ewa Kowalska. « Photonic Crystals for Plasmonic Photocatalysis ». Catalysts 10, n^o 8 (23 juillet 2020) : 827. http://dx.doi.org/10.3390/catal10080827.

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Noble metal (NM)-modified wide-bandgap semiconductors with activity under visible light (Vis) irradiation, due to localized surface plasmon resonance (LSPR), known as plasmonic photocatalysts, have been intensively studied over the last few years. Despite the novelty of the topic, a large number of reports have already been published, discussing the optimal properties, synthesis methods and mechanism clarification. It has been proposed that both efficient light harvesting and charge carriers’ migration are detrimental for high and stable activity under Vis irradiation. Accordingly, photonic crystals (PCs) with photonic bandgap (PBG) and slow photon effects seem to be highly attractive for efficient use of incident photons. Therefore, the study on PCs-based plasmonic photocatalysts has been conducted, mainly on titania inverse opal (IO) modified with nanoparticles (NPs) of NM. Although, the research is quite new and only several reports have been published, it might be concluded that the matching between LSPR and PBG (especially at red edge) by tuning of NMNPs size and IO-void diameter, respectively, is the most crucial for the photocatalytic activity.

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Ebel, Horst, Robert Svagera, Maria F. Ebel, Norbert Zagler, Wolfgang S. M. Wemer, Herbert Stön et Martin Gröschl. « On the Sampling Depth of Total Electron Yield (Tey) Measurements ». Advances in X-ray Analysis 39 (1995) : 665–74. http://dx.doi.org/10.1154/s0376030800023107.

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Photoabsorption of x-rays in solids causes primary and secondary photo and Auger electrons. The latter are from self absorption of characteristic radiations which have been produced in the solid by radiative de-excitation of photoionized atoms. Whereas the energy of the electrons at the origin is described by discrete values of a few eV up to nearly the energy of the photoabsorbed photons, we observe after the escape of the electrons from the solid a continuous energy distribution with a superposition of the original line spectrum. This is explained by inelastic collisions of the electrons in the course of their migration through the solid and the subsequent loss of kinetic energy. Since the electron range decreases with decreasing kinetic energy, only a relatively small amount of electrons is able to reach the surface and to escape from there.

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Zhong, Yi, Jinhui Xu, Xinyu Zhao, Tongfei Qu, Chen Guan, Chengzong Hou, Xuexi Tang et Ying Wang. « Balancing Damage via Non-Photochemical Quenching, Phenolic Compounds and Photorespiration in Ulva prolifera Induced by Low-Dose and Short-Term UV-B Radiation ». International Journal of Molecular Sciences 23, n^o 5 (28 février 2022) : 2693. http://dx.doi.org/10.3390/ijms23052693.

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The Yellow Sea green tide (YSGT) is the world’s largest transregional macroalgal blooms, and the causative species Ulva prolifera (U. prolifera) suffers from ultraviolet-b radiation (UVBR) during the floating migration process. Previous study confirmed that U. prolifera displayed a wide variety of physiological responses characterized as acclimation to UVBR, while the response mechanisms against low-dose and short-term radiation (LDSTR) are not clear. A study with photosynthetically active radiation (PAR) and UVBR was designed: normal light (NL: 72 μmol photons m−2 s−1), NL+0.3 (UVBR: 0.3 W·m−2), and NL+1.6 (UVBR: 1.6 W·m−2). The results showed that high-dose UVBR inhibited photosynthesis in thalli, especially under long-term exposure, while a variety of physiological responses were observed under LDSTR. The inhibition of photosynthesis appeared to be ameliorated by the algae under LDSTR. Further analysis showed that U. prolifera achieved balancing damage by means of non-photochemical quenching (NPQ), accumulation of phenolic compounds coupled with the ASA-GSH cycle involved in the antioxidant process and enhanced photorespiratory metabolism under LDSTR. This study provides new insights into the balancing damage mechanisms of U. prolifera under LDSTR, enabling the thalli to adapt to the light conditions during the long duration and distance involved in floating migration.

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Hossieni, H., et J. M. A. Fatah. « Spooky Birds and Origin of Life : A Quantum Mechanics Description of Bird Migration ». Jurnal Pendidikan Fisika Indonesia 15, n^o 1 (29 mai 2019) : 1–4. http://dx.doi.org/10.15294/jpfi.v15i1.13920.

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In this work we explain a strange quantum phenomenon in biology that the European Robin uses to navigate. The bird’s brain contains a chemical called cryptochromes which has two of its electrons entangled through collision with photons. These two electrons hop between singlet and triplet states. This hopping is sensitive to the earth’s magnetic field causing different signals to be transferred to its brain. It is believed that these birds use quantum entanglement for their navigations. We also discuss the importance of this phenomenon in trying to find the origin of life. We also explain the view of some who believe that quantum field is well entrenched in the origin of life and that we have to look for a quantum self-replicator that can repeat itself.Hasil penelitian ini mencoba menjelaskan fenomena kuantum yang aneh pada ranah biologi dimana burung robin eropa bernavigasi menggunakannya. Otak burung tersebut mengandung material kimia yang disebut dengan cryptochromes yang mempunyai dua buah elektron yang terjebak dalam pengaruh interaksi tumbukan antara elektron tersebut dengan foton. Dua elektron tersebut melompat di antara keadaan singlet dan triplet. Lompatan ini dipengaruhi oleh medan magnetik bumi yang memberikan sinyal berbeda-beda untuk ditransfer ke otaknya. Burung-burung ini diyakini menggunakan prinsip pengaruh kuantum untuk navigasinya. Kami juga mengungkap pentingnya fenomena ini dalam usaha mencari asal mula kehidupan. Kami juga menjelaskan sudut pandang yang mempercayai bahwa medan kuantum diyakini berperan penting dalam penjelasan tentang asal mula kehidupan dan bahwa kita harus mencari tahu tentang pembelahan materi dengan pengaruh kuantum yang dapat berlangsung berulang-ulang dengan sendirinya.

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ROMERO, GUSTAVO E., DANIELA PÉREZ et GABRIELA S. VILA. « SUPERMASSIVE BLACK HOLE BINARIES AT HIGH ENERGIES ». International Journal of Modern Physics : Conference Series 28 (janvier 2014) : 1460183. http://dx.doi.org/10.1142/s2010194514601835.

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An accretion disk around a supermassive black hole may be strongly perturbed by the presence of a secondary black hole. Recent simulations have shown that, under certain conditions, the tidal torques exerted by the secondary black hole may open an annular gap in the disk. In this regime, matter "overflows" across the secondary's orbit to accrete onto the primary and may feed a pair of relativistic jets. In this work we study the radiative properties of a binary system of supermassive black holes, assuming that a relativistic jet is launched from the primary and the migration of the secondary across the disk proceeds in the "overflowing" regime. The modified radiative spectrum of the disk is calculated accounting for strong gravitational effects in the innermost region. The jet emits non-thermal radiation all along the electromagnetic spectrum by interaction of locally accelerated electrons with the jet's magnetic field and internal and external radiation. In particular, we investigate whether the interaction of the relativistic electrons with the photons emitted by the accretion disk induces any signature in the spectral energy distribution of the jet that may reveal the presence of the secondary black hole.

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Ponzoni, Stefano, Sonia Freddi, Marta Agati, Vincent Le Borgne, Simona Boninelli, Richard Dolbec, My Ali El Khakani, Stefania Pagliara et Paola Castrucci. « Ultrafast Carrier Relaxation Dynamics in Quantum Confined Non-Isotropic Silicon Nanostructures Synthesized by an Inductively Coupled Plasma Process ». Materials 13, n^o 19 (25 septembre 2020) : 4267. http://dx.doi.org/10.3390/ma13194267.

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To exploit the optoelectronic properties of silicon nanostructures (SiNS) in real devices, it is fundamental to study the ultrafast processes involving the photogenerated charges separation, migration and lifetime after the optical excitation. Ultrafast time-resolved optical measurements provide such information. In the present paper, we report on the relaxation dynamics of photogenerated charge-carriers in ultrafine SiNS synthesized by means of inductively-coupled-plasma process. The carriers’ transient regime was characterized in high fluence regime by using a tunable pump photon energy and a broadband probe pulse with a photon energy ranging from 1.2 eV to 2.8 eV while varying the energy of the pump photons and their polarization. The SiNS consist of Si nanospheres and nanowires (NW) with a crystalline core embedded in a SiOx outer-shell. The NW inner core presents different typologies: long silicon nanowires (SiNW) characterized by a continuous core (with diameters between 2 nm and 15 nm and up to a few microns long), NW with disconnected fragments of SiNW (each fragment with a length down to a few nanometers), NW with a “chaplet-like” core and NW with core consisting of disconnected spherical Si nanocrystals. Most of these SiNS are asymmetric in shape. Our results reveal a photoabsorption (PA) channel for pump and probe parallel polarizations with a maximum around 2.6 eV, which can be associated to non-isotropic ultra-small SiNS and ascribed either to (i) electron absorption driven by the probe from some intermediate mid-gap states toward some empty state above the bottom of the conduction band or (ii) the Drude-like free-carrier presence induced by the direct-gap transition in the their band structure. Moreover, we pointed up the existence of a broadband and long-living photobleaching (PB) in the 1.2–2.0 eV energy range with a maximum intensity around 1.35 eV which could be associated to some oxygen related defect states present at the Si/SiOx interface. On the other hand, this wide spectral energy PB can be also due to both silicon oxide band-tail recombination and small Si nanostructure excitonic transition.

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Marciniak, A., C. Joblin, G. Mulas, V. Rao Mundlapati et A. Bonnamy. « Photodissociation of aliphatic PAH derivatives under relevant astrophysical conditions ». Astronomy & ; Astrophysics 652 (août 2021) : A42. http://dx.doi.org/10.1051/0004-6361/202140737.

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Context. The interaction of polycyclic aromatic hydrocarbons (PAHs) with vacuum ultraviolet (VUV) photons triggers the emission of the well-known aromatic infrared bands (AIBs), but other mechanisms, such as fragmentation, can be involved in this interaction. Fragmentation leads to selection effects that favor specific sizes and structures. Aims. Our aim is to investigate the impact of aliphatic bonds on the VUV photostability of PAH cations in a cryogenic and collisionless environment with conditions applicable for photodissociation regions (PDRs). Methods. The studied species are derived from pyrene (C16H10) and coronene (C24H12) and contain aliphatic bonds either in the form of methyl or ethyl sidegroups or of superhydrogenation. Their cations are produced by laser desorption ionization and isolated in the cryogenic ion cell of the PIRENEA setup, where they are submitted to VUV photons of 10.5 eV energy over long timescales (~1000 s). The parent and fragment ions are mass-analyzed and their relative intensities are recorded as a function of the irradiation time. The fragmentation cascades are analyzed with a simple kinetics model from which we identify fragmentation pathways and derive fragmentation rates and branching ratios for both the parents and their main fragments. Results. Aliphatic PAH derivatives are found to have a higher fragmentation rate and a higher carbon to hydrogen loss compared to regular PAHs. On the other hand, the fragmentation of PAHs with alkylated sidegroups forms species with peripheral pentagonal cycles, which can be as stable as, or even more stable than, the bare PAH cations. This stability is quantified for the main ions involved in the fragmentation cascades by the comparison of the fragmentation rates with the photoabsorption rates derived from theoretical photoabsorption cross sections. The most stable species for which there is an effective competition of fragmentation with isomerization and radiative cooling are identified, providing clues on the structures favored in PDRs. Conclusions. This work supports a scenario in which the evaporation of nanograins with a mixed aliphatic and aromatic composition followed by VUV photoprocessing results in both the production of the carriers of the 3.4 μm AIB by methyl sidegroups and in an abundant source of small hydrocarbons at the border of PDRs. An additional side effect is the efficient formation of stable PAHs that contain some peripheral pentagonal rings. Our experiments also support the role of isomerization processes in PAH photofragmentation, including the H-migration process, which could lead to an additional contribution to the 3.4 μm AIB.

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Yuan, Chengchao, Kohta Murase, Dafne Guetta, Asaf Pe’er, Imre Bartos et Péter Mészáros. « GeV Signatures of Short Gamma-Ray Bursts in Active Galactic Nuclei ». Astrophysical Journal 932, n^o 2 (1 juin 2022) : 80. http://dx.doi.org/10.3847/1538-4357/ac6ddf.

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Abstract The joint detection of gravitational waves and the gamma-ray counterpart of a binary neutron star merger event, GW170817, unambiguously validates the connection between short gamma-ray bursts and compact binary object (CBO) mergers. We focus on a special scenario where short gamma-ray bursts produced by CBO mergers are embedded in disks of active galactic nuclei (AGNs), and we investigate the γ-ray emission produced in the internal dissipation region via synchrotron, synchrotron self-Compton, and external inverse Compton (EIC) processes. In this scenario, isotropic thermal photons from the AGN disks contribute to the EIC component. We show that a low-density cavity can be formed in the migration traps, leading to the embedded mergers producing successful GRB jets. We find that the EIC component would dominate the GeV emission for typical CBO mergers with an isotropic-equivalent luminosity of L j,iso = 1048.5 erg s−1 that are located close to the central supermassive black hole. Considering a long-lasting jet of duration T dur ∼ 102–103 s, we find that the future Cherenkov Telescope Array (CTA) will be able to detect its 25–100 GeV emission out to a redshift z = 1.0. In the optimistic case, it is possible to detect the on-axis extended emission simultaneously with GWs within one decade using MAGIC, H.E.S.S., VERITAS, CTA, and LHAASO-WCDA. Early diagnosis of prompt emissions with Fermi-GBM and HAWC can provide valuable directional information for the follow-up observations.

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Zeiser, Robert, Vu Nguyen, Martin Buess, Mobin Karimi, Pia Bjorck, Jeanette Baker et Robert S. Negrin. « Prevention of Acute Graft-Versus-Host Disease by CD4+CD25+ Regulatory T Cells Is Dependent on the CD30/CD153 Pathway. » Blood 106, n^o 11 (16 novembre 2005) : 1299. http://dx.doi.org/10.1182/blood.v106.11.1299.1299.

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Abstract CD4+CD25+ regulatory T (Treg) cells suppress acute graft versus host disease (aGVHD), prevent autoimmunity and delay allograft rejection. CD30 and other TNF-R family members have been demonstrated to be expressed by Treg and to function as alternative costimulatory pathways for T cell activation. In this study we assessed the significance of the CD30/CD153 pathway in Tregs suppression of aGVHD in a murine major MHC mismatch BMT model. Using bioluminescence imaging proliferation of donor derived luciferase-labeled CD4+ and CD8+ T cells was quantified at serial time points after transplantation. Treg suppressed the early expansion of alloreactive T-cells. Immunofluorescence microscopy revealed a predominant infiltration of donor derived Treg in CD153 positive regions of secondary lymphoid organs, namely parafollicular T cell zones of lymph nodes and the subepithelial dome regions of Peyers Patches. In vivo blockade of the CD30/CD153 pathway with anti CD153 Ab did not alter Treg migration to secondary lymphoid organs but reduced their suppressive effect. Proliferation of donor T cells as measured in photons/second/mouse was significantly higher in animals receiving Treg and CD153 blocking antibodies as compared to recipients of Treg only (p=0.0038). Gene expression profiling of Treg with DNA microarrays indicated a Treg signature that was consistently found in different mouse strains. This Treg signature was altered after CD153 blockade in vitro. Importantly, aGVHD lethality was significantly increased (p=0.021) when CD30-CD153 interaction was blocked during Treg transfer. This study provides direct evidence that the TNF-R family member CD30 is critical for Treg cell function in the regulation of pathological T cell responses that lead to aGVHD.

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Kalef-Ezra, J. « A rebirth of radiation therapy with kV X-rays ? » HNPS Proceedings 23 (8 mars 2019) : 85. http://dx.doi.org/10.12681/hnps.1911.

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Novel clinical approaches using kV X-ray beams are currently under study, such as selective dose enhancement in malignant tissues due to the enhanced presence of atoms with high atomic number, Z, in tumors relative to normal tissues or the use of heavily spatially fractionated kV X-ray irradiation.Local dose enhancement by high Z atoms: A substantial dose gradient between normal and malignant tissues can be achieved by biologic targeting the cells to be “destroyed” with high Z atoms and its irradiation with photons in the energy region of tens of keV, such as synchrotron produced X-rays of energy above the K-edge. The selective accumulation of high Z atoms can be achieved by various techniques, such as by intravenous administration of a) contrast enhancement agents, b) some chemotherapeutic drugs c) nanoparticles and d) DNA precursors loaded with Z-atoms. Taking into account the limited availability and the high cost of GeV synchrotrons, brachytherapy sources could be used.Microbeam radiation therapy: Studies carried out in experimental models using spatially micro- fractionated beams have shown drastically elevated tissue radiation tolerance, with higher tissue sparing in healthy tissues than in malignant ones. This phenomenon is attributed by some investigators to the proliferation and migration of cells from the “low” dosed regions (~10 Gy) to the adjacent “heavily” dosed regions (many hundreds of grays). Multi-slit collimators allow for the production of X-ray microbeam arrays at 3rd generation synchrotron units. Monte Carlo simulations were tested versus direct dose measurements. Promising preclinical studies carried out so far, trigger studies on the development of alternative less expensive technologies.

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Leveson-Gower, Dennis B., Janelle A. Olson, Jeanette Baker, Robert Zeiser, Andreas Beilhack et Robert Negrin. « NKT Cells Are Potent Regulators of GVHD Following Adoptive Transfer in Allogeneic BMT. » Blood 110, n^o 11 (16 novembre 2007) : 353. http://dx.doi.org/10.1182/blood.v110.11.353.353.

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Abstract NKT cells, which are CD1d reactive and express an invariant TCR, are thought to play an immunoregulatory role in suppressing dysfunctional immune reactions including graft vs. host disease (GVHD). Whether non-manipulated donor-type NKT can suppress GVHD following adoptive transfer has not been addressed, nor has the trafficking pattern of NKT in a hematopoetic transplantation (HCT) setting. To determine how effectively NKT proliferate and traffic in a HCT setting, 5.5x105 highly purified (>95%) NKT (DX5+TCRβ+CD4+) from luciferase positive (luc+) C57BL/6 (H-2b) mice were transferred into lethally irradiated Balb/c (H-2d) recipients along with 5x106 T-cell depleted bone marrow (TCD-BM) from wild-type C57BL/6 mice. Proliferation and migration of luc+NKT was monitored by bioluminescence imaging (BLI). By day 4 after transfer, a prominent signal was observed in the spleen and lymph node (LN) sites. Between days 7 and 10, the NKT migrated to skin, while still remaining present in high numbers in LNs, but decreasing to low levels in spleen. The total photons emitted per mouse reached a peak at approximately 25 days after transplantation, followed by a steady decline. The NKT expansion was more vigorous than that of luc+CD4+CD25+ regulatory T cells (Tregs), which also peak around day 25, but do not show extensive migration to skin. Expansion of NKT was far less than conventional (CD4+ and CD8+) T cells (Tcon), with approximately 10 times more photons/mouse being emitted from 5x105 luc+Tcon as from 5.5x105 NKT. The NKT did not cause GVHD where Tcon rapidly resulted in acute GVHD and animal mortality. To assess the impact of donor-type NKT on GVHD induction by Tcon, we co-transferred various doses of highly purified wt NKT at day 0 with 5x106 TCD-BM, followed by 5x105 luc+Tcon at day 2. Weight and survival of groups were monitored, as well as the proliferation of Tcon by BLI. In groups receiving only Tcon, 50% of the mice died within 2 weeks, and 90% died by day 80. Remarkably, if 2.5x104 sorted NKT were transferred, 100% of the mice survived past day 100. To achieve the same effect with Tregs, 2.5x105 Tregs were required. Mice treated with 2.5x104 NKT lost more weight at early time points than those receiving 2.5x105 Tregs, but both groups recovered from this weight loss and did not exhibit other signs of GVHD (hair loss, hunched back, diarrhea, etc). Interestingly, 2.5x104 NKT caused only a slight reduction in Tcon proliferation, whereas 2.5x105 Treg strongly reduced Tcon proliferation. Surprisingly, when the dose of NKT was increased to 5x104, survival was only 62%, and when increased to 1x105 cells, only 50% of mice survived past day 100. To determine how NKT reduce GVHD, we examined intracellular levels of various cytokines in Tcon with or without 2.5x104 NKT, following HCT. At 8 days after HCT, mice receiving NKT had reductions in the number of IL-17-positive cells (CD4: 2.6% to 0.84%; CD8: 2.5% to 0.66%), and TNFα+ cells (CD4: 45% to 27%; CD8 36% to 24%) in cells from LNs. By day 11, IL-17-positive cells had declined to undetectable levels and TNF levels between groups were equivalent. IFNg levels, which were high in both NKT treated and untreated groups at day 8 (85%–95%), decreased significantly in NKT treated mice by day 11 (CD4: 40%; CD8: 43%), but were still abundant in Tcon only mice (CD4: 78%; CD8: 80%). Together these data indicate that NKT cells persist in vivo upon adoptive transfer and suppress GVHD by decreasing the percentage of Tcon secreting pro-inflammatory cytokines.

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Nguyen, Vu H., Courtney Wieland, Christopher Contag et Robert S. Negrin. « In Vivo Trafficking of CD4+CD25+ Regulatory T-Cells in Allogeneic Recipients Using Bioluminescence Imaging. » Blood 104, n^o 11 (16 novembre 2004) : 302. http://dx.doi.org/10.1182/blood.v104.11.302.302.

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Abstract CD4+CD25+ regulatory T-cells (Treg) have the potential to suppress aberrant immune responses and to regulate peripheral T cell homeostasis. In a murine allogeneic bone marrow transplantation (BMT) model, our laboratory has previously shown that Treg suppress graft-versus-host-disease (GVHD) without abrogating the beneficial graft-versus-tumor immunological effect. However, the mechanisms of immuno-regulation, in particular, the allorecognition properties of Treg, their effects on and interaction with other immune cells, and the sites of suppressive activity, remain unclear. In the current study, we investigate the in vivo trafficking of Treg to better understand how localization may affect their regulatory function. Interpretation of previous studies of Treg localization has been limited by several factors: the need to sacrifice mice does not permit tracking the same set of cells over time; data collected at several arbitrary times on selected tissues do not permit accurate determination of primary and secondary sites of migration, activation, proliferation, and suppression; and CD25 expression on activated CD4+CD25- T cells are difficult to distinguish from Treg. We have developed and characterized a transgenic mouse which constitutively expresses the luciferase gene in all hematologic cells. Treg (1x106 cells) from the spleen and lymph nodes of luc+ transgenic FVB/N (H-2q) mice were co-transplanted into lethally-irradiated (800cGy) Balb/c (H-2d) host along with 5x106 wild-type FVB/N T-cell depleted bone marrow (TCD-BM) cells and 2x106 whole splenocytes, the latter containing approximately 30% T cells (Tconv) which induce GVHD. Upon exposure to the substrate luciferin, the luciferase-expressing Treg emit light which can penetrate through living tissues and is captured by sensitive CCD camera detectors. Bioluminescence imaging (BLI) was performed at various time points established previously by our studies of BLI in GVHD. Within the first 48 hours, Treg localized to the cervical lymph nodes (LN) and the spleen. By day 3, signal is detected in other LN (axillary, mesenteric, inguinal) as well as Peyer’s patches and liver. Signal intensity, measured by photons/second/mouse, significantly increased and peaked on day 4, consistent with the migration and proliferation of Treg to and at these secondary lymphoid organs, respectively. Skin infiltration of Treg is noted on day 6, congruent with a decreased intensity in the spleen, liver, and lymph nodes. A similar pattern of early migration and proliferation of effector immune cells is noted in the GVHD control group, which is transplanted with wild-type FVB/N TCD-BM and luc+ FVB/N whole splenocytes. However, with the GVHD group, the signal intensity continues to increase at all sites. Continued BLI of the Treg group up to day 45 demonstrates persistent strong signal in lymphoid organs and skin sites. Clinically, the Treg group has no significant evidence of GVHD. Chimerism studies on day 45 show complete donor origin, however, lymphoid reconstitution of CD4+ and CD8+ T cells is delayed in the GVHD control group and enhanced in the recipients transplanted with Treg. The above results indicate that in vivo, Treg proliferate and survive long-term. In addition, they co-localize with effector immune cells to secondary lymphoid tissues to positively impact clinical outcomes and lymphoid reconstitution following major-MHC mismatched BMT.

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Nossal, Ralph, J. Kiefer, G. H. Weiss, R. Bonner, H. Taitelbaum et S. Havlin. « Photon migration in layered media ». Applied Optics 27, n^o 16 (15 août 1988) : 3382. http://dx.doi.org/10.1364/ao.27.003382.

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Everall, Neil, Thomas Hahn, Pavel Matousek, Anthony W. Parker et Michael Towrie. « Photon Migration in Raman Spectroscopy ». Applied Spectroscopy 58, n^o 5 (mai 2004) : 591–97. http://dx.doi.org/10.1366/000370204774103426.

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Havlin, S., R. Nossal, B. Trus et G. H. Weiss. « Photon migration in disordered media ». Physical Review A 45, n^o 10 (1 mai 1992) : 7511–19. http://dx.doi.org/10.1103/physreva.45.7511.

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Oliveira, Fernando A., Mariana P. Nucci, Javier B. Mamani, Arielly H. Alves, Gabriel N. A. Rego, Andrea T. Kondo, Nelson Hamerschlak, Mara S. Junqueira, Lucas E. B. de Souza et Lionel F. Gamarra. « Multimodal Tracking of Hematopoietic Stem Cells from Young and Old Mice Labeled with Magnetic–Fluorescent Nanoparticles and Their Grafting by Bioluminescence in a Bone Marrow Transplant Model ». Biomedicines 9, n^o 7 (29 juin 2021) : 752. http://dx.doi.org/10.3390/biomedicines9070752.

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This study proposes an innovative way to evaluate the homing and tracking of hematopoietic stem cells from young and old mice labeled with SPIONNIRF-Rh conjugated with two types of fluorophores (NIRF and Rhodamine), and their grafting by bioluminescence (BLI) in a bone marrow transplant (BMT) model. In an in vitro study, we isolated bone marrow mononuclear cells (BM-MNC) from young and old mice, and analyzed the physical–chemical characteristics of SPIONNIRF-Rh, their internalization, cell viability, and the iron quantification by NIRF, ICP-MS, and MRI. The in vivo study was performed in a BMT model to evaluate the homing, tracking, and grafting of young and old BM-MNC labeled with SPIONNIRF-Rh by NIRF and BLI, as well as the hematological reconstitution for 120 days. 5FU influenced the number of cells isolated mainly in young cells. SPIONNIRF-Rh had adequate characteristics for efficient internalization into BM-MNC. The iron load quantification by NIRF, ICP-MS, and MRI was in the order of 104 SPIONNIRF-Rh/BM-MNC. In the in vivo study, the acute NIRF evaluation showed higher signal intensity in the spinal cord and abdominal region, and the BLI evaluation allowed follow-up (11–120 days), achieving a peak of intensity at 30 days, which remained stable around 108 photons/s until the end. The hematologic evaluation showed similar behavior until 30 days and the histological results confirm that iron is present in almost all tissue evaluated. Our results on BM-MNC homing and tracking in the BMT model did not show a difference in migration or grafting of cells from young or old mice, with the hemogram analysis trending to differentiation towards the myeloid lineage in mice that received cells from old animals. The cell homing by NIRF and long term cell follow-up by BLI highlighted the relevance of the multimodal nanoparticles and combined techniques for evaluation.

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Figge, Marc Thilo, Alexandre Garin, Matthias Gunzer, Marie Kosco-Vilbois, Kai-Michael Toellner et Michael Meyer-Hermann. « Deriving a germinal center lymphocyte migration model from two-photon data ». Journal of Experimental Medicine 205, n^o 13 (1 décembre 2008) : 3019–29. http://dx.doi.org/10.1084/jem.20081160.

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Recently, two-photon imaging has allowed intravital tracking of lymphocyte migration and cellular interactions during germinal center (GC) reactions. The implications of two-photon measurements obtained by several investigators are currently the subject of controversy. With the help of two mathematical approaches, we reanalyze these data. It is shown that the measured lymphocyte migration frequency between the dark and the light zone is quantitatively explained by persistent random walk of lymphocytes. The cell motility data imply a fast intermixture of cells within the whole GC in approximately 3 h, and this does not allow for maintenance of dark and light zones. The model predicts that chemotaxis is active in GCs to maintain GC zoning and demonstrates that chemotaxis is consistent with two-photon lymphocyte motility data. However, the model also predicts that the chemokine sensitivity is quickly down-regulated. On the basis of these findings, we formulate a novel GC lymphocyte migration model and propose its verification by new two-photon experiments that combine the measurement of B cell migration with that of specific chemokine receptor expression levels. In addition, we discuss some statistical limitations for the interpretation of two-photon cell motility measurements in general.

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Lioi, David B., David J. Gosztola, Gary P. Wiederrecht et Goran Karapetrov. « Photon-induced selenium migration in TiSe2 ». Applied Physics Letters 110, n^o 8 (20 février 2017) : 081901. http://dx.doi.org/10.1063/1.4976745.

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Choe, Kibaek, Yusaku Hontani, Tianyu Wang, Eric Hebert, Dimitre Ouzounov et Chris Xu. « Intravital three-photon microscopy of T-cell migration in the T-cell zones over the entire depth of mouse popliteal lymph node. » Journal of Immunology 206, n^o 1_Supplement (1 mai 2021) : 26.04. http://dx.doi.org/10.4049/jimmunol.206.supp.26.04.

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Abstract Most T cells in a popliteal lymph node are located in T-cell zones at ~150 to ~600 μm below the cortical surface of the lymph node. For the last 20 years, intravital two-photon microscopy has been a powerful tool for observing the three dimensional T-cell migration in the T-cell zones. However, two-photon imaging can only visualize superficial T-cell zones to ~300 μm depth. In this work, we successfully visualized T-cell migration in T-cell zones over the entire depth of a mouse popliteal lymph node with intravital three-photon microscopy. We measured the change in lymphocyte velocity with increasing laser powers at 600 μm depth to determine the safe laser power range for visualizing T-cell migration. We found that, with less than 80 mW at 1300 nm excitation, the migration of EGFP-expressing lymphocytes were not perturbed by the laser illumination. Using the safe power of 1300 nm excitation, we observed dynamic migration of EGFP-expressing naïve CD4 T cells and DsRed-expressing naïve CD8 T cells simultaneously in T-cell zones at various depths. The naïve T cells were sparse at 0 ~150 μm depth in cortical side (follicular and interfollicular regions), dense in the T-cell zones, and less dense in the medulla, which was identified by labeling with eFluor615-conjugated LYVE-1 antibody in vivo. We found that the density distributions of CD4 and CD8 T cells were different in the T-cell zones. We also measured the migration velocity and motility coefficient for naïve CD4 and CD8 T cells in the T-cell zones over the entire depth of the lymph node. This work shows that three-photon microscopy has the potential to shed light on immune cell dynamics in the deep regions of lymph nodes that are typically inaccessible to conventional two-photon microscopy.

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Yanai, Nobuhiro, et Nobuo Kimizuka. « Recent emergence of photon upconversion based on triplet energy migration in molecular assemblies ». Chemical Communications 52, n^o 31 (2016) : 5354–70. http://dx.doi.org/10.1039/c6cc00089d.

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Mizuno, Rei, Yuji Kamioka, Kenji Kabashima, Masamichi Imajo, Kenta Sumiyama, Eiji Nakasho, Takeshi Ito et al. « In vivo imaging reveals PKA regulation of ERK activity during neutrophil recruitment to inflamed intestines ». Journal of Experimental Medicine 211, n^o 6 (19 mai 2014) : 1123–36. http://dx.doi.org/10.1084/jem.20132112.

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Many chemical mediators regulate neutrophil recruitment to inflammatory sites. Although the actions of each chemical mediator have been demonstrated with neutrophils in vitro, how such chemical mediators act cooperatively or counteractively in vivo remains largely unknown. Here, by in vivo two-photon excitation microscopy with transgenic mice expressing biosensors based on Förster resonance energy transfer, we time-lapse–imaged the activities of extracellular signal–regulated kinase (ERK) and protein kinase A (PKA) in neutrophils in inflamed intestinal tissue. ERK activity in neutrophils rapidly increased during spreading on the endothelial cells and showed positive correlation with the migration velocity on endothelial cells or in interstitial tissue. Meanwhile, in the neutrophils migrating in the interstitial tissue, high PKA activity correlated negatively with migration velocity. In contradiction to previous in vitro studies that showed ERK activation by prostaglandin E2 (PGE2) engagement with prostaglandin receptor EP4, intravenous administration of EP4 agonist activated PKA, inhibited ERK, and suppressed migration of neutrophils. The opposite results were obtained using nonsteroidal antiinflammatory drugs (NSAIDs). Therefore, NSAID-induced enteritis may be caused at least partially by the inhibition of EP4 receptor signaling of neutrophils. Our results demonstrate that ERK positively regulates the neutrophil recruitment cascade by promoting adhesion and migration steps.

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Ogata, Toshiyuki, Teruki Teshima, Kazufumi Kagawa, Yoshio Hishikawa, Yutaka Takahashi, Atsuko Kawaguchi, Yuko Suzumoto, Kumie Nojima, Yoshiya Furusawa et Nariaki Matsuura. « Particle Irradiation Suppresses Metastatic Potential of Cancer Cells ». Cancer Research 65, n^o 1 (1 janvier 2005) : 113–20. http://dx.doi.org/10.1158/0008-5472.113.65.1.

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Abstract Particle radiotherapy such as proton and carbon ion has been producing promising clinical results worldwide. The purpose of this study was to compare metastatic capabilities of malignant tumor cells after irradiation with photon, proton, and carbon ion beams to clarify their ion beam–specific biological effects. We examined the biological properties of highly aggressive HT1080 human fibrosarcoma cells to assess their metastatic processes in terms of cell adhesion capability to extracellular matrix, expression of integrins, cell migration, cell invasive capability, and matrix metalloproteinase-2 activity in vitro. We then assessed the metastatic capabilities of LM8 mouse osteosarcoma irradiated with carbon ion or photon beam in the syngeneic mice. Both proton and carbon ion irradiation decreased cell migration and invasion in a dose-dependent manner and strongly inhibited matrix metalloproteinase-2 activity. On the other hand, lower X-ray irradiation promoted cell migration and invasion concomitant with up-regulation of αVβ3 integrin. For cancer cells treated with carbon ion irradiation, the number of pulmonary metastasis was decreased significantly in vivo. These findings suggest that particle irradiation suppresses metastatic potential even at lower dose, whereas photon irradiation promotes cell migration and invasive capabilities at lower dose level, and provide preclinical evidence that ion beam radiotherapy may be superior to conventional photon beam therapy in possible preventive effects on metastases of irradiated malignant tumor cells.

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Godoy, Salvador, L. S. Garcı́a-Colı́n et M. A. Olivares-Robles. « Generalized two stream theory for photon migration ». Physica A : Statistical Mechanics and its Applications 261, n^o 3-4 (décembre 1998) : 435–50. http://dx.doi.org/10.1016/s0378-4371(98)00329-x.

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Binzoni, T., C. Courvoisier, R. Giust, G. Tribillon, T. Gharbi, J. C. Hebden, T. S. Leung, J. Roux et D. T. Delpy. « Anisotropic photon migration in human skeletal muscle ». Physics in Medicine and Biology 51, n^o 5 (15 février 2006) : N79—N90. http://dx.doi.org/10.1088/0031-9155/51/5/n01.

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Perelman, Lev T., Jun Wu, Yang Wang, Irving Itzkan, Ramachandra R. Dasari et Michael S. Feld. « Time-dependent photon migration using path integrals ». Physical Review E 51, n^o 6 (1 juin 1995) : 6134–41. http://dx.doi.org/10.1103/physreve.51.6134.

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Lubawy, Carmalyn, et Nirmala Ramanujam. « Endoscopically compatible near-infrared photon migration probe ». Optics Letters 29, n^o 17 (1 septembre 2004) : 2022. http://dx.doi.org/10.1364/ol.29.002022.

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Richter, Steven M., Rajesh R. Shinde, Ganesh V. Balgi et Eva M. Sevick-Muraca. « Particle Sizing Using Frequency Domain Photon Migration ». Particle & ; Particle Systems Characterization 15, n^o 1 (février 1998) : 9–15. http://dx.doi.org/10.1002/(sici)1521-4117(199802)15:1<9 ::aid-ppsc9>3.0.co;2-x.

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Zhao, Xiaofen, Hongyan Liu, Bin Zhang, Fei Liu, Jianwen Luo et Jing Bai. « Fast photon-boundary intersection computation for Monte Carlo simulation of photon migration ». Optical Engineering 52, n^o 1 (3 janvier 2013) : 019001. http://dx.doi.org/10.1117/1.oe.52.1.019001.

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Matloff, Gregory Lee. « The Solar-Electric Sail : Application to Interstellar Migration and Consequences for SETI ». Universe 8, n^o 5 (19 avril 2022) : 252. http://dx.doi.org/10.3390/universe8050252.

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The Solar-Electric Sail accelerates by reflecting positively charged solar wind ions. If it is used to propel an interstellar migration mission, its interstellar cruise velocity relative to the home star cannot exceed the solar wind velocity. In an effort to analytically determine interstellar cruise velocity for a 107 kg generation ship, a constant solar wind velocity within the heliosphere of a Sun-like star of 600 km/s is assumed. The solar wind proton density at 1 AU is also considered constant at 10 protons per cubic centimeter. Solar wind density is assumed to decrease with the inverse square of solar distance. It is shown that, to maintain sufficient acceleration to achieve an interstellar cruise velocity about 70% of the solar wind velocity, the radius of the sail’s electric field is enormous—greater than 105 km. Because the solar wind velocity and density are not constant, field strength must be varied rapidly to compensate for solar wind variation. Although not competitive with the ultimate theoretical performance of solar-photon sail propelled migrations departing from Sun-like stars, the solar-electric sail might be superior in this application for migration from dim K and M main sequence stars. Such migrations conducted during close stellar encounters might have durations < 1000 terrestrial years. If only a tiny fraction of M dwarf stars host star-faring civilizations, a significant fraction of Milky Way galaxy planetary systems may have been inhabited, even if no major advances over currently postulated interstellar transportation systems are postulated. SETI theoreticians should consider this when estimating the effects of interstellar colonization.

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Lu, Shiru, Zhisen Meng, Peng Xie, Enwei Liang et Zhao Wang. « Gas-phase formation of interstellar nucleobases from dehydrogenated formamide and vinyl cyanide ». Astronomy & ; Astrophysics 656 (décembre 2021) : A84. http://dx.doi.org/10.1051/0004-6361/202140744.

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Context. Cytosine, thymine, and uracil are three of the five primary nucleobases that function as the fundamental units of the genetic code in nucleic acids. In searching the extraterrestrial origins of microscopic life, previous studies have reported formation routes of nucleobases in interstellar ice analogs. The present work explores the possibility that nucleobases could form from small molecules through gas-phase reactions in the interstellar medium (ISM). Aims. We aim to search energetically favorable synthetic routes toward the formation of cytosine, thymine, and uracil via gas-phase reactions, using first principles calculations. Based on the computation of a reaction energy barrier and reactant formation energy, we tried to identify the specific interstellar environments favorable to the formation of the nucleobases, with respect to the previously reported detection of relevant reactants in the ISM. Methods. Density functional theory calculations were carried out to investigate the chemical reaction pathways using the M06 functional with 6-31+G(d,p)/6-311++G(d,p) basis sets. An ab initio Møller-Plesset perturbation theory in the second order (MP2) was also used to corroborate the results. Results. We report synthetic routes toward the formation of cytosine, thymine, and uracil through gas-phase reactions between partially dehydrogenated formamide (H2NCHO) and vinyl cyanide (H2CCHCN). The most energetically favorable pathway to the formation of 1H-pyrimidin-2-one (C4H4N2O), a direct precursor of nucleobases, was found in a molecule-radical reaction between HNCHO and H2CCHCN, with an energy barrier of 19.3 kcal mol−1. The energy barriers for the optimal reaction pathways between C4H4N2O and amino, methyl, or hydroxyl to finally produce cytosine, thymine, or uracil are about 11.3, 18.6, or 19.9 kcal mol−1, respectively. Conclusions. The optimal energy barriers of 19.3 and 23.8 kcal mol−1 roughly correspond to a reaction rate coefficient of 10−11 cm3 s−1 at 180 and 220 K, respectively. This indicates that the reaction could be thermally feasible through a gas-phase reaction in hot molecular cores or in the inner part of the protoplanetary disks. In contrast, the energy barriers for the reactions between other dehydrogenated radicals and molecules are relatively high, which corresponds to the extinction energy of far-ultraviolet photons in photo-dissociation regions. Furthermore, the computed pathways suggest that prior H migration in the reactants could be the key rate-determining process for the synthesis of the primary nucleobases.

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Schael, Frank, Oliver Reich et Sonja Engelhard. « Spectroscopy in heterogenous media and applications for bioprocess and environmental monitoring ». International Journal of Photoenergy 4, n^o 1 (2002) : 21–26. http://dx.doi.org/10.1155/s1110662x02000041.

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Diffuse reflectance measurements and photon migration studies with near infrared (NIR) diode lasers were employed to elucidate experimental methods for determining absorption and scattering coefficients and species concentrations in heterogenous media. Measurements were performed at a number of wavelengths utilizing several laser sources some of which were widely tunable. In order to establish the applicability of simple photon migration models derived from radiation transport theory and to check the experimental boundary conditions of our measurements, simple light scattering solutions (such as suspensions of titanium dioxide, latex particles, and solutions of milk powder) containing dyes (such as nile blue, isosulfan blue) were investigated. The results obtained from diffuse-reflectance studies at different sourcedetector distances were in accordance with predictions from simple photon diffusion theory. Applications of reflectance measurements for monitoring of cell growth during fermentation processes and forin-situinvestigations of soils are presented.

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Tabe, Yoko, Yuexi Shi, Zhihong Zeng, Linhua Jin, Yixin Zhou, Takashi Miida, Michael Andreeff et Marina Konopleva. « TGF-β Neutralizing Antibody 1D11 Inhibits LIF-JAK-Stat3 Signaling and Enhances Cytarabine Induced Apoptosis in AML Cells in Bone Marrow Microenvironment ». Blood 118, n^o 21 (18 novembre 2011) : 926. http://dx.doi.org/10.1182/blood.v118.21.926.926.

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Abstract Abstract 926 We have previously reported pro-survival effects of TGF-β1 in myelo-monocytic leukemia cells (Xu et al.,Br J Haematol.2008). Hypoxia and interactions with bone marrow (BM) stromal cells have emerged as essential components of leukemic BM microenvironment that promote leukemia cell survival and chemoresistance. Our preliminary data indicate that TGF-β neutralizing antibody 1D11 (Genzyme) prevents accumulation of AML cells in a quiescent G0 state under co-culture condition with BM-derived mesenchymal stromal cells (MSC) (Jin et al., ASH abstract 2010). In turn, the chemokine CXCL12 and its receptor CXCR4 play crucial roles in cell migration and stroma/leukemia cell interactions. In this study, we investigated the anti-leukemic effects and molecular mechanisms of action of TGF-β neutralizing antibody 1D11 under hypoxic conditions. We further investigated the anti-leukemic efficacy of 1D11 combined with CXCR4 antagonist plerixafor in the in vivo leukemia models. AML cells (MV4;11 and U937) were propagated under 1% O2 for at least 14 days to assure their sustained proliferation and survival. Isotype control antibody 13C4 combined with ara-C induced no significant change in apoptosis or cell cycle progression. In MV4;11 cells cultured with 2ng/mL rhTGF-β1, 1D11 (10 μg/mL) induced only minimal apoptosis by itself, yet enhanced low-dose cytarabine (AraC, 0.5 μM) induced apoptosis. This effect was more prominent under hypoxia compared to normoxia (% of subG1 fraction, 21% O2: ara-C, 2.6 ± 0.2%, ara-C + 1D11, 10.8 ± 2.5%, p=0.03; 1% O2: ara-C, 11.3 ± 2.7%, AraC + 1D11, 21.4 ± 0.5%, p=0.001). 1D11 with ara-C abrogated rhTGFβ1-induced accumulation of cells in G0/G1 phase (21% O2; cont, 73.8 ± 4.1, rhTGFβ, 82.2 ± 3.2, rhTGFβ + AraC, 65.4 ± 2.5, rhTGFβ + AraC + 1D11, 50.3 ± 1.9, p=0.001: in 1% O2; cont, 71.8 ± 1.3, rhTGFβ, 85.4 ± 1.4, rhTGFβ + AraC, 79.3 ± 5.1, rhTGFβ + AraC + 1D11, 67.1 ± 4.0, p = 0.03). The anti-leukemic efficacy of 1D11 was next examined in an in vivo leukemia model. 1D11 administered at 5 mg/kg IP every other day in combination with ara-C (50 mg/kg IP weekly) decreased leukemia burden of nude mice injected with Baf3/ITD-luciferase leukemia cells (p=0.002). Administration of small molecule CXCR4 inhibitor plerixafor, which successfully diminished cell migration to CXCL12 in vitro, in combination with 1D11 decreased leukemia burden in vivo (p=0.05), and co-administration of ara-C, plerixafor and 1D11 was most effective (bioluminescence intensity, ×107 photons/sec) control, 1.2 ± 0.2; ara-C, 0.94 ± 0.3; plerixafor + 1D11, 0.56 ± 0.1; plerixafor + 1D11 + ara-C, 0.23 ± 0.09, p=0.003). We next examined the molecular mechanisms responsible for chemosensitization through blockade of TGFβ with 1D11. Treatment with rhTGF-β1 induced upregulation of p21 expression as well as pro-survival phosphorylation of Stat3 in MV4;11 and U937 cells, and these effects were abrogated by 1D11. Knock-down of Stat3 by siRNA increased apoptosis induction in U937 cells cultured in the presence of rhTGFβ1. Notably, 4-fold upregulation of the established TGFβ target, leukemia inhibitory factor (LIF) gene mRNA, was observed after rhTGF-β1 treatment and this was reversed by 1D11. These results indicate that 1D11 inhibits rhTGF-β1-induced autocrine stimulation of pro-survival LIF-JAK-Stat3 signal transduction pathway in AML cells. In summary, blockade of TGF-β by 1D11, and abrogation of CXCL12/CXCR4 signaling may enhance the efficacy of chemotherapy against AML cells in the hypoxic BM microenvironment. These findings warrant further investigations in human clinical trials. Disclosures: Konopleva: Genzyme: Research Funding.

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Tromayer, Maximilian, Peter Gruber, Marica Markovic, Arnulf Rosspeintner, Eric Vauthey, Heinz Redl, Aleksandr Ovsianikov et Robert Liska. « A biocompatible macromolecular two-photon initiator based on hyaluronan ». Polymer Chemistry 8, n^o 2 (2017) : 451–60. http://dx.doi.org/10.1039/c6py01787h.

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Yang, Zhenhai, Weichuang Yang, Xi Yang, J. C. Greer, Jiang Sheng, Baojie Yan et Jichun Ye. « Device physics of back-contact perovskite solar cells ». Energy & ; Environmental Science 13, n^o 6 (2020) : 1753–65. http://dx.doi.org/10.1039/c9ee04203b.

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Cubeddu, Rinaldo, Antonio Pifferi, Paola Taroni, Alessandro Torricelli et Gianluca Valentini. « A solid tissue phantom for photon migration studies ». Physics in Medicine and Biology 42, n^o 10 (1 octobre 1997) : 1971–79. http://dx.doi.org/10.1088/0031-9155/42/10/011.

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Alerstam, Erik, Stefan Andersson-Engels et Tomas Svensson. « White Monte Carlo for time-resolved photon migration ». Journal of Biomedical Optics 13, n^o 4 (2008) : 041304. http://dx.doi.org/10.1117/1.2950319.

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Gandjbakhche, Amir H., Robert F. Bonner, Andrew E. Arai et Robert S. Balaban. « Visible-light photon migration through myocardium in vivo ». American Journal of Physiology-Heart and Circulatory Physiology 277, n^o 2 (1 août 1999) : H698—H704. http://dx.doi.org/10.1152/ajpheart.1999.277.2.h698.

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Empirical data between 510 and 590 nm of diffuse reflected light from the pig heart in vivo have shown that myoglobin and cytochrome c absorption peaks with little apparent contribution of red blood cell (RBC) Hb. Monte Carlo simulations of photon migration in tissue were performed to compare the effects of myoglobin and cytochromes with those of blood Hb on photon pathlengths and diffuse reflectance of visible wavelengths (450–600 nm) from the pig heart in vivo. Wavelength dependence of the input parameters, including the transport-corrected scattering coefficients (1.1–1.2 mm−1) and the absorption coefficients of blood-free solubilized heart tissue (0.43–1.47 mm−1), as well as the absorption coefficients of Hb, were determined by an integrating sphere method and standard spectrophotometry, respectively. The Monte Carlo simulations indicate that in the 510- to 590-nm range the mean path length within the myocardium for diffusely reflected light varies from 1.4 to 1.2 mm, whereas their mean penetration depth within the epicardium is only 330–400 μm for blood-free heart tissue. Analysis shows that the blood Hb absorption extrema are only observable between 510 and 590 nm when RBC concentration in tissue is >0.5%. Blood within vessels much larger than capillaries does not contribute significantly to the spectral features, because virtually all light in this spectral range is absorbed during transit through large vessels (>100 μm). This analysis suggests that diffuse reflected light in the 510- to 590-nm region will show spectral features uniquely associated with myoglobin and cytochrome c oxygenation states within 400 μm of the surface of the heart in situ as long as the capillary RBC concentration remains <0.5%.

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Yamada, Yukio, et Yasuo Hasegawa. « FEM Analysis of Photon Migration in Biological Tissues. » Transactions of the Japan Society of Mechanical Engineers Series B 60, n^o 579 (1994) : 3705–10. http://dx.doi.org/10.1299/kikaib.60.3705.

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Reynolds, J. S., T. L. Troy et E. M. Sevick-Muraca. « Multipixel Techniques for Frequency-Domain Photon Migration Imaging ». Biotechnology Progress 13, n^o 5 (7 octobre 1997) : 669–80. http://dx.doi.org/10.1021/bp970085g.

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Everall, N., T. Hahn, P. Matousek, A. Parker et M. Towrie. « Photon Migration and Spatial Resolution in Spectroscopic Imaging ». Microscopy and Microanalysis 9, S02 (24 juillet 2003) : 1064–65. http://dx.doi.org/10.1017/s1431927603445327.

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Fedele, Francesco, Margaret J. Eppstein, Jeffrey P. Laible, Anuradha Godavarty et Eva M. Sevick-Muraca. « Fluorescence photon migration by the boundary element method ». Journal of Computational Physics 210, n^o 1 (novembre 2005) : 109–32. http://dx.doi.org/10.1016/j.jcp.2005.04.003.

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Bonner, R. F., R. Nossal, S. Havlin et G. H. Weiss. « Model for photon migration in turbid biological media ». Journal of the Optical Society of America A 4, n^o 3 (1 mars 1987) : 423. http://dx.doi.org/10.1364/josaa.4.000423.

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Perelman, Lev T., Jun Wu, Irving Itzkan et Michael S. Feld. « Photon migration in turbid media using path integrals ». Physical Review Letters 72, n^o 9 (28 février 1994) : 1341–44. http://dx.doi.org/10.1103/physrevlett.72.1341.

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Lakowicz, Joseph R., et Klaus Berndt. « Frequency-domain measurements of photon migration in tissues ». Chemical Physics Letters 166, n^o 3 (février 1990) : 246–52. http://dx.doi.org/10.1016/0009-2614(90)80024-8.

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