Prospects for Observations of Pulsars and Pulsar Wind Nebulae with CTA

The last few years have seen a revolution in very-high gamma-ray astronomy (VHE; E>100 GeV) driven largely by a new generation of Cherenkov telescopes (namely the H.E.S.S. telescope array, the MAGIC and MAGIC-II large telescopes and the VERITAS telescope array). The Cherenkov Telescope Array (CTA) project foresees a factor of 5 to 10 improvement in sensitivity above 0.1 TeV, extending the accessible energy range to higher energies up to 100 TeV, in the Galactic cut-off regime, and down to a few tens GeV, covering the VHE photon spectrum with good energy and angular resolution. As a result of the fast development of the VHE field, the number of pulsar wind nebulae (PWNe) detected has increased from one PWN in the early '90s to more than two dozen firm candidates today. Also, the low energy threshold achieved and good sensitivity at TeV energies has resulted in the detection of pulsed emission from the Crab Pulsar (or its close environment) opening new and exiting expectations about the pulsed spectra of the high energy pulsars powering PWNe. Here we discuss the physics goals we aim to achieve with CTA on pulsar and PWNe physics evaluating the response of the instrument for different configurations.Comment: accepted for publication in Astroparticle Physic

Fermi Large Area Telescope Observations of the Crab Pulsar and Nebula

We report on gamma-ray observations of the Crab Pulsar and Nebula using 8 months of survey data with the Fermi Large Area Telescope (LAT). The high quality light curve obtained using the ephemeris provided by the Nancay and Jodrell Bank radio telescopes shows two main peaks stable in phase with energy. The first gamma-ray peak leads the radio main pulse by (281 \pm 12 \pm 21) mus, giving new constraints on the production site of non-thermal emission in pulsar magnetospheres. The improved sensitivity and the unprecedented statistics afforded by the LAT enable precise measurement of the Crab Pulsar spectral parameters: cut-off energy at E_c = (5.8 \pm 0.5 \pm 1.2) GeV, spectral index of Gamma = (1.97 \pm 0.02 \pm 0.06) and integral photon flux above 100 MeV of (2.09 \pm 0.03 \pm 0.18) x 10^{-6} cm^{-2} s^{-1}. The first errors represent the statistical error on the fit parameters, while the second ones are the systematic uncertainties. Pulsed gamma-ray photons are observed up to ~ 20 GeV which precludes emission near the stellar surface, below altitudes of around 4 to 5 stellar radii in phase intervals encompassing the two main peaks. The spectrum of the nebula in the energy range 100 MeV - 300 GeV is well described by the sum of two power-laws of indices Gamma_{sync} = (3.99 \pm 0.12 \pm 0.08) and Gamma_{IC} = (1.64 \pm 0.05 \pm 0.07), corresponding to the falling edge of the synchrotron and the rising edge of the inverse Compton components, respectively. This latter, which links up naturally with the spectral data points of Cherenkov experiments, is well reproduced via inverse Compton scattering from standard Magnetohydrodynamics (MHD) nebula models, and does not require any additional radiation mechanism.Comment: 17 pages, 9 figures, Accepted for publications in Astrophysical Journa

Fermi Large Area Telescope Observations of Gamma-ray Pulsars PSR J1057-5226, J1709-4429, and J1952+3252

The Fermi Large Area Telescope (LAT) data have confirmed the pulsed emission from all six high-confidence gamma-ray pulsars previously known from the EGRET observations. We report results obtained from the analysis of 13 months of LAT data for three of these pulsars (PSR J1057-5226, PSR J1709-4429, and PSR J1952+3252) each of which had some unique feature among the EGRET pulsars. The excellent sensitivity of LAT allows more detailed analysis of the evolution of the pulse profile with energy and also of the variation of the spectral shape with phase. We measure the cutoff energy of the pulsed emission from these pulsars for the first time and provide a more complete picture of the emission mechanism. The results confirm some, but not all, of the features seen in the EGRET data.Comment: Accepted for publication in ApJ. 45 pages, 12 figures, 11 tables. Corresponding authors: O. Celik, F. Gargano, T. Reposeur, D.J. Thompso

Fermi-LAT Search for Pulsar Wind Nebulae around gamma-ray Pulsars

The high sensitivity of the Fermi-LAT (Large Area Telescope) offers the first opportunity to study faint and extended GeV sources such as pulsar wind nebulae (PWNe). After one year of observation the LAT detected and identified three pulsar wind nebulae: the Crab Nebula, Vela-X and the PWN inside MSH 15-52. In the meantime, the list of LAT detected pulsars increased steadily. These pulsars are characterized by high energy loss rates from ~3 \times 10^{33} erg s$^{-1}$ to 5 \times 10$^{38}$ erg s$^{-1}$ and are therefore likely to power a PWN. This paper summarizes the search for PWNe in the off-pulse windows of 54 LAT-detected pulsars using 16 months of survey observations. Ten sources show significant emission, seven of these likely being of magnetospheric origin. The detection of significant emission in the off-pulse interval offers new constraints on the gamma-ray emitting regions in pulsar magnetospheres. The three other sources with significant emission are the Crab Nebula, Vela-X and a new pulsar wind nebula candidate associated with the LAT pulsar PSR J1023-5746, coincident with the TeV source HESS J1023-575. We further explore the association between the H.E.S.S. and the Fermi source by modeling its spectral energy distribution. Flux upper limits derived for the 44 remaining sources are used to provide new constraints on famous PWNe that have been detected at keV and/or TeV energies.Comment: Accepted for publication in Astrophysical Journal, 42 pages, 17 figure

Targeted Therapy for Glomerulonephritis Using Arterial Delivery of Encapsulated Etanercept

Complex immunosuppressive therapy is prescribed in medical practice to patients with glomerulonephritis to help them overcome symptoms and prevent chronic renal failure. Such an approach requires long-term systemic administration of strong medications, which causes severe side effects. This work shows the efficiency of polymer capsule accumulation (2.8 ± 0.4 µm) containing labeled etanercept (100 μg per dose) in the kidneys of mice. The comparison of injection into the renal artery and tail vein shows the significant superiority of the intra-arterial administration strategy. The etanercept retention rate of 18% and 8% ID in kidneys was found 1 min and 1 h after injection, respectively. The capsules were predominantly localized in the glomeruli after injection in mice using a model of acute glomerulonephritis. Histological analysis confirmed a significant therapeutic effect only in animals with intra-arterial administration of microcapsules with etanercept. The proposed strategy combines endovascular surgery and the use of polymer microcapsules containing a high molecular weight drug that can be successfully applied to treat a wide range of kidney diseases associated with glomerular pathology

Correction to “Development of Nanocarrier-Based Radionuclide and Photothermal Therapy in Combination with Chemotherapy in Melanoma Cancer Treatment”

Correction to “Development of Nanocarrier-Based Radionuclide and Photothermal Therapy in Combination with Chemotherapy in Melanoma Cancer Treatment

Mesenchymal Stem Cells Engineering: Microcapsules-Assisted Gene Transfection and Magnetic Cell Separation

Stem cell engineeringthe manipulation and functionalization of stem cells involving genetic modificationcan significantly expand their applicability for cell therapy in humans. Toward this aim, reliable, standardized, and cost-effective methods for cell manipulation are required. Here we explore the potential of magnetic multilayer capsules to serve as a universal platform for nonviral gene transfer, stem cell magnetization, and magnetic cell separation to improve gene transfer efficiency. In particular, the following experiments were performed: (i) a study of the process of internalization of magnetic capsules into stem cells, including capsule co-localization with established markers of endo-lysosomal pathway; (ii) characterization and quantification of capsule uptake with confocal microscopy, electron microscopy, and flow cytometry; (iii) intracellular delivery of messenger RNA and separation of gene-modified cells by magnetic cell sorting (MACS); and (iv) analysis of the influence of capsules on cell proliferation potential. Importantly, based on the internalization of magnetic capsules, transfected cells became susceptible to external magnetic fields, which made it easy to enrich gene-modified cells using MACS (purity ∼95%), and also to influence their migration behavior. In summary, our results underline the high potential of magnetic capsules in stem cell functionalization, namely (i) to increase gene-transfer efficiency and (ii) to facilitate enrichment and targeting of transfected cells. Finally, we did not observe a negative impact of the capsules used on the proliferative capacity of stem cells, proving their high biocompatibility

Variation in tumor pH affects pH-triggered delivery of peptide-modified magnetic nanoparticles

Acidification of the extracellular matrix, an intrinsic characteristic of many solid tumors, is widely exploited for physiologically triggered delivery of contrast agents, drugs, and nanoparticles to tumor. However, pH of tumor microenvironment shows intra- and inter-tumor variation. Herein, we investigate the impact of this variation on pH-triggered delivery of magnetic nanoparticles (MNPs) modified with pH-(low)-insertion peptide (pHLIP). Fluorescent flow cytometry, laser confocal scanning microscopy and transmission electron microscopy data proved that pHLIP-conjugated MNPs interacted with 4T1 cells in two-dimensional culture and in spheroids more effectively at pH 6.4 than at pH 7.2, and entered the cell via clathrin-independent endocytosis. The accumulation efficiency of pHLIP-conjugated MNPs in 4T1 tumors after their intravenous injection, monitored in vivo by magnetic resonance imaging, showed variation. Analysis of the tumor pH profiles recorded with implementation of original nanoprobe pH sensor, revealed obvious correlation between pH measured in the tumor with the amount of accumulated MNPs