Nanoparticles offer clear advantages for both passive and active penetration into biologically important membranes. However, the uptake and localization mechanism of nanoparticles within living ...plants, plant cells, and organelles has yet to be elucidated. Here, we examine the subcellular uptake and kinetic trapping of a wide range of nanoparticles for the first time, using the plant chloroplast as a model system, but validated in vivo in living plants. Confocal visible and near-infrared fluorescent microscopy and single particle tracking of gold-cysteine-AF405 (GNP-Cys-AF405), streptavidin-quantum dot (SA-QD), dextran and poly(acrylic acid) nanoceria, and various polymer-wrapped single-walled carbon nanotubes (SWCNTs), including lipid-PEG-SWCNT, chitosan-SWCNT and 30-base (dAdT) sequence of ssDNA (AT)15 wrapped SWCNTs (hereafter referred to as ss(AT)15-SWCNT), are used to demonstrate that particle size and the magnitude, but not the sign, of the zeta potential are key in determining whether a particle is spontaneously and kinetically trapped within the organelle, despite the negative zeta potential of the envelope. We develop a mathematical model of this lipid exchange envelope and penetration (LEEP) mechanism, which agrees well with observations of this size and zeta potential dependence. The theory predicts a critical particle size below which the mechanism fails at all zeta potentials, explaining why nanoparticles are critical for this process. LEEP constitutes a powerful particulate transport and localization mechanism for nanoparticles within the plant system.
This paper presents data and analysis of SN 2010kd, a low-redshift (z = 0.101) H-deficient superluminous supernova (SLSN), based on ultraviolet/optical photometry and optical spectroscopy spanning ...between −28 and +194 days relative to B-band maximum light. The B-band light-curve comparison of SN 2010kd with a subset of well-studied SLSNe I at comparable redshifts indicates that it is a slow-decaying PTF12dam-like SLSN. Analytical light-curve modeling using the Minim code suggests that the bolometric light curve of SN 2010kd favors circumstellar matter interaction for the powering mechanism. SYNAPPS modeling of the early-phase spectra does not identify broad H or He lines, whereas the photospheric-phase spectra are dominated by O i, O ii, C ii, C iv, and Si ii, in particular the presence of both low- and high-velocity components of O ii and Si ii lines. The nebular-phase spectra of SN 2010kd are dominated by O i and Ca ii emission lines similar to those seen in other SLSNe I. The line velocities in SN 2010kd exhibit flatter evolution curves similar to SN 2015bn but with comparatively higher values. SN 2010kd shows a higher single-zone local thermodynamic equilibrium temperature in comparison to PTF12dam and SN 2015bn, and it has an upper O i ejected mass limit of ∼10 M . The host of SN 2010kd is a dwarf galaxy with a high star formation rate (∼0.18 0.04 M yr−1) and extreme emission lines.
ABSTRACT
Photometric and spectroscopic analyses of the intermediate-luminosity Type Ib supernova (SN) 2015ap and of the heavily reddened Type Ib SN 2016bau are discussed. Photometric properties of ...the two SNe, such as colour evolution, bolometric luminosity, photospheric radius, temperature, and velocity evolution, are also constrained. The ejecta mass, synthesized nickel mass, and kinetic energy of the ejecta are calculated from their light-curve analysis. We also model and compare the spectra of SN 2015ap and SN 2016bau at various stages of their evolution. The P Cygni profiles of various lines present in the spectra are used to determine the velocity evolution of the ejecta. To account for the observed photometric and spectroscopic properties of the two SNe, we have computed 12 M⊙ zero-age main-sequence (ZAMS) star models and evolved them until the onset of core-collapse using the publicly available stellar-evolution codeMESA. Synthetic explosions were produced using the public version of STELLA and another publicly available code, SNEC, utilizing the MESA models. SNEC and stella provide various observable properties such as the bolometric luminosity and velocity evolution. The parameters produced by SNEC/STELLA and our observations show close agreement with each other, thus supporting a 12 M⊙ ZAMS star as the possible progenitor for SN 2015ap, while the progenitor of SN 2016bau is slightly less massive, being close to the boundary between SN and non-SN as the final product.
To compare the five scoring systems in assessing grading and staging of liver biopsies from patients with chronic viral hepatitis and their problems and pitfalls.
Liver biopsies from 25 patients with ...chronic viral hepatitis were studied. Sections were stained with Haematoxylin and Eosin, Reticulin and Masson's Trichrome stains. Van Gieson, Perl's and Shikata's Orcein stains were used as and when required. Coded histological sections were scored independently by three histopathologists using the Knodell Histology Activity Index (HAI), the Scheuer scoring system, Ishak's system, Metavir system and Ishak modified HAI.
There were 15 males and 10 females. Their mean age was 51.24 years. On histological examination, hepatocytes showed degenerative changes with varying grades of necrosis (spotty and confluent). Widening of portal tracts with varying severity of mononuclear inflammatory infiltrate and interface hepatitis was observed. Fibrosis appeared as periportal, portal-portal and portal-central septa. A significant agreement was found by kappa statistics for both grading (p< 0.001) as well as staging (p < 0.001) among all the five scoring systems. Lobular activity was the only parameter that showed some discrepancy. No significant intra observer difference was observed.
It is concluded that all the scoring systems are equally good for grading and staging in the hands of an experienced hepatopathologists.
ABSTRACT
We present and perform a detailed analysis of multiwavelength observations of GRB 140102A, an optical bright GRB with an observed reverse shock (RS) signature. Observations of this GRB were ...acquired with the BOOTES-4 robotic telescope, the Fermi, and the Swift missions. Time-resolved spectroscopy of the prompt emission shows that changes to the peak energy (Ep) tracks intensity and the low-energy spectral index seems to follow the intensity for the first episode, whereas this tracking behaviour is less clear during the second episode. The fit to the afterglow light curves shows that the early optical afterglow can be described with RS emission and is consistent with the thin shell scenario of the constant ambient medium. The late time afterglow decay is also consistent with the prediction of the external forward shock model. We determine the properties of the shocks, Lorentz factor, magnetization parameters, and ambient density of GRB 140102A, and compare these parameters with another 12 GRBs, consistent with having RS produced by thin shells in an interstellar medium like medium. The value of the magnetization parameter (RB ≈ 18) indicates a moderately magnetized baryonic dominant jet composition for GRB 140102A. We also report the host galaxy photometric observations of GRB 140102A obtained with 10.4 m GTC, 3.5 m Calar Alto Astronomical Observatory, and 3.6 m Devasthal optical telescope and find the host (photo z = $2.8^{+0.7}_{-0.9}$) to be a high-mass, star-forming galaxy with a star formation rate of $20 \pm 10 {\rm ~M_{\odot }}\, \rm yr^{-1}$.
•SATB1 is differentially expressed in various subsets of thymocytes.•SATB1 is downregulated in mature CD4+ cells that exit thymus.•TCR signaling positively regulates SATB1 expression during thymocyte ...development and in peripheral CD4+ T cells.•GATA-3 directly regulates SATB1 expression.•SATB1 and Foxp3 are expressed mutually exclusively during thymocyte development.
T lymphocyte development and differentiation is a multi-step process that begins in the thymus and completed in the periphery. Sequential development of thymocytes is dependent on T cell receptor (TCR) signaling and an array of transcription factors. In this study we show that special AT-rich binding protein 1 (SATB1), a T lineage-enriched chromatin organizer and regulator, is induced in response to TCR signaling during early thymocyte development. SATB1 expression profile coincides with T lineage commitment and upregulation of SATB1 correlates with positive selection of thymocytes. CD4 thymocytes exhibit a characteristic bimodal expression pattern that corresponds to immature and mature CD4 thymocytes. We also demonstrate that GATA3, the key transcriptional regulator of αβ T cells positively regulates SATB1 expression in thymocytes suggesting an important role for SATB1 during T cell development.
ABSTRACT
Multipulsed GRB 190530A, detected by the Gamma-ray Burst Monitor (GBM) and Large Area Telescope onboard Fermi, is the sixth most fluent GBM burst detected so far. This paper presents the ...timing, spectral, and polarimetric analysis of the prompt emission observed using AstroSat and Fermi to provide insight into the prompt emission radiation mechanisms. The time-integrated spectrum shows conclusive proof of two breaks due to peak energy and a second lower energy break. Time-integrated (55.43 ± 21.30 per cent) as well as time-resolved polarization measurements, made by the Cadmium Zinc Telluride Imager (CZTI) onboard AstroSat, show a hint of high degree of polarization. The presence of a hint of high degree of polarization and the values of low energy spectral index (αpt) do not run over the synchrotron limit for the first two pulses, supporting the synchrotron origin in an ordered magnetic field. However, during the third pulse, αpt exceeds the synchrotron line of death in few bins, and a thermal signature along with the synchrotron component in the time-resolved spectra is observed. Furthermore, we also report the earliest optical observations constraining afterglow polarization using the MASTER (P < 1.3 per cent) and the redshift measurement (z = 0.9386) obtained with the 10.4 m GTC (Gran Telescopio Canarias) telescopes. The broad-band afterglow can be described with a forward shock model for an ISM (interstellar medium)-like medium with a wide jet opening angle. We determine a circumburst density of n0 ∼ 7.41, kinetic energy EK ∼ 7.24 × 1054 erg, and radiated gamma-ray energy Eγ,iso ∼ 6.05 × 1054 erg.
The present work demonstrates a novel concept for intratumoral chemo-radio combination therapy for locally advanced solid tumors. For some locally advanced tumors, chemoradiation is currently ...standard of care. This combination treatment can cause acute and long term toxicity that can limit its use in older patients or those with multiple medical comorbidities. Intratumoral chemotherapy has the potential to address the problem of systemic toxicity that conventional chemotherapy suffers, and may, in our view, be a better strategy for treating certain locally advanced tumors. The present study proposes how intratumoral chemoradiation can be best implemented. The enabling concept is the use of a new chemotherapeutic formulation in which chemotherapy drugs (e.g., paclitaxel (PTX)) are co-encapsulated with radioluminecsnt nanoparticles (e.g., CaWO
(CWO) nanoparticles (NPs)) within protective capsules formed by biocompatible/biodegradable polymers (e.g., poly(ethylene glycol)-poly(lactic acid) or PEG-PLA). This drug-loaded polymer-encapsulated radioluminescent nanoparticle system can be locally injected in solution form into the patient's tumor before the patient receives normal radiotherapy (e.g., 30-40 fractions of 2-3 Gy daily X-ray dose delivered over several weeks for locally advanced head and neck tumors). Under X-ray irradiation, the radioluminescent nanoparticles produce UV-A light that has a radio-sensitizing effect. These co-encapsulated radioluminescent nanoparticles also enable radiation-triggered release of chemo drugs from the polymer coating layer. The non-toxic nature (absence of dark toxicity) of this drug-loaded polymer-encapsulated radioluminescent nanoparticle ("PEG-PLA/CWO/PTX") formulation was confirmed by the MTT assay in cancer cell cultures. A clonogenic cell survival assay confirmed that these drug-loaded polymer-encapsulated radioluminescent nanoparticles significantly enhance the cancer cell killing effect of radiation therapy. In vivo study validated the efficacy of PEG-PLA/CWO/PTX-based intratumoral chemo-radio therapy in mouse tumor xenografts (in terms of tumor response and mouse survival). Results of a small-scale NP biodistribution (BD) study demonstrate that PEG-PLA/CWO/PTX NPs remained at the tumor sites for a long period of time (> 1 month) following direct intratumoral administration. A multi-compartmental pharmacokinetic model (with rate constants estimated from in vitro experiments) predicts that this radiation-controlled drug release technology enables significant improvements in the level and duration of drug availability within the tumor (throughout the typical length of radiation treatment, i.e., > 1 month) over conventional delivery systems (e.g., PEG-PLA micelles with no co-encapsulated CaWO
, or an organic liquid, e.g., a 50:50 mixture of Cremophor EL and ethanol, as in Taxol), while it is capable of maintaining the systemic level of the chemo drug far below the toxic threshold limit over the entire treatment period. This technology thus has the potential to offer a new therapeutic option that has not previously been available for patients excluded from conventional chemoradiation protocols.
PDF
