Hybrid Nanoreactors: Enabling an Off‐the‐Shelf Strategy for Concurrently Enhanced Chemo‐immunotherapy

Immunosuppressive tumors generally exhibit poor response to immune checkpoint blockade based cancer immunotherapy. Rationally designed hybrid nanoreactors are now presented that have integrated functions as Fenton catalysts and glutathione depletion agents for amplifying the immunogenic cell death and activating immune cells. A simple physical mixture of nanoreactors and chemodrugs in combination with immune checkpoint blockades show synergistically and concurrently enhanced chemo‐immunotherapy efficacy, inhibiting the growth of both treated primary immunosuppressive tumors and untreated distant tumors. The off‐the‐shelf strategy uses tumor antigens generated in situ and avoids cargo loading, and is thus a substantial advance in personalized nanomedicine for clinical translation.     

Ruthenium(II) complexes of aroylhydrazones: structural,electrochemical and electrostatic interactions with DNA

Four Ru(II) complexes with tridentate ligands viz. (4-hydroxy-N′-(pyridin-2-yl-ethylene) benzohydrazide [Ru(L¹)(PPh₃)₂(Cl)] (1), N′-(pyridin-2-yl-methylene) nicotinohydrazide [Ru(L²)(PPh₃)₂(Cl)] (2), N′-(1H-imidazol-2-yl-methylene)-4-hydroxybenzohydrazide [Ru(L³)(PPh₃)₂(Cl)] (3), and N′-(1H-imidazol-2-yl-methylene) nicotinohydrazide [Ru(L⁴)(PPh₃)₂(Cl)] (4) have been synthesized and characterized. The methoxy-derivative of L³H (abbreviated as L³H*) exists in E configuration with torsional angle of 179.4° around C₇-N₈-N₉-C₁₀ linkage. Single crystal structures of acetonitrile coordinated ruthenium complexes of 1 and 3 having compositins as [Ru(L¹)(PPh₃)₂(CH₃CN)]Cl (1a) and [Ru(L³)(PPh₃)₂(CH₃CN)]Cl (3a) revealed coordination of tridentate ligands with significantly distorted octahedral geometry constructed by imine nitrogen, heterocyclic nitrogen, and enolate amide oxygen, forming a cis-planar ring with trans-placement of two PPh₃ groups and a coordinated acetonitrile. Ligands (L¹H-L⁴H) and their ruthenium complexes (1–4) are characterized by ¹H, ¹³C, ³¹P NMR, and IR spectral analysis. Ru(II) complexes have reversible to quasi-reversible redox behavior having Ru(II)/Ru(III) oxidation potentials in the range of 0.40–0.71 V. The DNA binding constants determined by absorption spectral titrations with Herring Sperm DNA (HS-DNA) reveal that L⁴H and 1 interact more strongly than other ligands and Ru(II) complexes. Complexes 1–3 exhibit DNA cleaving activity possibly due to strong electrostatic interactions while 4 displays intercalation.     

Effective atomic numbers of some H-, C-, N- and O-based composite materials derived from differential incoherent scattering cross-sections

In this work, we have made an effort to determine whether the effective atomic numbers of H-, C-, N- and O-based composite materials would indeed remain a constant over the energy grid of 280–1200 keV wherein incoherent scattering dominates their interaction with photons. For this purpose, the differential incoherent scattering cross-sections of Be, C, Mg, Al, Ca and Ti were measured for three scattering angles 60°, 80° and 100° at 279.1, 661.6 and 1115.5 keV using which an expression for the effective atomic number was derived. The differential incoherent scattering cross-sections of the composite materials of interest measured at these three angles in the same set-up and substituted in this expression would yield their effective atomic number at the three energies. Results obtained in this manner for bakelite, nylon, epoxy, teflon, perspex and some sugars, fatty acids as well as amino acids agreed to within 2% of some of the other available values. It was also observed that for each of these samples, Z _eff was almost a constant at the three energies which unambiguously justified the conclusions drawn by other authors earlier [Manjunathaguru and Umesh, J. Phys. B: At. Mol. Opt. Phys. 39, 3969 (2006); Manohara et al,Nucl. Instrum. Methods B266, 3906 (2008); Manohara et al Phys. Med. Biol. 53, M377 (2008)] based on total interaction cross-sections in the energy grid of interest.     

Performance limits on three-dimensional particle localization in photon-limited microscopy

We present the performance limits on three-dimensional (3D) localization accuracy of currently used methods of wide-field superlocalization microscopy. The three methods investigated are double-helix microscopy, astigmatic imaging, and biplane detection. In the shot-noise limit, Cramer-Rao lower bound calculations show that, among these techniques, the double-helix microscope exhibits the best axial and 3D localization accuracy over short as well as long depth-of-field systems. The fundamental advantage of engineered point-spread function systems, like the double-helix, stems from the additional degrees of freedom available to control diffraction in three dimensions over variable regions of interest.     

Density of states of the binary alloy in the coherent potential approximation

The density of states of an electron in a binary alloy in the tight binding model is calculated in the single site coherent potential approximation (CPA) as a function of the concentration and the site energy difference. The fluctuations in the site energies due to the random environment is taken into account approximately by giving width to the site energy probability distribution function, which is normally a sum of two delta functions with proper weight factor.     

Charged particle motion in an electromagnetic field on Kerr background geometry

In this paper we study the trajectories of charged particles in an electromagnetic field superimposed on the Kerr background. The electromagnetic fields considered are of two types: (i) a dipole magnetic field with an associated quadrupole electric field, (ii) a uniform magnetic field. The contribution of the background geometry to the electromagnetic field is taken through the solutions of Petterson and Wald respectively. The effective potential is studied in detail for ther-motion of the particles in the equatorial plane and the orbits are obtained. The most interesting aspect of the study is the illustration of the effect of inertial frame dragging due to the rotation of the central star. This appears through the existence of nongyrating bound orbits at and inside the ergo surface. The presence of the magnetic field seems to increase the range of stable orbits, as was found in a previous study involving the Schwarzschild background.     

Molecular-scale logic gates

Currently available approaches to molecular-scale logic gates are summarized and compared. These include: chemically-controlled fluorescent and transmittance-based switches concerned with small molecules, DNA oligonucleotides with fluorescence readout, oligonucleotide reactions with DNA-based catalysts, chemically-gated photochromics, reversibly denaturable proteins, molecular machines with optical and electronic signals, two-photon fluorophores and multichromophoric transient optical switches. The photochemical principles of electron and energy transfer are involved in several of these approaches. More complex molecular logic systems with reconfigurability and superposability provide contrasts with current semiconductor electronics. Integration of simple logic functions to produce more complex ones is also discussed in terms of recent developments.     

THE EFFECT OF TREATMENT OF CHLOROPLAST MEMBRANES WITH GUANIDINE HC1 AND AQUEOUS ACETONE ON THE FLUORESCENCE OF BOUND ANS AND CHLOROPHYLL-a†

Abstract The fluorescence intensity of the extrinsic chromophore 1-anilino-naphthalene-8-sulfonate (ANS) bound to pea chloroplast fragments shows a sigmoidal rise as the pH of the suspending medium is decreased by the addition of HC1. The abrupt increase occurs at pH – 4.5. A 70% decrease in the maximal fluorescence intensity (pH range 3.5-4.5) of bound ANS was observed when soluble chloroplast proteins were removed by washing with water. Extraction of chloroplast membranes with 6 M guanidine-HC1 abolishes the acid–induced enhancement of ANS fluorescence. However, the subsequent removal of lipids (by 80% acetone extraction) from the guanidine-HC1-extracted naked membranes restores the acid-induced fluorescence increase. These results suggest that ANS binds mainly to the surface of the chloroplast membrane and the fluorescence changes of ANS by acidification mainly reflect the changes in the associated proteins. The lack of enhancement of the fluorescence of ANS by acidification of the guanidine-HCl treated membranes and the recovery of the acid-induced fluorescence rise after extraction of the lipids from the guanidine-HCl treated membranes suggest that the boundary lipids somehow prevent the entry of the ANS molecules into the hydrophobic interior of the naked membrane. The lipid-depleted, guanidine-HCl extracted naked membrane fragments do not show any shift in the position of the peak of emission of ANS (λ= 470 nm) upon acidification as the lipid-depleted preparations without guanidine-HCl treatment do (shift from 460 to 470 nm). Divalent cations (Mn²⁺, Ca²⁺, Mg²⁺) also increased ANS fluorescence intensities when added to both types of lipid-depleted chloroplast preparations. A comparative analysis of ANS fluorescence bound to the lipid-depleted and guanidine-HCl treated chloroplast fragments with that of just lipid-depleted fragments shows that the acidification of the latter brings about a greater change in the value of the relative binding sites (n) and the dissociation constant k_d of ANS than the protonation of the former. The role of chloroplast protein and lipid components in the structural changes of the thylakoid membrane imposed by external perturbations is discussed.