The role of the immune system in brain metastasis

Metastatic brain tumors are the most common brain tumors in adults. With numerous successful advancements in systemic treatment of most common cancer types, brain metastasis is becoming increasingly important in the overall prognosis of cancer patients. Brain metastasis of peripheral tumor is the result of complex interplay of primary tumor, immune system and central nervous system microenvironment. Once formed, brain metastases hide behind the blood brain barrier and become inaccessible to chemotherapies that are otherwise successful in targeting systemic cancer. The approval of immune checkpoint inhibitors for several common cancers such as advanced melanoma and lung cancers brings with it the opportunity and obligation to further understand the mechanisms of immunosuppression by tumors that spread to the brain as well as the interaction between the brain environment and tumor microenvironment. In this review paper we define the central role of the immune system in the development of brain metastases. We performed a comprehensive review of the literature to outline the molecular mechanisms of immunosuppression used by tumors and how the immune system interacts with the central nervous system to facilitate brain metastasis. In particular we discuss the tumor-type-specific mechanisms of metastasis of cancers that preferentially metastasize to the brain as well as the therapies that effectively modulate the immune response, such as immune checkpoint inhibitors and vaccines

Is the iPhone an accurate and useful tool for the monitoring of spinal deformity?

The progression of spinal deformity is traditionally monitored by spinal surgeons using the Cobb method on hardcopy radiographs with a protractor and pencil. The rotation of the spine and ribcage (rib hump) in scoliosis is measured with a simple hand-held inclinometer (Scoliometer). The iPhone and other smart phones have the capability to accurately sense inclination, and can therefore be used to measure Cobb angles and rib hump angulation. The purpose of this study was to quantify the performance of the iPhone compared to a standard protractor for measuring Cobb angles and the Scoliometer for measuring rib humps. The study concluded that the iPhone is a clinically equivalent measuring tool to the traditional protractor and Scoliomete

Continuum states from time-dependent density functional theory

Linear response time-dependent density functional theory is used to study low-lying electronic continuum states of targets that can bind an extra electron. Exact formulas to extract scattering amplitudes from the susceptibility are derived in one dimension. A single-pole approximation for scattering phase shifts in three dimensions is shown to be more accurate than static exchange for singlet electron-He$^+$ scattering.Comment: 5 pages, 2 figures, J. Chem. Phys. accepte

Multielectron Redox Chemistry of Transition Metal Complexes Supported by a Non‐Innocent N3P2 Ligand: Synthesis, Characterization, and Catalytic Properties

A new redox‐active, diarylamido‐based ligand (LN3P2) capable of κ5‐N,N,N,P,P chelation has been used to prepare a series of complexes with the general formula [MII(LN3P2)]X, where M = Fe (1; X = OTf), Co (2; X = ClO4), or Ni (3; X = ClO4). The diarylamido core of monoanionic LN3P2 is derived from bis(2‐amino‐4‐methylphenyl)amine, which undergoes condensation with two equivalents of 2‐(diphenylphosphanyl)benzaldehyde to provide chelating arms with both arylphosphine and imine donors. X‐ray structural, magnetic, and spectroscopic studies indicate that the N3P2 coordination environment generally promotes low‐spin configurations. Three quasi‐reversible redox couples between +1.0 and –1.5 V (vs. Fc+/Fc) were observed in voltammetric studies of each complex, corresponding to MII/MIII oxidation, LN3P2‐based oxidation, and MII/MI reduction (in order of highest to lowest potential). Spectroscopic and computational analyses of 3ox – generated via chemical one‐electron oxidation of 3 – revealed that a stable diarylaminyl radical (LN3P2·) is formed upon oxidation. The ability of the CoII complex (2) to function as an electrocatalyst for H2 generation was evaluated in the presence of weak acids. Moderate activity was observed using 4‐tert‐butylphenol as the proton source at potentials below –2.0 V. The insights gained here will assist in the future design of pentadentate mixed N/P‐based chelates for catalytic processes

2D Multi-Angle, Multi-Group Neutrino Radiation-Hydrodynamic Simulations of Postbounce Supernova Cores

We perform axisymmetric (2D) multi-angle, multi-group neutrino radiation-hydrodynamic calculations of the postbounce phase of core-collapse supernovae using a genuinely 2D discrete-ordinate (S_n) method. We follow the long-term postbounce evolution of the cores of one nonrotating and one rapidly-rotating 20-solar-mass stellar model for ~400 milliseconds from 160 ms to ~550 ms after bounce. We present a multi-D analysis of the multi-angle neutrino radiation fields and compare in detail with counterpart simulations carried out in the 2D multi-group flux-limited diffusion (MGFLD) approximation to neutrino transport. We find that 2D multi-angle transport is superior in capturing the global and local radiation-field variations associated with rotation-induced and SASI-induced aspherical hydrodynamic configurations. In the rotating model, multi-angle transport predicts much larger asymptotic neutrino flux asymmetries with pole to equator ratios of up to ~2.5, while MGFLD tends to sphericize the radiation fields already in the optically semi-transparent postshock regions. Along the poles, the multi-angle calculation predicts a dramatic enhancement of the neutrino heating by up to a factor of 3, which alters the postbounce evolution and results in greater polar shock radii and an earlier onset of the initially rotationally weakened SASI. In the nonrotating model, differences between multi-angle and MGFLD calculations remain small at early times when the postshock region does not depart significantly from spherical symmetry. At later times, however, the growing SASI leads to large-scale asymmetries and the multi-angle calculation predicts up to 30% higher average integral neutrino energy deposition rates than MGFLD.Comment: 20 pages, 21 figures. Minor revisions. Accepted for publication in ApJ. A version with high-resolution figures may be obtained from http://www.stellarcollapse.org/papers/Ott_et_al2008_multi_angle.pd

Bimetallic Cooperativity in Proton Reduction with an Amido‐Bridged Cobalt Catalyst

The bimetallic catalyst [CoII2(L1)(bpy)2]ClO4 (1), in which L1 is an [NN′2O2] fused ligand, efficiently reduced H+ to H2 in CH3CN in the presence of 100 equiv of HOAc with a turnover number of 18 and a Faradaic efficiency of 94 % after 3 h of bulk electrolysis at −1.6 V (vs. Ag/AgCl). This observation allowed the proposal that this bimetallic cooperativity is associated with distance, angle, and orbital alignment of the two Co centers, as promoted by the unique Co−Namido−Co environment offered by L1. Experimental results revealed that the parent [CoIICoII] complex undergoes two successive metal‐based 1 e− reductions to generate the catalytically active species [CoICoI], and DFT calculations suggested that addition of a proton to one CoI triggers a cooperative 1 e− transfer by each of these CoI centers. This 2 e− transfer is an alternative route to generate a more reactive [CoII(CoII−H−)] hydride, thus avoiding the CoIII−H− required in monometallic species. This [CoII(CoII−H−)] species then accepts another H+ to release H2

Combined visible and near-infrared OPA for wavelength scaling experiments in strong-field physics

We report the operation of an optical parametric amplifier (OPA) capable of producing gigawatt peak-power laser pulses with tunable wavelength in either the visible or near-infrared spectrum. The OPA has two distinct operation modes (i) generation of >350 uJ, sub 100 fs pulses, tunable between 1250 - 1550 nm; (ii) generation of >190 uJ, sub 150 fs pulses tunable between 490 - 530 nm. We have recorded high-order harmonic spectra over a wide range of driving wavelengths. This flexible source of femtosecond pulses presents a useful tool for exploring the wavelength-dependence of strong-field phenomena, in both the multi-photon and tunnel ionization regimes.Comment: 14 pages, 9 figures, This paper was published in Proceedings of SPIE 10088, Nonlinear Frequency Generation and Conversion: Materials and Devices XVI, doi 10.1117/12.225077