Mechanism For Copper(II)-Mediated Disaggregation Of A Porphyrin J-Aggregate

J-aggregates of anionic meso-tetrakis(4-sulfonatophenyl)porphyrin form at intermediate pH (2.3–3.1) in the presence of NiSO₄ or ZnSO₄ (ionic strength, I.S. = 3.2 M). These aggregates convert to monomeric porphyrin units via metallation with copper(II) ions. The kinetics for the disassembly process, as monitored by UV/vis spectroscopy, exhibits zeroth-order behavior. The observed zeroth-order rate constants show a two-term dependence on copper(II) ion concentrations: linear and second order. Also observed is an inverse dependence on hydrogen ion concentration. Activation parameters have been determined for the disassembly process leading to ΔH^≠ = (+163 ± 15) kJ·mol⁻¹ and ΔS^≠ = (+136 ± 11) J·K⁻¹. A mechanism is proposed in which copper(II) cation is in pre-equilibrium with a reactive site at the rim of the J-aggregate. An intermediate copper species is thus formed that eventually leads to the final metallated porphyrin either through an assisted attack of a second metal ion or through a direct insertion of the metal cation into the macrocycle core

Performance of a Tungsten-Cerium Fluoride Sampling Calorimeter in High-Energy Electron Beam Tests

A prototype for a sampling calorimeter made out of cerium fluoride crystals interleaved with tungsten plates, and read out by wavelength-shifting fibres, has been exposed to beams of electrons with energies between 20 and 150 GeV, produced by the CERN Super Proton Synchrotron accelerator complex. The performance of the prototype is presented and compared to that of a Geant4 simulation of the apparatus. Particular emphasis is given to the response uniformity across the channel front face, and to the prototype's energy resolution.Comment: 6 pages, 6 figures, Submitted to NIM

Temporally stable coherent states for infinite well and P\"oschl-Teller potentials

This paper is a direct illustration of a construction of coherent states which has been recently proposed by two of us (JPG and JK). We have chosen the example of a particle trapped in an infinite square-well and also in P\"oschl-Teller potentials of the trigonometric type. In the construction of the corresponding coherent states, we take advantage of the simplicity of the solutions, which ultimately stems from the fact they share a common SU(1,1) symmetry \`a la Barut--Girardello. Many properties of these states are then studied, both from mathematical and from physical points of view.Comment: 48 pages, 21 figure

Entinostat for the treatment of breast cancer

Introduction: Breast cancer accounts for 29% of malignant tumors. It is an heterogenous disease covering a spectrum of different molecular subtypes. Epigenetic aberrations may affect gene expression through DNA and histone proteins modifications thus promoting tumor progression and resistance to anti- tumor treatment. Area covered: This article explores the potential role of entinostat in the treatment of breast cancer. The clinical trials evaluating entinostat are discussed, highlighting preclinical data and early-phase clinical studies results. The emerging activity of entinostat in several clinical settings is evaluated by focusing on endocrine-resistant, HER2 positive and triple-negative breast cancer with promising activity in boosting the immune-system. Expert opinion: Entinostat, a synthetic benzamide derivative class I histone deacetylases (HDACs) inhibitor, inhibits cell proliferation and promotes apoptosis in breast cancer. Several results from clinical trials demonstrate that the addition of an epigenetic therapy to antiestrogen therapy may be an effective approach to targeting resistance pathways in breast cancer, particularly in hormone-positive disease. Agents such as entinostat may have a role in immunogenic modulation. Genetic and pharmacological inhibition studies identified HDAC as a key determinant in the reversal of carcinoma immune escape. This offers the rationale for combining HDAC inhibitors with immunotherapy, including therapeutic cancer vaccines

Stable spinning optical solitons in three dimensions

We introduce spatiotemporal spinning solitons (vortex tori) of the three-dimensional nonlinear Schrodinger equation with focusing cubic and defocusing quintic nonlinearities. The first ever found completely stable spatiotemporal vortex solitons are demonstrated. A general conclusion is that stable spinning solitons are possible as a result of competition between focusing and defocusing nonlinearities.Comment: 4 pages, 6 figures, accepted to Phys. Rev. Let

Modulational instability in periodic quadratic nonlinear materials

We investigate the modulational instability of plane waves in quadratic nonlinear materials with linear and nonlinear quasi-phase-matching gratings. Exact Floquet calculations, confirmed by numerical simulations, show that the periodicity can drastically alter the gain spectrum but never completely removes the instability. The low-frequency part of the gain spectrum is accurately predicted by an averaged theory and disappears for certain gratings. The high-frequency part is related to the inherent gain of the homogeneous non-phase-matched material and is a consistent spectral feature.Comment: 4 pages, 7 figures corrected minor misprint

Modulational instability of solitary waves in non-degenerate three-wave mixing: The role of phase symmetries

We show how the analytical approach of Zakharov and Rubenchik [Sov. Phys. JETP {\bf 38}, 494 (1974)] to modulational instability (MI) of solitary waves in the nonlinear Schr\"oedinger equation (NLS) can be generalised for models with two phase symmetries. MI of three-wave parametric spatial solitons due to group velocity dispersion (GVD) is investigated as a typical example of such models. We reveal a new branch of neck instability, which dominates the usual snake type MI found for normal GVD. The resultant nonlinear evolution is thereby qualitatively different from cases with only a single phase symmetry.Comment: 4 pages with figure

Combined X-ray microfluorescence and atomic force microscopy studies of Mg distribution in whole cells

We present in this paper a novel methodology that combines scanning x\u2010ray fluorescencee microscopy and atomic force microscopy. The combination of these two techniques allows the determination of a concentration map of Mg in whole (not sectioned) cells

Knowledge, Practice, and Attitudes of Physicians in Low- and Middle-Income Countries on Fertility and Pregnancy-Related Issues in Young Women With Breast Cancer

PURPOSE Fertility and pregnancy-related issues are highly relevant for young (≤ 40 years) patients with breast cancer. Limited evidence exists on knowledge, practice, and attitudes of physicians from low- and middle-income countries (LMICs) regarding these issues. METHODS A 19-item questionnaire adapted from an international survey exploring issues about fertility preservation and pregnancy after breast cancer was sent by e-mail between November 2019 and January 2020 to physicians from LMICs involved in breast cancer care. Descriptive analyses were performed. RESULTS A total of 288 physicians from Asia, Africa, America, and Europe completed the survey. Median age was 38 years. Responders were mainly medical oncologists (44.4%) working in an academic setting (46.9%). Among responders, 40.2% and 53.8% reported having never consulted the available international guidelines on fertility preservation and pregnancy after breast cancer, respectively. 25.0%, 19.1%, and 24.3% of responders answered to be not at all knowledgeable about embryo, oocyte, or ovarian tissue cryopreservation, respectively; 29.2%, 23.6%, and 31.3% declared that embryo, oocyte, and ovarian tissue cryopreservation were not available in their countries, respectively. 57.6% of responders disagreed or were neutral on the statement that controlled ovarian stimulation can be considered safe in patients with breast cancer. 49.7% and 58.6% of responders agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence overall or only in those with hormone receptor–positive disease, respectively. CONCLUSION This survey showed suboptimal knowledge, practice, and attitudes of physicians from LMICs on fertility preservation and pregnancy after treatment completion in young women with breast cancer. Increasing awareness and education on these aspects are needed to improve adherence to available guidelines and to promote patients' oncofertility counseling.Supported in part by the Italian Ministry of Health—5x1000 funds 2017 (no grant number) and the Italian Association for Cancer Research (AIRC; MFAG 2020 ID 24698)

In vitro evaluation of amino acid prodrugs of novel antitumour 2-(4-amino-3-methylphenyl)benzothiazoles

Novel 2-(4-aminophenyl)benzothiazoles possess highly selective, potent antitumour properties in vitro and in vivo. They induce and are biotransformed by cytochrome P450 (CYP) 1A1 to putative active as well as inactive metabolites. Metabolic inactivation of the molecule has been thwarted by isosteric replacement of hydrogen with fluorine atoms at positions around the benzothiazole nucleus. The lipophilicity of these compounds presents limitations for drug formulation and bioavailability. To overcome this problem, water soluble prodrugs have been synthesised by conjugation of alanyl- and lysyl-amide hydrochloride salts to the exocyclic primary amine function of 2-(4-aminophenyl)benzothiazoles. The prodrugs retain selectivity with significant in vitro growth inhibitory potency against the same sensitive cell lines as their parent amine, but are inactive against cell lines inherently resistant to 2-(4-aminophenyl)benzothiazoles. Alanyl and lysyl prodrugs rapidly and quantitatively revert to their parent amine in sensitive and insensitive cell lines in vitro. Liberated parent compounds are sequestered and metabolised by sensitive cells only; similarly, CYP1A1 activity and protein expression are selectively induced in sensitive carcinoma cells. Amino acid prodrugs meet the criteria of aqueous solubility, chemical stability and quantitative reversion to parent molecule, and thus are suitable for in vivo preclinical evaluation