Mechanisms of growth inhibition of primary prostate epithelial cells following gamma irradiation or photodynamic therapy including senscence, necrosis, and autophagy, but not apoptosis

In comparison to more differentiated cells, prostate cancer stem-like cells are radioresistant, which could explain radio-recurrent prostate cancer. Improvement of radiotherapeutic efficacy may therefore require combination therapy. We have investigated the consequences of treating primary prostate epithelial cells with gamma irradiation and photodynamic therapy (PDT), both of which act through production of reactive oxygen species (ROS). Primary prostate epithelial cells were cultured from patient samples of benign prostatic hyperplasia and prostate cancer prior to treatment with PDT or gamma irradiation. Cell viability was measured using MTT and alamar blue assay, and cell recovery by colony-forming assays. Immunofluorescence of gamma-H2AX foci was used to quantify DNA damage, and autophagy and apoptosis were assessed using Western blots. Necrosis and senescence were measured by propidium iodide staining and beta-galactosidase staining, respectively. Both PDT and gamma irradiation reduced the colony-forming ability of primary prostate epithelial cells. PDT reduced the viability of all types of cells in the cultures, including stem-like cells and more differentiated cells. PDT induced necrosis and autophagy, whereas gamma irradiation induced senescence, but neither treatment induced apoptosis. PDT and gamma irradiation therefore inhibit cell growth by different mechanisms. We suggest these treatments would be suitable for use in combination as sequential treatments against prostate cancer

Evidence of light guiding in ion-implanted diamond

We demonstrate the feasibility of fabricating light-waveguiding microstructures in bulk single-crystal diamond by means of direct ion implantation with a scanning microbeam, resulting in the modulation of the refractive index of the ion-beam damaged crystal. Direct evidence of waveguiding through such buried microchannels is obtained with a phase-shift micro-interferometric method allowing the study of the multimodal structure of the propagating electromagnetic field. The possibility of defining optical and photonic structures by direct ion writing opens a range of new possibilities in the design of quantumoptical devices in bulk single-crystal diamond

SARS-CoV-2 Mproinhibition by a zinc ion: structural features and hints for drug design

The first structure of the SARS-CoV-2 main protease in complex with an isolated zinc ion provides solid ground for the design of potent and selective metal-conjugated inhibitors

Identification and Characterization of Human Monoclonal Antibodies for Immunoprophylaxis against Enterotoxigenic Escherichia coli

Background. Enterotoxigenic Escherichia coli (ETEC) infections are the major cause of diarrheal morbidity among children living in developing countries. ETEC mediates small intestine adherence through bacterial adhesion followed by production of enterotoxins that induce diarrhea. Currently there is no vaccine available for ETEC. One of the most predominant adhesin of pathogenic ETEC strains is colonization factor antigen I (CFA/I). The CFA/I adhesion tip, CfaE, is required for ETEC binding to human intestinal cells and colonization. Human antibodies against CfaE have potential to block colonization of ETEC and serve as a potent immunoprophylactic against ETEC-related diarrhea. Methods. A panel of human IgG1 monoclonal antibodies (HuMAbs) were generated against CfaE. The antibodies were tested in vitro for blockage of bacterial adhesion to intestinal cells and in vivo for inhibition of bacterial colonization in the ileum. Antibody epitope analysis were performed using BioLuminate software (Schrodinger, Inc.), followed by mutagenesis of the predicted residues located in the antibody/CfaE interface and in-vitro binding assays. Results. The lead IgG1 anti-CfaE HuMAbs blocked 50% of adhesion of ETEC bacterial cells to human intestinal cells at concentrations ranging from 0.3 to 1.3 ug/ml. In vivo studies revealed 2 to 4 log decrease in colony forming units in the small intestine when the bacteria were pre-incubated with anti-CfaE MAbs as compared to an irrelevant isotype control. In silico epitope analysis revealed critical residues involved in the MAbs interaction with CfaE. Two of the leads HuMabs recognize epitopes sequence conserved across other 6 major adhesins. Conclusions. We have identified a panel of fully human IgG1 monoclonal antibodies against CfaE protein of ETEC. These antibodies are capable of blocking in vitro and in vivo ETEC adhesion to intestinal cells at low concentrations. Two lead antibodies recognizing sequence conserved epitopes have the potential for cross-protection against multiple ETEC strains

Influence of bulla volume on postbullectomy outcome

Objective: To quantify the contribution of the resected volume and the presence of associated, functionally significant emphysema to the postoperative improvement of pulmonary function after resection of giant lung bullae. Design: Patients undergoing elective surgery for giant bullae who had complete pulmonary function and radiographic studies performed were reviewed retrospectively. Setting: All 25 patients underwent surgery at the thoracic surgery unit of the University of Pisa, Pisa, Italy. Methods: Pulmonary function was assessed before and 12 months after surgery. On the chest radiograph, the location of bullae, and the signs of compression and emphysema were evaluated. The radiographic total lung capacity (TLCX-ray) and the volume of bullae were measured according to the ellipse method. Postoperatively, functional and radiographic changes were analyzed. The percentage change in forced expiratory volume in 1 s(ΔFEV1%) after surgery was the main outcome measure. The influence of factors related to emphysema and bulla volume on the functional improvement postbullectomy was assessed by stepwise multiple regression. Results: Before surgery, the TLCx-ray overestimated the TLC measured by nitrogen washout, with a mean difference between the two measurements of 1.095 L. A close relationship was found between the TLCx-ray and the plethysmographic TLC (n=6; r=0.95). After surgery, dyspnea lessened (P<0.05) and FEV1 increased (P<0.01). Statistically, the radiographic bulla volume was the single most important factor determining the ΔFEV1% (r=0.80, P<0.0001). Conclusions: These findings suggest that the preoperative size of bullae is the most important contributor to the improvement in ventilatory capacity after bullectomy, and that it is possible to predict the expected increase of postoperative FEV1 from preoperative bulla volume

Micro-beam and pulsed laser beam techniques for the micro-fabrication of diamond surface and bulk structures

Micro-fabrication in diamond is involved in a wide set of emerging technologies, exploiting the exceptional characteristics of diamond for application in bio-physics, photonics, radiation detection. Micro ion-beam irradiation and pulsed laser irradiation are complementary techniques, which permit the implementation of complex geometries, by modification and functionalization of surface and/or bulk material, modifying the optical, electrical and mechanical characteristics of the material. In this article we summarize the work done in Florence (Italy) concerning ion beam and pulsed laser beam micro-fabrication in diamond.Comment: 14 pages, 5 figure

A representation theorem for MV-algebras

An {\em MV-pair} is a pair $(B,G)$ where $B$ is a Boolean algebra and $G$ is a subgroup of the automorphism group of $B$ satisfying certain conditions. Let $\sim_G$ be the equivalence relation on $B$ naturally associated with $G$. We prove that for every MV-pair $(B,G)$, the effect algebra $B/\sim_G$ is an MV- effect algebra. Moreover, for every MV-effect algebra $M$ there is an MV-pair $(B,G)$ such that $M$ is isomorphic to $B/\sim_G$

A quantum logical and geometrical approach to the study of improper mixtures

We study improper mixtures from a quantum logical and geometrical point of view. Taking into account the fact that improper mixtures do not admit an ignorance interpretation and must be considered as states in their own right, we do not follow the standard approach which considers improper mixtures as measures over the algebra of projections. Instead of it, we use the convex set of states in order to construct a new lattice whose atoms are all physical states: pure states and improper mixtures. This is done in order to overcome one of the problems which appear in the standard quantum logical formalism, namely, that for a subsystem of a larger system in an entangled state, the conjunction of all actual properties of the subsystem does not yield its actual state. In fact, its state is an improper mixture and cannot be represented in the von Neumann lattice as a minimal property which determines all other properties as is the case for pure states or classical systems. The new lattice also contains all propositions of the von Neumann lattice. We argue that this extension expresses in an algebraic form the fact that -alike the classical case- quantum interactions produce non trivial correlations between the systems. Finally, we study the maps which can be defined between the extended lattice of a compound system and the lattices of its subsystems.Comment: submitted to the Journal of Mathematical Physic