Phase diagrams of site diluted ferromagnetic semi infinite system

The spin correlations functions of face-centered cubic semi-infinite system are investigated by using the high  temperature series expansions extrapolated with the Padé approximant method for Heisenberg, XY and Ising models. The magnetic phase diagrams tc(n) versus the dilution x are obtained. The value obtained of the percolation threshold is. Xp≈0.2 The Xp is defined as the concentration at which tc =0The spin correlations functions of face-centered cubic semi-infinite system are investigated by using the high  temperature series expansions extrapolated with the Padé approximant method for Heisenberg, XY and Ising models. The magnetic phase diagrams tc(n) versus the dilution x are obtained. The value obtained of the percolation threshold is. Xp≈0.2 The Xp is defined as the concentration at which tc =

Phase diagrams of site diluted semi infinite ferromagnetic film

The magnetic susceptibility of a semi-infinite ferromagnetic films with a simple cubic lattice and the face centered cubic lattice is investigated by the method of exact high-temperature series expansions (HTSE) extrapolated with the Padé approximants method for Heisenberg, XY and Ising models. The magnetic phase diagrams in (tc (ν), c) plane are obtained. The value of the percolation threshold Xp is obtained. The Xp is defined at which tc= 0.The magnetic susceptibility of a semi-infinite ferromagnetic films with a simple cubic lattice and the face centered cubic lattice is investigated by the method of exact high-temperature series expansions (HTSE) extrapolated with the Padé approximants method for Heisenberg, XY and Ising models. The magnetic phase diagrams in (tc (ν), c) plane are obtained. The value of the percolation threshold Xp is obtained. The Xp is defined at which tc= 0

Phase diagrams of nanoparticles of diluted magnetic semiconductors

The magnetic properties of diluted magnetic semi conductors (DMS)Cd1-xMnxTe are investigated. Using the mean field theory, we have evaluated the critical temperature from the nearest neighbour interactions and the energy exchange for the different diameter of the Cd0.5Mn0.5Te nanoparticle. The critical exponents are obtained. The magnetic phase diagrams (Tc versus dilution ) have been determined by the High-temperature series expansions. The critical exponents associated with the magnetic susceptibility (g) and correlation lengths (v) are deduced.The magnetic properties of diluted magnetic semi conductors (DMS)Cd1-xMnxTe are investigated. Using the mean field theory, we have evaluated the critical temperature from the nearest neighbour interactions and the energy exchange for the different diameter of the Cd0.5Mn0.5Te nanoparticle. The critical exponents are obtained. The magnetic phase diagrams (Tc versus dilution ) have been determined by the High-temperature series expansions. The critical exponents associated with the magnetic susceptibility (g) and correlation lengths (v) are deduced

Study of the magnetic order in chromium spinel systems

We present a study of the magnetic properties of the A1-x CuxCr2X4 (A=Dp,Zn,....; X=S,Se,O,...)chromium spinel systems. Using the mean field theory, we have evaluated the nearest neighbour, the next-neighbour super-exchange, and the third next nearest neighbour interaction J1(x), J2(x) and J3(x), respectively for the Zn1-xCuxCr2Se4and J1(x), J2(x) for the Cd1-xCuxCr2Se4systems in the whole range of concentration 0≤x≤1. By using the high-temperature series expansions combined with the Padé approximants method, we have obtained the magnetic phase diagrams in Tc versus dilution c. A spin glass phase is predicted for intermediate range of concentration. The obtained results are in agreement with experimental ones obtained by magnetic measurements for the systems studied. The critical exponents associated with the magnetic susceptibility g and the correlation lengths n have been deduced. The obtained values are comparable to those of 3D Heisenberg model, and are insensitive to the dilution c.We present a study of the magnetic properties of the A1-x CuxCr2X4 (A=Dp,Zn,....; X=S,Se,O,...)chromium spinel systems. Using the mean field theory, we have evaluated the nearest neighbour, the next-neighbour super-exchange, and the third next nearest neighbour interaction J1(x), J2(x) and J3(x), respectively for the Zn1-xCuxCr2Se4and J1(x), J2(x) for the Cd1-xCuxCr2Se4systems in the whole range of concentration 0≤x≤1. By using the high-temperature series expansions combined with the Padé approximants method, we have obtained the magnetic phase diagrams in Tc versus dilution c. A spin glass phase is predicted for intermediate range of concentration. The obtained results are in agreement with experimental ones obtained by magnetic measurements for the systems studied. The critical exponents associated with the magnetic susceptibility g and the correlation lengths n have been deduced. The obtained values are comparable to those of 3D Heisenberg model, and are insensitive to the dilution c

Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer

Background: Effective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy. Results: Breast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to first–line chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes. Conclusion: This study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer

The Epistemology of Intentionality: Notional Constituents vs. Direct Grasp

Franz Brentano is well known for highlighting the importance of intentionality, but he said curiously little about the nature of intentionality. According to Mark Textor, there is a deep reason for this: Brentano took intentionality to be a conceptual primitive the nature of which is revealed only in direct grasp. Although there is certainly textual support for this interpretation, it appears in tension with Brentano’s repeated attempts to analyze intentionality in terms of ‘notional constituents’ – aspects of intentionality which cannot come apart in reality but which can be conceptually distinguished. After bringing out this tension, I explore some options for resolving it, ultimately offering my own favored interpretation

Comparative evaluation of NOTCH signaling molecules in the endometrium of women with various gynecological diseases during the window of implantation

Objective(s): NOTCH signaling pathway is well known for its role in cell fate, cell survival, cell differentiation, and apoptosis. Some of the NOTCH signaling genes are critical for endometrial function and implantation in animals and appear to play a similar role in humans. The purpose of the current study was to investigate the potential roles of some main components of the NOTCH family in human endometrium during implantation period in common gynecological diseases. Materials and Methods: Endometrial NOTCH receptors NOTCH1, 3, 4 and ligand JAG1, 2 and survivin mRNA expression were investigated using the Q-PCR technique and the amount of the JAG1, 2 proteins was also determined by Western blot. Samples were obtained from 12 patients with endometriosis, 12 patients with repeated implantation failure (RIF), 12 patients with Polycystic Ovary Syndrome (PCOS) and 10 healthy fertile women as a control group. Data were analyzed using SPSS version 18. Group comparisons were performed by one-way ANOVA or Kruskal-Wallis. Results: All patient groups failed to show the expected mid-luteal increase in NOTCH1, JAG 1, 2, and survivin expression as documented in the control group. Moreover, a significant rise in NOTCH3 expression levels was found only in PCOS women. There was a direct correlation between gene expression and protein level for JAG 1, 2. Conclusion: Aberrant NOTCH signaling molecules expression suggests that altered development of the endometrium at the molecular level may be associated with the impaired decidualization and implantation failure in gynecological disorders such as endometriosis, PCOS, and RIF. © 2019, Mashhad University of Medical Sciences. All rights reserved

A Phase 1, Dose Escalation Study of Guadecitabine (SGI-110) in Combination with Pembrolizumab in Patients with Solid Tumours

Background: Data suggest that immunomodulation induced by DNA hypomethylating agents can sensitize tumors to immune checkpoint inhibitors. We conducted a phase 1 dose-escalation trial (NCT02998567) of guadecitabine and pembrolizumab in patients with advanced solid tumors. We hypothesized that guadecitabine will overcome pembrolizumab resistance. Methods: Patients received guadecitabine (45 mg/m 2 or 30 mg/m 2, administered subcutaneously on days 1-4), with pembrolizumab (200 mg administered intravenously starting from cycle 2 onwards) every 3 weeks. Primary endpoints were safety, tolerability and maximum tolerated dose; secondary and exploratory endpoints included objective response rate (ORR), changes in methylome, transcriptome, immune contextures in pre-treatment and on-treatment tumor biopsies. Results: Between January 2017 and January 2020, 34 patients were enrolled. The recommended phase II dose was guadecitabine 30 mg/m 2, days 1-4, and pembrolizumab 200 mg on day 1 every 3 weeks. Two dose-limiting toxicities (neutropenia, febrile neutropenia) were reported at guadecitabine 45 mg/m 2 with none reported at guadecitabine 30 mg/m 2. The most common treatment-related adverse events (TRAEs) were neutropenia (58.8%), fatigue (17.6%), febrile neutropenia (11.8%) and nausea (11.8%). Common, grade 3+ TRAEs were neutropaenia (38.2%) and febrile neutropaenia (11.8%). There were no treatment-related deaths. Overall, 30 patients were evaluable for antitumor activity; ORR was 7% with 37% achieving disease control (progression-free survival) for ≥24 weeks. Of 12 evaluable patients with non-small cell lung cancer, 10 had been previously treated with immune checkpoint inhibitors with 5 (42%) having disease control ≥24 weeks (clinical benefit). Reduction in LINE-1 DNA methylation following treatment in blood (peripheral blood mononuclear cells) and tissue samples was demonstrated and methylation at transcriptional start site and 5' untranslated region gene regions showed enriched negative correlation with gene expression. Increases in intra-tumoural effector T-cells were seen in some responding patients. Patients having clinical benefit had high baseline inflammatory signature on RNAseq analyses. Conclusions: Guadecitabine in combination with pembrolizumab is tolerable with biological and anticancer activity. Reversal of previous resistance to immune checkpoint inhibitors is demonstrated

Phase 1, dose-escalation study of guadecitabine (SGI-110) in combination with pembrolizumab in patients with solid tumors

Background: Data suggest that immunomodulation induced by DNA hypomethylating agents can sensitize tumors to immune checkpoint inhibitors. We conducted a phase 1 dose-escalation trial (NCT02998567) of guadecitabine and pembrolizumab in patients with advanced solid tumors. We hypothesized that guadecitabine will overcome pembrolizumab resistance. Methods: Patients received guadecitabine (45 mg/m 2 or 30 mg/m 2, administered subcutaneously on days 1-4), with pembrolizumab (200 mg administered intravenously starting from cycle 2 onwards) every 3 weeks. Primary endpoints were safety, tolerability and maximum tolerated dose; secondary and exploratory endpoints included objective response rate (ORR), changes in methylome, transcriptome, immune contextures in pre-treatment and on-treatment tumor biopsies. Results: Between January 2017 and January 2020, 34 patients were enrolled. The recommended phase II dose was guadecitabine 30 mg/m 2, days 1-4, and pembrolizumab 200 mg on day 1 every 3 weeks. Two dose-limiting toxicities (neutropenia, febrile neutropenia) were reported at guadecitabine 45 mg/m 2 with none reported at guadecitabine 30 mg/m 2. The most common treatment-related adverse events (TRAEs) were neutropenia (58.8%), fatigue (17.6%), febrile neutropenia (11.8%) and nausea (11.8%). Common, grade 3+ TRAEs were neutropaenia (38.2%) and febrile neutropaenia (11.8%). There were no treatment-related deaths. Overall, 30 patients were evaluable for antitumor activity; ORR was 7% with 37% achieving disease control (progression-free survival) for ≥24 weeks. Of 12 evaluable patients with non-small cell lung cancer, 10 had been previously treated with immune checkpoint inhibitors with 5 (42%) having disease control ≥24 weeks (clinical benefit). Reduction in LINE-1 DNA methylation following treatment in blood (peripheral blood mononuclear cells) and tissue samples was demonstrated and methylation at transcriptional start site and 5' untranslated region gene regions showed enriched negative correlation with gene expression. Increases in intra-tumoural effector T-cells were seen in some responding patients. Patients having clinical benefit had high baseline inflammatory signature on RNAseq analyses. Conclusions: Guadecitabine in combination with pembrolizumab is tolerable with biological and anticancer activity. Reversal of previous resistance to immune checkpoint inhibitors is demonstrated

Epigenetic potentiation of somatostatin-2 by guadecitabine in neuroendocrine neoplasias as a novel method to allow delivery of peptide receptor radiotherapy

Background Somatostatin receptor-2 (SSTR2) is expressed on cell surface of neuroendocrine neoplasias; its presence is exploited for the delivery of peptide receptor radionuclide therapy (PRRT). Patients with no or low expression of SSTR2 are not candidates for PRRT. SSTR2 promotor undergoes epigenetic modification, known to regulate gene expression. We investigated whether the demethylation agent, guadecitabine, could enhance the expression of SSTR2 in NET models, using radioligand uptake/PET imaging as a biomarker of epigenetic modification. Methods The effects of guadecitabine on the transcriptional, translational, and functional regulation of SSTR2 both in vitro and in vivo using low (QGP-1) and high (BON-1) methylated neuroendocrine neoplasia models was characterised. Promotor region methylation profiling of clinical samples (n = 61) was undertaken. Safety of combination guadecitabine and PRRT was assessed in vivo. Results Pyrosequencing of cell lines illustrated differential methylation indices – BON: 1 94%, QGP: 1 21%. Following guadecitabine treatment, a dose-dependent increase in SSTR2 in BON-1 at a transcriptional, translational, and functional levels using the SSTR2-directed radioligand, 18F-FET-βAG-TOCA ([18F]-FETO) (150% increase [18F]-FETO uptake, p < 0.05) was observed. In vivo, guadecitabine treatment resulted in a 70% increase in [18F]-FETO uptake in BON-1 tumour models compared models with low baseline percentage methylation (p < 0.05). No additive toxicity was observed with the combination treatment of PRRT and guadecitabine in vivo. Methylation index in clinical samples was 10.5% compared to 5.2% in controls (p = 0.03) and correlated with SSTR2 expression (Wilcoxon rank sign −3.75,p < 0.01). Conclusion Guadecitabine increases SSTR2 expression both in vitro and in vivo. The combination of demethylation agents with PRRT warrants further investigation