Cs2NaAl1-xCrxF6: A family of compounds presenting magnetocaloric effect

FUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPIn this paper we explore the magnetocaloric effect (MCE) of chromium-doped elpasolite Cs2NaAl1-x,CrxF6 (x = 0.01 and 0.62) single crystals. Magnetization and heat capacity data show the magnetocaloric potentials to be comparable to those of garnets, perovskites, and other fluorides, producing magnetic entropy changes of 0.5 J/kg K (x = 0.01) and 11 J/kg K (x = 0.62), and corresponding adiabatic temperature changes of 4 and 8 K, respectively. These values are for a magnetic field change of 50 kOe at a temperature around 3 K. A clear Schottky anomaly below 10 K, which becomes more apparent when an external magnetic field is applied, was observed and related to the splitting of the Cr3+ energy levels. These results hint at a new family of materials with potential wide use in cryorefrigeration.90616FUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPSem informaçãoSem informaçãoSem informaçãoSem informaçãoSem informaçãoWe thank Pedro von Ranke (UERJ, Brazil) and Walter Kalceff (UTS, Australia) for fruitful discussions. J.C.G.T.’s participation in this work was financed by the Science without Borders Program. Access to CICECO/Chemistry Department (Aveiro, Portugal), GPMR-UNICAMP (Campinas, Brazil), LMBT- UFF (Niter´oi, Brazil), LBT-UFRJ (Rio de Janeiro, Brazil), BERII facilities, and LaMMB MagLab (Berlin, Germany) are gratefully acknowledged by all authors. Financial support was provided by Proppi/UFF, FAPERJ, FAPESP, CAPES, CNPq, and FINEP

Frequency dependent specific heat of viscous silica

We apply the Mori-Zwanzig projection operator formalism to obtain an expression for the frequency dependent specific heat c(z) of a liquid. By using an exact transformation formula due to Lebowitz et al., we derive a relation between c(z) and K(t), the autocorrelation function of temperature fluctuations in the microcanonical ensemble. This connection thus allows to determine c(z) from computer simulations in equilibrium, i.e. without an external perturbation. By considering the generalization of K(t) to finite wave-vectors, we derive an expression to determine the thermal conductivity \lambda from such simulations. We present the results of extensive computer simulations in which we use the derived relations to determine c(z) over eight decades in frequency, as well as \lambda. The system investigated is a simple but realistic model for amorphous silica. We find that at high frequencies the real part of c(z) has the value of an ideal gas. c'(\omega) increases quickly at those frequencies which correspond to the vibrational excitations of the system. At low temperatures c'(\omega) shows a second step. The frequency at which this step is observed is comparable to the one at which the \alpha-relaxation peak is observed in the intermediate scattering function. Also the temperature dependence of the location of this second step is the same as the one of the $\alpha-$peak, thus showing that these quantities are intimately connected to each other. From c'(\omega) we estimate the temperature dependence of the vibrational and configurational part of the specific heat. We find that the static value of c(z) as well as \lambda are in good agreement with experimental data.Comment: 27 pages of Latex, 8 figure

A phase I dose-escalation study to evaluate safety and tolerability of sorafenib combined with sirolimus in patients with advanced solid cancer

Contains fulltext : 87630.pdf (publisher's version ) (Closed access)BACKGROUND: The combination of sorafenib (vascular endothelial growth factor receptor 2 inhibitor) and sirolimus (mammalian target of rapamycin inhibitor) might work synergistically. METHODS: A phase I dose-escalation study with sorafenib twice a day (b.i.d.) and sirolimus once daily (q.d.) was performed to determine the recommended dose of the combination in patients with solid tumours. Secondary objectives were to determine the safety profile and maximum tolerated dose (MTD), and to evaluate the pharmacokinetics (PK) of the combination. RESULTS: Dose-limiting toxicities were transaminitis and cutaneous toxicity. The most frequently reported adverse events were elevated transaminases, hypophosphatemia, fatigue, anorexia, diarrhoea, nausea, rash and palmar-plantar erythrodysaesthesia. Sirolimus did not change the PK of sorafenib; in contrast, sorafenib reduced the AUC(0-96) and C(max) of sirolimus. No objective responses were observed; eight patients showed stable disease for a median of 16.3 weeks (range 8-24). The MTD of the combination was sorafenib 200 mg b.i.d. with sirolimus 1 mg q.d. CONCLUSION: The combination of sorafenib and sirolimus showed enhanced toxicity, which could not be explained by the PK of both drugs. The relative low doses at the MTD, in combination with the PK results, do not warrant further development of this combination

Photoactivatable prodrugs of antimelanoma agent Vemurafenib

In this study, we report on novel photoactivatable caged prodrugs of vemurafenib. This kinase inhibitor was the first approved drug for the personalized treatment of BRAF-mutated melanoma and showed impressive results in clinical studies. However, the occurrence of severe side effects and drug resistance illustrates the urgent need for innovative therapeutic approaches. To conquer these limitations, we implemented photoremovable protecting groups into vemurafenib. In general, this caging concept provides spatial and temporal control over the activation of molecules triggered by ultraviolet light. Thus, higher inhibitor concentrations in tumor tissues might be reached with less systemic effects. Our study describes the first development of caged vemurafenib prodrugs useful as pharmacological tools. We investigated their photochemical characteristics and photoactivation. <i>In vitro</i> evaluation proved the intended loss-of-function and the light-dependent recovery of efficacy in kinase and cellular assays. The reported vemurafenib photo prodrugs represent a powerful biological tool for novel pharmacological approaches in cancer research

Therapy-induced tumour secretomes promote resistance and tumour progression.

Drug resistance invariably limits the clinical efficacy of targeted therapy with kinase inhibitors against cancer. Here we show that targeted therapy with BRAF, ALK or EGFR kinase inhibitors induces a complex network of secreted signals in drug-stressed human and mouse melanoma and human lung adenocarcinoma cells. This therapy-induced secretome stimulates the outgrowth, dissemination and metastasis of drug-resistant cancer cell clones and supports the survival of drug-sensitive cancer cells, contributing to incomplete tumour regression. The tumour-promoting secretome of melanoma cells treated with the kinase inhibitor vemurafenib is driven by downregulation of the transcription factor FRA1. In situ transcriptome analysis of drug-resistant melanoma cells responding to the regressing tumour microenvironment revealed hyperactivation of several signalling pathways, most prominently the AKT pathway. Dual inhibition of RAF and the PI(3)K/AKT/mTOR intracellular signalling pathways blunted the outgrowth of the drug-resistant cell population in BRAF mutant human melanoma, suggesting this combination therapy as a strategy against tumour relapse. Thus, therapeutic inhibition of oncogenic drivers induces vast secretome changes in drug-sensitive cancer cells, paradoxically establishing a tumour microenvironment that supports the expansion of drug-resistant clones, but is susceptible to combination therapy

Cs2NaAl1-xCrxF6: A family of compounds presenting magnetocaloric effect

In this paper we explore the magnetocaloric effect (MCE) of chromium-doped elpasolite Cs2NaAl1-x,CrxF6 (x = 0.01 and 0.62) single crystals. Magnetization and heat capacity data show the magnetocaloric potentials to be comparable to those of garnets, perovskites, and other fluorides, producing magnetic entropy changes of 0.5 J/kg K (x = 0.01) and 11 J/kg K (x = 0.62), and corresponding adiabatic temperature changes of 4 and 8 K, respectively. These values are for a magnetic field change of 50 kOe at a temperature around 3 K. A clear Schottky anomaly below 10 K, which becomes more apparent when an external magnetic field is applied, was observed and related to the splitting of the Cr3+ energy levels. These results hint at a new family of materials with potential wide use in cryorefrigeration

In vivo Expansion of Naïve CD4+CD25high FOXP3+ Regulatory T Cells in Patients with Colorectal Carcinoma after IL-2 Administration

Regulatory T cells (Treg cells) are increased in context of malignancies and their expansion can be correlated with higher disease burden and decreased survival. Initially, interleukin 2 (IL-2) has been used as T-cell growth factor in clinical vaccination trials. In murine models, however, a role of IL-2 in development, differentiation, homeostasis, and function of Treg cells was established. In IL-2 treated cancer patients a further Treg-cell expansion was described, yet, the mechanism of expansion is still elusive. Here we report that functional Treg cells of a naïve phenotype - as determined by CCR7 and CD45RA expression - are significantly expanded in colorectal cancer patients. Treatment of 15 UICC stage IV colorectal cancer patients with IL-2 in a phase I/II peptide vaccination trial further enlarges the already increased naïve Treg-cell pool. Higher frequencies of T-cell receptor excision circles in naïve Treg cells indicate IL-2 dependent thymic generation of naïve Treg cells as a mechanism leading to increased frequencies of Treg cells post IL-2 treatment in cancer patients. This finding could be confirmed in naïve murine Treg cells after IL-2 administration. These results point to a more complex regulation of Treg cells in context of IL-2 administration. Future strategies therefore might aim at combining IL-2 therapy with novel strategies to circumvent expansion and differentiation of naïve Treg cells