352 research outputs found
Cs2NaAl1-xCrxF6: A family of compounds presenting magnetocaloric effect
FUNDAĂĂO CARLOS CHAGAS FILHO DE AMPARO Ă PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAĂĂO DE AMPARO Ă PESQUISA DO ESTADO DE SĂO PAULO - FAPESPCOORDENAĂĂO DE APERFEIĂOAMENTO DE PESSOAL DE NĂVEL SUPERIOR - CAPESCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTĂFICO E TECNOLĂGICO - 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.90616FUNDAĂĂO CARLOS CHAGAS FILHO DE AMPARO Ă PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAĂĂO DE AMPARO Ă PESQUISA DO ESTADO DE SĂO PAULO - FAPESPCOORDENAĂĂO DE APERFEIĂOAMENTO DE PESSOAL DE NĂVEL SUPERIOR - CAPESCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTĂFICO E TECNOLĂGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAĂĂO CARLOS CHAGAS FILHO DE AMPARO Ă PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAĂĂO DE AMPARO Ă PESQUISA DO ESTADO DE SĂO PAULO - FAPESPCOORDENAĂĂO DE APERFEIĂOAMENTO DE PESSOAL DE NĂVEL SUPERIOR - CAPESCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTĂFICO E TECNOLĂGICO - 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.âs 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 (NiterÂŽoi, 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
Patient-centric trials for therapeutic development in precision oncology
An enhanced understanding of the molecular pathology of disease gained from genomic studies is facilitating the development of treatments that target discrete molecular subclasses of tumours. Considerable associated challenges include how to advance and implement targeted drug-development strategies. Precision medicine centres on delivering the most appropriate therapy to a patient on the basis of clinical and molecular features of their disease. The development of therapeutic agents that target molecular mechanisms is driving innovation in clinical-trial strategies. Although progress has been made, modifications to existing core paradigms in oncology drug development will be required to realize fully the promise of precision medicine
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
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
Propriedades Ăłpticas de amostras policristalinas LiGaSiO4 contendo Fe3+ como impureza substitucional
Challenges and opportunities for converting renal cell carcinoma into a chronic disease with targeted therapies
Optimum efficacy is the primary goal for any cancer therapy, and entails controlling tumour growth and prolonging survival as far as possible. The prognosis for patients with metastatic renal cell carcinoma (mRCC) has greatly improved with the introduction of targeted therapies. This review examines the development and efficacy of targeted agents for the management of mRCC, the challenges offered by their rapid emergence, and discusses how mRCC treatment may evolve in the future. Improvements in progression-free survival and overall survival rates, observed with targeted agents, indicate that it may now be possible to change mRCC from a rapidly fatal and largely untreatable condition into a chronic disease. The major challenges to further advances in targeted therapy for mRCC include overcoming drug resistance, identifying the most effective sequence or combination of targeted agents, optimising clinical trial design and managing the cost of treatment
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
Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma
This randomised phase III trial compared standard of care Everolimus with the anti-PD1 monoclonal antibody Nivolumab in previously treated patients with locally advanced inoperable or metastatic clear cell renal cancer. 810 patients were randomised to receive either Everolimus 10 mg orally daily or 3 mg/kg of Nivolumab intravenously every two weeks. Patients were treated until unacceptable toxicity or disease progression. Patients could be treated beyond progression if the investigator believed that the patient was gaining clinical benefit. The primary endpoint was overall survival. The median survival was 25 months for Nivolumab and 19.8 months for Everolimus (p=0.002). The objective response rate was higher for Nivolumab (25 versus 5%; p=<0.001).The median progression free survivals were 4.6 & 4.4 months (p=0.11). Grade 3 & 4 treatment related toxicities were observed in 19 & 37% of patients on Nivolumab or Everolimus respectively. In patients with previously treated renal cell carcinoma Nivolumab produced superior survival and more tolerable treatment than Everolimus
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