Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.Fil: Sarduy, M. R.. Medical-surgical Research Center; CubaFil: García, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Coca, M. A.. Clinical Investigation Center; CubaFil: Perera, A.. Clinical Investigation Center; CubaFil: Torres, L. A.. Clinical Investigation Center; CubaFil: Valenzuela, C. M.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Baladrón, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Solares, M.. Hospital Materno Ramón González Coro; CubaFil: Reyes, V.. Center For Genetic Engineering And Biotechnology Havana; CubaFil: Hernández, I.. Isotope Center; CubaFil: Perera, Y.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Martínez, Y. M.. Medical-surgical Research Center; CubaFil: Molina, L.. Medical-surgical Research Center; CubaFil: González, Y. M.. Medical-surgical Research Center; CubaFil: Ancízar, J. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Prats, A.. Clinical Investigation Center; CubaFil: González, L.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Casacó, C. A.. Clinical Investigation Center; CubaFil: Acevedo, B. E.. Centro de Ingeniería Genética y Biotecnología; CubaFil: López Saura, P. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; ArgentinaFil: Gómez, R.. Elea Laboratories; ArgentinaFil: Perea Rodríguez, S. E.. Center For Genetic Engineering And Biotechnology Havana; Cuba. Centro de Ingeniería Genética y Biotecnología; Cub

Сравнение расхода топлива и уровня выбросов при обычной и гибридных конфигурациях трансмиссий c учетом циклов движения и степени гибридизации

Hybrid electric powertrains in automotive applications aim to improve emissions and fuel economy with respect to conventional internal combustion engine vehicles. Variety of design scenarios need to be addressed in designing a hybrid electric vehicle to achieve desired design objectives such as fuel consumption and exhaust gas emissions. The work in this paper presents an analysis of the design objectives for an automobile powertrain with respect to different design scenarios, i. e. target drive cycle and degree of hybridization. Toward these ends, four powertrain configuration models (i. e. internal combustion engine, series, parallel and complex hybrid powertrain configurations) of a small vehicle (motorized three-wheeler) are developed using Model Advisor software and simulated with varied drive cycles and degrees of hybridization. Firstly, the impact of vehicle power control strategy and operational characteristics of the different powertrain configurations are investigated with respect to exhaust gas emissions and fuel consumption. Secondly, the drive cycles are scaled according to kinetic intensity and the relationship between fuel consumption and drive cycles is assessed. Thirdly, three fuel consumption models are developed so that fuel consumption values for a real-world drive cycle may be predicted in regard to each powertrain configuration. The results show that when compared with a conventional powertrain fuel consumption is lower in hybrid vehicles. This work led to the surprisingly result showing higher CO emission levels with hybrid vehicles. Furthermore, fuel consumption of all four powertrains showed a strong correlation with kinetic intensity values of selected drive cycles. It was found that with varied drive cycles the average fuel advantage for each was: series 23 %, parallel 21 %, and complex hybrids 33 %, compared to an IC engine powertrain. The study reveals that performance of hybrid configurations vary significantly with drive cycle and degree of hybridization. The paper also suggests future areas of study

Organization of atomic bond tensions in model glasses

In order to understand whether internal stresses in glasses are correlated or randomly distributed, we study the organization of atomic bond tensions (normal forces between pairs of atoms). Measurements of the invariants of the atomic bond tension tensor in simulated 2D and 3D binary Lennard-Jones glasses, reveal new and unexpected correlations and provide support for Alexander's conjecture about the non-random character of internal stresses in amorphous solids

The AzTEC mm-Wavelength Camera

AzTEC is a mm-wavelength bolometric camera utilizing 144 silicon nitride micromesh detectors. Herein we describe the AzTEC instrument architecture and its use as an astronomical instrument. We report on several performance metrics measured during a three month observing campaign at the James Clerk Maxwell Telescope, and conclude with our plans for AzTEC as a facility instrument on the Large Millimeter Telescope.Comment: 13 pages, 15 figures, accepted for publication in Monthly Notice

The MacGyver effect: alive and well in health services research?

<p>Abstract</p> <p>Background</p> <p>In a manner similar to the television action hero MacGyver, health services researchers need to respond to the pressure of unpredictable demands and constrained time frames. The results are often both innovative and functional, with the creation of outputs that could not have been anticipated in the initial planning and design of the research.</p> <p>Discussion</p> <p>In the conduct of health services research many challenges to robust research processes are generated as a result of the interface between academic research, health policy and implementation agendas. Within a complex and rapidly evolving environment the task of the health services researcher is, therefore, to juggle sometimes contradictory pressures to produce valid results.</p> <p>Summary</p> <p>This paper identifies the MacGyver-type dilemmas which arise in health services research, wherein innovation may be called for, to maintain the intended scientific method and rigour. These 'MacGyver drivers' are framed as opposing issues from the perspective of both academic and public policy communities. The ideas expressed in this paper are illustrated by four examples from research projects positioned at the interface between public policy strategy and academia.</p

Competition between decay and dissociation of core-excited OCS studied by X-ray scattering

We show the first evidence of dissociation during resonant inelastic soft X-ray scattering. Carbon and oxygen K-shell and sulfur L-shell resonant and non-resonant X-ray emission spectra were measured using monochromatic synchrotron radiation for excitation and ionization. After sulfur, L2,3 -> {\pi}*, {\sigma}* excitation, atomic lines are observed in the emission spectra as a consequence of competition between de-excitation and dissociation. In contrast the carbon and oxygen spectra show weaker line shape variations and no atomic lines. The spectra are compared to results from ab initio calculations and the discussion of the dissociation paths is based on calculated potential energy surfaces and atomic transition energies.Comment: 12 pages, 6 pictures, 2 tables, http://link.aps.org/doi/10.1103/PhysRevA.59.428

Growing spatial correlations of particle displacements in a simulated liquid on cooling toward the glass transition

We define a correlation function that quantifies the spatial correlation of single-particle displacements in liquids and amorphous materials. We show for an equilibrium liquid that this function is related to fluctuations in a bulk dynamical variable. We evaluate this function using computer simulations of an equilibrium glass-forming liquid, and show that long range spatial correlations of displacements emerge and grow on cooling toward the mode coupling critical temperature