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

Identification of differential pharyngeal cytokine profiles during HIV infection

Significantly higher pharyngeal shedding of Epstein-Barr virus (EBV) is observed during HIV infection. Increased EBV shedding in pharynx is not affected even during highly active antiretroviral theyrapy (HAART). EBV positive monocyte populations have been shown to carry EBV to pharyngeal mucosa. Human cytokine profiles are often altered to facilitate herpes virus infection. Thus pharyngeal cytokine profiles may influence EBV reactivation and shedding during HIV infection. Our objective was to compare 37 pharyngeal cytokine profiles of HIV-seropositive patients who were or were not receiving HAART therapy

Fluids of hard ellipsoids: Phase diagram including a nematic instability from Percus-Yevick theory

An important aspect of molecular fluids is the relation between orientation and translation parts of the two-particle correlations. Especially the detailed knowledge of the influence of orientation correlations is needed to explain and calculate in detail the occurrence of a nematic phase. The simplest model system which shows both orientation and translation correlations is a system of hard ellipsoids. We investigate an isotropic fluid formed of hard ellipsoids with Percus-Yevick theory. Solving the Percus-Yevick equations self-consistently in the high density regime gives a clear criterion for a nematic instability. We calculate in detail the equilibrium phase diagram for a fluid of hard ellipsoids of revolution. Our results compare well with Monte Carlo Simulations and density functional theory.Comment: 7 pages including 4 figure

The Evolution of PSR J0737-3039B and a Model for Relativistic Spin Precession

We present the evolution of the radio emission from the 2.8-s pulsar of the double pulsar system PSR J0737-3039A/B. We provide an update on the Burgay et al. (2005) analysis by describing the changes in the pulse profile and flux density over five years of observations, culminating in the B pulsar's radio disappearance in 2008 March. Over this time, the flux density decreases by 0.177 mJy/yr at the brightest orbital phases and the pulse profile evolves from a single to a double peak, with a separation rate of 2.6 deg/yr. The pulse profile changes are most likely caused by relativistic spin precession, but can not be easily explained with a circular hollow-cone beam as in the model of Clifton & Weisberg (2008). Relativistic spin precession, coupled with an elliptical beam, can model the pulse profile evolution well. This particular beam shape predicts geometrical parameters for the two bright orbital phases which are consistent and similar to those derived by Breton et al. (2008). However, the observed decrease in flux over time and B's eventual disappearance cannot be easily explained by the model and may be due to the changing influence of A on B.Comment: 20 pages, 18 figures, Accepted by ApJ on 2 August 201

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

The Double Pulsar Eclipses I: Phenomenology and Multi-frequency Analysis

The double pulsar PSR J0737-3039A/B displays short, 30 s eclipses that arise around conjunction when the radio waves emitted by pulsar A are absorbed as they propagate through the magnetosphere of its companion pulsar B. These eclipses offer a unique opportunity to probe directly the magnetospheric structure and the plasma properties of pulsar B. We have performed a comprehensive analysis of the eclipse phenomenology using multi-frequency radio observations obtained with the Green Bank Telescope. We have characterized the periodic flux modulations previously discovered at 820 MHz by McLaughlin et al., and investigated the radio frequency dependence of the duration and depth of the eclipses. Based on their weak radio frequency evolution, we conclude that the plasma in pulsar B's magnetosphere requires a large multiplicity factor (~ 10^5). We also found that, as expected, flux modulations are present at all radio frequencies in which eclipses can be detected. Their complex behavior is consistent with the confinement of the absorbing plasma in the dipolar magnetic field of pulsar B as suggested by Lyutikov & Thompson and such a geometric connection explains that the observed periodicity is harmonically related to pulsar B's spin frequency. We observe that the eclipses require a sharp transition region beyond which the plasma density drops off abruptly. Such a region defines a plasmasphere which would be well inside the magnetospheric boundary of an undisturbed pulsar. It is also two times smaller than the expected standoff radius calculated using the balance of the wind pressure from pulsar A and the nominally estimated magnetic pressure of pulsar B.Comment: 9 pages, 7 figures, 3 tables, ApJ in pres

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

Current Treatment Approaches to HCC with a Special Consideration to Transplantation

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The mainstay of treatment of HCC has been both resectional and transplantation surgery. It is well known that, in selected, optimized patients, hepatectomy for HCC may be an option, even in patients with underlying cirrhosis. Resectable patients with early HCC and underlying liver disease are however increasingly being considered for transplantation because of potential for better disease-free survival and resolution of underlying liver disease, although this approach is limited by the availability of donor livers, especially in resectable patients. Outcomes following liver transplantation improved dramatically for patients with HCC following the implementation of the Milan criteria in the late 1990s. Ever since, the rather restrictive nature of the Milan criteria has been challenged with good outcomes. There has also been an increase in the donor pool with marginal donors including organs retrieved following cardiac death being used. Even so, patients still continue to die while waiting for a liver transplant. In order to reduce this attrition, bridging techniques and methods for downstaging disease have evolved. Additionally new techniques for organ preservation have increased the prospect of this potentially curative procedure being available for a greater number of patients

Current Treatment Approaches to HCC with a Special Consideration to Transplantation

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The mainstay of treatment of HCC has been both resectional and transplantation surgery. It is well known that, in selected, optimized patients, hepatectomy for HCC may be an option, even in patients with underlying cirrhosis. Resectable patients with early HCC and underlying liver disease are however increasingly being considered for transplantation because of potential for better disease-free survival and resolution of underlying liver disease, although this approach is limited by the availability of donor livers, especially in resectable patients. Outcomes following liver transplantation improved dramatically for patients with HCC following the implementation of the Milan criteria in the late 1990s. Ever since, the rather restrictive nature of the Milan criteria has been challenged with good outcomes. There has also been an increase in the donor pool with marginal donors including organs retrieved following cardiac death being used. Even so, patients still continue to die while waiting for a liver transplant. In order to reduce this attrition, bridging techniques and methods for downstaging disease have evolved. Additionally new techniques for organ preservation have increased the prospect of this potentially curative procedure being available for a greater number of patients