Assessment of a novel mutated Prostatic Acid Phosphatase-derived vaccine for the treatment of prostate cancer

Prostate cancer is the second most frequent cancer in men. Patients with a localized disease are treated with local therapies such as prostatectomy or radiation therapy whereas patients with a metastatic disease are treated with androgen deprivation therapies (ADT). However, patients ultimately develop resistance to ADT, thereby leading to a castrate resistant prostate cancer (CRPC). The treatment options for such disease are limited and not curative, with a median survival from diagnosis of 14 months. Among these treatments, the Sipuleucel-T based vaccine, FDA approved in 2010, has been shown to prolong the overall survival by 4 months. However, while this approach demonstrated the efficacy of targeting the Prostatic Acid Phosphatase (PAP) antigen, overexpressed in prostate cancer, to stimulate the patient's immune system to treat CRPC, it remains extremely expensive and limited in its efficacy. The aim of the study was to develop a new, less expensive and more effective PAP-based vaccine for the treatment of advanced prostate cancer. A 15mer PAP-derived vaccine, when injected as a DNA vaccine, was previously shown to induce PAP-specific T-cell responses and to reduce tumour growth in a syngeneic heterotopic murine prostate cancer model. A new form of the vaccine was subsequently developed by elongating (to 42mer) and introducing a single mutation to the PAP-derived peptide. Two pre-clinical murine models (C57Bl/6 mice and HHDII/DR1 transgenic) were used to assess the efficacy of the vaccine. The mutated PAP42mer sequence was the most immunogenic sequence in both models when administered as a peptide-based vaccine, as demonstrated by the higher number of IFNγ-releasing splenocytes following in vitro stimulation with PAP-derived class-I and class-II epitopes and by the higher functional avidity obtained. The vaccine immunogenicty was further enhanced by using stronger adjuvants and delivery systems. CAF09 adjuvant and ImmunoBody® DNA vaccine were superior to CpG adjuvant in inducing PAP-specific immune responses. This was demonstrated by the expression of activation and inhibitory markers, by the induction of a memory response and by the functional phenotype (cytokines release, proliferation, and degranulation) of CD8+ T cells following in vitro stimulation with shorter-vaccine-derived peptides. Splenocytes from vaccinated mice were capable of lysing target cells in a PAP-dependant manner in vitro. Vaccination slowed down the growth of human-PAP+ expressing tumours implanted in the HHDII/DR1 model but no anti-tumour effect was observed against TRAMP-C1 tumours in the C57Bl/6 model. Finally, circulating PAP42mer derived-specific CD8+ T cells were detected in the blood of patients with prostate cancer. In summary, this study demonstrated that a unique vaccine strategy could induce a robust anti-PAP immunity but with little effect on the growth of implanted PAP-expressing cancer cell-derived tumours in vivo. The presence of PAP-specific CD8+ T cells in the periphery of patients with advanced prostate cancer suggests that these patients could benefit from this new approach

Passado, presente e futuro da governação educativa na Região Autónoma da Madeira

La consagración, en la Constitución Portuguesa, de las Comunidades Autónomas y su desarrollo en términos competenciales vino a señalar, en el campo de la administración educativa, una ruptura ideológica, tal vez cultural, con la tradición centralista del Estado. Por otra parte, se puede decir que esta realidad ha traído a la dimensión organizativa del Estado, en su conjunto, analizada por un prisma de gobierno de la Educación, también la voluntad y intención de una redistribución del poder entre el centro y la periferia, teniendo como objetivo final salvaguardar el respeto por la diversidad y la proximidad de las políticas educativas que aluden a las realidades locales y a la idiosincrasia de las comunidades escolares. La Comunidad Autónoma de Madeira ha venido, desde los albores de la regionalización en la educación/enseñanza, a ‘debujar’, paso a paso, la construcción gradual de un modelo regional, inicialmente de sustitución y después de creación, cuya evolución, después de su consagración, ahora hay que esperar a ver la intención a darle por los responsables políticos y en qué sentido podemos esperar de ella en el futuro

Proportional green time scheduling for traffic lights

We consider the decentralized scheduling of a large number of urban traffic lights. We investigate factors determining system performance, in particular, the length of the traffic light cycle and the proportion of green time allocated to each junction. We study the effect of the length of the traffic cycle on the stability region a urban traffic network. We derive a simple square-root cycle length rule which is optimal for certain road traffic junctions. We prove the maximal stability of a road network under a proportional fair or P0 control scheme. Further, we support of analysis through a simulation analysis of our policy on the Melbourne CBD urban road network

Differential diagnosis of dna viruses related to reproductive disorder on sows by multiplex-pcr technique

The newly emerged diseases caused by ASFV and PCV3 and their confirmed prevelance in Vietnam whereas most of available common commercial methods such as ELISA or realtime PCR designed for detecting single pathogen per reaction, highlighted a necessity for another diagnostic method to simultaneously detect and differentiate DNA viruses that are related to reproductive failures in sow herds including PCV2, PCV3, PPV, ASFV. In this communication, a diagnostic multiplex-PCR (mPCR) was established with pathogen-specific primers selected from previous studies and another set of primers designed for COX1 gene serving as an internal amplification control (IAC). The predicted products of PCV2, PCV3, PPV, ASFV and IAC were 702 bp, 223 bp, 380 bp, 278 bp and 463 bp, respectively. After optimization, the mPCR functioned specifically at 62°C. Results revealed the consistent detection limit at 100 copies/gene/reaction. In application, 185 serum samples from sows were used to examine the presence of the related pathogens. mPCR results showed that the mono-infection rate of PCV2, PCV3, PPV, and ASFV was 0% (0/185), 40% (74/185), 28.1% (52/185), and 48.1% (89/185), respectively. Regarding coinfection rate, the data indicated that coinfections of 2, 3 and 4 pathogens were 20%, 8.1% and 0% accordingly. In conclusion, the mPCR assay was successfully established and ready to serve for diagnosis of PCV2, PCV3, PPV and ASFV infection in reality with high specificity and sensitivity. It is a good contribution to a better understanding of the epidemiology of these diseases in swine

Flocculation of Reactive Blue 19 (RB19) using Alum and the Effects of Catalysts Addition

There are a variety of primary coagulants which can be used in a water treatment plant. One of the earliest, and still the most extensively used, is aluminum sulfate, also known as alum. Aluminum Sulfate (Alum) is one of the most commonly used flocculent in waste water treatment processes. Effectiveness of Alum in flocculation process is determined by many factors such as the effluents pH, flocculent dose as well as the use of catalyst to improve efficiency rate of flocculation. Hence special attention to these factors especially the use of catalyst has been brought about by this study. Experiments were carried out using Reactive Blue 19 Dye as the contaminant of waste water and two catalysts namely Calcium Hydroxide (CaOH2) and Poly Aluminum Chloride (PACl) were evaluated. The results obtained proved that indeed after addition of catalysts, removal efficiency rates of Alum can be increased up to 25% using Calcium Hydroxide and up to 35% using Poly Aluminum Chloride compared to Alum alone. The optimum conditions for this study were at pH 5.5 ~7.5, 300 mg/L of Alum 30seconds of rapid mixing time with 300 rpm , 30rpm of mixing rate for 5 minutes and 30 minutes of settling time. Moreover, Alum showed the highest performance under these conditions and using 50 mg/L PACl as catalyst with 98.52% of COD reduction and 90.60% of color reduction. In conclusion, Alum with the support of PACl as catalyst is an effective coagulant, which can reduce the level of COD and Dye Color in Reactive Blue 19 contaminated wastewater

Интеллектуальная радиосеть с нечеткой конфигурацией

В статье обсуждаются возможности применения одноранговой радиосети стандарта IEEE 802.15.4 (ZigBee) диапазона 2,4 ГГц для работы системы, состоящей из группы малогабаритных мобильных роботов и одного командного пункта. Основная задача группы роботов – проведение разведки во время спасательных операций после техногенных и природных катастроф и аварий. Для сохранения управляемости отдельными роботами и системой в целом предлагается повысить «интеллект» системы связи за счет гибкой маршрутизации каналов между командным пунктом и конкретным мобильным роботом с тем, чтобы иметь систему с автоматическим, интеллектуальным восстановлением канала обмена данных.У статті обговорюються можливості застосування однорангової радіомережі стандарту ІЕЕ 802.15.4 (ZigBee) діапазону 2,4 Ггу для роботи системи, що складається з групи малогабаритних мобільних роботів та одного командного пункту. Основна задача групи роботів – проведення розвідки під час рятувальних операцій після техногенних та природних катастроф і аварій. Для збереження керованості окремими ротами та системою в цілому пропонується підвищити інтелект системи зв’язку за рахунок гнучкої маршрутитизації каналів між командним пунктом та конкретним мобільним роботом з тим, щоб мати систему з автоматичним, інтелектуальним відновлюванням каналу обміну даних.In the article the possibilities of application peer-to-peer radio networks of standard IEEE 802.15.4 (ZigBee) a range of 2,4 GHz for work of the system consisting of small-sized mobile robots group and one command point are discussed. The primary goal of group of robots – is carrying out of investigation during rescue operations after technogenic and natural accidents and failures. For controllability preservation by separate robots and system as a whole, it is offered to raise “intelligence” of a communication system at the expense of flexible routeing of channels between command point and the concrete mobile robot to have system with automatic, intellectual restoration of the channel of data exchange

Analytical Possibilities of Rutherford Backscattering Spectrometry and Elastic Recoil Detection Analysis Methods

This paper presents the results of an experimental study of three samples containing various elements in the near-surface layers. The depth profiles of all the elements of different atomic masses from hydrogen to silver were investigated by Rutherford Backscattering Spectrometry (RBS) and Elastic Recoil Detection Analysis (ERDA). The experiments were performed by using the low-energy (about 2 MeV) 4He+ ion beams. The obtained results demonstrate the possibility of the RBS and ERDA methods in the investigation of depth profiles of any mass element with an atomic concentration of about 0.01 at.% and a depth resolution close to 10 nm

Modelling of the anthropogenic tritium transient and its decay product helium-3 in the Mediterranean Sea using a high-resolution regional model

International audienceThis numerical study provides the first simulation of the anthropogenic tritium invasion and its decay product helium-3 (3 He) in the Mediterranean Sea. The simulation covers the entire tritium (3 H) transient generated by the atmospheric nuclear weapons tests performed in the 1950s and early 1960s and is run till 2011. Tritium, helium-3 and their derived age estimates are particularly suitable for studying intermediate and deep-water ventilation and spreading of water masses at intermediate/deep levels. The simulation is made using a high-resolution regional model NEMO (Nucleus for European Modelling of the Ocean), in a regional configuration for the Mediterranean Sea called MED12, forced at the surface with prescribed tritium evolution derived from observations. The simulation is compared to measurements of tritium and helium-3 performed along large-scale transects in the Mediterranean Sea during the last few decades on cruises of R/V Meteor: M5/6, M31/1, M44/4, M51/2, M84/3, and R/V Poseidon: 234. The results show that the input function used for the tritium generates a realistic distribution of the main hydrographic features of the Mediterranean Sea circulation. In the eastern basin, the results highlight the weak formation of Adriatic Deep Water in the model, which explains its weak contribution to the Eastern Mediterranean Deep Water (EMDW) in the Ionian sub-basin. It produces a realistic representation of the Eastern Mediterranean Transient (EMT) signal, simulating a deep-water formation in the Aegean sub-basin at the beginning of 1993, with a realistic timing of deep-water renewal in the eastern basin