23 resultados para siRNA interference
em Repositório Científico do Instituto Politécnico de Lisboa - Portugal
Resumo:
The main purpose of the present study is to determine if the circadian rhythms present in the human bone marrow are likely to influence 3’- deoxy- 3’-[18F] Fluorothymidine (18F-FLT) uptake in the same organ. The 18F-FLT is a Thymidine analogous proliferation agent. The relatively high physiological uptake of this tracer in the bone marrow diminishes the Tumor/Background (T/B) ratio, decreasing the detection accuracy of PET/CT and possibly affecting SUV quantifications.
Resumo:
In man brain cancer is an aggressive, malignant form of tumour, it is highly infiltrative in nature, is associated with cellular heterogeneity and affects cerebral hemispheres of the brain. Current drug therapies are inadequate and an unmet clinical need exists to develop new improved therapeutics. The ability to silence genes associated with disease progression by using short interfering RNA (siRNA) presents the potential to develop safe and effective therapies. In this work, in order to protect the siRNA from degradation, promote cell specific uptake and enhance gene silencing efficiency, a PEGylated cyclodextrin (CD)-based nanoparticle, tagged with a CNS-targeting peptide derived from the rabies virus glycoprotein (RVG) was formulated and characterized. The modified cyclodextrin derivatives were synthesized and co-formulated to form nanoparticles containing siRNA which were analysed for size, surface charge, stability, cellular uptake and gene-knockdown in brain cancer cells. The results identified an optimised co-formulation prototype at a molar ratio of 1:1.5:0.5 (cationic cyclodextrin:PEGylated cyclodextrin:RVG-tagged PEGylated cyclodextrin) with a size of 281±39.72nm, a surface charge of 26.73±3mV, with efficient cellular uptake and a 27% gene-knockdown ability. This CD-based formulation represents a potential nanocomplex for systemic delivery of siRNA targeting brain cancer.
Resumo:
Considering that recent european high-speed railway system has a traction power system of kV 50 Hz, which causes electromagnetic emission for the outside world, it is important to dimension the railway system emissions, using a frequency/distance dependent propagation model. This paper presents an enhanced theoretical model for VLF to UHF propagation, railway system oriented. It introduces the near field approach (crucial in low frequency propagation) and also considers the source characteristics and type of measuring antenna. Simulations are presented, and comparisons are set with earlier far field models. Using the developed model, a real case study was performed in partnership with Refer Telecom (portuguese telecom operator for railways). The new propagation model was used in order to predict the future high-speed railway electromagnetic emissions in the Lisbon north track. The results show the model's prediction capabilities and also its applicability to realistic scenarios.
Resumo:
We assess the performance of Gaussianity tests, namely the Anscombe-Glynn, Lilliefors, Cramér-von Mises, and Giannakis-Tsatsanis (G-T), with the purpose of detecting narrowband and wideband interference in GNSS signals. Simulations have shown that the G-T test outperforms the others being suitable as a benchmark for comparison with different types of interference detection algorithms. © 2014 EURASIP.
Resumo:
In animal cells the centrosome is positioned at the cell centre in close association with the nucleus. The mechanisms responsible for this are not completely understood. Here, we report the first characterization of human TBCC-domain containing 1 (TBCCD1), a protein related to tubulin cofactor C. TBCCD1 localizes at the centrosome and at the spindle midzone, midbody and basal bodies of primary and motile cilia. Knockdown of TBCCD1 in RPE-1 cells caused the dissociation of the centrosome from the nucleus and disorganization of the Golgi apparatus. TBCCD1-depleted cells are larger, less efficient in primary cilia assembly and their migration is slower in wound-healing assays. However, the major microtubule-nucleating activity of the centrosome is not affected by TBCCD1 silencing. We propose that TBCCD1 is a key regulator of centrosome positioning and consequently of internal cell organization.
Resumo:
We report the fabrication of planar sub-micron gratings in silicon with a period of 720 nm using a modified Michelson interferometer and femtosecond laser radiation. The gratings consist of alternated stripes of laser ablated and unmodified material. Ablated stripes are bordered by parallel ridges which protrude above the unmodified material. In the regions where ridges are formed, the laser radiation intensity is not sufficient to cause ablation. Nevertheless, melting and a significant temperature increase are expected, and ridges may be formed due to expansion of silicon during resolidification or silicon oxidation. These conclusions are consistent with the evolution of the stripes morphology as a function of the distance from the center of the grating. (C) 2013 Elsevier Ltd. All rights reserved.
Resumo:
This paper presents the characterization of an indoor Wimax radio channel using the Finite-Difference Time-Domain (FDTD) [1] method complemented with the Convolutional Perfect Matched Layer (CPML) technique [2]. An indoor 2D scenario is simulated in the 3.5GHz band (IEEE 802.16d-2004 and IEEE 802.16e-2005 [3]). In this study, we used two complementary techniques in both analysis, technique A and B for fading based on delay spread and technique C and D for fading based on Doppler spread. Both techniques converge to the same result. Simulated results define the channel as flat, slow and without inter-symbolic interference (ISI), making the application of the spatial diversity the most appropriate scheme.
Resumo:
Wireless local-area networks (WLANs) have been deployed as office and home communications infrastructures worldwide. The diversification of the standards, such as IEEE 802.11 series demands the design of RF front-ends. Low power consumption is one of the most important design concerns in the application of those technologies. To maintain competitive hardware costs, CMOS has been used since it is the best solution for low cost and high integration processing, allowing analog circuits to be mixed with digital ones. In the receiver chain, the low noise amplifier (LNA) is one of the most critical blocks in a transceiver design. The sensitivity is mainly determined by the LNA noise figure and gain. It interfaces with the pre-select filter and the mixer. Furthermore, since it is the first gain stage, care must be taken to provide accurate input match, low-noise figure, good linearity and a sufficient gain over a wide band of operation. Several CMOS LNAs have been reported during the last decade, showing that the most research has been done at 802.11/b and GSM standards (900-2400MHz spectrum) and more recently at 802.11/a (5GHz band). One of the more significant disadvantages of 802.11/b is that the frequency band is crowded and subject to interference from other technologies, as is 2.4GHz cordless phones and Bluetooth. As the demand for radio-frequency integrated circuits, operating at higher frequency bands, increases, the IEEE 802.11/a standard becomes a very attractive option to wireless communication system developers. This paper presents the design and implementation of a low power, low noise amplifier aimed at IEEE 802.11a for WLAN applications. It was designed to be integrated with an active balun and mixer, representing the first step toward a fully integrated monolithic WLAN receiver. All the required circuits are integrated at the same die and are powered by 1.8V supply source. Preliminary experimental results (S-parameters) are shown and promise excellent results. The LNA circuit design details are illustrated in Section 2. Spectre simulation results focused at gain, noise figure (NF) and input/output matching are presented in Section 3. Finally, conclusions and comparison with other recently reported LNAs are made in Section 4, followed by future work.
Resumo:
Microtubules are polymers of alpha/beta-tubulin participating in essential cell functions. A multistep process involving distinct molecular chaperones and cofactors produces new tubulin heterodimers competent to polymerise. In vitro cofactor A (TBCA) interacts with beta-tubulin in a quasi-native state behaving as a molecular chaperone. We have used siRNA to silence TBCA expression in HeLa and MCF-7 mammalian cell lines. TBCA is essential for cell viability and its knockdown produces a decrease in the amount of soluble tubulin, modifications in microtubules and G1 cell cycle arrest. In MCF-7 cells, cell death was preceded by a change in cell shape resembling differentiation.
Resumo:
It is now widely recognized that translation factors are involved in cancer development and that components of the translation machinery that are deregulated in cancer cells may become targets for cancer therapy. The eukaryotic Release Factor 3 (eRF3) is a GTPase that associates with eRF1 in a complex that mediates translation termination. eRF3a/GSPT1 first exon contains a (GGC)n expansion coding for proteins with different N-terminal extremities. Herein we show that the longer allele (12-GGC) is present in 5.1% (7/137) of the breast cancer patients analysed and is absent in the control population (0/135), corresponding to an increased risk for cancer development, as revealed by Odds Ratio analysis. mRNA quantification suggests that patients with the 12-GGC allele overexpress eRF3a/GSPT1 in tumor tissues relative to the normal adjacent tissues. However, using an in vivo assay for translation termination in HEK293 cells, we do not detect any difference in the activity of the eRF3a proteins encoded by the various eRF3a/GSPT1 alleles. Although the connection between the presence of eRF3a/GSPT1 12-GGC allele and tumorigenesis is still unknown, our data suggest that the presence of the 12-GGC allele provides a potential novel risk marker for various types of cancer.
Resumo:
A novel contribution to the leptonic CP asymmetries in type II seesaw leptogenesis scenarios is obtained for the cases in which flavor effects are relevant for the dynamics of leptogenesis. In the so-called flavored leptogenesis regime, the interference between the tree-level amplitude of the scalar triplet decaying into two leptons and the one-loop wave function correction with leptons in the loop, leads to a new nonvanishing CP asymmetry contribution. The latter conserves total lepton number but violates lepton flavor. Cases in which this novel contribution may be dominant in the generation of the baryon asymmetry are briefly discussed.
Resumo:
Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia de Electrónica e Telecomunicações
Resumo:
Huntington's disease (HD) is an incurable genetic neurodegenerative disorder that leads to motor and cognitive decline. It is caused by an expanded polyglutamine tract within the Huntingtin (HTT) gene, which translates into a toxic mutant HTT protein. Although no cure has yet been discovered, novel therapeutic strategies, such as RNA interference (RNAi), antisense oligonucleotides (ASO), ribozymes, DNA enzymes, and genome-editing approaches, aimed at silencing or repairing the mutant HTT gene hold great promise. Indeed, several preclinical studies have demonstrated the utility of such strategies to improve HD neuropathology and symptoms. In this review, we critically summarise the main advances and limitations of each gene-silencing technology as an effective therapeutic tool for the treatment of HD.
Resumo:
With the increasing complexity of current networks, it became evident the need for Self-Organizing Networks (SON), which aims to automate most of the associated radio planning and optimization tasks. Within SON, this paper aims to optimize the Neighbour Cell List (NCL) for Long Term Evolution (LTE) evolved NodeBs (eNBs). An algorithm composed by three decisions were were developed: distance-based, Radio Frequency (RF) measurement-based and Handover (HO) stats-based. The distance-based decision, proposes a new NCL taking account the eNB location and interference tiers, based in the quadrants method. The last two algorithms consider signal strength measurements and HO statistics, respectively; they also define a ranking to each eNB and neighbour relation addition/removal based on user defined constraints. The algorithms were developed and implemented over an already existent radio network optimization professional tool. Several case studies were produced using real data from a Portuguese LTE mobile operator. © 2014 IEEE.
Resumo:
We consider the two-Higgs-doublet model as a framework in which to evaluate the viability of scenarios in which the sign of the coupling of the observed Higgs boson to down-type fermions (in particular, b-quark pairs) is opposite to that of the Standard Model (SM), while at the same time all other tree-level couplings are close to the SM values. We show that, whereas such a scenario is consistent with current LHC observations, both future running at the LHC and a future e(+)e(-) linear collider could determine the sign of the Higgs coupling to b-quark pairs. Discrimination is possible for two reasons. First, the interference between the b-quark and the t-quark loop contributions to the ggh coupling changes sign. Second, the charged-Higgs loop contribution to the gamma gamma h coupling is large and fairly constant up to the largest charged-Higgs mass allowed by tree-level unitarity bounds when the b-quark Yukawa coupling has the opposite sign from that of the SM (the change in sign of the interference terms between the b-quark loop and the W and t loops having negligible impact).