GC-selective DNA-binding antibiotic, Mithramycin A, reveals multiple points of control in the regulation of Hdm2 protein synthesis

The primary role of the Hdm2/Mdm2 oncoprotein is to regulate the levels and activity of the transcription factor p53. Hdm2 synthesis is itself tightly controlled and, as demonstrated by a recently described SNP (SNP309) in the hdm2-P2 promoter, minor variations in Hdm2 expression have phenotypic consequences on radiation sensitivity and cancer predisposition. To further define mechanisms regulating Hdm2 expression, we have investigated the effects of the GC-selective DNA-binding drug, Mithramycin A (MA) on hdm2 mRNA transcription, trafficking, and translation. Firstly we show that the constitutive hdm2-P1 promoter is inhibited by MA. We define, for the first time, the minimal sequence elements that are required for P1-promoter activity and identify those which confer MA sensitivity. Secondly, MA induces p53-dependent transcription from the hdm2-P2 promoter. Thirdly, and critically, MA also inhibits Hdm2 synthesis at the post-transcriptional level, with negative effects on hdm2 mRNA nuclear export and translation. This study highlights the complex interplay between the pathways that regulate Hdm2 protein synthesis in cancer cells, and furthermore emphasizes the export of hdm2 mRNA from the nucleus to the cytoplasm as a key point of control in this process.<br/><br/

From the 'cinematic' to the 'anime-ic': Issues of movement in anime

This is the author's accepted manuscript. The final published article is available from the link below.This article explores the way that movement is formally depicted in anime. Drawing on Thomas Lamarre's concepts of the `cinematic' and the `anime-ic', the article interrogates further the differences in movement and action in anime from traditional filmic form. While often considered in terms of `flatness', anime offers spectacle, character development and, ironically, depth through the very form of movement put to use in such texts.The article questions whether the modes of address at work in anime are unique to this form of animation.Taking into account how the terms `cinematic' and `anime-ic' can be understood (and by extension the cinematic and animatic apparatus), the article also begins to explore how viewers might identify with such images

Investigation into Rain Attenuation Prediction Models at Locations in Lagos Using Remote Sensing

This paper investigated the performances of some rain attenuation prediction models at some GSM network locations in Lagos, Nigeria, using remote sensing at Ku band. Remote sensing is a collection and interpretation of information about an object without physical contact with the object being measured. Three popular terrestrial prediction models were considered in this work. These are ITU-R P.530-17, Lin and Silva Mello Models. Ten years (2010-2019) annual rainfall data with hourly integration time were sourced from the Nigerian Meteorological Agency (NIMET) and link budgets for three microwave links (Tarzan Yard, Kofo Abayomi and GLO Shop) in Victoria Island at 18 GHz were obtained from Global Communications Limited (GLO), Nigeria. Data analysis and comparison of the microwave links rainfall estimates were carried out to identify the most suitable of the three models at the selected locations of interest. Measurement data obtained from both NIMET and GLO were used to validate the predicted attenuation data from the three selected models. The ITU-R P.530-17 prediction model overestimated the measurement at Tarzan Yard; closely followed by Silva Mello, while Lin underestimated the measured data. Again, at Kofo Abayomi station, the ITU-R model overestimated the measurement, while both Silva Mello and Lin models underestimated the measurement. At the GLO Shop, the Silva Mello overestimated the measured value, while ITU-R and Lin underestimated the measurement. At 0.01% of time exceeded, NIMET measurement was higher (at 48.2 dB) than that of Tarzan Yard, Kofo Abayomi and GLO shop (43.1, 46.3 and 37.0 dB respectively). These results will provide useful information in mitigating signal outages due to rain for mobile communication systems

Peroxynitrite releases copper from caeruloplasmin: implications for atherosclerosis

AbstractPeroxynitrite may be formed in the vasculature by the reaction of puperoxide with nitric oxide. When the blue copper-containing protein, caeruloplasmin, is incubated with peroxynitrite, copper is released, and ferroxidase activity and the blue colouration are lost. When plasma from normal subjects is incubated with peroxynitrite, the oxidant reacts with numerous plasma constituents but is still able to release copper from caeruloplasmin. As the ferroxidase activity of caeruloplasmin is lost in plasma in the presence of peroxynitrite, a second ferroxidase activity associated with peroxidised lipids, and not inhibited by azide, is formed

Cross-linguistic study of vocal pathology: perceptual features of spasmodic dysphonia in French-speaking subjects

Clinical characterisation of Spasmodic Dysphonia of the adductor type (SD) in French speakers by Klap and colleagues (1993) appears to differ from that of SD in English. This perceptual analysis aims to describe the phonetic features of French SD. A video of 6 French speakers with SD supplied by Klap and colleagues was analysed for frequency of phonatory breaks, pitch breaks, harshness, creak, breathiness and falsetto voice, rate of production, and quantity of speech output. In contrast to English SD, the French speaking SD patients demonstrated no evidence pitch breaks, but phonatory breaks, harshness and breathiness were prominent features. This verifies the French authors’ (1993) clinical description. These findings suggest that phonetic properties of a specific language may affect the manifestation of pathology in neurogenic voice disorders

Finding and Resolving Security Misusability with Misusability Cases

Although widely used for both security and usability concerns, scenarios used in security design may not necessarily inform the design of usability, and vice- versa. One way of using scenarios to bridge security and usability involves explicitly describing how design deci- sions can lead to users inadvertently exploiting vulnera- bilities to carry out their production tasks. This paper describes how misusability cases, scenarios that describe how design decisions may lead to usability problems sub- sequently leading to system misuse, address this problem. We describe the related work upon which misusability cases are based before presenting the approach, and illus- trating its application using a case study example. Finally, we describe some findings from this approach that further inform the design of usable and secure systems

A vocação da Amazônia é florestal e a criação de novos estados pode levar ao aumento do desflorestamento na Amazônia brasileira

The state of Pará has a rich diversity of ecosystems. However, it is one of the states that the most contribute with the deforestation of Amazonian. Actually, 22% of the state was deforested. Currently, a new policy of occupation is being studied for the Amazonian, based on the creation of new states. The creation of new states can increase deforestation in the Amazonian, especially in regions where the agricultural frontier and minerals activities are intense such as the state of Para. This study compares the changes of the representativeness of protected areas and deforestation, considering the proposed of division of the Para in three new states. The creation of new states can lead to a reduction or elimination of the protected areas resulting in the increase of the deforestation. Another serious consequence of the creation of new states will be the extinction of the Ecological-Economic Zoning of Para, an important instrument of public policy. The creation of new states must be preceded by studies involving the evaluation of the environmental, social and economic variables. One of the most serious consequences if it is not taken into consideration is the creation of a legal vacuum that will be used to increase the pressure on natural resources of the Amazon.O Pará detém uma rica diversidade de ecossistemas. Contudo, é um dos Estados que mais contribuem para o desmatamento na Amazônia. Atualmente, 22% do Estado foram desflorestados. Uma nova política de ocupação está sendo estudada para a Amazônia, baseada na criação de novos Estados. A criação de novos Estados pode aumentar o desmatamento na Amazônia, especialmente em regiões onde a fronteira agropecuária e mineraria é intensa como no Pará. Este estudo compara as mudanças da representatividade das áreas protegidas e do desmatamento, considerando a proposta de divisão do Estado do Pará em três novos Estados. A criação dos novos Estados pode levar a uma diminuição ou mesmo eliminação de algumas unidades de conservação, o que terá como consequência direta o aumento do desmatamento. Outra consequência grave da criação de novos Estados será a extinção do Zoneamento Ecológico-Econômico do Pará, um importante instrumento de políticas públicas. A criação de novos Estados deve ser precedida de estudos que envolvam uma avaliação criteriosa dos impactos ambientais, sociais e econômicos. Umas das consequências mais graves se isso não for levado em consideração é a criação de um vácuo jurídico que será aproveitado para aumentar a pressão nos recursos naturais da Amazônia