The use of computational QSAR analysis in the toxicological evaluation of a series of 2-pyridylcarboxamidrazone candidate anti-tuberculosis compounds

A series of N1-benzylidene pyridine-2-carboxamidrazone anti-tuberculosis compounds has been evaluated for their cytotoxicity using human mononuclear leucocytes (MNL) as target cells. All eight compounds were significantly more toxic than dimethyl sulphoxide control and isoniazid (INH) with the exception of a 4-methoxy-3-(2-phenylethyloxy) derivative, which was not significantly different in toxicity compared with INH. The most toxic agent was an ethoxy derivative, followed by 3-nitro, 4-methoxy, dimethylpropyl, 4-methylbenzyloxy, 3-methoxy-4-(-2-phenylethyloxy) and 4-benzyloxy in rank order. In comparison with the effect of selected carboxamidrazone agents on cells alone, the presence of either N-acetyl cysteine (NAC) or glutathione caused a significant reduction in the toxicity of INH, as well as on the 4-benzyloxy derivative, although both increased the toxicity of a 4-N,N-dimethylamino-1-naphthylidene and a 2-t-butylthio derivative. The derivatives from this and three previous studies were subjected to computational analysis in order to derive equations designed to establish quantitative structure activity relationships for these agents. Twenty-five compounds were thus resolved into two groups (1 and 2), which on analysis yielded equations with r2 values in the range 0.65-0.92. Group 1 shares a common mode of toxicity related to hydrophobicity, where cytotoxicity peaked at logP of 3.2, while Group 2 toxicity was strongly related to ionisation potential. The presence of thiols such as NAC and GSH both promoted and attenuated toxicity in selected compounds from Group 1, suggesting that secondary mechanisms of toxicity were operating. These studies will facilitate the design of future low toxicity high activity anti-tubercular carboxamidrazone agents. © 2003 Elsevier Science B.V. All rights reserved.

Performance evaluation of adaptive context aware rate selection algorithm (ACARS) for road safety applications in vehicular network

One of the major drawbacks for mobile nodes in wireless networks is power management. Our goal is to evaluate the performance power control scheme to be used to reduce network congestion, improve quality of service and collision avoidance in vehicular network and road safety application. Some of the importance of power control (PC) are improving spatial reuse, and increasing network capacity in mobile wireless communications. In this simulation we have evaluated the performance of existing rate algorithms compared with context Aware Rate selection algorithm (ACARS) and also seen the performance of ACARS and how it can be applied to road safety, improve network control and power management. Result shows that ACARS is able to minimize the total transmit power in the presence of propagation processes and mobility of vehicles, by adapting to the fast varying channels conditions with the Path loss exponent values that was used for that environment which is shown in the network simulation parameter. Our results have shown that ACARS is a very robust algorithm which performs very well with the effect of propagation processes that is prone to every transmitted signal in mobile networks. © 2013 IEEE.

Clinical evaluation of the Shin-Nippon SRW-5000 autorefractor in adults:an update

Purpose: The Shin-Nippon SRW-5000 is an open view autorefractor that superseded the Canon R-1 autorefractor in the mid-1990s and has been used widely in optometry and vision science laboratories. It has been used to measure refractive error, accommodation responses both statically and dynamically, off-axis refractive error, and adapted to measure pupil size. This paper presents an overview of the original 2001 clinical evaluation of the SRW-5000 in adults (Mallen et al., Ophthal Physiol Opt 2001; 21: 101) and provides an update on the use and modification of the instrument since the original publication. Recent findings: The SRW-5000 instrument, and the family of devices which followed, have shown excellent validity, repeatability, and utility in clinical and research settings. The instruments have also shown great potential for increased research functionality following a number of modifications. Summary: The SRW-5000 and its derivatives have been, and continue to be, of significant importance in our drive to understand myopia progression, myopia control techniques, and oculomotor function in human vision.

A seismic shift? An evaluation of the impact of new media on perceptions of freedom of expression and privacy

New media platforms have changed the media landscape forever, as they have altered our perceptions of the limits of communication, and reception of information. Platforms such as Facebook, Twitter and WhatsApp enable individuals to circumvent the traditional mass media, converging audience and producer to create millions of ‘citizen journalists’. This new breed of journalist uses these platforms as a way of, not only receiving news, but of instantaneously, and often spontaneously, expressing opinions and venting and sharing emotions, thoughts and feelings. They are liberated from cultural and physical restraints, such as time, space and location, and they are not constrained by factors that impact upon the traditional media, such as editorial control, owner or political bias or the pressures of generating commercial revenue. A consequence of the way in which these platforms have become ingrained within our social culture is that habits, conventions and social norms, that were once informal and transitory manifestations of social life, are now infused within their use. What were casual and ephemeral actions and/or acts of expression, such as conversing with friends or colleagues or swapping/displaying pictures, or exchanging thoughts that were once kept private, or maybe shared with a select few, have now become formalised and potentially permanent, on view for the world to see. Incidentally, ‘traditional’ journalists and media outlets are also utilising new media, as it allows them to react, and disseminate news, instantaneously, within a hyper-competitive marketplace. However, in a world where we are saturated, not only by citizen journalists, but by traditional media outlets, offering access to news and opinion twenty-four hours a day, via multiple new media platforms, there is increased pressure to ‘break’ news fast and first. This paper will argue that new media, and the culture and environment it has created, for citizen journalists, traditional journalists and the media generally, has altered our perceptions of the limits and boundaries of freedom of expression dramatically, and that the corollary to this seismic shift is the impact on the notion of privacy and private life. Consequently, this paper will examine what a reasonable expectation of privacy may now mean, in a new media world.

Dissociation of detection and evaluation of facial expressions in adolescence

Holistic face perception, i.e. the mandatory integration of featural information across the face, hasbeen considered to play a key role when recognizing emotional face expressions (e.g., Tanaka et al.,2002). However, despite their early onset holistic processing skills continue to improvethroughout adolescence (e.g., Schwarzer et al., 2010) and therefore might modulate theevaluation of facial expressions. We tested this hypothesis using an attentional blink (AB)paradigm to compare the impact of happy, fearful and neutral faces in adolescents (10–13 years)and adults on subsequently presented neutral target stimuli (animals, plants and objects) in a rapidserial visual presentation stream. Adolescents and adults were found to be equally reliable whenreporting the emotional expression of the face stimuli. However, the detection of emotional butnot neutral faces imposed a significantly stronger AB effect on the detection of the neutral targetsin adults compared to adolescents. In a control experiment we confirmed that adolescents ratedemotional faces lower in terms of valence and arousal than adults. The results suggest a protracteddevelopment of the ability to evaluate facial expressions that might be attributed to the latematuration of holistic processing skills.