Numerical simulation of neutron radiation effects in avalanche photodiodes

A new one-dimensional (1-D) device model developed for the simulation of neutron radiation effects in silicon avalanche photodiodes is described. The model uses a finite difference technique to solve the time-independent semiconductor equations across a user specified structure. The model includes impact ionization and illumination allowing accurate simulation with minimal assumptions. The effect of neutron radiation damage is incorporated via the introduction of deep acceptor levels subject to Shockley-Read-Hall statistics. Preliminary analysis of an EG&G reverse APD structure is compared with experimental data from a commercial EG&G C30719F APD

Towards scalable end-to-end QoS provision for VoIP applications

The growth of the Internet and the development of its new applications have increased the demand for providing a certain level of resource assurance and service support. The concept of ensuring quality of service (QoS) has been introduced in order to provide the support and assurance for these services. Different QoS mechanisms, such as integrated services (IntServ) and differentiated services (DiffServ), have been developed and introduced to provide different levels of QoS provision. However, IntServ can suffer from scalability issues that make it infeasible for large-scale network implementations. On the other hand, the aggregated-based per-flow technique of DiffServ does not provide such an end-to-end QoS guarantee. Recently, the IETF have proposed a new QoS architecture that implements IntServ over DiffServ in order to provide an end-to-end QoS for scalable networks. Hence, it became possible to provide and support a certain level of QoS for some delay sensitive and bandwidth-demanding applications such as voice over Internet Protocol (VoIP). With regard to VoIP applications, delay, jitter and packet loss are crucial issues that have to be taken into consideration for any VoIP system design and such parameters need a distinct level of QoS support

Howzat! Expert umpires use a gaze anchor to overcome the processing demands of leg before wicket decisions.

Cricket umpires are required to make high-pressure, match-changing decisions based on multiple complex information sources under severe temporal constraints. The aim of this study was to examine the decision-making and perceptual-cognitive differences between expert and novice cricket umpires when judging leg before wicket (LBW) decisions. Twelve expert umpires and 19 novice umpires were fitted with an eye-tracker before viewing video-based LBW appeals. Dependent variables were radial error (cm), number of fixations, average fixation duration (ms), final fixation duration (ms), and final fixation location (%). Expert umpires were significantly more accurate at adjudicating on all aspects of the LBW law, compared to the novice umpires (p < .05). The expert umpires' final fixation prior to ball-pad contact was directed significantly more towards the stumps (p < .05), whereas the novice umpires directed their final fixation significantly more towards a good length (p < .05). These data suggest that expert umpires utilize specialized perceptual-cognitive skills, consisting of a gaze anchor on the stumps in order to overcome the processing demands of the task. These data have implications for the training of current and aspiring umpires in order to enhance the accuracy of LBW decision-making across all levels of the cricketing pyramid

Regulation of G protein-coupled receptors by palmitoylation and cholesterol

Due to their membrane location, G protein-coupled receptors (GPCRs) are subject to regulation by soluble and integral membrane proteins as well as membrane components, including lipids and sterols. GPCRs also undergo a variety of post-translational modifications, including palmitoylation. A recent article by Zheng et al. in BMC Cell Biology demonstrates cooperative roles for receptor palmitoylation and cholesterol binding in GPCR dimerization and G protein coupling, underlining the complex regulation of these receptors

Global governance and the broader determinants of health: A comparative case study of UNDP's and WTO's engagement with global health

This comparative case study investigated how two intergovernmental organisations without formal health mandates - the United Nations Development Programme (UNDP) and the World Trade Organization (WTO) - have engaged with global health issues. Triangulating insights from key institutional documents, ten semi-structured interviews with senior officials, and scholarly books tracing the history of both organisations, the study identified an evolving and broadened engagement with global health issues in UNDP and WTO. Within WTO, the dominant view was that enhancing international trade is instrumental to improving global health, although the need to resolve tensions between public health objectives and WTO agreements was recognised. For UNDP, interviewees reported that the agency gained prominence in global health for its response to HIV/AIDS in the 1990s and early 2000s. Learning from that experience, the agency has evolved and expanded its role in two respects: it has increasingly facilitated processes to provide global normative direction for global health issues such as HIV/AIDS and access to medicines, and it has expanded its focus beyond HIV/AIDS. Overall, the study findings suggest the need for seeking greater integration among international institutions, closing key global institutional gaps, and establishing a shared global institutional space for promoting action on the broader determinants of health

Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing

Confab - Systematic generation of diverse low-energy conformers

<p>Abstract</p> <p>Background</p> <p>Many computational chemistry analyses require the generation of conformers, either on-the-fly, or in advance. We present Confab, an open source command-line application for the systematic generation of low-energy conformers according to a diversity criterion.</p> <p>Results</p> <p>Confab generates conformations using the 'torsion driving approach' which involves iterating systematically through a set of allowed torsion angles for each rotatable bond. Energy is assessed using the MMFF94 forcefield. Diversity is measured using the heavy-atom root-mean-square deviation (RMSD) relative to conformers already stored. We investigated the recovery of crystal structures for a dataset of 1000 ligands from the Protein Data Bank with fewer than 1 million conformations. Confab can recover 97% of the molecules to within 1.5 Å at a diversity level of 1.5 Å and an energy cutoff of 50 kcal/mol.</p> <p>Conclusions</p> <p>Confab is available from <url>http://confab.googlecode.com</url>.</p

Three dimensional structure directs T-cell epitope dominance associated with allergy

<p>Abstract</p> <p>Background</p> <p>CD4+ T-cell epitope immunodominance is not adequately explained by peptide selectivity in class II major histocompatibility proteins, but it has been correlated with adjacent segments of conformational flexibility in several antigens.</p> <p>Methods</p> <p>The published T-cell responses to two venom allergens and two aeroallergens were used to construct profiles of epitope dominance, which were correlated with the distribution of conformational flexibility, as measured by crystallographic B factors, solvent-accessible surface, COREX residue stability, and sequence entropy.</p> <p>Results</p> <p>Epitopes associated with allergy tended to be excluded from and lie adjacent to flexible segments of the allergen.</p> <p>Conclusion</p> <p>During the initiation of allergy, the N- and/or C-terminal ends of proteolytic processing intermediates were preferentially loaded into antigen presenting proteins for the priming of CD4+ T cells.</p

Insights Into the Structure-Function Relationships of Dimeric C3d Fragments

\ua9 Copyright \ua9 2021 Wahid, Dunphy, Macpherson, Gibson, Kulik, Whale, Back, Hallam, Alkhawaja, Martin, Meschede, Laabei, Lawson, Holers, Watts, Crennell, Harris, Marchbank and van den Elsen.Cleavage of C3 to C3a and C3b plays a central role in the generation of complement-mediated defences. Although the thioester-mediated surface deposition of C3b has been well-studied, fluid phase dimers of C3 fragments remain largely unexplored. Here we show C3 cleavage results in the spontaneous formation of C3b dimers and present the first X-ray crystal structure of a disulphide-linked human C3d dimer. Binding studies reveal these dimers are capable of crosslinking complement receptor 2 and preliminary cell-based analyses suggest they could modulate B cell activation to influence tolerogenic pathways. Altogether, insights into the physiologically-relevant functions of C3d(g) dimers gained from our findings will pave the way to enhancing our understanding surrounding the importance of complement in the fluid phase and could inform the design of novel therapies for immune system disorders in the future