Allosteric Modulation of the HIV-1 gp120-gp41 Association Site by Adjacent gp120 Variable Region 1 (V1) N-Glycans Linked to Neutralization Sensitivity

The HIV-1 gp120-gp41 complex, which mediates viral fusion and cellular entry, undergoes rapid evolution within its external glycan shield to enable escape from neutralizing antibody (NAb). Understanding how conserved protein determinants retain functionality in the context of such evolution is important for their evaluation and exploitation as potential drug and/ or vaccine targets. In this study, we examined how the conserved gp120-gp41 association site, formed by the N- and Cterminal segments of gp120 and the disulfide-bonded region (DSR) of gp41, adapts to glycan changes that are linked to neutralization sensitivity. To this end, a DSR mutant virus (K601D) with defective gp120-association was sequentially passaged in peripheral blood mononuclear cells to select suppressor mutations. We reasoned that the locations of suppressors point to structural elements that are functionally linked to the gp120-gp41 association site. In culture 1, gp120 association and viral replication was restored by loss of the conserved glycan at Asn136 in V1 (T138N mutation) in
conjunction with the L494I substitution in C5 within the association site. In culture 2, replication was restored with deletion of the N139INN sequence, which ablates the overlapping Asn141-Asn142-Ser-Ser potential N-linked glycosylation sequons in
V1, in conjunction with D601N in the DSR. The 136 and 142 glycan mutations appeared to exert their suppressive effects by altering the dependence of gp120-gp41 interactions on the DSR residues, Leu593, Trp596 and Lys601. The 136 and/or 142
glycan mutations increased the sensitivity of HIV-1 pseudovirions to the glycan-dependent NAbs 2G12 and PG16, and also pooled IgG obtained from HIV-1-infected individuals. Thus adjacent V1 glycans allosterically modulate the distal gp120-
gp41 association site. We propose that this represents a mechanism for functional adaptation of the gp120-gp41 association site to an evolving glycan shield in a setting of NAb selection.

The dependent variable in social media use

What is the dependent variable in social media use? From a research perspective, this is a pertinent question to help explain and understand the behaviors that underpin the widespread adoption and use of social media throughout society. From a practical
perspective, the question is relevant for social media technology providers, for businesses that use social media, and community organizations that turn towards social media to reach out to their constituents. We propose the construct 'sense of community' as the dependent variable, which is reflected in four sub-constructs related to the behaviors of social media users. These behaviors are information seeking, hedonic activities, sustaining of strong ties and extending weak ties. Empirical evidence for these constructs comes from a survey of social media use by 18-25 year-olds in Indonesia, a ,country with exceptionally high utilization of social media. We outline practical implications of the  findings and areas for further theoretical development.

On some properties of weighted averaging with variable weights

Density-based means have been recently proposed as a method for dealing with outliers in the stream processing of data. Derived from a weighted arithmetic mean with variable weights that depend on the location of all data samples, these functions are not monotonic and hence cannot be classified as aggregation functions. In this article we establish the weak monotonicity of this class of averaging functions and use this to establish robust generalisations of these means. Specifically, we find that as proposed, the density based means are only robust to isolated outliers. However, by using penalty based formalisms of averaging functions and applying more sophisticated and robust density estimators, we are able to define a broader family of density based means that are more effective at filtering both isolated and clustered outliers. © 2014 Elsevier Inc. All rights reserved.

An analytical approach to predict web-warping and longitudinal strain in flexible roll formed sections of variable width

To reduce weight and improve passenger safety there is an increased need in the automotive industry to use Ultra High Strength Steel (UHSS) for structural and crash components. However, the application of UHSS is restricted by their limited formability and the difficulty of forming them in conventional stamping. An alternative method of manufacturing structural auto body parts from UHSS is the flexible roll forming process, which allows the manufacture of metal sheet with high strength and limited ductility into complex and weight-optimized components. One major problem in the flexible roll forming of UHSS is the web-warping defect, which is the deviation in height of the web area over the length of the profile. It has been shown that web-warping is strongly dependant to the permanent longitudinal strain formed in the flange of the part. Flexible roll forming is a continuous process with many roll stands, which makes numerical analysis extremely time intensive and computationally expensive. An analytical model of web-warping is therefore critical to improve design efficiency during the early process design stage before FEA is applied. This paper establishes for the first time an analytical model for the prediction of web-warping for the flexible roll forming of a section with variable width. The model is based on evaluating longitudinal edge strain in the flange of the part. This information is then used in combination with a simple geometrical model to investigate the relationship between web-warping and longitudinal strain with respect to process parameters.

A hybrid cuckoo search and variable neighborhood descent for single and multiobjective scheduling problems

Cuckoo search (CS) is a relatively new meta-heuristic that has proven its strength in solving continuous optimization problems. This papers applies cuckoo search to the class of sequencing problems by hybridizing it with a variable neighborhood descent local search for enhancing the quality of the obtained solutions. The Lévy flight operator proposed in the original CS is modified to address the discrete nature of scheduling problems. Two well-known problems are used to demonstrate the effectiveness of the proposed hybrid CS approach. The first is the NP-hard single objective problem of minimizing the weighted total tardiness time (Formula presented.) and the second is the multiobjective problem of minimizing the flowtime ¯ and the maximum tardiness Tmaxfor single machine (Formula presented.). For the first problem, computational results show that the hybrid CS is able to find the optimal solutions for all benchmark test instances with 40, 50, and 100 jobs and for most instances with 150, 200, 250, and 300 jobs. For the second problem, the hybrid CS generated solutions on and very close to the exact Pareto fronts of test instances with 10, 20, 30, and 40 jobs. In general, the results reveal that the hybrid CS is an adequate and robust method for tackling single and multiobjective scheduling problems.

Ecosystem relevance of variable jellyfish biomass in the Irish Sea between years, regions and water types

Monitoring the abundance and distribution of taxa is essential to assess their contribution to ecosystem processes. For marine taxa that are difficult to study or have long been perceived of little ecological importance, quantitative information is often lacking. This is the case for jellyfish (medusae and other gelatinous plankton). In the present work, 4 years of scyphomedusae by-catch data from the 2007-2010 Irish Sea juvenile gadoid fish survey were analysed with three main objectives: (1) to provide quantitative and spatially-explicit species-specific biomass data, for a region known to have an increasing trend in jellyfish abundance; (2) to investigate whether year-to-year changes in catch-biomass are due to changes in the numbers or in the size of medusa (assessed as the mean mass per individual), and (3) to determine whether inter-annual variation patterns are consistent between species and water masses. Scyphomedusae were present in 97% of samples (N=306). Their overall annual median catch-biomass ranged from 0.19 to 0.92gm-3 (or 8.6 to 42.4gm-2). Aurelia aurita and Cyanea spp. (Cyanea lamarckii and Cyanea capillata) made up 77.7% and 21.5% of the total catch-biomass respectively, but species contributions varied greatly between sub-regions and years. No consistent pattern was detected between the distribution and inter-annual variations of the two genera, and contrasting inter-annual patterns emerged when considering abundance either as biomass or as density. Significantly, A.aurita medusae were heavier in stratified than in mixed waters, which we hypothesize may be linked to differences in timing and yield of primary and secondary productions between water masses. These results show the vulnerability of time-series from bycatch datasets to phenological changes and highlight the importance of taking species- and population-specific distribution patterns into account when integrating jellyfish into ecosystem models.

Paradox lost: variable colour-pattern geometry is associated with differences in movement in aposematic frogs

Aposematic signal variation is a paradox: predators are better at learning and retaining the association between conspicuousness and unprofitability when signal variation is low. Movement patterns and variable colour patterns are linked in non-aposematic species: striped patterns generate illusions of altered speed and direction when moving linearly, affecting predators' tracking ability; blotched patterns benefit instead from unpredictable pauses and random movement. We tested whether the extensive colour-pattern variation in an aposematic frog is linked to movement, and found that individuals moving directionally and faster have more elongated patterns than individuals moving randomly and slowly. This may help explain the paradox of polymorphic aposematism: variable warning signals may reduce protection, but predator defence might still be effective if specific behaviours are tuned to specific signals. The interacting effects of behavioural and morphological traits may be a key to the evolution of warning signals. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

New variable step-sizes minimizing mean-square deviation for the lms-type algorithms

The least-mean-square-type (LMS-type) algorithms are known as simple and effective adaptation algorithms. However, the LMS-type algorithms have a trade-off between the convergence rate and steady-state performance. In this paper, we investigate a new variable step-size approach to achieve fast convergence rate and low steady-state misadjustment. By approximating the optimal step-size that minimizes the mean-square deviation, we derive variable step-sizes for both the time-domain normalized LMS (NLMS) algorithm and the transform-domain LMS (TDLMS) algorithm. The proposed variable step-sizes are simple quotient forms of the filtered versions of the quadratic error and very effective for the NLMS and TDLMS algorithms. The computer simulations are demonstrated in the framework of adaptive system modeling. Superior performance is obtained compared to the existing popular variable step-size approaches of the NLMS and TDLMS algorithms. © 2014 Springer Science+Business Media New York.

Using occupancy as a state variable for monitoring the critically endangered Alaotran gentle lemur Hapalemur alaotrensis

Although monitoring is an essential tool for biodiversity conservation, monitoring programmes are often poorly designed and thus unlikely to produce results that are meaningful for management. Monitoring is especially challenging when dealing with rare and elusive species in areas where conservation resources are particularly limited. In such cases, monitoring techniques aimed at estimating occupancy represent an attractive alternative to traditional methods concerned with estimating population size, as the collection of detection/non-detection data is in general less costly and easier to implement. In this study, we evaluated the use of occupancy as a state variable for the monitoring of the Alaotran gentle lemur Hapalemur alaotrensis, a Critically Endangered primate exclusively inhabiting the dense marshes around Lake Alaotra in Madagascar. We used a likelihood-based modelling approach that explicitly accounts for detectability. This showed that the probability of detection of H. alaotrensis was extremely low and depended on site characteristics that can vary in space and time, confirming the need to account for imperfect detection when monitoring this species. We used our models to explore factors affecting the probability of occupancy and detection to identify management implications, and also developed recommendations for the ongoing monitoring of this species. The method applied in this study provides an efficient tool for the monitoring of an elusive species and has the potential to provide a flexible sampling framework for local community based monitoring initiatives.