Crowding, molecular volume and plasticity: An assessment involving crystallography, NMR and simulations

The discrepancy between the X-ray and NMR structures of Mycobacterium tuberculosis peptidyl-tRNA hydrolase in relation to the functionally important plasticity of the molecule led to molecular dynamics simulations. The X-ray and the NMR studies along with the simulations indicated an inverse correlation between crowding and molecular volume. A detailed comparison of proteins for which X-ray and the NMR structures appears to confirm this correlation. In consonance with the reported results of the investigations in cellular compartments and aqueous solution, the comparison indicates that the crowding results in compaction of the molecule as well as change in its shape, which could specifically involve regions of the molecule important in function. Crowding could thus influence the action of proteins through modulation of the functionally important plasticity of the molecule. Selvaraj M, Ahmad R, Varshney U and Vijayan M 2012 Crowding, molecular volume and plasticity: An assessment involving crystallography, NMR and simulations. J. Biosci. 37 953-963] DOI 10.1007/s12038-012-9276-5

Finding hidden females in a crowd: Mate recognition in fig wasps

Multi-species mating aggregations are crowded environments within which mate recognition must occur. Mating aggregations of fig wasps can consist of thousands of individuals of many species that attain sexual maturity simultaneously and mate in the same microenvironment, i.e, in syntopy, within the close confines of an enclosed globular inflorescence called a syconium - a system that has many signalling constraints such as darkness and crowding. All wasps develop within individual galled flowers. Since mating mostly occurs when females are still confined within their galls,, male wasps have the additional burden of detecting conspecific females that are ``hidden'' behind barriers consisting of gall walls. In Ficus racemosa, we investigated signals used by pollinating fig wasp males to differentiate conspecific females from females of other syntopic fig wasp species. Male Ceratosolen fusciceps could detect conspecific females using cues from galls containing females, empty galls, as well as cues from gall volatiles and gall surface hydrocarbons. In many figs, syconia are pollinated by single foundress wasps, leading to high levels of wasp inbreeding due to sibmating. In F. racemosa, as most syconia contain many foundresses, we expected male pollinators to prefer non-sib females to female siblings to reduce inbreeding. We used galls containing females from non-natal figs as a proxy for non-sibs and those from natal figs as a proxy for sibling females. We found that males preferred galls of female pollinators from natal figs. However, males were undecided when given a choice between galls containing non-pollinator females from natal syconia and pollinator females from non-natal syconia, suggesting olfactory imprinting by the natal syconial environment. (C) 2013 Elsevier Masson SAS. All rights reserved.

Periodically Grafted Amphiphilic Copolymers: Effects of Steric Crowding and Reversal of Amphiphilicity

Two series of periodically clickable polyesters were prepared; one of them carries alkylene segments along its backbone, whereas the other carries poly(ethylene glycol) (PEG) segments. These polyesters were clicked with either MPEG-350 azide or docosyl (C22) azide to yield periodically grafted amphiphilic copolymers (PGACs) carrying either flexible hydrophilic or crystallizable hydrophobic backbone segments. The immiscibility between hydrocarbon and PEG segments causes both of these systems to fold in either a zigzag or hairpin-like conformation; the hairpin-like conformation appears to be preferred when flexible PEG segments are present in the backbone. The folded chains further reorganize in the solid state to develop a lamellar morphology that permits the collocation of the PEG and hydrocarbon (HC) segments within alternate domains; evidence for the self-segregation was gained from DSC, SAXS, and AFM studies. SAXS studies revealed the formation of an extended lamellar structure, whereas AFM images showed uniform layered morphology with layer heights that matched reasonably well with the interlamellar spacing obtained from the SAXS study. Labeling One representative PGAC, carrying crystallizable long alkylene segments in the backbone and pendant PEG-350 side chains, with a small mole fraction of pyrene fluorophore permitted the examination of the conformational transition that occurs upon going from a good to a poor solvent; this single-chain folded conformation, we postulate, is the intermediate that organizes into the lamellar morphology.

Targeting human telomeric G-quadruplex DNA with curcumin and its synthesized analogues under molecular crowding conditions

The formation of telomeric G-quadruplexes has been shown to inhibit telomerase activity. Indeed, a number of small molecules capable of p-stacking with G-tetrads have shown the ability to inhibit telomerase activity through the stabilization of G-quadruplexes. Curcumin displays a wide spectrum of medicinal properties ranging from anti-bacterial, anti-viral, anti-protozoal, anti-fungal and anti-inflammatory to anti-cancer activity. We have investigated the interactions of curcumin and its structural analogues with the human telomeric sequence AG(3)(T(2)AG(3))(3) under molecular crowding conditions. Experimental studies indicated the existence of a AG(3)(T(2)AG(3))(3)/curcumin complex with binding affinity of 0.72 x 10(6) M-1 under molecular crowding conditions. The results from UV-visible absorption spectroscopy, a fluorescent TO displacement assay, circular dichroism and molecular docking studies, imply that curcumin and their analogues interact with G-quadruplex DNA via groove binding. While other analogs of curcumin studied here bind to G-quadruplexes in a qualitatively similar manner their affinities are relatively lower in comparison to curcumin. The Knoevenagel condensate, a methoxy-benzylidene derivative of curcumin, also exhibited significant binding to G-quadruplex DNA, although with two times decreased affinity. Our study establishes the potential of curcumin as a promising natural product for G-quadruplex specific ligands.

Targeting human telomeric G-quadruplex DNA with curcumin and its synthesized analogues under molecular crowding conditions

The formation of telomeric G-quadruplexes has been shown to inhibit telomerase activity. Indeed, a number of small molecules capable of p-stacking with G-tetrads have shown the ability to inhibit telomerase activity through the stabilization of G-quadruplexes. Curcumin displays a wide spectrum of medicinal properties ranging from anti-bacterial, anti-viral, anti-protozoal, anti-fungal and anti-inflammatory to anti-cancer activity. We have investigated the interactions of curcumin and its structural analogues with the human telomeric sequence AG(3)(T(2)AG(3))(3) under molecular crowding conditions. Experimental studies indicated the existence of a AG(3)(T(2)AG(3))(3)/curcumin complex with binding affinity of 0.72 x 10(6) M-1 under molecular crowding conditions. The results from UV-visible absorption spectroscopy, a fluorescent TO displacement assay, circular dichroism and molecular docking studies, imply that curcumin and their analogues interact with G-quadruplex DNA via groove binding. While other analogs of curcumin studied here bind to G-quadruplexes in a qualitatively similar manner their affinities are relatively lower in comparison to curcumin. The Knoevenagel condensate, a methoxy-benzylidene derivative of curcumin, also exhibited significant binding to G-quadruplex DNA, although with two times decreased affinity. Our study establishes the potential of curcumin as a promising natural product for G-quadruplex specific ligands.

Emergency department crowding: prioritising quantified crowding measures using a Delphi study.

AimsEmergency department (ED) crowding has been associated with a number of negative health outcomes, including unnecessary deaths, increased waiting times and a decrease in care quality. Despite the seriousness of this issue, there is little agreement on appropriate crowding measures to assess crowding effects on ED operations. The objective of this study was to prioritise a list of quantified crowding measures that would assess the current state of a department.MethodsA three round Delphi study was conducted via email and an Internet based survey tool. The panel consisted of 40 professionals who had exposure to and expertise in crowding. Participants submitted quantified crowding measures which, through three rounds, were evaluated and ranked to assess participant agreement for inclusion.ResultsThe panel identified 27 measures of which eight (29.6%) reached consensus at the end of the study. These measures comprised: (1) ability of ambulances to offload; (2) patients who leave without being seen or treated; (3) time until triage; (4) ED occupancy rate; (5) patients' total length of stay in the ED; (6) time to see a physician; (7) ED boarding time; and (8) number of patients boarding in the ED.ConclusionsThis study resulted in the identification of eight quantified crowding measures, which present a comprehensive view of how crowding is affecting ED operations, and highlighted areas of concern. These quantified measures have the potential to make a considerable contribution to decision making by ED management and to provide a basis for learning across different departments.

A neurophysiologically plausible population code model for feature integration explains visual crowding.

An object in the peripheral visual field is more difficult to recognize when surrounded by other objects. This phenomenon is called "crowding". Crowding places a fundamental constraint on human vision that limits performance on numerous tasks. It has been suggested that crowding results from spatial feature integration necessary for object recognition. However, in the absence of convincing models, this theory has remained controversial. Here, we present a quantitative and physiologically plausible model for spatial integration of orientation signals, based on the principles of population coding. Using simulations, we demonstrate that this model coherently accounts for fundamental properties of crowding, including critical spacing, "compulsory averaging", and a foveal-peripheral anisotropy. Moreover, we show that the model predicts increased responses to correlated visual stimuli. Altogether, these results suggest that crowding has little immediate bearing on object recognition but is a by-product of a general, elementary integration mechanism in early vision aimed at improving signal quality.

A crowding model of visual clutter.

Visual information is difficult to search and interpret when the density of the displayed information is high or the layout is chaotic. Visual information that exhibits such properties is generally referred to as being "cluttered." Clutter should be avoided in information visualizations and interface design in general because it can severely degrade task performance. Although previous studies have identified computable correlates of clutter (such as local feature variance and edge density), understanding of why humans perceive some scenes as being more cluttered than others remains limited. Here, we explore an account of clutter that is inspired by findings from visual perception studies. Specifically, we test the hypothesis that the so-called "crowding" phenomenon is an important constituent of clutter. We constructed an algorithm to predict visual clutter in arbitrary images by estimating the perceptual impairment due to crowding. After verifying that this model can reproduce crowding data we tested whether it can also predict clutter. We found that its predictions correlate well with both subjective clutter assessments and search performance in cluttered scenes. These results suggest that crowding and clutter may indeed be closely related concepts and suggest avenues for further research.

Analysis on the off-state design and characterization of LIGBTs in partial SOI technology

Classical high voltage devices fabricated on SOI substrates suffer from a backside coupling effect which could result in premature breakdown. This phenomenon becomes more prominent if the structure is an IGBT which features a p-type injector. To suppress the premature breakdown due to crowding of electro-potential lines within a confined SOI/buried oxide structure, the partial SOI (PSOI) technique is being introduced. This paper analyzes the off-state behavior of an n-type Superjunction (SJ) LIGBT fabricated on PSOI substrate. During the initial development stage the SJ LIGBT was found to have very high leakage. This was attributed to the back and side coupling effects. This paper discusses these effects and shows how this problem could be successfully addressed with minimal modifications of device layout. The off-state performance of the SJ LIGBT at different temperatures is assessed and a comparison to an equivalent LDMOSFET is given. © 2014 Elsevier Ltd. All rights reserved.

Single-walled carbon nanotubes binding to human telomeric i-motif DNA under molecular-crowding conditions: More water molecules released

The natural occurrence of the human telomeric G-quadruplex or i-motif in vivo has not been demonstrated and the biological effects of the induction of these structures need to be clarified. Intracellular environments are highly crowded with various biomolecules and in vitro studies under molecular-crowding conditions will provide important information on how biomolecules behave in cells. Here we report that cell-mimic crowding can increase i-motif stability at acid pH and cause dehydration.

Sleep-disordered breathing and orthodontic variables in children-Pilot study

Introduction: Sleep Disordered Breathing (SDB) is a highly prevalent condition associated with orofacial and dentofacial characteristics.Objective: the aim of this study was to verify the association of dental malocclusion, molar relationship, crossbite, open bite, overjet, overbite, and crowding with SDB in children aged 7-9 years.Materials and methods: Participating schools were selected randomly from within the public elementary school system. in the first phase of the study, the parents of 1216 children aged between 7 and 9 years old completed the Sleep Disturbance Scale for Children (SDSC) questionnaire and the children had to participate in a dental examination. the evaluation of occlusion was divided into sagittal analysis, vertical analysis, and transverse analysis. in the second phase, 60 children were selected randomly to be undergone polysomnography (PSG) at a sleep clinic.Results: Among the children included, 242 (19.9%) children had normal occlusion. of the 60 children, 50 underwent PSG and 40(80%) had SDB. the crossbite and open bite showed association with SDB, p = 0.04 in both.Conclusion: Crossbite and open bite malocclusions were associated with SDB, and may be predictive of SDB in children. Studies with larger numbers of participants are needed to investigate the association of other malocclusions with SDB, and randomized clinical trials are also needed to see whether orthodontic and/or functional jaw orthopedic treatment is an option for treating children with malocclusion and SDB. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Public service employment and the public-private wage differential in British regions

Thomas, Dennis, Henley, Andrew, 'Public service employment and the public-private wage differential in British regions', Regional Studies (2001) 35(3) pp.229-240 RAE2008

Where does energy R&D come from? Examining crowding out from energy R&D

Recent efforts to endogenize technological change in climate policy models demonstrate the importance of accounting for the opportunity cost of climate R&D investments. Because the social returns to R&D investments are typically higher than the social returns to other types of investment, any new climate mitigation R&D that comes at the expense of other R&D investment may dampen the overall gains from induced technological change. Unfortunately, there has been little empirical work to guide modelers as to the potential magnitude of such crowding out effects. This paper considers both the private and social opportunity costs of climate R&D. Addressing private costs, we ask whether an increase in climate R&D represents new R&D spending, or whether some (or all) of the additional climate R&D comes at the expense of other R&D. Addressing social costs, we use patent citations to compare the social value of alternative energy research to other types of R&D that may be crowded out. Beginning at the industry level, we find no evidence of crowding out across sectors-that is, increases in energy R&D do not draw R&D resources away from sectors that do not perform R&D. Given this, we proceed with a detailed look at alternative energy R&D. Linking patent data and financial data by firm, we ask whether an increase in alternative energy patents leads to a decrease in other types of patenting activity. While we find that increases in alternative energy patents do result in fewer patents of other types, the evidence suggests that this is due to profit-maximizing changes in research effort, rather than financial constraints that limit the total amount of R&D possible. Finally, we use patent citation data to compare the social value of alternative energy patents to other patents by these firms. Alternative energy patents are cited more frequently, and by a wider range of other technologies, than other patents by these firms, suggesting that their social value is higher. © 2011 Elsevier B.V.

High current density induced damage mechanisms in electronic solder joints: a state-of-the-art review

High current density induced damages such as electromigration in the on-chip interconnection /metallization of Al or Cu has been the subject of intense study over the last 40 years. Recently, because of the increasing trend of miniaturization of the electronic packaging that encloses the chip, electromigration as well as other high current density induced damages are becoming a growing concern for off-chip interconnection where low melting point solder joints are commonly used. Before long, a huge number of publications have been explored on the electromigration issue of solder joints. However, a wide spectrum of findings might confuse electronic companies/designers. Thus, a review of the high current induced damages in solder joints is timely right this moment. We have selected 6 major phenomena to review in this paper. They are (i) electromigration (mass transfer due electron bombardment), (ii) thermomigration (mass transfer due to thermal gradient), (iii) enhanced intermetallic compound growth, (iv) enhanced current crowding, (v) enhanced under bump metallisation dissolution and (vi) high Joule heating and (vii) solder melting. the damage mechanisms under high current stressing in the tiny solder joint, mentioned in the review article, are significant roadblocks to further miniaturization of electronics. Without through understanding of these failure mechanisms by experiments coupled with mathematical modeling work, further miniaturization in electronics will be jeopardized