Structural behaviour and design criteria of under-deck cable-stayed bridges subjected to seismic action

Under-deck cable-stayed bridges are very effective structural systems for which the strong contribution of the stay cables under live loading allows for the design of very slender decks for persistent and transient loading scenarios. Their behaviour when subjected to seismic excitation is investigated herein and a set of design criteria are presented that relate to the type and arrangement of bearings, the number and configuration of struts, and the transverse distribution of stay cables. The nonlinear behaviour of these bridges when subject to both near-field and far-field accelerograms has been thoroughly investigated through the use of incremental dynamic analyses. An intensity measure that reflects the pertinent contributions to response when several vibration modes are activated was proposed and is shown to be effective for the analysis of this structural type. The under-deck cable-stay system contributes in a very positive manner to reducing the response when the bridges are subject to very strong seismic excitation. For such scenarios, the reduction in the stiffness of the deck because of crack formation, when prestressed concrete decks are used, mobilises the cable system and enhances the overall performance of the system. Sets of natural accelerograms that are compliant with the prescriptions of Eurocode 8 were also applied to propose a set of design criteria for this bridge type in areas prone to earthquakes. Particular attention is given to outlining the optimal strategies for the deployment of bearings

Early-life exposure to endotoxin alters hypothalamic–pituitary–adrenal function and predisposition to inflammation

We have investigated whether exposure to Gram-negative bacterial endotoxin in early neonatal life can alter neuroendocrine and immune regulation in adult animals. Exposure of neonatal rats to a low dose of endotoxin resulted in long-term changes in hypothalamic–pituitary–adrenal (HPA) axis activity, with elevated mean plasma corticosterone concentrations that resulted from increased corticosterone pulse frequency and pulse amplitude. In addition to this marked effect on the development of the HPA axis, neonatal endotoxin exposure had long-lasting effects on immune regulation, including increased sensitivity of lymphocytes to stress-induced suppression of proliferation and a remarkable protection from adjuvant-induced arthritis. These findings demonstrate a potent and long-term effect of neonatal exposure to inflammatory stimuli that can program major changes in the development of both neuroendocrine and immunological regulatory mechanisms.

Construction of neocentromere-based human minichromosomes by telomere-associated chromosomal truncation

Neocentromeres (NCs) are fully functional centromeres that arise ectopically in noncentromeric regions lacking α-satellite DNA. Using telomere-associated chromosome truncation, we have produced a series of minichromosomes (MiCs) from a mardel(10) marker chromosome containing a previously characterized human NC. These MiCs range in size from ≈0.7 to 1.8 Mb and contain single-copy intact genomic DNA from the 10q25 region. Two of these NC-based Mi-Cs (NC-MiCs) appear circular whereas one is linear. All demonstrate stability in both structure and mitotic transmission in the absence of drug selection. Presence of a functional NC is shown by binding a host of key centromere-associated proteins. These NC-MiCs provide direct evidence for mitotic segregation function of the NC DNA and represent examples of stable mammalian MiCs lacking centromeric repeats.

Regulation of the p21-activated kinase (PAK) by a human Gβ-like WD-repeat protein, hPIP1

The family of p21-activated protein kinases (PAKs) is composed of serine–threonine kinases whose activity is regulated by the small guanosine triphosphatases (GTPases) Rac and Cdc42. In mammalian cells, PAKs have been implicated in the regulation of mitogen-activated protein cascades, cellular morphological and cytoskeletal changes, neurite outgrowth, and cell apoptosis. Although the ability of Cdc42 and Rac GTPases to activate PAK is well established, relatively little is known about the negative regulation of PAK or the identity of PAK cellular targets. Here, we describe the identification and characterization of a human PAK-interacting protein, hPIP1. hPIP1 contains G protein β-like WD repeats and shares sequence homology with the essential fission yeast PAK regulator, Skb15, as well as the essential budding yeast protein, MAK11. Interaction of hPIP1 with PAK1 inhibits the Cdc42/Rac-stimulated kinase activity through the N-terminal regulatory domains of PAK1. Cotransfection of hPIP1 in mammalian cells inhibits PAK-mediated c-Jun N-terminal kinase and nuclear factor κ B signaling pathways. Our results demonstrate that hPIP1 is a negative regulator of PAK and PAK signaling pathways.

Identification of the endothelial cell binding site for factor IX.

We previously demonstrated that the primary region of factor IX and IXa responsible for saturable specific binding to bovine aortic endothelial cells resides in residues 3-11 at the amino terminus of factor IX. We also demonstrated that mutations of lysine to alanine at residue 5, factor IX K5A, or valine to lysine at residue 10, factor IX V10K, resulted in a molecule unable to bind to endothelial cells. Moreover, a mutation with lysine to arginine at residue 5, factor IX K5R, resulted in a factor IX molecule with increased affinity for the endothelial cell binding site. In this paper we report that collagen IV is a strong candidate for the factor IX binding site on endothelial cells. Factor IX and factor IX K5R compete with 125I-labeled factor IX for binding to tetrameric collagen IV immobilized on microtiter plates, while factor X, factor VII, and factor IX K5A or V10K fail to compete. The Kd for wild-type factor IX binding to collagen IV in the presence of heparin was 6.8 +/- 2 nM, and the Kd for factor IX K5R was 1.1 +/- 0.2 nM, which agrees well with our previously published Kd values of 7.4 and 2.4 nM for binding of the same proteins to endothelial cells. Our working assumption is that we have identified the endothelial cell binding site and that it is collagen IV. Its physiological relevance remains to be determined.

Isolation and characterization of a MAGE gene family in the Xp21.3 region.

A human gene with strong homology to the MAGE gene family located in Xq27-qter has been isolated by using exon-trapping of cosmids in the Xp21.3 region. We have mapped and sequenced cDNA and genomic clones corresponding to this gene, MAGE-Xp, and shown that the last exon contains the open reading frame and is present in a minimum of five copies in a 30-kb interval. MAGE-Xp is expressed only in testis and, unlike the Xq27-qter MAGE genes, it is not expressed in any of 12 different tumor tissues tested. However, the gene and predicted protein structure are conserved, suggesting a similar function. MAGE-Xp is located in the 160-kb critical interval defined for the locus involved in sex determination within Xp21 and is 50 kb distal to the DAX-1 gene, which is responsible for X-chromosome-linked adrenal hypoplasia congenita.

Profiling in sport using momentum and perturbations

Examining a team’s performance from a physical point of view their momentum might indicate unexpected turning points in defeat or success. Physicists describe this value as to require some effort to be started, but also that it is relatively easy to keep it going once a sufficient level is reached (Reed and Hughes, 2006). Unlike football, rugby, handball and many more sports, a regular volleyball match is not limited by time but by points that need to be gathered. Every minute more than one point is won by either one team or the other. That means a series of successive points enlarges the gap between the teams making it more and more difficult to catch up with the leading one. This concept of gathering momentum, or the reverse in a performance, can give the coaches, athletes and sports scientists further insights into winning and losing performances. Momentum investigations also contain dependencies between performances or questions if future performances are reliant upon past streaks. Squash and volleyball share the characteristic of being played up to a certain amount of points. Squash was examined according to the momentum of players by Hughes et al. (2006). The initial aim was to expand normative profiles of elite squash players using momentum graphs of winners and errors to explore ‘turning points’ in a performance. Dynamic systems theory has enabled the definition of perturbations in sports exhibiting rhythms (Hughes et al., 2000; McGarry et al., 2002; Murray et al., 2008), and how players and teams cause these disruptions of rhythm can inform on the way they play, these techniques also contribute to profiling methods. Together with the analysis of one’s own performance it is essential to have an understanding of your oppositions’ tactical strengths and weaknesses. By modelling the oppositions’ performance it is possible to predict certain outcomes and patterns, and therefore intervene or change tactics before the critical incident occurs. The modelling of competitive sport is an informative analytic technique as it directs the attention of the modeller to the critical aspects of data that delineate successful performance (McGarry & Franks, 1996). Using tactical performance profiles to pull out and visualise these critical aspects of performance, players can build justified and sophisticated tactical plans. The area is discussed and reviewed, critically appraising the research completed in this element of Performance Analysis.

Almanac, annotated, 1744

Interleaved copy of Joseph Stafford's An Almanack for the Year of our Lord Christ, 1744 ... (Boston, 1744) annotated by Andrew Bordman II with regular entries about the weather, and occasionally community news. An October entry notes that an "Irish man" was hanged in Worcester for murder.