Testing Scalar-Tensor Gravity Using Space Gravitational-Wave Interferometers

We calculate the bounds which could be placed on scalar-tensor theories of gravity of the Jordan, Fierz, Brans and Dicke type by measurements of gravitational waveforms from neutron stars (NS) spiralling into massive black holes (MBH) using LISA, the proposed space laser interferometric observatory. Such observations may yield significantly more stringent bounds on the Brans-Dicke coupling parameter \omega than are achievable from solar system or binary pulsar measurements. For NS-MBH inspirals, dipole gravitational radiation modifies the inspiral and generates an additional contribution to the phase evolution of the emitted gravitational waveform. Bounds on \omega can therefore be found by using the technique of matched filtering. We compute the Fisher information matrix for a waveform accurate to second post-Newtonian order, including the effect of dipole radiation, filtered using a currently modeled noise curve for LISA, and determine the bounds on \omega for several different NS-MBH canonical systems. For example, observations of a 1.4 solar mass NS inspiralling to a 1000 solar mass MBH with a signal-to-noise ratio of 10 could yield a bound of \omega > 240,000, substantially greater than the current experimental bound of \omega > 3000.Comment: 18 pages, 4 figures, 1 table; to be submitted to Phys. Rev.

RSV in Young Children During and After the COVID-19 Pandemic – Implications for Delaying the Age of First Infection

Nonpharmaceutical interventions introduced in the United Kingdom’s response to the COVID-19 pandemic disrupted the transmission of other childhood infections. We report changes in seasonality, age dynamics and severity of respiratory syncytial virus infections between 2019 and 2023. These data show the potential effects of delaying respiratory syncytial virus exposure and may provide insights for the implementation of treatments preventing infection during early infancy

How to humiliate and shame: A reporter's guide to the power of the mugshot

This is an Author's Accepted Manuscript of an article published in Social Semiotics, 24(1), 56-87, 2014, copyright Taylor & Francis, available online at: http://www.tandfonline.com/The judicial photograph – the “mugshot” – is a ubiquitous and instantly recognisable form, appearing in the news media, on the internet, on book covers, law enforcement noticeboards and in many other mediums. This essay attempts to situate the mugshot in a historical and theoretical context to explain the explicit and implicit meaning of the genre as it has developed, focussing in particular on their use in the UK media in late modernity. The analysis is based on the author's reflexive practice as a journalist covering crime in the national news media for 30 years and who has used mugshots to illustrate stories for their explicit and specific content. The author argues that the visual limitations of the standardised “head and shoulders” format of the mugshot make it a robust subject for analysing the changing meaning of images over time. With little variation in the image format, arguments for certain accreted layers of signification are easier to make. Within a few years of the first appearance of the mugshot form in the mid-19th century, it was adopted and adapted as a research tool by scientists and criminologists. While the positivist scientists claimed empirical objectivity we can now see that mugshots played a part in the construction of subjective notions of “the other”, “the lesser” or “sub-human” on the grounds of class, race and religion. These dehumanising ideas later informed the theorists and bureaucrats of National Socialist ideology from the 1920s to 1940s. The author concludes that once again the mugshot has become, in certain parts of the media, a signifier widely used to exclude or deride certain groups. In late modernity, the part of the media that most use mugshots – the tabloid press and increasingly tabloid TV – is part of a neo-liberal process that, in a conscious commercial appeal to the paying audience, seeks to separate rather than unify wider society

Preferences for Physical Activity: a Conjoint Analysis Involving People with Chronic Knee Pain

Objective To investigate individual preferences for physical activity (PA) attributes in adults with chronic knee pain, to identify clusters of individuals with similar preferences, and to identify whether individuals in these clusters differ by their demographic and health characteristics. Design An adaptive conjoint analysis (ACA) was conducted using the Potentially All Pairwise RanKings of all possible Alternatives (PAPRIKA) method to determine preference weights representing the relative importance of six PA attributes. Cluster analysis was performed to identify clusters of participants with similar weights. Chi-square and ANOVA were used to assess differences in individual characteristics by cluster. Multinomial logistic regression was used to assess associations between individual characteristics and cluster assignment. Results The study sample included 146 participants; mean age 65, 72% female, 47% white, non-Hispanic. The six attributes (mean weights in parentheses) are: health benefit (0.26), enjoyment (0.24), convenience (0.16), financial cost (0.13), effort (0.11) and time cost (0.10). Three clusters were identified: Cluster 1 (n = 33): for whom enjoyment (0.35) is twice as important as health benefit; Cluster 2 (n = 63): for whom health benefit (0.38) is most important; and Cluster 3 (n = 50): for whom cost (0.18), effort (0.18), health benefit (0.17) and enjoyment (0.18) are equally important. Cluster 1 was healthiest, Cluster 2 most self-efficacious, and Cluster 3 was in poorest health. Conclusions Patients with chronic knee pain have preferences for PA that can be distinguished effectively using ACA methods. Adults with chronic knee pain, clustered by PA preferences, share distinguishing characteristics. Understanding preferences may help clinicians and researchers to better tailor PA interventions

Very Red and Extremely Red Galaxies in the Fields of z ~ 1.5 Radio-Loud Quasars

We previously identified an excess of mostly red galaxies around 31 RLQs at z=1-2. These fields have an ERO (extremely red object, R-K>6) density 2.7 times higher than the field. Assuming the EROs are passively evolved galaxies at the quasar redshifts, they have characteristic luminosities of only ~L^*. We also present new observations of four z~1.54 RLQ fields: (1) Wide-field J & Ks data confirm an Abell richness ~2 excess within 140" of Q0835+580 but an excess only within 50" of Q1126+101. (2) In 3 fields we present deep narrow-band redshifted H-alpha observations. We detect five candidate galaxies at the quasar redshifts, a surface density 2.5x higher than the field. (3) SCUBA sub-mm observations of 3 fields detect 2 quasars and 2 galaxies with SEDs best fit as highly reddened galaxies at the quasar z. (4) H-band adaptive optics (AO) imaging is used to estimate redshifts for 2 red, bulge-dominated galaxies using the Kormendy relation. Both have structural redshifts foreground to the quasar, but these are not confirmed by photometric redshifts, possibly because their optical photometry is corrupted by scattered light from the AO guidestar. (5) We use quantitative SED fits to constrain the photometric redshifts z_ph for some galaxies. Most galaxies near Q0835+580 are consistent with being at its redshift, including a candidate very old passively evolving galaxy. Many very & extremely red objects have z_ph z_q, and dust reddening is required to fit most of them, including many objects whose fits also require relatively old stellar populations. Large reddenings of E(B-V)~0.6 are required to fit four J-K selected EROs, though all but one of them have best-fit z_ph>z_q. These objects may represent a population of dusty high-z galaxies underrepresented in optically selected samples. (Abridged)Comment: Missing object 1126.424 added to Table 4; title changed to save people the apparent trouble of reading the abstract. 38 pages, 16 figures, 2 in color; all-PostScript figure version available from http://astro.princeton.edu/~pathall/tp3.ps.g

Cytoplasmic expression systems triggered by mRNA yield increased gene expression in post-mitotic neurons

Non-viral vectors are promising vehicles for gene therapy but delivery of plasmid DNA to post-mitotic cells is challenging as nuclear entry is particularly inefficient. We have developed and evaluated a hybrid mRNA/DNA system designed to bypass the nuclear barrier to transfection and facilitate cytoplasmic gene expression. This system, based on co-delivery of mRNA(A64) encoding for T7 RNA polymerase (T7 RNAP) with a T7-driven plasmid, produced between 10- and 2200-fold higher gene expression in primary dorsal root ganglion neuronal (DRGN) cultures isolated from Sprague–Dawley rats compared to a cytomegalovirus (CMV)-driven plasmid, and 30-fold greater expression than the enhanced T7-based autogene plasmid pR011. Cell-free assays and in vitro transfections highlighted the versatility of this system with small quantities of T7 RNAP mRNA required to mediate expression at levels that were significantly greater than with the T7-driven plasmid alone or supplemented with T7 RNAP protein. We have also characterized a number of parameters, such as mRNA structure, intracellular stability and persistence of each nucleic acid component that represent important factors in determining the transfection efficiency of this hybrid expression system. The results from this study demonstrate that co-delivery of mRNA is a promising strategy to yield increased expression with plasmid DNA, and represents an important step towards improving the capability of non-viral vectors to mediate efficient gene transfer in cell types, such as in DRGN, where the nuclear membrane is a significant barrier to transfection

Rfam: updates to the RNA families database

Rfam is a collection of RNA sequence families, represented by multiple sequence alignments and covariance models (CMs). The primary aim of Rfam is to annotate new members of known RNA families on nucleotide sequences, particularly complete genomes, using sensitive BLAST filters in combination with CMs. A minority of families with a very broad taxonomic range (e.g. tRNA and rRNA) provide the majority of the sequence annotations, whilst the majority of Rfam families (e.g. snoRNAs and miRNAs) have a limited taxonomic range and provide a limited number of annotations. Recent improvements to the website, methodologies and data used by Rfam are discussed. Rfam is freely available on the Web at http://rfam.sanger.ac.uk/and http://rfam.janelia.org/

Coevolved mutations reveal distinct architectures for two core proteins in the bacterial flagellar motor

Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC) "torque" helix with the stator complexes. Atomic models based on the Salmonella entrovar C-ring electron microscopy reconstruction have implications for switching, but lack consensus on the relative locations of the FliG armadillo (ARM) domains (amino-terminal (FliGN), middle (FliGM) and FliGC) as well as changes during chemotaxis. The generality of the Salmonella model is challenged by the variation in motor morphology and response between species. We studied coevolved residue mutations to determine the unifying elements of switch architecture. Residue interactions, measured by their coevolution, were formalized as a network, guided by structural data. Our measurements reveal a common design with dedicated switch and motor modules. The FliM middle domain (FliMM) has extensive connectivity most simply explained by conserved intra and inter-subunit contacts. In contrast, FliG has patchy, complex architecture. Conserved structural motifs form interacting nodes in the coevolution network that wire FliMM to the FliGC C-terminal, four-helix motor module (C3-6). FliG C3-6 coevolution is organized around the torque helix, differently from other ARM domains. The nodes form separated, surface-proximal patches that are targeted by deleterious mutations as in other allosteric systems. The dominant node is formed by the EHPQ motif at the FliMMFliGM contact interface and adjacent helix residues at a central location within FliGM. The node interacts with nodes in the N-terminal FliGc α-helix triad (ARM-C) and FliGN. ARM-C, separated from C3-6 by the MFVF motif, has poor intra-network connectivity consistent with its variable orientation revealed by structural data. ARM-C could be the convertor element that provides mechanistic and species diversity.JK was supported by Medical Research Council grant U117581331. SK was supported by seed funds from Lahore University of Managment Sciences (LUMS) and the Molecular Biology Consortium

Structure-guided selection of specificity determining positions in the human kinome

Background: The human kinome contains many important drug targets. It is well-known that inhibitors of protein kinases bind with very different selectivity profiles. This is also the case for inhibitors of many other protein families. The increased availability of protein 3D structures has provided much information on the structural variation within a given protein family. However, the relationship between structural variations and binding specificity is complex and incompletely understood. We have developed a structural bioinformatics approach which provides an analysis of key determinants of binding selectivity as a tool to enhance the rational design of drugs with a specific selectivity profile. Results: We propose a greedy algorithm that computes a subset of residue positions in a multiple sequence alignment such that structural and chemical variation in those positions helps explain known binding affinities. By providing this information, the main purpose of the algorithm is to provide experimentalists with possible insights into how the selectivity profile of certain inhibitors is achieved, which is useful for lead optimization. In addition, the algorithm can also be used to predict binding affinities for structures whose affinity for a given inhibitor is unknown. The algorithm’s performance is demonstrated using an extensive dataset for the human kinome. Conclusion: We show that the binding affinity of 38 different kinase inhibitors can be explained with consistently high precision and accuracy using the variation of at most six residue positions in the kinome binding site. We show for several inhibitors that we are able to identify residues that are known to be functionally important