Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.

Diagnostic accuracy of post-mortem MRI for thoracic abnormalities in fetuses and children

OBJECTIVES: To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for non-cardiac thoracic pathology in fetuses and children, compared with conventional autopsy. METHODS: Institutional ethics approval and parental consent was obtained. A total of 400 unselected fetuses and children underwent PMMR before conventional autopsy, reported blinded to the other dataset. RESULTS: Of 400 non-cardiac thoracic abnormalities, 113 (28 %) were found at autopsy. Overall sensitivity and specificity (95 % confidence interval) of PMMR for any thoracic pathology was poor at 39.6 % (31.0, 48.9) and 85.5 % (80.7, 89.2) respectively, with positive predictive value (PPV) 53.7 % (42.9, 64.0) and negative predictive value (NPV) 77.0 % (71.8, 81.4). Overall agreement was 71.8 % (67.1, 76.2). PMMR was most sensitive at detecting anatomical abnormalities, including pleural effusions and lung or thoracic hypoplasia, but particularly poor at detecting infection. CONCLUSIONS: PMMR currently has relatively poor diagnostic detection rates for the commonest intra-thoracic pathologies identified at autopsy in fetuses and children, including respiratory tract infection and diffuse alveolar haemorrhage. The reasonable NPV suggests that normal thoracic appearances at PMMR exclude the majority of important thoracic lesions at autopsy, and so could be useful in the context of minimally invasive autopsy for detecting non-cardiac thoracic abnormalities. KEY POINTS: • PMMR has relatively poor diagnostic detection rates for common intrathoracic pathology • The moderate NPV suggests that normal PMMR appearances exclude most important abnormalities • Lung sampling at autopsy remains the "gold standard" for pulmonary pathology

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

'So wide and varied': The origins and character of British information science

This paper examines some characteristics of the ‘British School’ of information science. Three main forces driving the development of the new subject in Britain are identified: the documentation movement; special libraries; and the need for better treatment of scientific and technical information. Five characteristics which, taken together, distinguish the early British approach to information science from those adopted elsewhere are identified: its subject-based nature; its broad approach to information and information science; its status as an academic subject with a strong professional remit; its involvement with, but distinction from, information technology; and its involvement with memory institutions. Lessons are drawn for the future development of the information sciences

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

Foreign policy and globalization theory: The case of Israel

Since the early 1990s, international relations has witnessed a stimulating debate on globalization. This debate laid the foundations for globalization theory (GT), providing the tools for an empirical examination of the globalization of multiple activities: from politics and organized violence, to finance, trade and production, through culture and environmental degradation. However, examination of what appear to be the best-known works on globalization reveals that foreign policy has been virtually excluded from GT. In this context, based on what is described here as a synergistic transformationalist approach (STA) to globalization, I provide a critique of GT. The critique is geared towards examining why foreign policy hitherto has been overlooked by contemporary GT. I expose the problems this generates and address them by exploring how STA enables GT to incorporate foreign policy. I use the case of Israel heuristically to elicit how incorporating foreign policy into GT may provide a better understanding of the relationship between foreign policy and globalization. Three themes are highlighted: the role of foreign policy in inducing and reproducing globalization; determining the mutually constitutive relationship between globalization and the state; and shaping the interfacing between international politics and globalization

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

The wonders of flap endonucleases: structure, function, mechanism and regulation.

Processing of Okazaki fragments to complete lagging strand DNA synthesis requires coordination among several proteins. RNA primers and DNA synthesised by DNA polymerase α are displaced by DNA polymerase δ to create bifurcated nucleic acid structures known as 5'-flaps. These 5'-flaps are removed by Flap Endonuclease 1 (FEN), a structure-specific nuclease whose divalent metal ion-dependent phosphodiesterase activity cleaves 5'-flaps with exquisite specificity. FENs are paradigms for the 5' nuclease superfamily, whose members perform a wide variety of roles in nucleic acid metabolism using a similar nuclease core domain that displays common biochemical properties and structural features. A detailed review of FEN structure is undertaken to show how DNA substrate recognition occurs and how FEN achieves cleavage at a single phosphate diester. A proposed double nucleotide unpairing trap (DoNUT) is discussed with regards to FEN and has relevance to the wider 5' nuclease superfamily. The homotrimeric proliferating cell nuclear antigen protein (PCNA) coordinates the actions of DNA polymerase, FEN and DNA ligase by facilitating the hand-off intermediates between each protein during Okazaki fragment maturation to maximise through-put and minimise consequences of intermediates being released into the wider cellular environment. FEN has numerous partner proteins that modulate and control its action during DNA replication and is also controlled by several post-translational modification events, all acting in concert to maintain precise and appropriate cleavage of Okazaki fragment intermediates during DNA replication

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes