An item's status in semantic memory determines how it is recognized : dissociable patterns of brain activity observed for famous and unfamiliar faces

This work was supported by a grant from the Biotechnology and Biological Sciences Research Council, United Kingdom (BB/L023644/1).Are all faces recognized in the same way, or does previous experience with a face change how it is retrieved? Previous research using human scalp-recorded Event-Related Potentials (ERPs) demonstrates that recognition memory can produce dissociable brain signals under a variety of circumstances. While many studies have reported dissociations between the putative ‘dual processes’ of familiarity and recollection, a growing number of reports demonstrate that recollection itself may be fractionated into component processes. Many recognition memory studies using lexical materials as stimuli have reported a left parietal ERP old/new effect for recollection; however, when unfamiliar faces are recollected, an anterior effect can be observed. This paper addresses two separate hypotheses concerning the functional significance of the anterior old/new effect: perceptual retrieval and semantic status. The perceptual retrieval view is that the anterior effect reflects reinstatement of perceptual information bound up in an episodic representation, while the semantic status view is that information not represented in semantic memory pre-experimentally elicits the anterior effect instead of the left parietal effect. We tested these two competing accounts by investigating recognition memory for unfamiliar faces and famous faces in two separate experiments, in which same or different pictures of studied faces were presented as test items to permit brain activity associated with retrieving face and perceptual information to be examined independently. The difference in neural activity between same and different picture hits was operationalized as a pattern of activation associated with perceptual retrieval; while the contrast between different picture hits and correct rejection of new faces was assumed to reflect face retrieval. In Experiment 1, using unfamiliar faces, the anterior old/new effect (500–700 ms) was observed for face retrieval but not for perceptual retrieval, challenging the perceptual retrieval hypothesis. In Experiment 2, using famous faces, face retrieval was associated with a left parietal effect (500–700 ms), supporting the semantic representation hypothesis. A between-subjects analysis comparing scalp topography across the two experiments found that the anterior effect observed for unfamiliar faces is dissociable from the left parietal effect found for famous faces. This pattern of results supports the hypothesis thatPublisher PDFPeer reviewe

An item's status in semantic memory determines how it is recognized: Dissociable patterns of brain activity observed for famous and unfamiliar faces

Are all faces recognized in the same way, or does previous experience with a face change how it is retrieved? Previous research using human scalp-recorded Event-Related Potentials (ERPs) demonstrates that recognition memory can produce dissociable brain signals under a variety of circumstances. While many studies have reported dissociations between the putative ‘dual processes’ of familiarity and recollection, a growing number of reports demonstrate that recollection itself may be fractionated into component processes. Many recognition memory studies using lexical materials as stimuli have reported a left parietal ERP old/new effect for recollection; however, when unfamiliar faces are recollected, an anterior effect can be observed. This paper addresses two separate hypotheses concerning the functional significance of the anterior old/new effect: perceptual retrieval and semantic status. The perceptual retrieval view is that the anterior effect reflects reinstatement of perceptual information bound up in an episodic representation, while the semantic status view is that information not represented in semantic memory pre-experimentally elicits the anterior effect instead of the left parietal effect. We tested these two competing accounts by investigating recognition memory for unfamiliar faces and famous faces in two separate experiments, in which same or different pictures of studied faces were presented as test items to permit brain activity associated with retrieving face and perceptual information to be examined independently. The difference in neural activity between same and different picture hits was operationalized as a pattern of activation associated with perceptual retrieval; while the contrast between different picture hits and correct rejection of new faces was assumed to reflect face retrieval. In Experiment 1, using unfamiliar faces, the anterior old/new effect (500–700msec) was observed for face retrieval but not for perceptual retrieval, challenging the perceptual retrieval hypothesis. In Experiment 2, using famous faces, face retrieval was associated with a left parietal effect (500–700msec), supporting the semantic representation hypothesis. A between-subjects analysis comparing scalp topography across the two experiments found that the anterior effect observed for unfamiliar faces is dissociable from the left parietal effect found for famous faces. This pattern of results supports the hypothesis that an item's status in semantic memory determines how it is recognized

Quantitative prediction of in vivo inhibitory interactions involving glucuronidated drugs from in vitro data: the effect of fluconazole on zidovudine glucuronidation

Using the fluconazole–zidovudine (AZT) interaction as a model, to determine whether inhibition of UDP–glucuronosyltransferase (UGT) catalysed drug metabolism in vivo could be predicted quantitatively from in vitro kinetic data generated in the presence and absence bovine serum albumin (BSA). Methods Kinetic constants for AZT glucuronidation were generated using human liver microsomes (HLM) and recombinant UGT2B7, the principal enzyme responsible for AZT glucuronidation, as the enzyme sources with and without fluconazole. K i values were used to estimate the decrease in AZT clearance in vivo . Results Addition of BSA (2%) to incubations decreased the K m values for AZT glucuronidation by 85–90% for the HLM (923 ± 357 to 91 ± 9 µm) and UGT2B7 (478–70 µm) catalysed reactions, with little effect on V max . Fluconazole, which was shown to be a selective inhibitor of UGT2B7, competitively inhibited AZT glucuronidation by HLM and UGT2B7. Like the K m , BSA caused an 87% reduction in the K i for fluconazole inhibition of AZT glucuronidation by HLM (1133 ± 403 to 145 ± 36 µm) and UGT2B7 (529 to 73 µm). K i values determined for fluconazole using HLM and UGT2B7 in the presence (but not absence) of BSA predicted an interaction in vivo . The predicted magnitude of the interaction ranged from 41% to 217% of the reported AUC increase in patients, depending on the value of the in vivo fluconazole concentration employed in calculations. Conclusions K i values determined under certain experimental conditions may quantitatively predict inhibition of UGT catalysed drug glucuronidation in vivo .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72685/1/j.1365-2125.2006.02588.x.pd

Dengue and climate change in Australia: predictions for the future should incorporate knowledge from the past

•Dengue transmission in Australia is currently restricted to Queensland, where the vector mosquito Aedes aegypti is established. Locally acquired infections have been reported only from urban areas in the north-east of the state, where the vector is most abundant. •Considerable attention has been drawn to the potential impact of climate change on dengue distribution within Australia, with projections for substantial rises in incidence and distribution associated with increasing temperatures. •However, historical data show that much of Australia has previously sustained both the vector mosquito and dengue viruses. Although current vector distribution is restricted to Queensland, the area inhabited by A. aegypti is larger than the disease-transmission areas, and is not restricted by temperature (or vector-control programs); thus, it is unlikely that rising temperatures alone will bring increased vector or virus distribution. •Factors likely to be important to dengue and vector distribution in the future include increased dengue activity in Asian and Pacific nations that would raise rates of virus importation by travellers, importation of vectors via international ports to regions without A. aegypti, higher rates of domestic collection and storage of water that would provide habitat in urban areas, and growing human populations in northern Australia. •Past and recent successful control initiatives in Australia lend support to the idea that well resourced and functioning surveillance programs, and effective public health intervention capabilities, are essential to counter threats from dengue and other mosquito-borne diseases. •Models projecting future activity of dengue (or other vector-borne disease) with climate change should carefully consider the local historical and contemporary data on the ecology and distribution of the vector and local virus transmission

Infrared spectra and fragmentation dynamics of isotopologue-selective mixed-ligand complexes †

Isolated mixed-ligand complexes provide tractable model systems in which to study competitive and cooperative binding effects as well as controlled energy flow. Here, we report spectroscopic and isotopologue-selective infrared photofragmentation dynamics of mixed gas-phase Au(12/13CO)n(N2O)m+ complexes. The rich infrared action spectra, which are reproduced well using simulations of calculated lowest energy structures, clarify previous ambiguities in the assignment of vibrational bands, especially accidental coincidence of CO and N2O bands. The fragmentation dynamics exhibit the same unexpected behaviour as reported previously in which, once CO loss channels are energetically accessible, these dominate the fragmentation branching ratios, despite the much lower binding energy of N2O. We have investigated the dynamics computationally by considering anharmonic couplings between a relevant subset of normal modes involving both ligand stretch and intermolecular modes. Discrepancies between correlated and uncorrelated model fit to the ab initio potential energy curves are quantified using a Boltzmann sampled root mean squared deviation providing insight into efficiency of vibrational energy transfer between high frequency ligand stretches and the softer intermolecular modes which break during fragmentation

High-precision αs\alpha_s measurements from LHC to FCC-ee

This document provides a writeup of all contributions to the workshop on "High precision measurements of $\alpha_s$: From LHC to FCC-ee" held at CERN, Oct. 12--13, 2015. The workshop explored in depth the latest developments on the determination of the QCD coupling $\alpha_s$ from 15 methods where high precision measurements are (or will be) available. Those include low-energy observables: (i) lattice QCD, (ii) pion decay factor, (iii) quarkonia and (iv) $\tau$ decays, (v) soft parton-to-hadron fragmentation functions, as well as high-energy observables: (vi) global fits of parton distribution functions, (vii) hard parton-to-hadron fragmentation functions, (viii) jets in $e^\pm$p DIS and $\gamma$-p photoproduction, (ix) photon structure function in $\gamma$-$\gamma$, (x) event shapes and (xi) jet cross sections in $e^+e^-$ collisions, (xii) W boson and (xiii) Z boson decays, and (xiv) jets and (xv) top-quark cross sections in proton-(anti)proton collisions. The current status of the theoretical and experimental uncertainties associated to each extraction method, the improvements expected from LHC data in the coming years, and future perspectives achievable in $e^+e^-$ collisions at the Future Circular Collider (FCC-ee) with $\cal{O}$(1--100 ab$^{-1}$) integrated luminosities yielding 10$^{12}$ Z bosons and jets, and 10$^{8}$ W bosons and $\tau$ leptons, are thoroughly reviewed. The current uncertainty of the (preliminary) 2015 strong coupling world-average value, $\alpha_s(m_Z)$ = 0.1177 $\pm$ 0.0013, is about 1\%. Some participants believed this may be reduced by a factor of three in the near future by including novel high-precision observables, although this opinion was not universally shared. At the FCC-ee facility, a factor of ten reduction in the $\alpha_s$ uncertainty should be possible, mostly thanks to the huge Z and W data samples available.Comment: 135 pages, 56 figures. CERN-PH-TH-2015-299, CoEPP-MN-15-13. This document is dedicated to the memory of Guido Altarell

Incomplete Polyp Resection During Colonoscopy—Results of the Complete Adenoma Resection (CARE) Study

Although the adenoma detection rate is used as a measure of colonoscopy quality, there are limited data on the quality of endoscopic resection of detected adenomas. We determined the rate of incompletely resected neoplastic polyps in clinical practice.We performed a prospective study on 1427 patients who underwent colonoscopy at 2 medical centers and had at least 1 nonpedunculated polyp (5-20 mm). After polyp removal was considered complete macroscopically, biopsies were obtained from the resection margin. The main outcome was the percentage of incompletely resected neoplastic polyps (incomplete resection rate [IRR]) determined by the presence of neoplastic tissue in post-polypectomy biopsies. Associations between IRR and polyp size, morphology, histology, and endoscopist were assessed by regression analysis. Of 346 neoplastic polyps (269 patients; 84.0% men; mean age, 63.4 years) removed by 11 gastroenterologists, 10.1% were incompletely resected. IRR increased with polyp size and was significantly higher for large (10-20 mm) than small (5-9 mm) neoplastic polyps (17.3% vs 6.8%; relative risk = 2.1), and for sessile serrated adenomas/polyps than for conventional adenomas (31.0% vs 7.2%; relative risk = 3.7). The IRR for endoscopists with at least 20 polypectomies ranged from 6.5% to 22.7%; there was a 3.4-fold difference between the highest and lowest IRR after adjusting for size and sessile serrated histology. Neoplastic polyps are often incompletely resected, and the rate of incomplete resection varies broadly among endoscopists. Incomplete resection might contribute to the development of colon cancers after colonoscopy (interval cancers). Efforts are needed to ensure complete resection, especially of larger lesions

Murray Valley encephalitis virus surveillance and control initiatives in Australia.

Mechanisms for monitoring Murray Valley encephalitis (MVE) virus activity include surveillance of human cases, surveillance for activity in sentinel animals, monitoring of mosquito vectors and monitoring of weather conditions. The monitoring of human cases is only one possible trigger for public health action and the additional surveillance systems are used in concert to signal the risk of human disease, often before the appearance of human cases. Mosquito vector surveillance includes mosquito trapping for speciation and enumeration of mosquitoes to monitor population sizes and relative composition. Virus isolation from mosquitoes can also be undertaken. Monitoring of weather conditions and vector surveillance determines whether there is a potential for MVE activity to occur. Virus isolation from trapped mosquitoes is necessary to define whether MVE is actually present, but is difficult to deliver in a timely fashion in some jurisdictions. Monitoring of sentinel animals indicates whether MVE transmission to vertebrates is actually occurring. Meteorological surveillance can assist in the prediction of potential MVE virus activity by signalling conditions that have been associated with outbreaks of Murray Valley encephalitis in humans in the past. Predictive models of MVE virus activity for south-eastern Australia have been developed, but due to the infrequency of outbreaks, are yet to be demonstrated as useful for the forecasting of major outbreaks. Surveillance mechanisms vary across the jurisdictions. Surveillance of human disease occurs in all States and Territories by reporting of cases to health authorities. Sentinel flocks of chickens are maintained in 4 jurisdictions (Western Australia, the Northern Territory, Victoria and New South Wales) with collaborations between Western Australia and the Northern Territory. Mosquito monitoring complements the surveillance of sentinel animals in these jurisdictions. In addition, other mosquito monitoring programs exist in other States (including South Australia and Queensland). Public health control measures may include advice to the general public and mosquito management programs to reduce the numbers of both mosquito larvae and adult vectors. Strategic plans for public health action in the event of MVE virus activity are currently developed or being developed in New South Wales, the Northern Territory, South Australia, Western Australia and Victoria. A southern tri-State agreement exists between health departments of New South Wales, Victoria and South Australia and the Commonwealth Department of Health and Aged Care. All partners have agreed to co-operate and provide assistance in predicting and combatting outbreaks of mosquito-borne disease in south-eastern Australia. The newly formed National Arbovirus Advisory Committee is a working party providing advice to the Communicable Diseases Network Australia on arbovirus surveillance and control. Recommendations for further enhancement of national surveillance for Murray Valley encephalitis are described

Scaling of the B and D meson spectrum in lattice QCD

We give results for the $B$ and the $D$ meson spectrum using NRQCD on the lattice in the quenched approximation. The masses of radially and orbitally excited states are calculated as well as $S$-wave hyperfine and $P$-wave fine structure. Radially excited $P$-states are observed for the first time. Radial and orbital excitation energies match well to experiment, as does the strange-non-strange $S$-wave splitting. We compare the light and heavy quark mass dependence of various splittings to experiment. Our $B$-results cover a range in lattice spacings of more than a factor of two. Our $D$-results are from a single lattice spacing and we compare them to numbers in the literature from finer lattices using other methods. We see no significant dependence of physical results on the lattice spacing. PACS: 11.15.Ha 12.38.Gc 14.40.Lb 14.40.NdComment: 78 pages, 29 tables, 30 figures Revised version. Minor corrections to spelling and wordin

Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour

The mechanism of eukaryotic chemotaxis remains unclear despite intensive study. The most frequently described mechanism acts through attractants causing actin polymerization, in turn leading to pseudopod formation and cell movement. We recently proposed an alternative mechanism, supported by several lines of data, in which pseudopods are made by a self-generated cycle. If chemoattractants are present, they modulate the cycle rather than directly causing actin polymerization. The aim of this work is to test the explanatory and predictive powers of such pseudopod-based models to predict the complex behaviour of cells in chemotaxis. We have now tested the effectiveness of this mechanism using a computational model of cell movement and chemotaxis based on pseudopod autocatalysis. The model reproduces a surprisingly wide range of existing data about cell movement and chemotaxis. It simulates cell polarization and persistence without stimuli and selection of accurate pseudopods when chemoattractant gradients are present. It predicts both bias of pseudopod position in low chemoattractant gradients and-unexpectedly-lateral pseudopod initiation in high gradients. To test the predictive ability of the model, we looked for untested and novel predictions. One prediction from the model is that the angle between successive pseudopods at the front of the cell will increase in proportion to the difference between the cell's direction and the direction of the gradient. We measured the angles between pseudopods in chemotaxing Dictyostelium cells under different conditions and found the results agreed with the model extremely well. Our model and data together suggest that in rapidly moving cells like Dictyostelium and neutrophils an intrinsic pseudopod cycle lies at the heart of cell motility. This implies that the mechanism behind chemotaxis relies on modification of intrinsic pseudopod behaviour, more than generation of new pseudopods or actin polymerization by chemoattractant