Artificial neural networks reveal individual differences in metacognitive monitoring of memory.

Previous work supports an age-specific impairment for recognition memory of pairs of words and other stimuli. The present study tested the generalization of an associative deficit across word, name, and nonword stimulus types in younger and older adults. Participants completed associative and item memory tests in one of three stimulus conditions and made metacognitive ratings of perceptions of self-efficacy, task success ("postdictions"), strategy success, task effort, difficulty, fatigue, and stamina. Surprisingly, no support was found for an age-related associative deficit on any of the stimulus types. We analyzed our data further using a multilayer perceptron artificial neural network. The network was trained to classify individuals as younger or older and its hidden unit activities were examined to identify data patterns that distinguished younger from older participants. Analysis of hidden unit activities revealed that the network was able to correctly classify by identifying three different clusters of participants, with two qualitatively different groups of older individuals. One cluster of older individuals found the tasks to be relatively easy, they believed they had performed well, and their beliefs were accurate. The other cluster of older individuals found the tasks to be difficult, believed they were performing relatively poorly, yet their beliefs did not map accurately onto their performance. Crucially, data from the associative task were more useful for neural networks to discriminate between younger and older adults than data from the item task. This work underscores the importance of considering both individual and age differences as well as metacognitive responses in the context of associative memory paradigms

Development of hepatic pathology in GBV‐B‐infected red‐bellied tamarins (Saguinus labiatus)

GB virus B (GBV‐B) is a new world monkey‐associated flavivirus used to model acute hepatitis C virus (HCV) infection. Critical for evaluation of antiviral or vaccine approaches is an understanding of the effect of HCV on the liver at different stages of infection. In the absence of longitudinal human tissue samples at defined time points, we have characterized changes in tamarins. As early as 2 weeks post‐infection histological changes were noticeable, and these were established in all animals by 6 weeks. Despite high levels of liver‐associated viral RNA, there was reversal of hepatic damage on clearance of peripheral virus though fibrosis was demonstrated in four tamarins. Notably, viral RNA burden in the liver dropped to near undetectable or background levels in all animals which underwent a second viral challenge, highlighting the efficacy of the immune response in removing foci of replication in the liver. These data add to the knowledge of GBV‐B infection in New World primates which can offer attractive systems for the testing of prophylactic and therapeutic treatments and the evaluation of their utility in preventing or reversing liver pathology

Characterization of Shewanella oneidensis MtrC: a cell-surface decaheme cytochrome involved in respiratory electron transport to extracellular electron acceptors

MtrC is a decaheme c-type cytochrome associated with the outer cell membrane of Fe(III)-respiring species of the Shewanella genus. It is proposed to play a role in anaerobic respiration by mediating electron transfer to extracellular mineral oxides that can serve as terminal electron acceptors. The present work presents the first spectropotentiometric and voltammetric characterization of MtrC, using protein purified from Shewanella oneidensis MR-1. Potentiometric titrations, monitored by UV–vis absorption and electron paramagnetic resonance (EPR) spectroscopy, reveal that the hemes within MtrC titrate over a broad potential range spanning between approximately +100 and approximately -500 mV (vs. the standard hydrogen electrode). Across this potential window the UV–vis absorption spectra are characteristic of low-spin c-type hemes and the EPR spectra reveal broad, complex features that suggest the presence of magnetically spin-coupled low-spin c-hemes. Non-catalytic protein film voltammetry of MtrC demonstrates reversible electrochemistry over a potential window similar to that disclosed spectroscopically. The voltammetry also allows definition of kinetic properties of MtrC in direct electron exchange with a solid electrode surface and during reduction of a model Fe(III) substrate. Taken together, the data provide quantitative information on the potential domain in which MtrC can operate

Local Expansion of Donation After Circulatory Death Kidney Transplant Activity Improves Waitlisted Outcomes and Addresses Inequities of Access to Transplantation

In the United Kingdom, donation after circulatory death (DCD) kidney transplant activity has increased rapidly, but marked regional variation persists. We report how increased DCD kidney transplant activity influenced waitlisted outcomes for a single center. Between 2002–2003 and 2011–2012, 430 (54%) DCD and 361 (46%) donation after brain death (DBD) kidney-only transplants were performed at the Cambridge Transplant Centre, with a higher proportion of DCD donors fulfilling expanded criteria status (41% DCD vs. 32% DBD; p = 0.01). Compared with U.K. outcomes, for which the proportion of DCD:DBD kidney transplants performed is lower (25%; p 65 years; waiting time 730 vs. 1357 days nationally; p < 0.001), who received predominantly DCD kidneys from older donors (mean donor age 64 years), whereas younger recipients received equal proportions of living donor, DBD and DCD kidney transplants. Death-censored kidney graft survival was nevertheless comparable for younger and older recipients, although transplantation conferred a survival benefit from listing for only younger recipients. Local expansion in DCD kidney transplant activity improves survival outcomes for younger patients and addresses inequity of access to transplantation for older recipients

Chiral tunneling and the Klein paradox in graphene

The so-called Klein paradox - unimpeded penetration of relativistic particles through high and wide potential barriers - is one of the most exotic and counterintuitive consequences of quantum electrodynamics (QED). The phenomenon is discussed in many contexts in particle, nuclear and astro- physics but direct tests of the Klein paradox using elementary particles have so far proved impossible. Here we show that the effect can be tested in a conceptually simple condensed-matter experiment by using electrostatic barriers in single- and bi-layer graphene. Due to the chiral nature of their quasiparticles, quantum tunneling in these materials becomes highly anisotropic, qualitatively different from the case of normal, nonrelativistic electrons. Massless Dirac fermions in graphene allow a close realization of Klein's gedanken experiment whereas massive chiral fermions in bilayer graphene offer an interesting complementary system that elucidates the basic physics involved.Comment: 15 pages, 4 figure

Analytic Continuation of Liouville Theory

Correlation functions in Liouville theory are meromorphic functions of the Liouville momenta, as is shown explicitly by the DOZZ formula for the three-point function on the sphere. In a certain physical region, where a real classical solution exists, the semiclassical limit of the DOZZ formula is known to agree with what one would expect from the action of the classical solution. In this paper, we ask what happens outside of this physical region. Perhaps surprisingly we find that, while in some range of the Liouville momenta the semiclassical limit is associated to complex saddle points, in general Liouville's equations do not have enough complex-valued solutions to account for the semiclassical behavior. For a full picture, we either must include "solutions" of Liouville's equations in which the Liouville field is multivalued (as well as being complex-valued), or else we can reformulate Liouville theory as a Chern-Simons theory in three dimensions, in which the requisite solutions exist in a more conventional sense. We also study the case of "timelike" Liouville theory, where we show that a proposal of Al. B. Zamolodchikov for the exact three-point function on the sphere can be computed by the original Liouville path integral evaluated on a new integration cycle.Comment: 86 pages plus appendices, 9 figures, minor typos fixed, references added, more discussion of the literature adde

Scientific discovery as a combinatorial optimisation problem: How best to navigate the landscape of possible experiments?

A considerable number of areas of bioscience, including gene and drug discovery, metabolic engineering for the biotechnological improvement of organisms, and the processes of natural and directed evolution, are best viewed in terms of a ‘landscape’ representing a large search space of possible solutions or experiments populated by a considerably smaller number of actual solutions that then emerge. This is what makes these problems ‘hard’, but as such these are to be seen as combinatorial optimisation problems that are best attacked by heuristic methods known from that field. Such landscapes, which may also represent or include multiple objectives, are effectively modelled in silico, with modern active learning algorithms such as those based on Darwinian evolution providing guidance, using existing knowledge, as to what is the ‘best’ experiment to do next. An awareness, and the application, of these methods can thereby enhance the scientific discovery process considerably. This analysis fits comfortably with an emerging epistemology that sees scientific reasoning, the search for solutions, and scientific discovery as Bayesian processes

Cancer mortality differences among urban and rural residents in Lithuania

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to describe and to compare the cancer mortality rates in urban and rural residents in Lithuania.</p> <p>Methods</p> <p>Cancer mortality has been studied using the materials of the Lithuanian cancer registry. For the period 1993–2004 age-standardized urban and rural population mortality rates (World standard) were calculated for all malignant neoplasm's and for stomach, colorectal, lung, prostate, breast and cervical cancers. The annual percentage change (APC) was calculated using log-linear regression model, two-sided Mantel-Haenzel test was used to evaluate differences in cancer mortality among rural and urban populations.</p> <p>Results</p> <p>For males in rural population cancer mortality was higher than in urban (212.2 and 197.0 cases per 100000) and for females cancer mortality was higher in urban population (103.5 and 94.2 cases per 100000, p < 0.05). During the study period the age-standardized mortality rates decreased in both sexes in urban residents. The decreasing mortality trend in urban population was contributed by decline of the rates of lung and stomach cancer in male and breast, stomach and colorectal cancer in female. Mortality rates in both urban and rural population were increasing for prostate and cervical cancers.</p> <p>Conclusion</p> <p>This study shows that large rural and urban inequalities in cancer mortality exist in Lithuania. The contrast between the health of residents in urban and rural areas invites researchers for research projects to develop, implement, and enhance cancer prevention and early detection intervention strategies for rural populations.</p

Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis.

Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers