bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers
Authors: Nho Kwangsik , Kueider‐Paisley Alexandra , MahmoudianDehkordi Siamak , Arnold Matthias , Risacher Shannon L. , Louie Gregory , Blach Colette , Baillie Rebecca , Han Xianlin , Kastenmüller Gabi , Jia Wei , Xie Guoxiang , Ahmad Shahzad , Hankemeier Thomas , van Duijn Cornelia M. , Trojanowski John Q. , Shaw Leslie M. , Weiner Michael W. , Doraiswamy P. Murali , Saykin Andrew J. , Kaddurah‐Daouk Rima ,   for the Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium
Published: October 2018

Introduction

Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co‐metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer's disease (AD) including neuroinflammation and amyloid‐β deposition.

Method

Serum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n = 1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the “A/T/N” (amyloid, tau, and neurodegeneration) biomarkers for AD: cerebrospinal fluid (CSF) biomarkers, atrophy (magnetic resonance imaging), and brain glucose metabolism ([18F]FDG PET).

Results

Of 23 BAs and relevant calculated ratios after quality control procedures, three BA signatures were associated with CSF Aβ1‐42 (“A”) and three with CSF p‐tau181 (“T”) (corrected P < .05). Furthermore, three, twelve, and fourteen BA signatures were associated with CSF t‐tau, glucose metabolism, and atrophy (“N”), respectively (corrected P < .05).

Discussion

This is the first study to show serum‐based BA metabolites are associated with “A/T/N” AD biomarkers, providing further support for a role of BA pathways in AD pathophysiology. Prospective clinical observations and validation in model systems are needed to assess causality and specific mechanisms underlying this association.
AMYPAD Diagnostic and Patient Management Study: Rationale and design
Authors: Frisoni Giovanni B. , Barkhof Frederik , Altomare Daniele , Berkhof Johannes , Boccardi Marina , Canzoneri Elisa , Collij Lyduine , Drzezga Alexander , Farrar Gill , Garibotto Valentina , Gismondi Rossella , Gispert Juan‐Domingo , Jessen Frank , Kivipelto Miia , Lopes Alves Isadora , Molinuevo José Luis , Nordberg Agneta , Payoux Pierre , Ritchie Craig , Savicheva Irina , Scheltens Philip , Schmidt Mark E. , Schott Jonathan M. , Stephens Andrew , van Berckel Bart , Vellas Bruno , Walker Zuzana , Raffa Nicola
Published: October 2018

Introduction

Reimbursement of amyloid–positron emission tomography (PET) is lagging due to the lack of definitive evidence on its clinical utility and cost‐effectiveness. The Amyloid Imaging to Prevent Alzheimer's Disease–Diagnostic and Patient Management Study (AMYPAD‐DPMS) is designed to fill this gap.

Methods

AMYPAD‐DPMS is a phase 4, multicenter, prospective, randomized controlled study. Nine hundred patients with subjective cognitive decline plus, mild cognitive impairment, and dementia possibly due to Alzheimer's disease will be randomized to ARM1, amyloid‐PET performed early in the diagnostic workup; ARM2, amyloid‐PET performed after 8 months; and ARM3, amyloid‐PET performed whenever the physician chooses to do so.

Endpoints

The primary endpoint is the difference between ARM1 and ARM2 in the proportion of patients receiving a very‐high‐confidence etiologic diagnosis after 3 months. Secondary endpoints address diagnosis and diagnostic confidence, diagnostic/therapeutic management, health economics and patient‐related outcomes, and methods for image quantitation.

Expected Impacts

AMYPAD‐DPMS will supply physicians and health care payers with real‐world data to plan management decisions.
Instruments and methods: a case study of ice core bubbles as strain indicators
Authors: Fegyveresi John M. , Alley Richard B. , Voigt Donald E. , Fitzpatrick Joan J. , Wilen Lawrence A.
Published: October 2018

Measurements of a sample from ~580 m depth in the WAIS Divide (WDC06A) ice core reveal that bubbles are preferentially elongated in the basal plane of their parent grain, as expected if bubble shape preserves the record of dominant basal glide. This suggests that a method using bubbles as strain gauges could provide insights to grain-scale ice deformation. We introduce a technique using fabric and image analyses of paired thin and thick sections. Comparison of the crystallographic orientations of 148 grains and the shape orientations of 2377 intragrain bubbles reveals a strongly preferred elongation of bubbles in the grain basal planes (R2 = 0.96). Elongation magnitudes are consistent with a balance between ice flow deformation and diffusive restoration, with larger bubbles more elongated. Assuming bubbles record ice strain, grains with greater resolved stress on their basal planes from the far-field ice flow stresses show greater deformation, but with large variability suggesting that heterogeneity of the local stress field causes deformation even in unfavorably oriented grains. A correlation is also observed among bubble elongation, grain size, and bubble size, explaining a small but significant fraction of the variance ( P< 0.05), with implications for controls on ice deformation, as discussed here.
The Ruamano Project: Raising Expectations, Realising Community Aspirations and Recognising Gifted Potential in Māori Boys
Authors: Webber Melinda , Riley Tracy , Sylva Katrina , Scobie-Jennings Emma
Published: October 2018

When gifted Māori students feel they belong and find their realities reflected in the curriculum, conversations and interactions of schooling, they are more likely to engage in programmes of learning and experience greater school success. This article reports on a teacher-led project called the Ruamano Project, which investigated whether Maker and Zimmerman's (2008) Real Engagement in Active Problem Solving model (REAPS) could be adapted successfully to identify talents and benefit the student achievement and engagement of Māori boys in two rural Northland, New Zealand secondary school contexts. The project aimed to implement Treaty of Waitangi-responsive and place-based science practices by improving home–school–community relationships through the authentic engagement of whānau and iwi into the schools’ planning, implementation and evaluation of a REAPS unit. As a result of this innovation, teachers’ perceptions of Māori boys shifted, their teaching practices changed, more junior secondary Māori boys were identified as gifted by way of improved academic performance, and iwi and community members were engaged in co-designing the inquiry projects. Our research indicated that the local adaptation of the REAPS model was effective in engaging and promoting the success of gifted and talented Māori boys.
Saliva cortisol responses to altered plasma PUFA patterns in guinea pigs
Authors: Nemeth Matthias , Millesi Eva , Wagner Karl-Heinz , Wallner Bernard
Published: October 2018

PUFA modulate hypothalamic–pituitary–adrenal (HPA) axis activity and cortisol concentrations and therefore affect physiological stress responses and the regulation of energy balance in the short- and long-term. Especially dietary intake ofn-3 PUFA and a loweredn-6:n-3 ratio are highly encouraged due to beneficial and diminishing effects on basal cortisol secretions. However, the time of such effects to occur and how plasma PUFA patterns affect cortisol concentrations in the short-term was rarely investigated. In order to address this, we supplemented forty male and forty female guinea pigs with diets high in the essential PUFAα-linolenic acid (ALA, 18 : 3n-3) and linoleic acid (LA, 18 : 2n-6) for 20 d. Saliva cortisol concentrations in relation to altering plasma PUFA patterns during this time span were analysed in a repeated measurement design both during basal conditions (individual housing) in 5-d intervals and during stressful social confrontations. We detected very fast plasma PUFA accumulation rates, corresponding to the major dietary PUFA, which resulted in plasma PUFA plateau phases after 10 d. ALA negatively and LA positively affected saliva cortisol concentrations throughout the study. A positive effect of the plasman-6:n-3 ratio on saliva cortisol concentrations was detected during peak plasma PUFA accumulations and social confrontations, while no effects were detected in relation to plasma PUFA plateau phases. These results suggest that the plasman-6:n-3 ratio diminishes HPA axis activity during altered physiological conditions only and highlights the importance of altering plasma PUFA patterns for HPA axis functions and the control of energy balance and physiological stress.
An Inverse Result of Approximation by Sampling Kantorovich Series
Authors: Costarelli Danilo , Vinti Gianluca
Published: October 2018

In the present paper, an inverse result of approximation, i.e. a saturation theorem for the sampling Kantorovich operators, is derived in the case of uniform approximation for uniformly continuous and bounded functions on the whole real line. In particular, we prove that the best possible order of approximation that can be achieved by the above sampling series is the order one, otherwise the function being approximated turns out to be a constant. The above result is proved by exploiting a suitable representation formula which relates the sampling Kantorovich series with the well-known generalized sampling operators introduced by Butzer. At the end, some other applications of such representation formulas are presented, together with a discussion concerning the kernels of the above operators for which such an inverse result occurs.
Saline injection to determine the volume required for personalised patulous Eustachian tube augmentation with long-standing material
Authors: Jančatová D , Zeleník K , Komínek P , Formánek M
Published: October 2018

Objective

There is currently no general consensus on patulous Eustachian tube management. Injection of autologous fat, cartilage or hydroxylapatite has been described for Eustachian tube occlusion, with promising results. However, complete resolution of symptoms is not achieved in all cases. This could be connected to the amount of material injected into the surroundings of the Eustachian tube, as this greatly differs among existing studies. Identifying the appropriate volume of injected material could be challenging because anatomical conditions vary among patients, and there is always a risk of chronic Eustachian tube obstruction and its related complications when too much long-standing material is injected.

Case report

A case is presented wherein saline was injected under local anaesthesia to determine the volume required and to predict the success of patulous Eustachian tube augmentation with long-standing material.

Conclusion

This approach could allow more personalised treatment and help identify patients likely to benefit from the procedure.
Unveiling patterns of genetic variation in parasite–host associations: an example with pinworms and Neotropical primates
Authors: Solórzano García Brenda , Melin Amanda D. , Aureli Filippo , Pérez Ponce de León Gerardo
Published: October 2018

Patterns of genetic variation among populations can reveal the evolutionary history of species. Pinworm parasites are highly host specific and form strong co-evolutionary associations with their primate hosts. Here, we describe the genetic variation observed in four Trypanoxyuris species infecting different howler and spider monkey subspecies in Central America to determine if historical dispersal processes and speciation in the host could explain the genetic patterns observed in the parasites. Mitochondrial (cox1) and ribosomal (28S) DNA were analysed to assess genetic divergence and phylogenetic history of these parasites. Sequences of the 28S gene were identical within pinworms species regardless of host subspecies. However, phylogenetic analyses, haplotype relationships and genetic divergence with cox1 showed differentiation between pinworm populations according to host subspecies in three of the four Trypanoxyuris species analysed. Haplotype separation between host subspecies was not observed in Trypanoxyuris minutus, nor in Trypanoxyuris atelis from Ateles geoffoyi vellerosus and Ateles geoffoyi yucatanensis. Levels of genetic diversity and divergence in these parasites relate with such estimates reported for their hosts. This study shows how genetic patterns uncovered in parasitic organisms can reflect the host phylogenetic and biogeographic histories.
A measure theoretic approach to traffic flow optimisation on networks
Authors: CACACE SIMONE , CAMILLI FABIO , DE MAIO RAUL , TOSIN ANDREA
Published: October 2018

We consider a class of optimal control problems for measure-valued nonlinear transport equations describing traffic flow problems on networks. The objective is to minimise/maximise macroscopic quantities, such as traffic volume or average speed, controlling few agents, e.g. smart traffic lights and automated cars. The measure theoretic approach allows to study in a same setting local and non-local drivers interactions and to consider the control variables as additional measures interacting with the drivers distribution. We also propose a gradient descent adjoint-based optimisation method, obtained by deriving first-order optimality conditions for the control problem, and we provide some numerical experiments in the case of smart traffic lights for a 2–1 junction.
The Two Cultures at Cambridge
Authors: Lachmann Peter
Published: October 2018

Charles Percy Snow was born in Leicester in 1905 and – like his fictional alter ago Lewis Eliot – determined from an early age to be remembered. The essays in this issue, some 60 years after he first wrote about ‘The Two Cultures’, give testimony that in this respect he has been successful. There is still merit in his essential contentions that there are graduates in the humanities who remain out of touch with scientific developments – and science graduates who don’t read novels. But the world has changed: the computer revolution and the World Wide Web have permitted far broader access to each of the two cultures. While the split between the humanities and the sciences may have grown less, another fissure has become prominent: the sharp divide between those I call the true children of the European enlightenment and those who reject these values, the ‘fideists’. This argument began at Christ’s College, Cambridge.
Moral Enhancement and Moral Freedom: A Critique of the Little Alex Problem
Authors: Danaher John
Published: October 2018

A common objection to moral enhancement is that it would undermine our moral freedom and that this is a bad thing because moral freedom is a great good. Michael Hauskeller has defended this view on a couple of occasions using an arresting thought experiment called the “Little Alex” problem. In this chapter, I reconstruct the argument Hauskeller derives from this thought experiment and subject it to critical scrutiny. I claim that the argument ultimately fails because (a) it assumes that moral freedom is an intrinsic good when, in fact, it is more likely to be an axiological catalyst; and (b) there are reasons to think that moral enhancement does not undermine moral freedom.
Retributivism and the Moral Enhancement of Criminals Through Brain Interventions
Authors: Shaw Elizabeth
Published: October 2018

This chapter will focus on the biomedical moral enhancement of offenders – the idea that we could modify offenders’ brains in order to reduce the likelihood that they would engage in immoral, criminal behaviour. Discussions of the permissibility of using biomedical means to address criminal behaviour typically analyse the issues from the perspective of medical ethics, rather than penal theory. However, recently certain theorists have discussed whether brain interventions could be legitimately used for punitive (as opposed to purely therapeutic) purposes. For instance, Jesper Ryberg argues (although he himself is not a retributivist) that there is nothing to prevent retributivists from endorsing brain interventions as a legitimate form of retributive punishment. Legal academics have not yet paid sufficient attention to whether this proposal would be compatible with international human rights law, nor have retributivist philosophers discussed whether their favoured penal theories have the conceptual resources to explain why brain interventions would not be an appropriate method of punishment. This chapter considers whether there is any indication that these interventions are being used at present for punitive purposes and whether this would violate the European Convention on Human Rights. It examines different versions of retributivism and considers which theory is in the best position to challenge the use of brain interventions as a form of punishment. Finally, it considers whether offering these interventions as an alternative to punishment would violate principles of proportionality.
Lone Wolf Terrorists and the Impotence of Moral Enhancement
Authors: Hardcastle Valerie Gray
Published: October 2018

In their recent bookUnfit for the Future, Persson and Savulescu make a heartfelt plea for the increasing necessity of “moral enhancement”, interventions that improve human capacities for moral behaviour.3They argue that, with all the technological advances of the 20thand 21stcenturies, the sheer scope of horror that humans can now potentially wreak on their neighbours or the world is staggering. Hence, we are morally obliged to use interventions at our disposal to prevent such atrocities. However, as we learn more about human behaviour and decision-making, the argument that we are morally obligated to morally enhance our friends, neighbours, or countrymen starts to fall apart. For us to be more moral requires more than sharpening our reasoning capacities so that we can more effectively recognise what is better or increasing personal motivation so that we are more likely to do what is good. It requires that we all agree on what the good is and how to achieve it, and that there are no social, cultural, physical, or psychological impediments that prevent us from recognising the good or acting on it. To illustrate my position, I use the phenomenon of self-radicalised terrorists as a case study. In particular, I focus on how historians, psychologists, sociologists, criminologists, and political scientists understand the process of self-radicalisation, who self-radicalises, and why, and what all this tells us about it should be “treated”. Part of my purpose in working my way through this case study is to demonstrate that many philosophers misunderstand or over-simplify the science behind so-called immoral actions; consequently, their discussions of whether to enhance someone's morality miss their mark.
The Experimental Psychology of Moral Enhancement: We Should If We Could, But We Can't
Authors: Terbeck Sylvia , Francis Kathryn B.
Published: October 2018

In this chapter we will review experimental evidence related to pharmacological moral enhancement. Firstly, we will present our recent study in which we found that a drug called propranolol could change moral judgements. Further research, which also investigated this, found similar results. Secondly, we will discuss the limitations of such approaches, when it comes to the idea of general “human enhancement”. Whilst promising effects on certain moral concepts might be beneficial to the development of theoretical moral psychology, enhancement of human moral behaviour in general – to our current understanding – has more side-effects than intended effects, making it potentially harmful. We give an overview of misconceptions when taking experimental findings beyond the laboratory and discuss the problems and solutions associated with the psychological assessment of moral behaviour. Indeed, how is morality “measured” in psychology, and are those measures reliable?
An Unfit Future: Moral Enhancement and Technological Harm
Authors: Coyne Lewis
Published: October 2018

This essay addresses two aspects of Persson and Savulescu's case for moral enhancement: 1) the precise technological nature of ultimate harm, particularly as it applies to the ecological crisis, and 2) what is at stake in the solution they propose. My claim is that Persson and Savulescu's treatment of both issues is inadequate: the ecological crisis is a more complex phenomenon than they suppose, and more is at stake in moral enhancement than they claim. To make my case I draw on the work of Hans Jonas, who presciently and insightfully dealt with related questions. Jonas’ philosophy unites bioethical, technological, and environmental concerns and so offers a useful contrast to Persson and Savulescu's proposal. If my analysis is correct then we have both practical and principled reasons to be sceptical about the prospect of moral bioenhancement, which I assume, for the sake of argument, to be feasible.1
Psychedelic Moral Enhancement
Authors: Earp Brian D.
Published: October 2018

The moral enhancement (or bioenhancement) debate seems stuck in a dilemma. On the one hand, the more radical proposals, while certainly novel and interesting, seem unlikely to be feasible in practice, or if technically feasible then most likely imprudent. But on the other hand, the more sensible proposals – sensible in the sense of being both practically achievable and more plausibly ethically justifiable – can be rather hard to distinguish from both traditional forms of moral enhancement, such as non-drug-mediated social or moral education, and non-moral forms of bioenhancement, such as smart-drug style cognitive enhancement. In this essay, I argue that bioethicists have paid insufficient attention to an alternative form of moral bioenhancement – or at least a likely candidate – that falls somewhere between these two extremes, namely the (appropriately qualified) use of certain psychedelic drugs.
Contrast-enhanced ultrasound of the abdominal aorta – current status and future perspectives
Authors: Li Xin , Staub Daniel , Rafailidis Vasileios , Al-Natour Mohammed , Kalva Sanjeeva , Partovi Sasan
Published: October 2018

Abstract. Ultrasound has been established as an important diagnostic tool in assessing vascular abnormalities. Standard B-mode and Doppler techniques have inherent limitations with regards to detection of slow flow and small vasculature. Contrast-enhanced ultrasound (CEUS) is a complementary tool and is useful in assessing both the macro- and microvascular anatomy of the aorta. CEUS can also provide valuable physiological information in real-time scanning sessions due to the physical and safety profiles of the administered microbubbles. From a macrovascular perspective, CEUS has been used to characterize aortic aneurysm rupture, dissection and endoleaks post-EVAR repair. With regard to microvasculature CEUS enables imaging of adventitial vasa vasorum thereby assessing aortic inflammation processes, such as monitoring treatment response in chronic periaortitis. CEUS may have additional clinical utility since adventitial vasa vasorum has important implications in the pathogenesis of aortic diseases. In recent years, there have been an increasing number of studies comparing CEUS to cross-sectional imaging for aortic applications. For endoleak surveillance CEUS has been shown to be equal or in certain cases superior in comparison to CT angiography. The recent advancement of CEUS software along with the ongoing development of drug-eluting contrast microbubbles has allowed improved targeted detection and real-time ultrasound guided therapy for aortic vasa vasorum inflammation and neovascularization in animal models. Therefore, CEUS is uniquely suited to comprehensively assess and potentially treat aortic vascular diseases in the future.
Reconstruction of Storm‐Time Total Electron Content Using Ionospheric Tomography and Artificial Neural Networks: A Comparative Study Over the African Region
Authors: Uwamahoro Jean Claude , Giday Nigussie M. , Habarulema John Bosco , Katamzi‐Joseph Zama T. , Seemala Gopi Krishna
Published: October 2018

The work presented here aims to evaluate the capabilities of Multi‐Instrument Data Analysis System (MIDAS) compared with artificial neural networks (ANNs) to reconstruct storm‐time total electron content (TEC) over the African low‐latitude and midlatitude regions. For MIDAS, the inversion was done based on the Global Positioning System (GPS) measurements from receiver stations extending from −30∘ to 36∘ in latitude and 30∘ to 44∘ in longitude while for ANNs, individual storm‐time models based on historical GPS data from receivers within the same region covered by MIDAS were used. Based on the minimum Dst index reached during the storm period, moderate (−50 nT
−100 nT), strong (−100 nT 
200 nT), and severe (−200 nT 
350 nT) storms were used for validation. MIDAS and ANNs results were compared with IRI‐2016 predictions and validated with real GPS TEC observations. A statistical analysis revealed that MIDAS and ANNs provide comparable results in storm‐time TEC reconstruction with average mean absolute errors of 4.81 and 4.18 TECU respectively. However, MIDAS performed better compared to ANNs in following TEC enhancements and depletions as well as short‐term features observed during the selected storm periods. In terms of latitude, it was found that on average, MIDAS performs 13% better than ANNs in the African midlatitude, while ANN model performs 24% better than MIDAS in low latitudes. Furthermore, comparisons with IRI predictions showed that both MIDAS and ANNs produce more accurate estimations of the storm‐time TEC than IRI model.
Near‐Surface Environmentally Forced Changes in the Ross Ice Shelf Observed With Ambient Seismic Noise
Authors: Chaput J. , Aster R. C. , McGrath D. , Baker M. , Anthony R. E. , Gerstoft P. , Bromirski P. , Nyblade A. , Stephen R. A. , Wiens D. A. , Das S. B. , Stevens L. A.
Published: October 2018

Continuous seismic observations across the Ross Ice Shelf reveal ubiquitous ambient resonances at frequencies >5 Hz. These firn‐trapped surface wave signals arise through wind and snow bedform interactions coupled with very low velocity structures. Progressive and long‐term spectral changes are associated with surface snow redistribution by wind and with a January 2016 regional melt event. Modeling demonstrates high spectral sensitivity to near‐surface (top several meters) elastic parameters. We propose that spectral peak changes arise from surface snow redistribution in wind events and to velocity drops reflecting snow lattice weakening near 0°C for the melt event. Percolation‐related refrozen layers and layer thinning may also contribute to long‐term spectral changes after the melt event. Single‐station observations are inverted for elastic structure for multiple stations across the ice shelf. High‐frequency ambient noise seismology presents opportunities for continuous assessment of near‐surface ice shelf or other firn environments.
Appreciation of Peer Reviewers for 2017
Authors: Florindo Fabio , Moldwin Mark , Okin Gregory , Robock Alan , Rohling Eelco J. , Halekas Jasper S.
Published: October 2018

On behalf of the authors and readers of Reviews of Geophysics, the American Geophysical Union, and the broader scientific community, the Editors wish to wholeheartedly thank those who reviewed the manuscripts for Reviews of Geophysics in 2017. The journal could not exist without your investment of time and effort, lending your expertise to ensure that the papers published in this journal meet the standards that the research community expects for it. We sincerely appreciate all that you do, and we are very grateful for your willingness and readiness to serve in this role.
Lithospheric Alteration, Intraplate Crustal Deformation, and Topography in Eastern China
Authors: Deng Yangfan , Levandowski Will
Published: October 2018

Topography can be directly observed, but what controls topographic variation is not readily known. To investigate a prominent and remarkably consistent along‐trend topographic gradient belt (TGB) in intraplate eastern China and its connection to ongoing deformation and geodynamics, we examine the regional density structure of the crust and mantle lithosphere. We first use S velocities to derive an initial density and then refine the density model by joint inversion of topography and gravity. We use the final density model and receiver functions to strip away topographic contributions from the crust, and we subsequently estimate the thickness of the mantle lithosphere required to satisfy flexural isostasy. Crustal buoyancy overcompensates for the elevation change across the TGB. East of the TGB (eastern north China craton and southeastern south China), the lithosphere is thin (~ 90 km), suggesting that not only the eastern north China craton but also much of the eastern China has experienced lithospheric dismemberment. The TGB behaves as an important contour for the lithospheric thickness, except for the northeast China and Qinling‐Dabie. Proposed refertilization of the altered mantle lithosphere in the east side of TGB would result in even lower lithospheric thickness, while hydration and asthenosphere upwelling have the opposite effect. This systematic calculation gives a regional analysis of eastern China and could be a useful guide for the regions lacking seismic investigations.
Integrated silicon qubit platform with single-spin addressability, exchange control and single-shot singlet-triplet readout
Authors: Fogarty M. A. , Chan K. W. , Hensen B. , Huang W. , Tanttu T. , Yang C. H. , Laucht A. , Veldhorst M. , Hudson F. E. , Itoh K. M. , Culcer D. , Ladd T. D. , Morello A. , Dzurak A. S.
Published: October 2018

Silicon quantum dot spin qubits provide a promising platform for large-scale quantum computation because of their compatibility with conventional CMOS manufacturing and the long coherence times accessible using 28Si enriched material. A scalable error-corrected quantum processor, however, will require control of many qubits in parallel, while performing error detection across the constituent qubits. Spin resonance techniques are a convenient path to parallel two-axis control, while Pauli spin blockade can be used to realize local parity measurements for error detection. Despite this, silicon qubit implementations have so far focused on either single-spin resonance control, or control and measurement via voltage-pulse detuning in the two-spin singlet–triplet basis, but not both simultaneously. Here, we demonstrate an integrated device platform incorporating a silicon metal-oxide-semiconductor double quantum dot that is capable of single-spin addressing and control via electron spin resonance, combined with high-fidelity spin readout in the singlet-triplet basis.
Distinct population codes for attention in the absence and presence of visual stimulation
Authors: Snyder Adam C. , Yu Byron M. , Smith Matthew A.
Published: October 2018

Visual neurons respond more vigorously to an attended stimulus than an unattended one. How the brain prepares for response gain in anticipation of that stimulus is not well understood. One prominent proposal is that anticipation is characterized by gain-like modulations of spontaneous activity similar to gains in stimulus responses. Here we test an alternative idea: anticipation is characterized by a mixture of both increases and decreases of spontaneous firing rates. Such a strategy would be adaptive as it supports a simple linear scheme for disentangling internal, modulatory signals from external, sensory inputs. We recorded populations of V4 neurons in monkeys performing an attention task, and found that attention states are signaled by different mixtures of neurons across the population in the presence or absence of a stimulus. Our findings support a move from a stimulation-invariant account of anticipation towards a richer view of attentional modulation in a diverse neuronal population.
Cyclophilin J limits inflammation through the blockage of ubiquitin chain sensing
Authors: Sheng Chunjie , Yao Chen , Wang Ziyang , Chen Hongyuan , Zhao Yu , Xu Dazhi , Huang Haojie , Huang Wenlin , Chen Shuai
Published: October 2018

Maintaining innate immune homeostasis is important for individual health. Npl4 zinc finger (NZF) domain-mediated ubiquitin chain sensing is reported to function in the nuclear factor-kappa B (NF-κB) signal pathway, but the regulatory mechanism remains elusive. Here we show that cyclophilin J (CYPJ), a member of the peptidylprolyl isomerase family, is induced by inflammation. CYPJ interacts with the NZF domain of transform growth factor-β activated kinase 1 binding protein 2 and 3 as well as components of the linear ubiquitin chain assembly complex to block the binding of ubiquitin-chain and negatively regulates NF-κB signaling. Mice with Cypj deficiency are susceptible to lipopolysaccharide and heat-killed Listeria monocytogenes-induced sepsis and dextran sulfate sodium-induced colitis. These findings identify CYPJ as a negative feedback regulator of the NF-κB signaling pathway, and provide insights for understanding the homeostasis of innate immunity.
Scaling and data collapse from local moments in frustrated disordered quantum spin systems
Authors: Kimchi Itamar , Sheckelton John P. , McQueen Tyrel M. , Lee Patrick A.
Published: October 2018

Recently measurements on various spin–1/2 quantum magnets such as H3LiIr2O6, LiZn2Mo3O8, ZnCu3(OH)6Cl2 and 1T-TaS2—all described by magnetic frustration and quenched disorder but with no other common relation—nevertheless showed apparently universal scaling features at low temperature. In particular the heat capacity C[H, T] in temperature T and magnetic field H exhibits T/H data collapse reminiscent of scaling near a critical point. Here we propose a theory for this scaling collapse based on an emergent random-singlet regime extended to include spin-orbit coupling and antisymmetric Dzyaloshinskii-Moriya (DM) interactions. We derive the scaling C[H, T]/T ~ H−γFq[T/H] with Fq[x] = xq at small x, with q ∈ {0, 1, 2} an integer exponent whose value depends on spatial symmetries. The agreement with experiments indicates that a fraction of spins form random valence bonds and that these are surrounded by a quantum paramagnetic phase. We also discuss distinct scaling for magnetization with a q-dependent subdominant term enforced by Maxwell’s relations.
Universality of defect-skyrmion interaction profiles
Authors: Lima Fernandes Imara , Bouaziz Juba , Blügel Stefan , Lounis Samir
Published: October 2018

Magnetic skyrmions are prime candidates for future spintronic devices. However, incorporating them as information carriers hinges on their interaction with defects ubiquitous in any device. Here we map from first-principles, the energy profile of single skyrmions interacting with single-atom impurities, establishing a generic shape as function of the defect’s electron filling. Depending on their chemical nature, foreign 3d and 4d transition metal adatoms or surface implanted defects can either repel or pin skyrmions in PdFe/Ir(111) thin films, which we relate to the degree of filling of bonding and anti-bonding electronic states inherent to the proximity of the non-collinear magnetic structure. Similarities with key concepts of bond theories in catalysis and surface sciences imbue the universality of the shape of the interaction profile and the potential of predicting its interaction. The resulting fundamental understanding may give guidance for the design of devices with surface implanted defects to generate and control skyrmions.
Encoding of long-term associations through neural unitization in the human medial temporal lobe
Authors: Rey Hernan G. , De Falco Emanuela , Ison Matias J. , Valentin Antonio , Alarcon Gonzalo , Selway Richard , Richardson Mark P. , Quian Quiroga Rodrigo
Published: October 2018

Besides decades of research showing the role of the medial temporal lobe (MTL) in memory and the encoding of associations, the neural substrates underlying these functions remain unknown. We identified single neurons in the human MTL that responded to multiple and, in most cases, associated stimuli. We observed that most of these neurons exhibit no differences in their spike and local field potential (LFP) activity associated with the individual response-eliciting stimuli. In addition, LFP responses in the theta band preceded single neuron responses by ~70 ms, with the single trial phase providing fine tuning of the spike response onset. We postulate that the finding of similar neuronal responses to associated items provides a simple and flexible way of encoding memories in the human MTL, increasing the effective capacity for memory storage and successful retrieval.
ZZ-dependent regulation of p62/SQSTM1 in autophagy
Authors: Zhang Yi , Mun Su Ran , Linares Juan F. , Ahn JaeWoo , Towers Christina G. , Ji Chang Hoon , Fitzwalter Brent E. , Holden Michael R. , Mi Wenyi , Shi Xiaobing , Moscat Jorge , Thorburn Andrew , Diaz-Meco Maria T. , Kwon Yong Tae , Kutateladze Tatiana G.
Published: October 2018

Autophagic receptor p62 is a critical mediator of cell detoxification, stress response, and metabolic programs and is commonly deregulated in human diseases. The diverse functions of p62 arise from its ability to interact with a large set of ligands, such as arginylated (Nt-R) substrates. Here, we describe the structural mechanism for selective recognition of Nt-R by the ZZ domain of p62 (p62ZZ). We show that binding of p62ZZ to Nt-R substrates stimulates p62 aggregation and macroautophagy and is required for autophagic targeting of p62. p62 is essential for mTORC1 activation in response to arginine, but it is not a direct sensor of free arginine in the mTORC1 pathway. We identified a regulatory linker (RL) region in p62 that binds p62ZZ in vitro and may modulate p62 function. Our findings shed new light on the mechanistic and functional significance of the major cytosolic adaptor protein p62 in two fundamental signaling pathways.
Testicular endothelial cells are a critical population in the germline stem cell niche
Authors: Bhang Dong Ha , Kim Bang-Jin , Kim Byung Gak , Schadler Keri , Baek Kwan-Hyuck , Kim Yong Hee , Hsiao Wayland , Ding Bi-Sen , Rafii Shahin , Weiss Mitchell J. , Chou Stella T. , Kolon Thomas F. , Ginsberg Jill P. , Ryu Buom-Yong , Ryeom Sandra
Published: October 2018

Maintenance of adult tissues depends on stem cell self-renewal in local niches. Spermatogonial stem cells (SSC) are germline adult stem cells necessary for spermatogenesis and fertility. We show that testicular endothelial cells (TECs) are part of the SSC niche producing glial cell line-derived neurotrophic factor (GDNF) and other factors to support human and mouse SSCs in long-term culture. We demonstrate that FGF-2 binding to FGFR1 on TECs activates the calcineurin pathway to produce GDNF. Comparison of the TEC secretome to lung and liver endothelial cells identified 5 factors sufficient for long-term maintenance of human and mouse SSC colonies in feeder-free cultures. Male cancer survivors after chemotherapy are often infertile since SSCs are highly susceptible to cytotoxic injury. Transplantation of TECs alone restores spermatogenesis in mice after chemotherapy-induced depletion of SSCs. Identifying TECs as a niche population necessary for SSC self-renewal may facilitate fertility preservation for prepubertal boys diagnosed with cancer.
Effect of hydrophobic cations on the oxygen reduction reaction on single‒crystal platinum electrodes
Authors: Kumeda Tomoaki , Tajiri Hiroo , Sakata Osami , Hoshi Nagahiro , Nakamura Masashi
Published: October 2018

Highly active catalysts for the oxygen reduction reaction are essential for the widespread and economically viable use of polymer electrolyte fuel cells. Here we report the oxygen reduction reaction activities of single‒crystal platinum electrodes in acidic solutions containing tetraalkylammonium cations with different alkyl chain lengths. The high hydrophobicity of a tetraalkylammonium cation with a longer alkyl chain enhances the oxygen reduction reaction activity. The activity on Pt(111) in the presence of tetra‒n‒hexylammonium cation is eight times as high as that without this cation, which is comparable to the activities on Pt3Co(111) and Pt3Ni(111) electrodes. Hydrophobic cations and their hydration shells destabilize the adsorbed hydroxide and adsorbed water. The hydrophobic characteristics of non‒specifically adsorbed cations can prevent the adsorption of poisoning species on the platinum electrode and form a highly efficient interface for the oxygen reduction reaction.
Analysis of influencing factors on soil Zn content using generalized additive model
Authors: Jiang Yan , Gao Wen-Wu , Zhao Jin-Ling , Chen Qian , Liang Dong , Xu Chao , Huang Lin-Sheng , Ruan Li-Min
Published: October 2018

Soil zinc (Zn) plays a crucial role in plant growth, but excessive accumulation in the environment may lead to air, water and soil pollution. It is affected by various chemical, environmental and spatial factors. Therefore, it is important to identify the factors influencing Zn content in the landscape. The main motivation for this study is to determine the suitability of a generalized additive model (GAM) to describe change in soil Zn content due to influencing factors. A total of 1497 soil nutrient samples were collected in Fangshan District, Beijing, China. Organic matter (OM), available phosphorus (AP), available potassium (AK), alkali-hydrolyzed nitrogen (AHN) and slowly available potassium (SAK) are considered. The relationship between Zn, nutrients and geographic location (latitude & longitude) is investigated using the GAM. More precisely, the Akaike information criterion (AIC) is used to select influencing factors on Zn content and cross-validated to avoid overfitting of the multivariate model. The results show that Zn content reaches its maximum at latitude 39.8°N and longitude 115.9°E. Zinc content increases as AP increases to 150 mg/kg. When OM content is greater than 90 g/kg, Zinc content decreases with an increase in OM content. Factors that affected Zn content, in descending order of significance derived from deviance explained and adjustment coefficient of determination (Adj.R2) were AP, latitude, AHN, AK and OM. Moreover, the interactions between latitude and longitude, AHN and AP, OM and AK have significant impact on Zn.
Disrupted prefrontal functional connectivity during post-stress adaption in high ruminators
Authors: Rosenbaum David , Hilsendegen Paula , Thomas Mara , Haeussinger Florian B. , Nuerk Hans-Christoph , Fallgatter Andreas J. , Nieratschker Vanessa , Ehlis Ann-Christine , Metzger Florian G.
Published: October 2018

Rumination is a perseverative thinking style that is associated with adverse mental and physical health. Stressful situations have been considered as a trigger for this kind of thinking. Until today, there are mixed findings with respect to the relations of functional connectivity (FC) and rumination. The study at hand aimed to investigate, in how far high and low ruminators would show elevated levels of state rumination after a stress induction and if these changes would show corresponding changes in FC in the cognitive control network (CCN) and dorsal attention network (DAN). 23 high and 22 low trait ruminators underwent resting-state measurements before and after a stress induction with the Trier Social Stress Test (TSST). Changes in rsFC through the TSST were measured with functional near-infrared spectroscopy within and between regions of the CCN. Stress successfully induced state rumination in both groups but stronger in the high trait ruminators. High trait ruminators showed elevated FC within the CCN at baseline, but attenuated increase in FC following the TSST. Increases in FC correlated negatively with state rumination. A lack of FC reactivity within the CCN in high ruminators might reflect reduced network integration between brain regions necessary for emotion regulation and cognitive control.
Author Correction: Microsatellite analysis for differentiating the origin of renal angiomyolipoma and involved regional lymph node
Authors: Tan Ping , Xu Huan , Jiang Yong , Yang Lu , Zou Yan , Liu Liangren , Liu Nian , Cao Dehong , Fan Yu , Li Qiyuan , Wei Qiang
Published: October 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Ars2 promotes cell proliferation and tumorigenicity in glioblastoma through regulating miR-6798-3p
Authors: Chen Yibiao , Hu Xiaoye , Li Yunong , Zhang Hongwei , Fu Ruoqiu , Liu Yanxia , Hu Jinjiao , Deng Qin , Luo Qingsong , Zhang Dunke , Gao Ning , Cui Hongjuan
Published: October 2018

Arsenic resistance protein 2 (Ars2) is a component of the nuclear RNA cap-binding complex (CBC) that is important for some microRNA biogenesis and it is critical for cell proliferation and tumorigenicity. However, mechanism of Ars2-regulated cellular proliferation and tumorigenicity in glioblastoma has not been fully understood. Western blotting was used to detect the expressions of Ars2, p53, p21, and cleavage/activation of caspases-3 (C-Caspase 3). Microarray and Quantitative Real-time PCR (qRT-PCR) were performed to identify the Ars2-regulated microRNAs. Apoptosis assessed by flow cytometry analysis was used to evaluate the role of Ars2 in cells proliferation. The lentivirus-mediated gene knockdown approach was conducted to determine the function of Ars2. The orthotopic glioblastoma xenograft was used to demonstrate the role of Ars2 in glioblastoma growth in vivo. The high expression of Ars2 was observed in several glioblastoma cell lines and was significantly associated with poorer overall survival. Importantly, the overexpression of Ars2 promoted cell proliferation and colony formation in glioblastoma cells, whereas the depletion of Ars2 inhibited cell proliferation, colony formation, and tumor growth. Mechanistic study revealed that knockdown of Ars2 reduced the expression levels of miR-6798-3p, which was responsible for the up-regulation of p53 and p21, leading to apoptosis. Furthermore, the knockdown of Ars2 suppressed tumor growth in orthotopic glioblastoma xenograft model and significantly prolonged the survival time of the tumor-bearing mice. These findings identify a critical role for Ars2 in regulation of proliferation and tumorigenicity in glioblastoma and suggest that Ars2 could be a critical therapeutic target for glioblastoma intervention.
A radiogenomic dataset of non-small cell lung cancer
Authors: Bakr Shaimaa , Gevaert Olivier , Echegaray Sebastian , Ayers Kelsey , Zhou Mu , Shafiq Majid , Zheng Hong , Benson Jalen Anthony , Zhang Weiruo , Leung Ann N. C. , Kadoch Michael , Hoang Chuong D. , Shrager Joseph , Quon Andrew , Rubin Daniel L. , Plevritis Sylvia K. , Napel Sandy
Published: October 2018

Medical image biomarkers of cancer promise improvements in patient care through advances in precision medicine. Compared to genomic biomarkers, image biomarkers provide the advantages of being non-invasive, and characterizing a heterogeneous tumor in its entirety, as opposed to limited tissue available via biopsy. We developed a unique radiogenomic dataset from a Non-Small Cell Lung Cancer (NSCLC) cohort of 211 subjects. The dataset comprises Computed Tomography (CT), Positron Emission Tomography (PET)/CT images, semantic annotations of the tumors as observed on the medical images using a controlled vocabulary, and segmentation maps of tumors in the CT scans. Imaging data are also paired with results of gene mutation analyses, gene expression microarrays and RNA sequencing data from samples of surgically excised tumor tissue, and clinical data, including survival outcomes. This dataset was created to facilitate the discovery of the underlying relationship between tumor molecular and medical image features, as well as the development and evaluation of prognostic medical image biomarkers.