Breath-based non-invasive diagnosis of Alzheimer’s disease:A pilot study

Early detection of Alzheimer's disease (AD) will help researchers to better understand the disease and develop improved treatments. Recent developments have thus focused on identifying biomarkers for mild cognitive impairment due to AD (MCI) and AD during the preclinical phase. The aim of this pilot study is to determine whether exhaled volatile organic compounds (VOCs) can be used as a non-invasive method to distinguish controls from MCI, controls from AD and to determine whether there are differences between MCI and AD. The study used gas chromatography – ion mobility spectrometry (GC-IMS) techniques. Confounding factors, such as age, smoking habits, gender and alcohol consumption are investigated to demonstrate the efficacy of results. One hundred subjects were recruited including 50 controls, 25 AD and 25 MCI patients. The subject cohort was age- and gender-matched to minimise bias. Breath samples were analysed using a commercial GC-IMS instrument (G.A.S. BreathSpec, Dortmund, Germany). Data analysis indicates that the GC-IMS signal was consistently able to separate between diagnostic groups [AUC±95%, sensitivity, specificity], controls vs MCI: [0.77 (0.64 – 0.90), 0.68, 0.80], controls vs AD: [0.83 (0.72 – 0.94), 0.60, 0.96], and MCI vs AD: [0.70 (0.55 – 0.85), 0.60, 0.84]. VOC analysis indicates that six compounds play a crucial role in distinguishing between diagnostic groups. Analysis of possible confounding factors indicate that gender, age, smoking habits and alcohol consumption have insignificant influence on breath content. This pilot study confirms the utility of exhaled breath analysis to distinguish between AD, MCI and control subjects. Thus, GC-IMS offers great potential as a non-invasive, high-throughput, diagnostic technique for diagnosing and potentially monitoring AD in a clinical setting

Spin-polarized tunneling of La0.67Sr0.33MnO3/YBa2Cu3O7-d junctions

The transport properties between ferromagnets and high-Tc superconductors are investigated in La0.67Sr0.33MnO3/YBa2Cu3O7-d (LSMO/YBCO)junctions in the geometry of cross-strip lines. The conductance spectra show zero-bias conductance peaks (ZBCP), reflecting the charge transport in the ab-plane. When an external magnetic field is applied to the junctions, the conductance spectra show two notable features, i.e., an increase of background conductance and an asymmetric ZBCP splitting whose amplitude responds nonlinearly to the applied field. It is shown that the magnetic field response are consistent with a theoretical prediction of tunneling spectroscopy when the presence of a ferromagnetic barrier between a spin-polarized ferromagnet and a d-wave superconductor is assumed.Comment: 10 Pages, 7 EPS figures, Submitted to Phys. Rev.

Spin current in ferromagnet/insulator/superconductor junctions

A theory of spin polarized tunneling spectroscopy based on a scattering theory is given for tunneling junctions between ferromagnets and d-wave superconductors. The spin filtering effect of an exchange field in the insulator is also treated. We clarify that the properties of the Andreev reflection are largely modified due to a presence of an exchange field in the ferromagnets, and consequently the Andreev reflected quasiparticle shows an evanescent-wave behavior depending on the injection angle of the quasiparticle. Conductance formulas for the spin current as well as the charge current are given as a function of the applied voltage and the spin-polarization in the ferromagnet for arbitrary barrier heights. It is shown that the surface bound states do not contribute to the spin current and that the zero-bias conductance peak expected for a d-wave superconductor splits into two peaks under the influence of the exchange interaction in the insulator.Comment: 14 pages, 11 figure

How Design Features in Digital Math Games Support Learning and Mathematics Connections

Current research shows that digital games can significantly enhance children’s learning. The purpose of this study was to examine how design features in 12 digital math games influenced children’s learning. The participants in this study were 193 children in Grades 2 through 6 (ages 8-12). During clinical interviews, children in the study completed pre-tests, interacted with digital math games, responded to questions about the digital math games, and completed post-tests. We recorded the interactions using two video perspectives that recorded children’s gameplay and responses to interviewers. We employed mixed methods to analyze the data and identify salient patterns in children’s experiences with the digital math games. The analysis revealed significant gains for 9 of the 12 digital games and most children were aware of the design features in the games. There were eight prominent categories of design features in the video data that supported learning and mathematics connections. Six categories focused on how the design features supported learning in the digital games. These categories included: accuracy feedback, unlimited/multiple attempts, information tutorials and hints, focused constraint, progressive levels, and game efficiency. Two categories were more specific to embodied cognition and action with the mathematics, and focused on how design features promoted mathematics connections. These categories included: linked representations and linked physical actions. The digital games in this study that did not include linked representations and opportunities for linked physical actions as design features did not produce significant gains. These results suggest the key role of mathematics-specific design features in the design of digital math games

Oxford SWIFT IFS and multi-wavelength observations of the Eagle galaxy at z=0.77

The `Eagle' galaxy at a redshift of 0.77 is studied with the Oxford Short Wavelength Integral Field Spectrograph (SWIFT) and multi-wavelength data from the All-wavelength Extended Groth strip International Survey (AEGIS). It was chosen from AEGIS because of the bright and extended emission in its slit spectrum. Three dimensional kinematic maps of the Eagle reveal a gradient in velocity dispersion which spans 35-75 +/- 10 km/s and a rotation velocity of 25 +/- 5 km/s uncorrected for inclination. Hubble Space Telescope images suggest it is close to face-on. In comparison with galaxies from AEGIS at similar redshifts, the Eagle is extremely bright and blue in the rest-frame optical, highly star-forming, dominated by unobscured star-formation, and has a low metallicity for its size. This is consistent with its selection. The Eagle is likely undergoing a major merger and is caught in the early stage of a star-burst when it has not yet experienced metal enrichment or formed the mass of dust typically found in star-forming galaxies.Comment: accepted for publication in MNRA

Galaxy Formation Theory

We review the current theory of how galaxies form within the cosmological framework provided by the cold dark matter paradigm for structure formation. Beginning with the pre-galactic evolution of baryonic material we describe the analytical and numerical understanding of how baryons condense into galaxies, what determines the structure of those galaxies and how internal and external processes (including star formation, merging, active galactic nuclei etc.) determine their gross properties and evolution. Throughout, we highlight successes and failings of current galaxy formation theory. We include a review of computational implementations of galaxy formation theory and assess their ability to provide reliable modelling of this complex phenomenon. We finish with a discussion of several "hot topics" in contemporary galaxy formation theory and assess future directions for this field.Comment: 58 pages, to appear in Physics Reports. This version includes minor corrections and a handful of additional reference

Systems Biology of the Clock in Neurospora crassa

A model-driven discovery process, Computing Life, is used to identify an ensemble of genetic networks that describe the biological clock. A clock mechanism involving the genes white-collar-1 and white-collar-2 (wc-1 and wc-2) that encode a transcriptional activator (as well as a blue-light receptor) and an oscillator frequency (frq) that encodes a cyclin that deactivates the activator is used to guide this discovery process through three cycles of microarray experiments. Central to this discovery process is a new methodology for the rational design of a Maximally Informative Next Experiment (MINE), based on the genetic network ensemble. In each experimentation cycle, the MINE approach is used to select the most informative new experiment in order to mine for clock-controlled genes, the outputs of the clock. As much as 25% of the N. crassa transcriptome appears to be under clock-control. Clock outputs include genes with products in DNA metabolism, ribosome biogenesis in RNA metabolism, cell cycle, protein metabolism, transport, carbon metabolism, isoprenoid (including carotenoid) biosynthesis, development, and varied signaling processes. Genes under the transcription factor complex WCC ( = WC-1/WC-2) control were resolved into four classes, circadian only (612 genes), light-responsive only (396), both circadian and light-responsive (328), and neither circadian nor light-responsive (987). In each of three cycles of microarray experiments data support that wc-1 and wc-2 are auto-regulated by WCC. Among 11,000 N. crassa genes a total of 295 genes, including a large fraction of phosphatases/kinases, appear to be under the immediate control of the FRQ oscillator as validated by 4 independent microarray experiments. Ribosomal RNA processing and assembly rather than its transcription appears to be under clock control, suggesting a new mechanism for the post-transcriptional control of clock-controlled genes

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma

BACKGROUND Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. METHODS We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. RESULTS Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2'antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). CONCLUSIONS Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renalcell carcinoma consisted of at least three subtypes based on molecular and phenotypic features

Large Values of Hydraulic Roughness in Subglacial Conduits during Conduit Enlargement: Implications for Modeling Conduit Evolution

Hydraulic roughness accounts for energy dissipated as heat and should exert an important control on rates of subglacial conduit enlargement by melting. Few studies, however, have quantified how subglacial conduit roughness evolves over time or how that evolution affects models of conduit enlargement. To address this knowledge gap, we calculated values for two roughness parameters, the Darcy–Weisbach friction factor (f) and the Manning roughness coefficient (n), using dye tracing data from a mapped subglacial conduit at Rieperbreen, Svalbard. Values of f and n calculated from dye traces were compared with values of f and n calculated from commonly used relationships between surface roughness heights and conduit hydraulic diameters. Roughness values calculated from dye tracing ranged from 75–0.97 for f and from 0.68–0.09 s m‐1/3 for n. Equations that calculate roughness parameters from surface roughness heights underpredicted values of f by as much as a factor of 326 and values of n by a factor of 17 relative to values obtained from the dye tracing study. We argue these large underpredictions occur because relative roughness in subglacial conduits during the early stages of conduit enlargement exceeds the 5% range of relative roughness that can be used to directly relate values of f and n to flow depth and surface roughness heights. Simple conduit hydrological models presented here show how parameterization of roughness impacts models of conduit discharge and enlargement rate. We used relationships between conduit relative roughness and values of f and n calculated from our dye tracing study to parameterize a model of conduit enlargement. Assuming a fixed hydraulic gradient of 0.01 and ignoring creep closure, it took conduits 9.25 days to enlarge from a diameter of 0.44 m to 3 m, which was 6–7‐fold longer than using common roughness parameterizations