Neural Network Approaches and Their Reproducibility in the Study of Verbal Working Memory and Alzheimer's Disease

As clinical and cognitive neurosciences mature, the need for sophisticated neuroimaging analysis becomes more apparent. Multivariate analysis techniques have recently received increasing attention because they have attractive features that cannot be easily realized by the more commonly used univariate, voxel-wise, techniques. Multivariate approaches evaluate correlation/covariance of activation across brain regions, rather than proceeding on a voxel-by-voxel basis. Thus, their results can be more easily interpreted as a signature of neural networks. Univariate approaches, in contrast, cannot directly address functional connectivity in the brain. Apart from this conceptual difference, the covariance approach can also result in greater statistical power when compared with univariate techniques, which are forced to employ very stringent, and often overly conservative, corrections for voxel-wise multiple comparisons. Multivariate techniques also lend themselves much better to prospective application of results from the analysis of one dataset to entirely new datasets. We provide two examples that illustrate different uses of multivariate techniques in cognitive and clinical neuroscience. We hope this contribution helps facilitate wider dissemination of these techniques in the research communit

Transport signatures of fractional quantum Hall binding transitions

Certain fractional quantum Hall edges have been predicted to undergo quantum phase transitions which reduce the number of edge channels and at the same time bind electrons together. However, detailed studies of experimental signatures of such a “binding transition” remain lacking. Here, we propose quantum transport signatures with focus on the edge at filling ν=9/5. We demonstrate theoretically that in the regime of nonequilibrated edge transport, the bound and unbound edge phases have distinct conductance and noise characteristics. We also show that for a quantum point contact in the strong back-scattering (SBS) regime, the bound phase produces a minimum Fano factor F$_{SBS}$=3 corresponding to three-electron tunneling, whereas single-electron tunneling is strongly suppressed at low energies. Together with recent experimental developments, our results will be useful for detecting binding transitions in the fractional quantum Hall regime

Transport signatures of fractional quantum Hall binding transitions

Certain fractional quantum Hall edges have been predicted to undergo quantum phase transitions which reduce the number of edge channels and at the same time bind electrons together. However, detailed studies of experimental signatures of such a ``binding transition\u27\u27 remain lacking. Here, we propose quantum transport signatures with focus on the edge at filling ν=9/5. We demonstrate theoretically that in the regime of non-equilibrated edge transport, the bound and unbound edge phases have distinct conductance and noise characteristics. We also show that for a quantum point contact in the strong back-scattering regime, the bound phase produces a minimum Fano-factor F$_{SBS}$=3 corresponding to three-electron tunneling, whereas single electron tunneling is strongly suppressed at low energies. Together with recent experimental developments, our results will be useful for detecting binding transitions in the fractional quantum Hall regime

Wood Ant (Formica polyctena) Services and Disservices in a Danish Apple Plantation

Ants possess properties that can be used to optimize plant production in agricultural systems. Ant services can be herbivore and pathogen protection and fertilization of their plant partners. They may, however, also harm plants by facilitating ant-attended herbivorous homopterans. To assess whether wood ants can be used in IPM-systems to improve apple production, we transplanted wood ants into a Danish apple plantation and tested whether ants (i) reduced the number of herbivores, (ii) led to higher amounts of leaf nutrients, (iii) controlled apple pathogens, (iv) increased homopteran abundance and (iv) whether these effects affected apple yields. During a two year study, we found that the wood ants significantly reduced the numbers of winter moth larvae, increased magnesium content in apple leaves (but did not affect 10 other nutrients), reduced the number of apples infected with apple brown rot and apple scab (on one apple variety) and increased aphid infections. In the first year, this led to higher apple production on ant trees, whereas ants had no effect on yields in the second year. It was evident that ants provided both services and disservices. If mutualistic ant-homopteran interactions can be disrupted, this would favor plant growth and open for the use of wood ants in sustainable plant management. We discuss how this may be accomplished. Alternatively, ants may be used short term to knock down pest outbreaks (before building up homopteran populations) or used in crops that do not host ant-attended homopterans

Doping high Tc superconductors with oxygen and metallic atoms: A molecular dynamics study

Using classical molecular dynamics based on Lennard-Jones-like potentials, a mechanically stable YBa2Cu3O7 high Tc superconductor structure is generated. This process is controlled via interactive computer graphics. After doping atoms into or removing atoms from the sample using a recently implemented picking mechanism, the lattice oscillation energy is annihilated with a simulated annealing procedure. The remaining minimum ground state energy allows marking of the preferred doping location. Information on the doping mechanism is important because the magnetic and superconducting properties of these compounds depend very strongly on their oxygen conten

TERRA transcript expression in tumor cell lines and establishment of constructs for alteration of this expression

Vor kurzem wurde entdeckt, dass Telomere in eine nicht-kodierende RNA genannt telomeric repeat containing RNA (TERRA) oder auch telomerische RNA (telRNA) transkribiert werden. TERRA fungiert als natürlicher Ligand und Hemmstoff für die Telomerase, dem Enzym das von ca. 85% der Tumorzellen verwendet wird, um Telomerlängen aufrecht zu erhalten und damit eine uneingeschränkte Anzahl von Zellteilungen zu ermöglichen. In der Literatur ist bekannt, dass unterschiedliche Promotoren für die Expression zuständig sind und das polyadenylierte und nicht-polyadenylierte TERRAs existieren, wobei nur die Nicht-polyadenylierte an den Chromosomenenden lokalisiert ist. Der Transkriptionsstartpunkt von TERRA Transkripten ist in der subtelomerischen Region lokalisiert. Aus diesem Grund besteht auch ein Teil der TERRA Transkripte aus subtelomerischen Sequenzen. Der Methylierungsgrad der subtelomerischen Regionen unterscheidet sich in verschiedenen Tumor Zelllinien. In einer unserer vorangegangenen Studien wurde der Methylierungsgrad der CpG Inseln der Chromosomenenden 2p TERRA Promoter Regionen von Saos-2 und T98-G mittels aufwendiger Bisulfit Konvertierung untersucht. Wir fanden eine CpG Position in dieser Promoter Region die sich in der Erkennungssequenz und Schnittstelle eines Restriktionsenzym befindet. In meiner Studie wurden pENTR-Vektoren und anschließend adenovirale Vektoren mit Promtoren für verschieden RNA-Polymerasen, mit einem 0,8kb Telomer-Fragment in sense und antisense Orientierung produziert. Diese Vektoren dienen zukünftigen Expressions- und Inhibitorstudien. Zell-Zyklus-FACS Analysen zeigten den Einfluss der Konfluenz auf den Zell-Zyklus Status und Real-Time PCRs den Einfluss der Konfluenz auf das TERRA Expressionslevel. Die untersuchten Telomerase negativen Zelllinien die ALT (Alternative lengthening of telomeres) assoziiert sind, zeigten im Vergleich mit den Telomerase positiven Zelllinien allgemein höhere TERRA-Werte. Ausserdem konnte bei allen Zelllinien ein Trend von erhöhter TERRA-Expression mit steigender Konfluenz ermittelt werden. Chromosomenenden spezifische 2p, 18p, 10p und 10q TERRA Expression wurde mit spezifischen Primern gemessen und es wurden unterschiedliche Expressionslevels in den untersuchten Zelllinien gefunden. Der neu entwickelte methylierungsspezifische Real-Time PCR Assay ermöglicht die Berechnung des Methylierungsgrades einer CpG-Insel im Chromosomenende 2p TERRA Promoter. Wenn es möglich ist andere Loci wie diesen in anderen subtelomerischen TERRA Promoter Regionen zu finden, könnten weitere Assays entwickelt werden. Die Erkenntnisse dieser Studie werden als Startpunkt für zukünftige Studien und Untersuchungen dienen. Die erstellten Konstrukte spielen eine wichtige Rolle um neue Erkenntnisse über TERRA-Expression, -Regulierung und -Funktion zu gewinnen und dienen vielleicht dazu neue Mechanismen der Telomerase Inhibierung und damit auch der Tumorinhibierung zu entwickeln.Recently it was discovered that telomeres are transcribed into a non-coding RNA called telomeric repeat-containing RNA (TERRA) or telomeric RNA (telRNA). TERRA acts as a natural ligand and inhibitor of telomerase, the enzyme that is used by about 85% of tumor cells to maintain telomere length, which allows an unlimited number of cell divisions. In the literature it is known that different promoters are responsible for TERRA-expression and that non-polyadenylated and polyadenylated TERRAs exist, but only non-polyadenylated is localized at chromosome ends. The transcription start point of TERRA transcripts is localized in the subtelomeric region. For this reason, parts of TERRA transcripts are subtelomeric derivation. The methylation levels of subtelomeric regions differ in several tumor cell lines. In our previous study, methylation levels of CpG islands of chromosome end 2p TERRA promoter region of Saos-2 and T98-G were examined, by the laborious technique of bisulfit conversion. We found a CpG position in this promoter region, located in the recognition and cutting site of a restriction enzyme. In my study, pENTR vectors and then adenoviral vectors were produced with promotors for different RNA polymerases and with a 0.8kb telomere fragment in sense and antisense orientation. These vectors serve for future expression and inhibitor studies. Cell cycle FACS analysis showed the influence of confluence on cell cycle state and Real-time PCR the effect of confluence on TERRA expression level. The investigated telomerase negative cell lines which are associated to ALT (alternative lengthening of telomeres), showed, in comparison to telomerase positive cell line generally higher TERRA levels. Also in all cell lines a trend of increasing TERRA expression by increasing confluence could be determined. Chromosome end specific 2p, 18p, 10p and 10q TERRA expression levels were measured using specific primers and determined levels differ in the examined cell lines. The newly developed methylation-specific Real-time PCR assay allows calculations of methylation grade of a CpG island of chromosome end 2p TERRA promoter. Perhaps it is possible to find other loci such as those in other subtelomeric TERRA promoter regions and to develop additional assays. The findings from this study will serve as a starting point for future studies and investigations. The generated constructs play an important role to new insights into TERRA-expression, regulation and function and perhaps serve to develope new mechanism of telomerase inhibition and hence tumor inhibition

The role of the blackbird (Turdus merula), redwing (Turdus iliacus) and song trush (Turdus philomelos) as blood hosts for ticks (Acari: Ixodidae) and reservoir hosts for four genospecies of the Borrelia burgdorferi-complex

Vögel spielen vor allem aufgrund ihrer Häufigkeit in natürlichen und anthropogenen Habitaten sowie ihrer von anderen Wirbeltieren unübertroffenen Mobilität als natürliche Reservoire von Krankheitserregern eine bedeutende infektionsepidemiologische Rolle. Darüber hinaus können Zugvögel während ihrer Migration Erreger wie Vektoren über hunderte oder tausende von Kilometern transportieren und in ihrer Verbreitung extrem begünstigen. Dass Vögel neben anderen Tiergruppen eine wichtige Wirtsfunktion für Zecken besitzen, ist bekannt. Ebenso wird Vögeln eine Reservoirfunktion für bestimmte Genospezies des Borrelia burgdorferi-Artenkomplexes zugesprochen (GERN et al. 1998; GYLFE et al. 2000). In welchem Maße verschiedene Vogelarten an der geographischen Verbreitung dieser Bakterienarten beteiligt sind, ist jedoch noch weitgehend unklar. In dieser Studie sollte durch die Untersuchung von an Vögeln abgesammelten Zecken (Ixoes ricinus) die Bedeutung von drei Drosselarten (Turdidae) für den Lebenszyklus der Borrelien genauer untersucht werden. Des Weiteren wurde die Reservoirfunktion dieser Vogelarten für vier verschiedene Genospezies des B. burgdorferi-Komplexes geprüft.In spring 2003, 251 specimens of the three bird species, blackbird (Turdus merula), redwing (Turdus iliacus) and song trush (Turdus philomelos) that had been trapped on the Greifswalder Oie, a small German island in the Baltic sea, were examined for ticks (I. ricinus). 806 ticks (305 larvae, 508 nymphs) were removed from the birds and stored in 80% ethanol or, in the case of full engorgement, kept alive until moulting. The infestation prevalences of the three bird species ranged from 39,5 % to 68,2 % demonstrating the important role of these species as tick hosts. Out of 377 ticks, 104 were tested DNA-positive for B. burgdorferi sensu lato by a polymerase chain reaction assay. The increasing infection prevalences of larvae (19,7 %), nymphs (30,0 %) and adults obtained from repleted nymphs (38,9 %) display the reservoir function of the birds for B. burgdorferi s.l.. The Borrelia-positive tick specimens were additionally tested for the respective B. burgdorferi-genospecies present, B. burgdorferi sensu stricto, B. afzelii, B. garinii and/or B. valaisiana, via DNA-hybridisation. 94,8 % of the ticks were found positive for B. garinii or B. valaisiana. Although these two genospecies are known to be bird-specific, so far there is little evidence on different bird species having different kinds of reservoir competence. According to the results of this study, however, a special correlation between infecting genospecies and avian reservoir host species appears to be likely and has to be proven by further epidemiological and immunological studies

Multivariate Data Analysis for Neuroimaging Data: Overview and Application to Alzheimer's Disease

As clinical and cognitive neuroscience mature, the need for sophisticated neuroimaging analysis becomes more apparent. Multivariate analysis techniques have recently received increasing attention as they have many attractive features that cannot be easily realized by the more commonly used univariate, voxel-wise, techniques. Multivariate approaches evaluate correlation/covariance of activation across brain regions, rather than proceeding on a voxel-by-voxel basis. Thus, their results can be more easily interpreted as a signature of neural networks. Univariate approaches, on the other hand, cannot directly address functional connectivity in the brain. The covariance approach can also result in greater statistical power when compared with univariate techniques, which are forced to employ very stringent, and often overly conservative, corrections for voxel-wise multiple comparisons. Multivariate techniques also lend themselves much better to prospective application of results from the analysis of one dataset to entirely new datasets. Multivariate techniques are thus well placed to provide information about mean differences and correlations with behavior, similarly to univariate approaches, with potentially greater statistical power and better reproducibility checks. In contrast to these advantages is the high barrier of entry to the use of multivariate approaches, preventing more widespread application in the community. To the neuroscientist becoming familiar with multivariate analysis techniques, an initial survey of the field might present a bewildering variety of approaches that, although algorithmically similar, are presented with different emphases, typically by people with mathematics backgrounds. We believe that multivariate analysis techniques have sufficient potential to warrant better dissemination. Researchers should be able to employ them in an informed and accessible manner. The following article attempts to provide a basic introduction with sample applications to simulated and real-world data sets

The Indirect Effect of Age Group on Switch Costs Via Gray Matter Volume and Task-Related Brain Activity

Healthy aging simultaneously affects brain structure, brain function, and cognition. These effects are often investigated in isolation ignoring any relationships between them. It is plausible that age related declines in cognitive performance are the result of age-related structural and functional changes. This straightforward idea is tested in within a conceptual research model of cognitive aging. The current study tested whether age-related declines in task-performance were explained by age-related differences in brain structure and brain function using a task-switching paradigm in 175 participants. Sixty-three young and 112 old participants underwent MRI scanning of brain structure and brain activation. The experimental task was an executive context dual task with switch costs in response time as the behavioral measure. A serial mediation model was applied voxel-wise throughout the brain testing all pathways between age group, gray matter volume, brain activation and increased switch costs, worsening performance. There were widespread age group differences in gray matter volume and brain activation. Switch costs also significantly differed by age group. There were brain regions demonstrating significant indirect effects of age group on switch costs via the pathway through gray matter volume and brain activation. These were in the bilateral precuneus, bilateral parietal cortex, the left precentral gyrus, cerebellum, fusiform, and occipital cortices. There were also significant indirect effects via the brain activation pathway after controlling for gray matter volume. These effects were in the cerebellum, occipital cortex, left precentral gyrus, bilateral supramarginal, bilateral parietal, precuneus, middle cingulate extending to medial superior frontal gyri and the left middle frontal gyri. There were no significant effects through the gray matter volume alone pathway. These results demonstrate that a large proportion of the age group effect on switch costs can be attributed to individual differences in gray matter volume and brain activation. Therefore, age-related neural effects underlying cognitive control are a complex interaction between brain structure and function. Furthermore, the analyses demonstrate the feasibility of utilizing multiple neuroimaging modalities within a conceptual research model of cognitive aging

Single flavor staggered fermions

Based on recent work by Adams, I construct a lattice fermion operator that fully lifts the staggered flavor degeneracy. The resulting operator is of Wilson type but smaller by a factor of 4, better conditioned and contains 3 instead of 15 doublers. It is further suggested that this operator may be used as a candidate kernel operator to an overlap construction. Prospects for practical applications and potential problems of the new discretizations are briefly discussed.Comment: 9 pages, 1 table, 1 figure. Referencing slightly modified. Final version, to appear in Phys.Lett.