Elucidating the internal structure of psychophysical timing performance in the sub-second and second range by utilizing confirmatory factor analysis

The most influential theoretical account in time psychophysics assumes the existence of a unitary internal clock based on neural counting. The distinct timing hypothesis, on the other hand, suggests an automatic timing mechanism for processing of durations in the sub-second range and a cognitively controlled timing mechanism for processing of durations in the range of seconds. Although several psychophysical approaches can be applied for identifying the internal structure of interval timing in the second and sub-second range, the existing data provide a puzzling picture of rather inconsistent results. In the present chapter, we introduce confirmatory factor analysis (CFA) to further elucidate the internal structure of interval timing performance in the sub-second and second range. More specifically, we investigated whether CFA would rather support the notion of a unitary timing mechanism or of distinct timing mechanisms underlying interval timing in the sub-second and second range, respectively. The assumption of two distinct timing mechanisms which are completely independent of each other was not supported by our data. The model assuming a unitary timing mechanism underlying interval timing in both the sub-second and second range fitted the empirical data much better. Eventually, we also tested a third model assuming two distinct, but functionally related mechanisms. The correlation between the two latent variables representing the hypothesized timing mechanisms was rather high and comparison of fit indices indicated that the assumption of two associated timing mechanisms described the observed data better than only one latent variable. Models are discussed in the light of the existing psychophysical and neurophysiological data.

Towards Faster Method Search Through Static Ecosystem Analysis

Software developers are often unsure of the exact name of the method they need to use to invoke the desired behavior in a given context. This results in a process of searching for the correct method name in documentation, which can be lengthy and distracting to the developer. We can decrease the method search time by enhancing the documentation of a class with the most frequently used methods. Usage frequency data for methods is gathered by analyzing other projects from the same ecosystem - written in the same language and sharing dependencies. We implemented a proof of concept of the approach for Pharo Smalltalk and Java. In Pharo Smalltalk, methods are commonly searched for using a code browser tool called "Nautilus", and in Java using a web browser displaying HTML based documentation - Javadoc. We developed plugins for both browsers and gathered method usage data from open source projects, in order to increase developer productivity by reducing method search time. A small initial evaluation has been conducted showing promising results in improving developer productivity.

cDNA Library Generation for the Analysis of Small RNAs by High-Throughput Sequencing

The RNome of a cell is highly diverse and consists besides messenger RNAs (mRNAs), transfer RNAs (tRNAs), and ribosomal RNAs (rRNAs) also of other small and long transcript entities without apparent coding potential. This class of molecules, commonly referred to as non-protein-coding RNAs (ncRNAs), is involved in regulating numerous biological processes and thought to contribute to cellular complexity. Therefore, much effort is put into their identification and further functional characterization. Here we provide a cost-effective and reliable method for cDNA library construction of small RNAs in the size range of 20-500 residues. The effectiveness of the described method is demonstrated by the analysis of ribosome-associated small RNAs in the eukaryotic model organism Trypanosoma brucei.

A class of exact Navier-Stokes solutions for homogeneous flat-plate boundary layers and their linear stability

We introduce a new boundary layer formalism on the basis of which a class of exact solutions to the Navier–Stokes equations is derived. These solutions describe laminar boundary layer flows past a flat plate under the assumption of one homogeneous direction, such as the classical swept Hiemenz boundary layer (SHBL), the asymptotic suction boundary layer (ASBL) and the oblique impingement boundary layer. The linear stability of these new solutions is investigated, uncovering new results for the SHBL and the ASBL. Previously, each of these flows had been described with its own formalism and coordinate system, such that the solutions could not be transformed into each other. Using a new compound formalism, we are able to show that the ASBL is the physical limit of the SHBL with wall suction when the chordwise velocity component vanishes while the homogeneous sweep velocity is maintained. A corresponding non-dimensionalization is proposed, which allows conversion of the new Reynolds number definition to the classical ones. Linear stability analysis for the new class of solutions reveals a compound neutral surface which contains the classical neutral curves of the SHBL and the ASBL. It is shown that the linearly most unstable Görtler–Hämmerlin modes of the SHBL smoothly transform into Tollmien–Schlichting modes as the chordwise velocity vanishes. These results are useful for transition prediction of the attachment-line instability, especially concerning the use of suction to stabilize boundary layers of swept-wing aircraft.

Does upward social mobility increase life satisfaction? A longitudinal analysis using British and Swiss panel data

A main assumption of social production function theory is that status is a major determinant of subjective well-being (SWB). From the perspective of the dissociative hypothesis, however, upward social mobility may be linked to identity problems, distress, and reduced levels of SWB because upwardly mobile people lose their ties to their class of origin. In this paper, we examine whether or not one of these arguments holds. We employ the United Kingdom and Switzerland as case studies because both are linked to distinct notions regarding social inequality and upward mobility. Longitudinal multilevel analyses based on panel data (UK: BHPS, Switzerland: SHP) allow us to reconstruct individual trajectories of life satisfaction (as a cognitive component of SWB) along with events of intragenerational and intergenerational upward mobility—taking into account previous levels of life satisfaction, dynamic class membership, and well-studied determinants of SWB. Our results show some evidence for effects of social class and social mobility on well-being in the UK sample, while there are no such effects in the Swiss sample. The UK findings support the idea of dissociative effects in terms of a negative effect of intergenerational upward mobility on SWB.

Flexibility Properties in Complex Analysis and Affine Algebraic Geometry

In the last decades affine algebraic varieties and Stein manifolds with big (infinite-dimensional) automorphism groups have been intensively studied. Several notions expressing that the automorphisms group is big have been proposed. All of them imply that the manifold in question is an Oka–Forstnerič manifold. This important notion has also recently merged from the intensive studies around the homotopy principle in Complex Analysis. This homotopy principle, which goes back to the 1930s, has had an enormous impact on the development of the area of Several Complex Variables and the number of its applications is constantly growing. In this overview chapter we present three classes of properties: (1) density property, (2) flexibility, and (3) Oka–Forstnerič. For each class we give the relevant definitions, its most significant features and explain the known implications between all these properties. Many difficult mathematical problems could be solved by applying the developed theory, we indicate some of the most spectacular ones.

A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12.

Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds-the Gordon Setter, Hovawart and the Rhodesian Ridgeback. Using a genome-wide association approach and meta-analysis, we identified a major hypothyroidism risk locus shared by these breeds on chromosome 12 (p = 2.1x10-11). Further characterisation of the candidate region revealed a shared ~167 kb risk haplotype (4,915,018-5,081,823 bp), tagged by two SNPs in almost complete linkage disequilibrium. This breed-shared risk haplotype includes three genes (LHFPL5, SRPK1 and SLC26A8) and does not extend to the dog leukocyte antigen (DLA) class II gene cluster located in the vicinity. These three genes have not been identified as candidate genes for hypothyroid disease previously, but have functions that could potentially contribute to the development of the disease. Our results implicate the potential involvement of novel genes and pathways for the development of canine hypothyroidism, raising new possibilities for screening, breeding programmes and treatments in dogs. This study may also contribute to our understanding of the genetic etiology of human hypothyroid disease, which is one of the most common endocrine disorders in humans.

Size parameters, size-class distribution and area-number relationship of microscopic charcoal: relevance for fire reconstruction

Charcoal analysis was conducted on sediment cores from three lakes to assess the relationship between the area and number of charcoal particles. Three charcoal-size parameters (maximum breadth, maximum length and area) were measured on sediment samples representing various vegetation types, including shrub tundra, boreal forest and temperate forest. These parameters and charcoal size-class distributions do not differ statistically between two sites where the same preparation technique (glycerine pollen slides) was used, but they differ for the same core when different techniques were applied. Results suggest that differences in charcoal size and size-class distribution are mainly caused by different preparation techniques and are not related to vegetation-type variation. At all three sites, the area and number concentrations of charcoal particles are highly correlated in standard pollen slides; 82–83% of the variability of the charcoal-area concentration can be explained by the particle-number concentration. Comparisons between predicted and measured area concentrations show that regression equations linking charcoal number and area concentrations can be used across sites as long as the same pollen-preparation technique is used. Thus it is concluded that it is unnecessary to measure charcoal areas in standard pollen slides – a time-consuming and tedious process.

Towards an analysis of tonal patterns in Amawaka, a Panoan language of Peru and Brazil

Amawaka ([ɑmɨ̃ˈwɐkɑ]) is a highly endangered and underdocumented tonal language of the Headwaters (Fleck 2011) subgroup of the Panoan family in the Southwest Amazon Basin, spoken by approximately 200 people. Undocumented phonetic and phonological phenomena of Amawaka include its tonal structure, both in terms of surface realizations and the patterns underlying these realizations. Original audiovisual data from the author’s fieldwork in various Amawaka communities at the Peru-Brazil border will illuminate the as-yet obscure tonal systematicity of the language. Unlike other elements, monosyllabic bimoraic phonological nominal words with long vowels display variation in their surface realization. All the words with the open back unrounded /ɑ/, like /ˈkɑ̀:/ (a traditional Amazonian dish), /ˈnɑ̀:/ “mestizo” etc. [with the exception of /ˈtɑ:/ “reed”, which surfaces with either a H or L tone] bear a low tone in isolation. This realization contrasts with all the encountered nominal monosyllables with vowels from the close and close-mid front and central spectrum /i, ɘ, ɨ, ɨ̃/, which clearly surface as high tone words in isolation, for example /ˈmɨ̃́:/ (a clay-lick for animals), /ˈwí:/ “Anopheles, spp. mosquito”. Monosyllables with close-mid back rounded /o/ have a less restrictive pitch that varies among speakers from low to high realizations, and sometimes even across the speech tokens from an individual speaker, e.g. /wó:/ or /wō:/ “hair”, /ɧō:/ or /ɧò:/ (a type of tarantula). Phrasal tonal phonology is more complex, when these three kinds of monosyllables appear in larger noun phrases. Some retain the same surface tones as their isolation form, while others seem to vary freely in their surface realization, e.g. /ˈtɘ́:.nɑ̀:/ or /ˈtɘ́:.nɑ́:/ ‘one mestizo’. Yet other monosyllables, e.g. /mɑ̀:/, exhibit a falling tone when preceded by a H syllable, suggesting probably latent tone sandhi phenomena, e.g /ˈtɘ́:.mɑ̂:/ (one clay-lick for parrots). In disyllabic, trisyllabic and quadrisyllabic nouns, tonal and stress patterns generally seem to be more consistent and tend to be retained both in isolation and in larger intonational phrases. Disyllabic nouns, for instance, surface as L-H or L-L when a glottal stop is in coda position. The association of L with a glottal stop is a feature that occurs in other Panoan languages as well, like Capanahua (Loos 1969), and more generally it is an areal feature, found in other parts of Amazonia (Hyman 2010). So, tone has significant interactions with the glottal stop and glottalization, which generally co-occurs with L. The data above suggest that the underlying tonal system of Amawaka is much more complex than the privative one-tone analysis (/H/ vs. Ø, i.e. lack of tone) that was proposed by Russell and Russell (1959). Evidence from field data suggests either an equipollent (Hyman 2010) two-tone opposition between /H/ and /L/, or a hybrid system, with both equipollent and privative features; that is, /H/ vs. /L/ vs. either Ø or /M/. This first systematic description of Amawaka tone, in conjunction with ongoing research, is poised to address broader questions concerning interrelationships between surface/underlying tone and other suprasegmental features, such as nasality, metrical stress, and intonation. References Fleck, David W. 2011. Panoan languages and linguistics. In Javier Ruedas and David W. Fleck (Eds.), Panoan Histories and Interethnic Identities, To appear. Hyman, Larry. 2010. Amazonia and the typology of tone systems. Presented at the conference Amazonicas III: The structure of the Amazonian languages. Bogotá. Loos, Eugene E. 1969. The phonology of Capanahua and its grammatical basis. Norman: SIL and U. Oklahoma. Russell, Robert & Dolores. 1959. Syntactotonemics in Amahuaca (Pano). Série Lingüistica Especial, 128-167. Publicaçoes do Museu Nacional, Rio de Janeiro, Brasil.

Tandem Mass Spectrometric Analysis of Metallocene Adducts with Short Oligonucleotides

Metallocene dichlorides constitute a remarkable class of antineoplastic agents that are highly effective against several cancer cell lines. They were shown to accumulate in the DNA-rich region, which suggests DNA as the primary target. These compounds exhibit two cyclopentadienyl ligands and two labile halide ligands, resulting in a bent sandwich structure. The cis-dihalide motif is structurally related to the cis-chloro configuration of cisplatin and similar modes of action can thus be assumed. Cisplatin binds to two neighboring guanine nucleobases in DNA and consequently, distorts the double-helix, thereby inhibiting DNA replication and transcription. Platinum is classified as a soft Lewis acid and binds preferentially to the nitrogen atoms within the nucleobases. The metallocene dichlorides investigated in this study comprise the metal centers Ti, V, Nb, Mo, Hf, and W, which are classified as hard or intermediate Lewis acids, and thus, favor binding to the phosphate oxygen. Although several studies reported adduct formation of metallocene dichlorides with nucleic acids, substantial information about the adduct composition, the binding pattern, and the nucleobase selectivity has not been provided yet. ESI-MS analyses gave evidence for the formation of metallocene adducts (M = Ti, V, Mo, and W) with single-stranded DNA homologues at pH 7. No adducts were formed with Nb and Hf at neutral pH, albeit adducts with Nb were observed at a low pH. MS2 data revealed considerable differences of the adduct compositions. The product ion spectra of DNA adducts with hard Lewis acids (Ti, V) gave evidence for the loss of metallocene ligands and only moderate backbone fragmentation was observed. By contrast, adducts with intermediate Lewis acids (Mo, W) retained the hydroxy ligands. Preliminary results are in good agreement with the Pearson concept and DFT calculations. Since the metallodrugs were not lost upon CID, the nucleobase selectivity, stoichiometry, and binding patterns can be elucidated by means of tandem mass spectrometry.

Comparison of prasugrel and clopidogrel-treated patients with acute coronary syndrome undergoing percutaneous coronary intervention: A propensity score-matched analysis of the Acute Myocardial Infarction in Switzerland (AMIS)-Plus Registry

OBJECTIVE The purpose of this study was to investigate outcomes of patients treated with prasugrel or clopidogrel after percutaneous coronary intervention (PCI) in a nationwide acute coronary syndrome (ACS) registry. BACKGROUND Prasugrel was found to be superior to clopidogrel in a randomized trial of ACS patients undergoing PCI. However, little is known about its efficacy in everyday practice. METHODS All ACS patients enrolled in the Acute Myocardial Infarction in Switzerland (AMIS)-Plus registry undergoing PCI and being treated with a thienopyridine P2Y12 inhibitor between January 2010-December 2013 were included in this analysis. Patients were stratified according to treatment with prasugrel or clopidogrel and outcomes were compared using propensity score matching. The primary endpoint was a composite of death, recurrent infarction and stroke at hospital discharge. RESULTS Out of 7621 patients, 2891 received prasugrel (38%) and 4730 received clopidogrel (62%). Independent predictors of in-hospital mortality were age, Killip class >2, STEMI, Charlson comorbidity index >1, and resuscitation prior to admission. After propensity score matching (2301 patients per group), the primary endpoint was significantly lower in prasugrel-treated patients (3.0% vs 4.3%; p=0.022) while bleeding events were more frequent (4.1% vs 3.0%; p=0.048). In-hospital mortality was significantly reduced (1.8% vs 3.1%; p=0.004), but no significant differences were observed in rates of recurrent infarction (0.8% vs 0.7%; p=1.00) or stroke (0.5% vs 0.6%; p=0.85). In a predefined subset of matched patients with one-year follow-up (n=1226), mortality between discharge and one year was not significantly reduced in prasugrel-treated patients (1.3% vs 1.9%, p=0.38). CONCLUSIONS In everyday practice in Switzerland, prasugrel is predominantly used in younger patients with STEMI undergoing primary PCI. A propensity score-matched analysis suggests a mortality benefit from prasugrel compared with clopidogrel in these patients.

Quantitative analysis of arachidonic acid, endocannabinoids, N-acylethanolamines and steroids in biological samples by LCMS/MS: Fit to purpose.

Arachidonic acid (5Z,8Z,11Z,14Z-eicosatetraenoic acid; C20:4) (arachidonate, AA) is a vital polyunsaturated omega-6 fatty acid (PUFA) without its presence the mammalian brain, muscles, and possibly other organs cannot develop or function [1] and [2]. AA fulfils numerous known and possibly yet unknown functions as integral part of mammalian phospholipid membranes and as free AA which also acts as a precursor of a variety of biologically active lipid mediators generally referred to as eicosanoids (e.g., prostaglandins, leukotrienes). A more recent class of eicosanoids is composed of the endogenous cannabinoids (endocannabinoids) 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide, AEA), which act on cannabinoid CB1 and CB2 receptors but also modulate ion channels and nuclear receptors [3] and [4]. In recent years, the role of endocannabinoids as prominent anti-inflammatory and neuromodulatory eicosanoids has been shown by numerous studies [5].

T-cell reprogramming through targeted CD4-coreceptor and T-cell receptor expression on maturing thymocytes by latent Circoviridae family member porcine circovirus type 2 cell infections in the thymus

Although porcine circovirus type 2 (PCV2)-associated diseases have been evaluated for known immune evasion strategies, the pathogenicity of these viruses remained concealed for decades. Surprisingly, the same viruses that cause panzootics in livestock are widespread in young, unaffected animals. Recently, evidence has emerged that circovirus-like viruses are also linked to complex diseases in humans, including children. We detected PCV2 genome-carrying cells in fetal pig thymi. To elucidate virus pathogenicity, we developed a new pig infection model by in vivo transfection of recombinant PCV2 and the immunosuppressant cofactor cyclosporine A. Using flow cytometry, immunofluorescence and fluorescence in situ hybridization, we found evidence that PCV2 dictates positive and negative selection of maturing T cells in the thymus. We show for the first time that PCV2-infected cells reside at the corticomedullary junction of the thymus. In diseased animals, we found polyclonal deletion of single positive cells (SPs) that may result from a loss of major histocompatibility complex class-II expression at the corticomedullary junction. The percentage of PCV2 antigen-presenting cells correlated with the degree of viremia and, in turn, the severity of the defect in thymocyte maturation. Moreover, the reversed T-cell receptor/CD4-coreceptor expression dichotomy on thymocytes at the CD4(+)CD8(interm) and CD4SP cell stage is viremia-dependent, resulting in a specific hypo-responsiveness of T-helper cells. We compare our results with the only other better-studied member of Circoviridae, chicken anemia virus. Our data show that PCV2 infection leads to thymocyte selection dysregulation, adding a valuable dimension to our understanding of virus pathogenicity.

Influence of unilateral maxillary first molar extraction treatment on second and third molar inclination in Class II subdivision patients.

OBJECTIVE To assess the maxillary second molar (M2) and third molar (M3) inclination following orthodontic treatment of Class II subdivision malocclusion with unilateral maxillary first molar (M1) extraction. MATERIALS AND METHODS Panoramic radiographs of 21 Class II subdivision adolescents (eight boys, 13 girls; mean age, 12.8 years; standard deviation, 1.7 years) before treatment, after treatment with extraction of one maxillary first molar and Begg appliances and after at least 1.8 years in retention were retrospectively collected from a private practice. M2 and M3 inclination angles (M2/ITP, M2/IOP, M3/ITP, M3/IOP), constructed by intertuberosity (ITP) and interorbital planes (IOP), were calculated for the extracted and nonextracted segments. Random effects regression analysis was performed to evaluate the effect on the molar angulation of extraction, time, and gender after adjusting for baseline measurements. RESULTS Time and extraction status were significant predictors for M2 angulation. M2/ITP and M2/IOP decreased by 4.04 (95% confidence interval [CI]: -6.93, 1.16; P  =  .001) and 3.67 (95% CI: -6.76, -0.58; P  =  .020) in the extraction group compared to the nonextraction group after adjusting for time and gender. The adjusted analysis showed that extraction was the only predictor for M3 angulation that reached statistical significance. M3 mesial inclination increased by 7.38° (95% CI: -11.2, -3.54; P < .001) and 7.33° (95% CI: -11.48, -3.19; P  =  .001). CONCLUSIONS M2 and M3 uprighting significantly improved in the extraction side after orthodontic treatment with unilateral maxillary M1 extraction. There was a significant increase in mesial tipping of maxillary second molar crowns over time.

Long-term evaluation of Class II subdivision treatment with unilateral maxillary first molar extraction

OBJECTIVE To evaluate the long-term effects of asymmetrical maxillary first molar (M1) extraction in Class II subdivision treatment. MATERIALS AND METHODS Records of 20 Class II subdivision whites (7 boys, 13 girls; mean age, 13.0 years; SD, 1.7 years) consecutively treated with the Begg technique and M1 extraction, and 15 untreated asymmetrical Class II adolescents (4 boys, 11 girls; mean age, 12.2 years; SD, 1.3 years) were examined in this study. Cephalometric analysis and PAR assessment were carried out before treatment (T1), after treatment (T2), and on average 2.5 years posttreatment (T3) for the treatment group, and at similar time points and average follow-up of 1.8 years for the controls. RESULTS The adjusted analysis indicated that the maxillary incisors were 2.3 mm more retracted in relation to A-Pog between T1 and T3 (β  =  2.31; 95% CI; 0.76, 3.87), whereas the mandibular incisors were 1.3 mm more protracted (β  =  1.34; 95% CI; 0.09, 2.59), and 5.9° more proclined to the mandibular plane (β  =  5.92; 95% CI; 1.43, 10.41) compared with controls. The lower lip appeared 1.4 mm more protrusive relative to the subnasale-soft tissue-Pog line throughout the observation period in the treated adolescents (β  =  1.43; 95% CI; 0.18, 2.67). There was a significant PAR score reduction over the entire follow-up period in the molar extraction group (β  =  -6.73; 95% CI; -10.7, -2.7). At T2, 65% of the subjects had maxillary midlines perfectly aligned with the face. CONCLUSIONS Unilateral M1 extraction in asymmetrical Class II cases may lead to favorable occlusal outcomes in the long term without harming the midline esthetics and soft tissue profile.