Comparing Offline Decoding Performance in Physiologically Defined Neuronal Classes

Objective: Recently, several studies have documented the presence of a bimodal distribution of spike waveform widths in primary motor cortex. Although narrow and wide spiking neurons, corresponding to the two modes of the distribution, exhibit different response properties, it remains unknown if these differences give rise to differential decoding performance between these two classes of cells. Approach: We used a Gaussian mixture model to classify neurons into narrow and wide physiological classes. Using similar-size, random samples of neurons from these two physiological classes, we trained offline decoding models to predict a variety of movement features. We compared offline decoding performance between these two physiologically defined populations of cells. Main results: We found that narrow spiking neural ensembles decode motor parameters better than wide spiking neural ensembles including kinematics, kinetics, and muscle activity. Significance: These findings suggest that the utility of neural ensembles in brain machine interfaces may be predicted from their spike waveform widths

Hierarchical Likelihood Inference on Clustered Competing Risks Data

Frailties models, an extension of the proportional hazards model, are used to model clustered survival data. In some situations there may be competing risks within a cluster. When this happens the basic frailty model is no longer appropriate. Depending on the purpose of the analysis, either the cause-specific hazard frailty model or the subhazard frailty model needs to be used. In this work, hierarchical likelihood (h-likelihood) methods are extended to provide a new method for fitting both types of competing risks frailty models. Methods for model selection as well as testing for covariate and clustering effects are discussed. Simulations show that in cases with little information, the h-likelihood method can perform better than the penalized partial likelihood method for estimating the subhazard frailty model. Additional simulations demonstrate that h-likelihood performs well when estimating the cause-specific hazard frailty model assuming both a univariate and bivariate frailty distribution. A real example from a breast cancer clinical trial is used to demonstrate using h-likelihood to fit both types of competing risks frailty models.Public health significance: When researchers have clustered survival data and the observations within those clusters can experience multiple types of events the popular proportional hazards model is no longer appropriate and can lead to biased estimates. For the results of a clinical study to be meaningful the estimated effects of treatments and other covariates needs to be accurate. H-likelihood methods are an alternative to existing procedures and can provide less bias and more accurate information which will ultimately lead to better patient care

SeekDeep: single-base resolution de novo clustering for amplicon deep sequencing

PCR amplicon deep sequencing continues to transform the investigation of genetic diversity in viral, bacterial, and eukaryotic populations. In eukaryotic populations such as Plasmodium falciparum infections, it is important to discriminate sequences differing by a single nucleotide polymorphism. In bacterial populations, single-base resolution can provide improved resolution towards species and strains. Here, we introduce the SeekDeep suite built around the qluster algorithm, which is capable of accurately building de novo clusters representing true, biological local haplotypes differing by just a single base. It outperforms current software, particularly at low frequencies and at low input read depths, whether resolving single-base differences or traditional OTUs. SeekDeep is open source and works with all major sequencing technologies, making it broadly useful in a wide variety of applications of amplicon deep sequencing to extract accurate and maximal biologic information

Observation of Wannier-Stark localization at the surface of BaTiO3_3 films by photoemission

Observation of Bloch oscillations and Wannier-Stark localization of charge carriers is typically impossible in single-crystals, because an electric field higher than the breakdown voltage is required. In BaTiO$_3$ however, high intrinsic electric fields are present due to its ferroelectric properties. With angle-resolved photoemission we directly probe the Wannier-Stark localized surface states of the BaTiO$_3$ film-vacuum interface and show that this effect extends to thin SrTiO$_3$ overlayers. The electrons are found to be localized along the in-plane polarization direction of the BaTiO$_3$ film

Filaggrin-stratified transcriptomic analysis of pediatric skin identifies mechanistic pathways in patients with atopic dermatitis

BackgroundAtopic dermatitis (AD; eczema) is characterized by a widespread abnormality in cutaneous barrier function and propensity to inflammation. Filaggrin is a multifunctional protein and plays a key role in skin barrier formation. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a highly significant risk factor for atopic disease, but the molecular mechanisms leading to dermatitis remain unclear.ObjectiveWe sought to interrogate tissue-specific variations in the expressed genome in the skin of children with AD and to investigate underlying pathomechanisms in atopic skin.MethodsWe applied single-molecule direct RNA sequencing to analyze the whole transcriptome using minimal tissue samples. Uninvolved skin biopsy specimens from 26 pediatric patients with AD were compared with site-matched samples from 10 nonatopic teenage control subjects. Cases and control subjects were screened for FLG genotype to stratify the data set.ResultsTwo thousand four hundred thirty differentially expressed genes (false discovery rate, P < .05) were identified, of which 211 were significantly upregulated and 490 downregulated by greater than 2-fold. Gene ontology terms for “extracellular space” and “defense response” were enriched, whereas “lipid metabolic processes” were downregulated. The subset of FLG wild-type cases showed dysregulation of genes involved with lipid metabolism, whereas filaggrin haploinsufficiency affected global gene expression and was characterized by a type 1 interferon–mediated stress response.ConclusionThese analyses demonstrate the importance of extracellular space and lipid metabolism in atopic skin pathology independent of FLG genotype, whereas an aberrant defense response is seen in subjects with FLG mutations. Genotype stratification of the large data set has facilitated functional interpretation and might guide future therapy development

Magnetic assessment and modelling of the Aramis undulator beamline

Within the SwissFEL project at the Paul Scherrer Institute (PSI), the hard X-ray line (Aramis) has been equipped with short-period in-vacuum undulators, known as the U15 series. The undulator design has been developed within the institute itself, while the prototyping and the series production have been implemented through a close collaboration with a Swiss industrial partner, Max Daetwyler AG, and several subcontractors. The magnetic measurement system has been built at PSI, together with all the data analysis tools. The Hall probe has been designed for PSI by the Swiss company SENIS. In this paper the general concepts of both the mechanical and the magnetic properties of the U15 series of undulators are presented. A description of the magnetic measurement equipment is given and the results of the magnetic measurement campaign are reported. Lastly, the data reduction methods and the associated models are presented and their actual implementation in the control system is detailed.peer-reviewe

Aviram-Ratner rectifying mechanism for DNA base pair sequencing through graphene nanogaps

We demonstrate that biological molecules such as Watson-Crick DNA base pairs can behave as biological Aviram-Ratner electrical rectifiers because of the spatial separation and weak hydrogen bonding between the nucleobases. We have performed a parallel computational implementation of the ab-initio non-equilibrium Green's function (NEGF) theory to determine the electrical response of graphene---base-pair---graphene junctions. The results show an asymmetric (rectifying) current-voltage response for the Cytosine-Guanine base pair adsorbed on a graphene nanogap. In sharp contrast we find a symmetric response for the Thymine-Adenine case. We propose applying the asymmetry of the current-voltage response as a sensing criterion to the technological challenge of rapid DNA sequencing via graphene nanogaps