Asymptotics of Bayesian Uncertainty Estimation in Random Features Regression

In this paper we compare and contrast the behavior of the posterior predictive distribution to the risk of the maximum a posteriori estimator for the random features regression model in the overparameterized regime. We will focus on the variance of the posterior predictive distribution (Bayesian model average) and compare its asymptotics to that of the risk of the MAP estimator. In the regime where the model dimensions grow faster than any constant multiple of the number of samples, asymptotic agreement between these two quantities is governed by the phase transition in the signal-to-noise ratio. They also asymptotically agree with each other when the number of samples grow faster than any constant multiple of model dimensions. Numerical simulations illustrate finer distributional properties of the two quantities for finite dimensions. We conjecture they have Gaussian fluctuations and exhibit similar properties as found by previous authors in a Gaussian sequence model, which is of independent theoretical interest.Comment: 11 pages, 3 figure

Estimating the Performance of Entity Resolution Algorithms: Lessons Learned Through PatentsView.org

This paper introduces a novel evaluation methodology for entity resolution algorithms. It is motivated by PatentsView.org, a U.S. Patents and Trademarks Office patent data exploration tool that disambiguates patent inventors using an entity resolution algorithm. We provide a data collection methodology and tailored performance estimators that account for sampling biases. Our approach is simple, practical and principled -- key characteristics that allow us to paint the first representative picture of PatentsView's disambiguation performance. This approach is used to inform PatentsView's users of the reliability of the data and to allow the comparison of competing disambiguation algorithms.Comment: 19 pages, 4 figure

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Nec‐1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice

Abstract Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive symptoms of learning and memory deficits. Such cognitive impairments are attributed to brain atrophy resulting from progressive neuronal and synaptic loss; therefore, alleviation of neural cell death is as an important target of treatment as other classical hallmarks of AD, such as aggregation of amyloid‐β (Aβ) and hyperphosphorylation of tau. Here, we found that an anti‐necroptotic molecule necrostatin‐1 (Nec‐1) directly targets Aβ and tau proteins, alleviates brain cell death and ameliorates cognitive impairment in AD models. In the cortex and hippocampus of APP/PS1 double‐transgenic mice, Nec‐1 treatment reduced the levels of Aβ oligomers, plaques and hyperphosphorylated tau without affecting production of Aβ, while it altered the levels of apoptotic marker proteins. Our results showing multiple beneficial modes of action of Nec‐1 against AD provide evidence that Nec‐1 may serve an important role in the development of preventive approach for AD

A microphysiological system-based potency bioassay for the functional quality assessment of mesenchymal stromal cells targeting vasculogenesis

Mesenchymal stromal cells (MSCs) continue to be proposed for use in clinical trials to treat various diseases due to their therapeutic potential to pleiotropically influence endogenous regenerative processes, such as vasculo-genesis. However, the functional heterogeneity of MSCs has hampered their clinical success and poses a sig-nificant manufacturing challenge with respect to MSC quality control. Here, we evaluated and qualified a quantitative bioassay based on an enhanced-throughput, microphysiological system to measure the specific paracrine bioactivity of MSCs to stimulate vasculogenesis as a measure of MSC potency. Using this novel bioassay, MSCs derived from multiple donors at different passages were co-cultured with human umbilical vein endothelial cells (HUVECs) and exhibited significant heterogeneity in vasculogenic potency between donors and cell passage. Using our microphysiological system (MPS)-based platform, we demonstrated that variations in MSC vasculogenic bioactivity were maintained when assayed across laboratories and operators. The differences in MSC vasculogenic bioactivity were also correlated with the baseline expression of several genes involved in vasculogenesis (hepatocyte growth factor (HGF), angiopoietin-1 (ANGPT)) or the production of matricellular proteins (fibronectin (FN), insulin-like growth factor-binding protein 7 (IGFBP7)). These findings emphasize the significant functional heterogeneity of MSCs in vasculogenic bioactivity and suggest that changes in baseline gene expression of vasculogenic or matricellular protein genes during manufacturing may affect this bioactivity. The development of a reliable and functionally relevant potency assay for measuring the specific vasculogenic bioactivity of manufactured MSCs will help to reliably assure their quality when used in appropriate clinical trials.Y

Longitudinal profiling of oligomeric A beta in human nasal discharge reflecting cognitive decline in probable Alzheimer's disease

Despite clinical evidence indicating a close relationship between olfactory dysfunction and Alzheimer’s disease (AD), further investigations are warranted to determine the diagnostic potential of nasal surrogate biomarkers for AD. In this study, we first identified soluble amyloid-β (Aβ), the key biomarker of AD, in patient nasal discharge using proteomic analysis. Then, we profiled the significant differences in Aβ oligomers level between patient groups with mild or moderate cognitive decline (n = 39) and an age-matched normal control group (n = 21) by immunoblot analysis and comparing the levels of Aβ by a self-standard method with interdigitated microelectrode sensor systems. All subjects received the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and the Global Deterioration Scale (GDS) for grouping. We observed higher levels of Aβ oligomers in probable AD subjects with lower MMSE, higher CDR, and higher GDS compared to the normal control group. Moreover, mild and moderate subject groups could be distinguished based on the increased composition of two oligomers, 12-mer Aβ*56 and 15-mer AβO, respectively. The longitudinal cohort study confirmed that the cognitive decline of mild AD patients with high nasal discharge Aβ*56 levels advanced to the moderate stage within three years. Our clinical evidence strongly supports the view that the presence of oligomeric Aβ proteins in nasal discharge is a potential surrogate biomarker of AD and an indicator of cognitive decline progression. © 2020, The Author(s).1

Upcycling of plastic waste into carbon nanotubes as efficient battery additives

Carbon nanotubes (CNTs) were produced from waste face masks and non-recyclable mixed plastic waste via pyrolysis-chemical vapor deposition (CVD). The yield and properties of the prepared CNTs depended on the feedstock and catalyst used. CoMo/MgO and FeMo/MgO were proven suitable catalysts for producing few-walled and multi-walled CNTs, respectively, regardless of the feedstock. Both mask waste and the FeMo/MgO catalyst led to excellent carbon yield (516.7 wt%) and CNT purity (97.9 wt%). The resulting CNTs were mixed with LiNi0.8Co0.1Mn0.1O2 (NCM811) active material and poly(vinylidene fluoride) binder to fabricate cathodes. Electrochemical measurements showed that CNTs grown on the FeMo/MgO catalyst outperformed commercial carbon black and CNTs. C1-C3 hydrocarbons and H2 present in the plastic pyrolysis gas can be directly used for CNT production without gas separation or purification, therefore, the proposed pyrolysis-CVD process is favorable for efficient plastic upcycling and advanced battery applications. Carbon nanotubes (CNTs) were produced from waste face mask and non-recyclable mixed plastic waste via pyrolysis-chemical vapor deposition (CVD)

Nec‐1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive symptoms of learning and memory deficits. Such cognitive impairments are attributed to brain atrophy resulting from progressive neuronal and synaptic loss; therefore, alleviation of neural cell death is as an important target of treatment as other classical hallmarks of AD, such as aggregation of amyloid‐β (Aβ) and hyperphosphorylation of tau. Here, we found that an anti‐necroptotic molecule necrostatin‐1 (Nec‐1) directly targets Aβ and tau proteins, alleviates brain cell death and ameliorates cognitive impairment in AD models. In the cortex and hippocampus of APP/PS1 double‐transgenic mice, Nec‐1 treatment reduced the levels of Aβ oligomers, plaques and hyperphosphorylated tau without affecting production of Aβ, while it altered the levels of apoptotic marker proteins. Our results showing multiple beneficial modes of action of Nec‐1 against AD provide evidence that Nec‐1 may serve an important role in the development of preventive approach for AD