How Can Subsampling Reduce Complexity in Sequential MCMC Methods and Deal with Big Data in Target Tracking?

Target tracking faces the challenge in coping with large volumes of data which requires efficient methods for real time applications. The complexity considered in this paper is when there is a large number of measurements which are required to be processed at each time step. Sequential Markov chain Monte Carlo (MCMC) has been shown to be a promising approach to target tracking in complex environments, especially when dealing with clutter. However, a large number of measurements usually results in large processing requirements. This paper goes beyond the current state-of-the-art and presents a novel Sequential MCMC approach that can overcome this challenge through adaptively subsampling the set of measurements. Instead of using the whole large volume of available data, the proposed algorithm performs a trade off between the number of measurements to be used and the desired accuracy of the estimates to be obtained in the presence of clutter. We show results with large improvements in processing time, more than 40 % with a negligible loss in tracking performance, compared with the solution without subsampling

A hollow-core fiber based stand-alone multimodal (2-photon, 3-photon, SHG, THG) nonlinear flexible imaging endoscope

Multimodal nonlinear endoscopes have been a topic of intense research over the past two decades, enabling sub-cellular and label-free imaging in areas not reachable with table-top microscopes. They are sophisticated systems that can be implemented on an optical table in a lab environment, but they cannot be easily moved within or out of the lab. We present here a multimodal and flexible nonlinear endoscope system able to perform two photon excited fluorescence and second harmonic generation imaging with a stand-alone and moveable kart integrating a compact ultrashort laser source. In addition, the system can perform three photon excited fluorescence and third harmonic generation thanks to a delivery optical fiber used to deliver ultrashort pulses from massive and not movable laser systems into the stand-alone kart. The endoscopic fiber probes and delivery optical fibers are based on functionalized negative curvature hollow core fibers. The endoscope distal head has a diameter <2.2mm and can perform nonlinear imaging at max 10 frames/s over a field of view up to 600 $\mu$m with a ~1 $\mu$m spatial resolution

Oral processing and oral comfort appreciation of whey-enriched dairy products by older adults

Consuming proteins rich in leucine, such as whey, has documented benefits for muscle health in older adults. The objective of this study was to evaluate the sensory suitability for this population of whey protein-enriched dairy products prototypes, resembling respectively a yoghurt and a cream cheese. Prototypes and in vitro boli were characterized instrumentally (rheology and tribology) and in vivo data on oral processing (microscopical characterization of expectorated boli) and oral comfort (sensory questionnaire) were acquired on a panel of 80 older adults. The rheological properties of both prototypes were comparable to those of some commercial yoghurt and cream cheese. Based on tribological measurements and compared to the yoghurt prototype, the cheese prototype showed higher lubrication properties, which even increased in presence of model saliva. The in vitro boli of cheese were also characterized by a shift in size of small particles, presumably free fat globules, into bigger particles. Microscopical observations of boli produced in vivo confirmed that larger fat droplets were formed by coalescence during food oral processing of the cheese prototype. In-mouth time residency and insalivation rates suggested that both prototypes required very little oral manipulation before swallowing. The sensory attributes sticky, pasty and melting were those contributing most to the oral comfort, but both prototypes were judged as very comfortable to eat independently of the dental status and salivary flow of the subjects. To conclude, these whey-enriched dairy products would be suitable as part of a diet aiming at optimizing protein intake in older adults

Short-term effects of amelogenin gene splice products A+4 and A-4 implanted in the exposed rat molar pulp

In order to study the short-time effects of two bioactive low-molecular amelogenins A+4 and A-4, half-moon cavities were prepared in the mesial aspect of the first maxillary molars, and after pulp exposure, agarose beads alone (controls) or beads soaked in A+4 or A-4 (experimental) were implanted into the pulp. After 1, 3 or 7 days, the rats were killed and the teeth studied by immunohistochemistry. Cell proliferation was studied by PCNA labeling, positive at 3 days, but decreasing at day 7 for A+4, whilst constantly high between 3 and 7 days for A-4. The differentiation toward the osteo/odontoblast lineage shown by RP59 labeling was more apparent for A-4 compared with A+4. Osteopontin-positive cells were alike at days 3 and 7 for A-4. In contrast, for A+4, the weak labeling detected at day 3 became stronger at day 7. Dentin sialoprotein (DSP), an in vivo odontoblast marker, was not detectable until day 7 where a few cells became DSP positive after A-4 stimulation, but not for A+4. These results suggest that A +/- 4 promote the proliferation of some pulp cells. Some of them further differentiate into osteoblast-like progenitors, the effects being more precocious for A-4 (day 3) compared with A+4 (day 7). The present data suggest that A +/- 4 promote early recruitment of osteogenic progenitors, and evidence functional differences between A+4 and A-4

Whole blood methylome-derived features to discriminate endocrine hypertension

Background: Arterial hypertension represents a worldwide health burden and a major risk factor for cardiovascular morbidity and mortality. Hypertension can be primary (primary hypertension, PHT), or secondary to endocrine disorders (endocrine hypertension, EHT), such as Cushing's syndrome (CS), primary aldosteronism (PA), and pheochromocytoma/paraganglioma (PPGL). Diagnosis of EHT is currently based on hormone assays. Efficient detection remains challenging, but is crucial to properly orientate patients for diagnostic confirmation and specific treatment. More accurate biomarkers would help in the diagnostic pathway. We hypothesized that each type of endocrine hypertension could be associated with a specific blood DNA methylation signature, which could be used for disease discrimination. To identify such markers, we aimed at exploring the methylome profiles in a cohort of 255 patients with hypertension, either PHT (n = 42) or EHT (n = 213), and at identifying specific discriminating signatures using machine learning approaches. Results: Unsupervised classification of samples showed discrimination of PHT from EHT. CS patients clustered separately from all other patients, whereas PA and PPGL showed an overall overlap. Global methylation was decreased in the CS group compared to PHT. Supervised comparison with PHT identified differentially methylated CpG sites for each type of endocrine hypertension, showing a diffuse genomic location. Among the most differentially methylated genes, FKBP5 was identified in the CS group. Using four different machine learning methods—Lasso (Least Absolute Shrinkage and Selection Operator), Logistic Regression, Random Forest, and Support Vector Machine—predictive models for each type of endocrine hypertension were built on training cohorts (80% of samples for each hypertension type) and estimated on validation cohorts (20% of samples for each hypertension type). Balanced accuracies ranged from 0.55 to 0.74 for predicting EHT, 0.85 to 0.95 for predicting CS, 0.66 to 0.88 for predicting PA, and 0.70 to 0.83 for predicting PPGL. Conclusions: The blood DNA methylome can discriminate endocrine hypertension, with methylation signatures for each type of endocrine disorder

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

Introduction: There is conflicting evidence whether high-density lipoprotein cholesterol (HDL-C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered HDL-C. We aimed to assess AD risk by genetically predicted HDL-C. Methods: Ten single nucleotide polymorphisms within the CETP locus predicting HDL-C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR-Egger. Results: Based on 10 single nucleotide polymorphisms distinctly predicting HDL-C in the CETP locus, we found that HDL-C was not associated with risk of AD (P > .7). Discussion: Our study does not support the role of HDL-C on risk of AD through HDL-C altered by CETP. This study does not rule out other mechanisms by which HDL-C affects risk of AD