Cerebrospinal fluid P-tau(181P):biomarker for improved differential dementia diagnosis

The goal of this study is to investigate the value of tau phosphorylated at threonine 181 (P-tau(181p)) in the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker panel for differential dementia diagnosis in autopsy confirmed AD and non-AD patients. The study population consisted of 140 autopsy confirmed AD and 77 autopsy confirmed non-AD dementia patients. CSF concentrations of amyloid-beta peptide of 42 amino acids (A(beta 1-42)), total tau protein (T-tau), and P-tau(181p) were determined with single analyte ELISA-kits (INNOTEST, Fujirebio, Ghent, Belgium). Diagnostic accuracy was assessed through receiver operating characteristic (ROC) curve analyses to obtain area under the curve (AUG) values and to define optimal cutoff values to discriminate AD from pooled and individual non-AD groups. ROC curve analyses were only performed on biomarkers and ratios that differed significantly between the groups. Pairwise comparison of AUG values was performed by means of DeLong tests. The A(beta 1-42)/P-tau(181p) ratio (AUG = 0.770) performed significantly better than A(beta 1-42) (AUG = 0.677, P = 0.004), T-tau (AUG = 0.592, P <0.001), and A beta(1-42)/T-tau (AUG = 0.678, P = 0.001), while Ptau(181p) (AUG = 0.720) performed significantly better than T-tau (AUG = 0.592, P <0.001) to discriminate between AD and the pooled non-AD group. When comparing AD and the individual non-AD diagnoses, A beta(1-42)/P-tau(181P) (AUG =0.894) discriminated AD from frontotemporal dementia significantly better than A(beta 1-42) (AUG = 0.776, P = 0.020) and T-tau (AUG = 0.746, P = 0.004), while P-tauisip/T-tau (AUG = 0.958) significantly improved the differentiation between AD and Creutzfeldt-Jakob disease as compared to A beta(1-42) (AUG = 0.688, P = 0.004), T-tau (AUG = 0.874, P = 0.040), and A beta(1-42)/P-tau(181P) (AUG = 0.760, P = 0.003). In conclusion, this study demonstrates P-tau(181P) P is an essential component of the AD CSF biomarker panel, and combined assessment of A beta(1-42), Ttau, and P-tau(181p) renders, to present date, the highest diagnostic power to discriminate between AD and non-AD dementias

High-Cardinality Hybrid Shaping for 4D Modulation Formats in Optical Communications Optimized via End-to-End Learning

In this paper we carry out a joint optimization of probabilistic (PS) and geometric shaping (GS) for four-dimensional (4D) modulation formats in long-haul coherent wavelength division multiplexed (WDM) optical fiber communications using an auto-encoder framework. We propose a 4D 10 bits/symbol constellation which we obtained via end-to-end deep learning over the split-step Fourier model of the fiber channel. The constellation achieved 13.6% reach increase at a data rate of approximately 400 Gbits/second in comparison to the ubiquitously employed polarization multiplexed 32-QAM format at a forward error correction overhead of 20%.Comment: 5 pages, 3 figure

Enumerative Sphere Shaping for Rate Adaptation and Reach Increase in WDM Transmission Systems

The performance of enumerative sphere shaping (ESS), constant composition distribution matching (CCDM), and uniform signalling are compared at the same forward error correction rate. ESS is shown to offer a reach increase of approximately 10% and 22% compared to CCDM and uniform signalling, respectively.Comment: 4 Pages, 4 figure

Revisiting Efficient Multi-Step Nonlinearity Compensation with Machine Learning: An Experimental Demonstration

Efficient nonlinearity compensation in fiber-optic communication systems is considered a key element to go beyond the "capacity crunch''. One guiding principle for previous work on the design of practical nonlinearity compensation schemes is that fewer steps lead to better systems. In this paper, we challenge this assumption and show how to carefully design multi-step approaches that provide better performance--complexity trade-offs than their few-step counterparts. We consider the recently proposed learned digital backpropagation (LDBP) approach, where the linear steps in the split-step method are re-interpreted as general linear functions, similar to the weight matrices in a deep neural network. Our main contribution lies in an experimental demonstration of this approach for a 25 Gbaud single-channel optical transmission system. It is shown how LDBP can be integrated into a coherent receiver DSP chain and successfully trained in the presence of various hardware impairments. Our results show that LDBP with limited complexity can achieve better performance than standard DBP by using very short, but jointly optimized, finite-impulse response filters in each step. This paper also provides an overview of recently proposed extensions of LDBP and we comment on potentially interesting avenues for future work.Comment: 10 pages, 5 figures. Author version of a paper published in the Journal of Lightwave Technology. OSA/IEEE copyright may appl

Real-time transmission of geometrically-shaped signals using a software-defined GPU-based optical receiver

A software-defined optical receiver is implemented on an off-the-shelf commercial graphics processing unit (GPU). The receiver provides real-time signal processing functionality to process 1 GBaud minimum phase (MP) 4-, 8-, 16-, 32-, 64-, 128-ary quadrature amplitude modulation (QAM) as well as geometrically shaped (GS) 8- and 128-QAM signals using Kramers-Kronig (KK) coherent detection. Experimental validation of this receiver over a 91 km field-deployed optical fiber link between two Tokyo locations is shown with detailed optical signal-to-noise ratio (OSNR) investigations. A net data rate of 5 Gbps using 64-QAM is demonstrated.</p

First Experimental Demonstration of Probabilistic Enumerative Sphere Shaping in Optical Fiber Communications

We transmit probabilistic enumerative sphere shaped dual-polarization 64-QAM at 350Gbit/s/channel over 1610km SSMF using a short blocklength of 200. A reach increase of 15% over constant composition distribution matching with identical blocklength is demonstrated

A universal fixation method based on quaternary ammonium salts (RNAlater) for omics-technologies: Saccharomyces cerevisiae as a case study

Abstract Genomics, transcriptomics, proteomics and fluxomics are powerful omics-technologies that play a major role in today&apos;s research. For each of these techniques good sample quality is crucial. Major factors contributing to the quality of a sample is the actual sampling procedure itself and the way the sample is stored directly after sampling. It has already been described that RNAlater can be used to store tissues and cells in a way that the RNA quality and quantity are preserved. In this paper, we demonstrate that quaternary ammonium salts (RNAlater) are also suitable to preserve and store samples from Saccharomyces cerevisiae for later use with the four major omics-technologies. Moreover, it is shown that RNAlater also preserves the cell morphology and the potential to recover growth, permitting microscopic analysis and yeast cell culturing at a later stage

MISpheroID: a knowledgebase and transparency tool for minimum information in spheroid identity

Spheroids are three-dimensional cellular models with widespread basic and translational application across academia and industry. However, methodological transparency and guidelines for spheroid research have not yet been established. The MISpheroID Consortium developed a crowdsourcing knowledgebase that assembles the experimental parameters of 3,058 published spheroid-related experiments. Interrogation of this knowledgebase identified heterogeneity in the methodological setup of spheroids. Empirical evaluation and interlaboratory validation of selected variations in spheroid methodology revealed diverse impacts on spheroid metrics. To facilitate interpretation, stimulate transparency and increase awareness, the Consortium defines the MISpheroID string, a minimum set of experimental parameters required to report spheroid research. Thus, MISpheroID combines a valuable resource and a tool for three-dimensional cellular models to mine experimental parameters and to improve reproducibility. © 2021, The Author(s)

The global dissemination of hospital clones of Enterococcus faecium.

BACKGROUND: The hospital-adapted A1 group of Enterococcus faecium remains an organism of significant concern in the context of drug-resistant hospital-associated infections. How this pathogen evolves and disseminates remains poorly understood. METHODS: A large, globally representative collection of short-read genomic data from the hospital-associated A1 group of Enterococcus faecium was assembled (n = 973). We analysed, using a novel analysis approach, global diversity in terms of both the dynamics of the accessory genome and homologous recombination among conserved genes. RESULTS: Two main modes of genomic evolution continue to shape E. faecium: the acquisition and loss of genes, including antimicrobial resistance genes, through mobile genetic elements including plasmids, and homologous recombination of the core genome. These events lead to new clones emerging at the local level, followed by the erosion of signals of clonality through recombination, and in some identifiable cases producing new clonal clusters. These patterns lead to new, emerging lineages which are able to spread globally over relatively short timeframes. CONCLUSIONS: The ability of A1 E. faecium to continually present new combinations of genes for potential selection suggests that controlling this pathogen will remain challenging but establishing a framework for understanding genomic evolution is likely to aid in tracking the threats posed by newly emerging lineages

Anthropogenic perturbation of the carbon fluxes from land to ocean

A substantial amount of the atmospheric carbon taken up on land through photosynthesis and chemical weathering is transported laterally along the aquatic continuum from upland terrestrial ecosystems to the ocean. So far, global carbon budget estimates have implicitly assumed that the transformation and lateral transport of carbon along this aquatic continuum has remained unchanged since pre-industrial times. A synthesis of published work reveals the magnitude of present-day lateral carbon fluxes from land to ocean, and the extent to which human activities have altered these fluxes. We show that anthropogenic perturbation may have increased the flux of carbon to inland waters by as much as 1.0 Pg C yr-1 since pre-industrial times, mainly owing to enhanced carbon export from soils. Most of this additional carbon input to upstream rivers is either emitted back to the atmosphere as carbon dioxide (~0.4 Pg C yr-1) or sequestered in sediments (~0.5 Pg C yr-1) along the continuum of freshwater bodies, estuaries and coastal waters, leaving only a perturbation carbon input of ~0.1 Pg C yr-1 to the open ocean. According to our analysis, terrestrial ecosystems store ~0.9 Pg C yr-1 at present, which is in agreement with results from forest inventories but significantly differs from the figure of 1.5 Pg C yr-1 previously estimated when ignoring changes in lateral carbon fluxes. We suggest that carbon fluxes along the land–ocean aquatic continuum need to be included in global carbon dioxide budgets.Peer reviewe