julilili42/papers huggingface dataset:
Critical assessment of relevant methods in the field of biosensors with direct optical detection based on fibers and waveguides using plasmonic, resonance, and interference effects
2020-04-20

Abstract Direct optical detection has proven to be a highly interesting tool in biomolecular interaction analysis to be used in drug discovery, ligand/receptor interactions, environmental analysis, clinical diagnostics, screening of large data volumes in immunology, cancer therapy, or personalized medicine. In this review, the fundamental optical principles and applications are reviewed. Devices are based on concepts such as refractometry, evanescent field, waveguides modes, reflectometry, resonance and/or interference. They are realized in ring resonators; prism couplers; surface plasmon resonance; resonant mirror; Bragg grating; grating couplers; photonic crystals, Mach-Zehnder, Young, Hartman interferometers; backscattering; ellipsometry; or reflectance interferometry. The physical theories of various optical principles have already been reviewed in detail elsewhere and are therefore only cited. This review provides an overall survey on the application of these methods in direct optical biosensing. The “historical” development of the main principles is given to understand the various, and sometimes only slightly modified variations published as “new” methods or the use of a new acronym and commercialization by different companies. Improvement of optics is only one way to increase the quality of biosensors. Additional essential aspects are the surface modification of transducers, immobilization strategies, selection of recognition elements, the influence of non-specific interaction, selectivity, and sensitivity. Furthermore, papers use for reporting minimal amounts of detectable analyte terms such as value of mass, moles, grams, or mol/L which are difficult to compare. Both these essential aspects (i.e., biochemistry and the presentation of LOD values) can be discussed only in brief (but references are provided) in order to prevent the paper from becoming too long. The review will concentrate on a comparison of the optical methods, their application, and the resulting bioanalytical quality.
Stochasticity in microbiology: managing unpredictability to reach the Sustainable Development Goals
2020-04-20

Summary Pure (single) cultures of microorganisms and mixed microbial communities (microbiomes) have been important for centuries in providing renewable energy, clean water and food products to human society and will continue to play a crucial role to pursue the Sustainable Development Goals. To use microorganisms effectively, microbial engineered processes require adequate control. Microbial communities are shaped by manageable deterministic processes, but also by stochastic processes, which can promote unforeseeable variations and adaptations. Here, we highlight the impact of stochasticity in single culture and microbiome engineering. First, we discuss the concepts and mechanisms of stochasticity in relation to microbial ecology of single cultures and microbiomes. Second, we discuss the consequences of stochasticity in relation to process performance and human health, which are reflected in key disadvantages and important opportunities. Third, we propose a suitable decision tool to deal with stochasticity in which monitoring of stochasticity and setting the boundaries of stochasticity by regulators are central aspects. Stochasticity may give rise to some risks, such as the presence of pathogens in microbiomes. We argue here that by taking the necessary precautions and through clever monitoring and interpretation, these risks can be mitigated.
Generating evidence for precision medicine: considerations made by the Ubiquitous Pharmacogenomics Consortium when designing and operationalizing the PREPARE study
2020-04-20

Objectives Pharmacogenetic panel-based testing represents a new model for precision medicine. A sufficiently powered prospective study assessing the (cost-)effectiveness of a panel-based pharmacogenomics approach to guide pharmacotherapy is lacking. Therefore, the Ubiquitous Pharmacogenomics Consortium initiated the PREemptive Pharmacogenomic testing for prevention of Adverse drug Reactions (PREPARE) study. Here, we provide an overview of considerations made to mitigate multiple methodological challenges that emerged during the design. Methods An evaluation of considerations made when designing the PREPARE study across six domains: study aims and design, primary endpoint definition and collection of adverse drug events, inclusion and exclusion criteria, target population, pharmacogenomics intervention strategy, and statistical analyses. Results Challenges and respective solutions included: (1) defining and operationalizing a composite primary endpoint enabling measurement of the anticipated effect, by including only severe, causal, and drug genotype-associated adverse drug reactions; (2) avoiding overrepresentation of frequently prescribed drugs within the patient sample while maintaining external validity, by capping drugs of enrolment; (3) designing the pharmacogenomics intervention strategy to be applicable across ethnicities and healthcare settings; and (4) designing a statistical analysis plan to avoid dilution of effect by initially excluding patients without a gene–drug interaction in a gatekeeping analysis. Conclusion Our design considerations will enable quantification of the collective clinical utility of a panel of pharmacogenomics-markers within one trial as a proof-of-concept for pharmacogenomics-guided pharmacotherapy across multiple actionable gene–drug interactions. These considerations may prove useful to other investigators aiming to generate evidence for precision medicine.
Evidence against a large effect of sleep in protecting verbal memories from interference
2020-04-20

Abstract The human brain has evolved to acquire novel information rapidly while serving the need to store long‐term memories in a stable and lasting form. Presenting interfering information directly after learning can lead to forgetting of the original material. It has been suggested that sleep aids the stabilization of new memories and protects them from interference. Here, we aim to replicate in two separate experiments the claim that sleep protects memories from retroactive interference ( Current Biology , 16, 2006 and 1290; PLoS ONE , 4, 2009 and e4117). We let participants study wordlists before letting them sleep for an afternoon nap or for a full night. In a control condition, subjects stayed awake for the same amount of time. After the consolidation interval, participants learnt an interfering wordlist and were tested on memory of the original wordlist. Sleep did not stabilize memory for the original wordlist in either study. We discuss our findings in the light of recent advances in computational neuroscience, and conclude that the stabilizing effect of sleep against interference has been overestimated.
The Notorious Difficulty of Comparing Human and Machine Perception
2020-04-20

With the rise of machines to human-level performance in complex tasks, a growing amount of work is directed towards comparing information processing in humans and machines. These works have the potential to deepen our understanding of the inner mechanisms of human perception and to improve machine learning. Drawing robust conclusions from comparison studies, however, turns out to be difficult. Here, we highlight common shortcomings that can easily lead to fragile conclusions. First, if a model does achieve high performance on a task similar to humans, its decision-making process is not necessarily human-like. Moreover, further analyses can reveal differences. Second, the performance of neural networks is sensitive to training procedures and architectural details. Thus, generalizing conclusions from specific architectures is difficult. Finally, when comparing humans and machines, equivalent experimental settings are crucial in order to identify innate differences. Addressing these shortcomings alters or refines the conclusions of studies. We show that, despite their ability to solve closed-contour tasks, our neural networks use different decision-making strategies than humans. We further show that there is no fundamental difference between same-different and spatial tasks for common feed-forward neural networks and finally, that neural networks do experience a recognition gap on minimal recognizable images. All in all, care has to be taken to not impose our human systematic bias when comparing human and machine perception.
Recurrent Episodes of Paraphilic Behavior Possibly Associated With Olanzapine and Aripiprazole Treatment in a Patient With Schizophrenia
2020-04-20

This case illustrates that hypersexuality may be a rare adverse effect of treatment with second-generation antipsychotics. Although aripiprazole is a drug with a well-established risk for hypersexuality, the question of whether a causal association between hypersexuality and olanzapine exists remains currently unresolved. As the currently limited amount of available evidence precludes any definitive conclusions, additional research is warranted to delineate the possible neurobiological substrates of hypersexual and paraphilic disorders in patients treated with second-generation antipsychotics.
Is there an association between social determinants and care dependency risk? A multi‐state model analysis of a longitudinal study
2020-04-20

Abstract Despite a growing body of knowledge about the morbidities and functional impairment that frequently lead to care dependency, the role of social determinants is not yet well understood. The purpose of this study was to examine the effect of social determinants on care dependency onset and progression. We used data from the Berlin Initiative Study, a prospective, population‐based cohort study including 2,069 older participants living in Berlin. Care dependency was defined as requiring substantial assistance in at least two activities of daily living for 90 min daily (level 1) or 3+ hours daily (level 2). Multi‐state time to event regression modeling was used to estimate the effects of social determinants (partnership status, education, income, and sex), morbidities, and health behaviors, characteristics, and conditions. During the study period, 556 participants (27.5%) changed their status of care dependency. Participants without a partner at baseline were at a higher risk to become care‐dependent than participants with a partner (hazard ratio [HR], 95% confidence interval [CI]: 1.24 (1.02–1.51)). After adjustment for other social determinants, morbidities and health behaviors, characteristics, and conditions the risk decreased to a HR of 1.19 (95% CI: 0.79–1.79). Results indicate that older people without a partner may tend to be at higher risk of care dependency onset but not at higher risk of care dependency progression. Clinicians should inquire about and consider patients’ partnership status as they evaluate care needs.
Linking land subsidence to soil types within Hue city in Central Vietnam
2020-04-20

Coastal areas of Southeast Asia are progressively threatened by flooding as a consequence of more frequent precipitation extremes and rising sea levels. Especially urban areas are affected by flood risk which is additionally increased by surface subsidence related to building activities and groundwater extraction. However, the severity of subsidence as well as its triggers and environmental interrelations are only little understood. This study measures surface subsidence for Hue city by using persistent scatterer radar interferometry (PS-InSAR). A series of 53 images acquired by the Sentinel-1 radar satellite between 2018 and 2019 was analyzed to reliably retrieve surface changes at the millimeter scale. The overall displacement ranges between -25 and +10 millimeters per year. Its spatial distribution was then compared to the extent of different soil types in the study area to conduct an analysis of variance (ANOVA). The results confirmed a significant difference between the soil types with Plinthic Acrisols as the soil type having the largest negative average surface velocity. Possible triggers are the intrusion of slack water from the surrounding rice cultivation areas and construction activities which lead to increasing weight and soil compaction. The findings shall raise awareness for the topic and underline the demand for further research. Mưa lớn và nước biển dâng là những nguyên nhân gây lũ lụt ngày càng nghiêm trọng ở các khu vực ven biển Đông Nam Á. Đặc biệt việc gia tăng công trình xây dựng và khai thác nước ngầm gây sụt lún bề mặt dẫn đến ngập lụt ở các vùng đô thị. Tuy nhiên, các nghiên cứu về mối tương quan giữa sụt lún bề mặt với các hiện tượng môi trường chưa được chú trọng nhiều. Trong nghiên cứu này, độ lún bề mặt của thành phố Hue được đo bằng phương pháp giao thoa radar tán xạ liên tục (PS-InSAR). Phân tích 53 ảnh vệ tinh Sentinel-1 từ năm 2018-2019 cho thấy sự thay đổi tổng thể bề mặt dao động từ -25mm đến 10mm mỗi năm. Phân tích phương sai (ANOVA) cho thấy sự thay đổi bề mặt khác nhau tùy từng loại đất, trong đó đất đỏ vàng (Plinthic Acrisols) có tốc độ sụt lún trung bình cao nhất. Các tác nhân có thể là do sự xâm nhập của nước từ các vùng trồng lúa xung quanh và các hoạt động xây dựng dẫn đến tăng trọng lượng và nén đất. Những phát hiện này là cơ hội nâng cao nhận thức về sự sụt lún bề mặt và cần được nghiên cứu thêm.
Psycho-computational modelling of the mental lexicon
2020-04-20

Over the last decades, a growing body of evidence on the mechanisms governing lexical storage, access, acquisition and processing has questioned traditional models of language architecture and word usage based on the hypothesis of a direct correspondence between modular components of grammar competence (lexicon vs. rules), processing correlates (memory vs. computation) and neuro-anatomical localizations (prefrontal vs. temporo-parietal perisylvian areas of the left hemisphere). In the present chapter, we explore the empirical and theoretical consequences of a distributed, integrative model of the mental lexicon, whereby words are seen as emergent properties of the functional interaction between basic, language-independent processing principles and the language- specific nature and organization of the input. From this perspective, language learning appears to be inextricably related to the way language is processed and internalized by the speakers, and key to an interdisciplinary understanding of such a way, in line with Tomaso Poggio’s suggestion that the development of a cognitive skill is causally and ontogenetically prior to its execution (and sits “on top of it”). In particular, we discuss conditions, potential and prospects of the epistemological continuity between psycholinguistic and computational modelling of word learning, and illustrate the yet largely untapped potential of their integration. We use David Marr’s hierarchy to clarify the complementarity of the two viewpoints. Psycholinguistic models are informative about how speakers learn to use language (interfacing Marr’s levels 1 and 2). When we move from the psycholinguistic analysis of the functional operations involved in language learning to an algorithmic description of how they are computed, computer simulations can help us explore the relation between speakers’ behavior and general learning principles in more detail. In the end, psycho-computational models can be instrumental to bridge Marr’s levels 2 and 3, bringing us closer to understanding the nature of word knowledge in the brain.
Pentavalent Sialic Acid Conjugates Block Coxsackievirus A24 Variant and Human Adenovirus Type 37 – Viruses That Cause Highly Contagious Eye Infections
2020-04-20

Coxsackievirus A24 variant (CVA24v) and human adenovirus 37 (HAdV-37) are leading causative agents of the severe and highly contagious ocular infections acute hemorrhagic conjunctivitis and epidemic keratoconjunctivitis, respectively. Currently, neither vaccines nor antiviral agents are available for treating these diseases, which affect millions of individuals worldwide. CVA24v and HAdV-37 utilize sialic acid as attachment receptors facilitating entry into host cells. Previously, we and others have shown that derivatives based on sialic acid are effective in preventing HAdV-37 binding and infection of cells. Here, we designed and synthesized novel pentavalent sialic acid conjugates and studied their inhibitory effect against CVA24v and HAdV-37 binding and infection of human corneal epithelial cells. The pentavalent conjugates are the first reported inhibitors of CVA24v infection, and proved efficient in blocking HAdV-37 binding. Taken together, the pentavalent conjugates presented here form a basis for the development of general inhibitors of these highly contagious ocular pathogens.
Reprogramming acetogenic bacteria with CRISPR-targeted base editingviadeamination
2020-04-20

Abstract Acetogenic bacteria are rising in popularity as chassis microbes in biotechnology due to their capability of converting inorganic one-carbon (C1) gases to organic chemicals. To fully uncover the potential of acetogenic bacteria, synthetic-biology tools are imperative to either engineer designed functions or to interrogate the physiology. Here, we report a genome-editing tool at a one-nucleotide resolution, namely base editing, for acetogenic bacteria based on CRISPR-targeted deamination. This tool combines nuclease deactivated Cas9 with activation-induced cytidine deaminase to enable cytosine-to-thymine substitution without DNA cleavage, homology-directed repair, and donor DNA, which are generally the bottlenecks for applying conventional CRISPR-Cas systems in bacteria. We designed and validated a modularized base-editing tool in the model acetogenic bacterium Clostridium ljungdahlii . The editing principles were investigated, and an in-silico analysis revealed the capability of base editing across the genome. Moreover, genes related to acetate and ethanol production were disrupted individually by installing premature STOP codons to reprogram carbon flux towards improved acetate production. This resulted in engineered C. ljungdahlii strains with the desired phenotypes and stable genotypes. Our base-editing tool promotes the application and research in acetogenic bacteria and provides a blueprint to upgrade CRISPR-Cas-based genome editing in bacteria in general. Significance Acetogenic bacteria metabolize one-carbon (C1) gases, such as industrial waste gases, to produce fuels and commodity chemicals. However, the lack of efficient gene-manipulation approaches hampers faster progress in the application of acetogenic bacteria in biotechnology. We developed a CRISPR-targeted base-editing tool at a one-nucleotide resolution for acetogenic bacteria. Our tool illustrates great potential in engineering other A-T-rich bacteria and links designed single-nucleotide variations with biotechnology. It provides unique advantages for engineering industrially relevant bacteria without creating genetically modified organisms (GMOs) under the legislation of many countries. This base-editing tool provides an example for adapting CRISPR-Cas systems in bacteria, especially those that are highly sensitive to heterologously expressed Cas proteins and have limited ability of receiving foreign DNA.
Fingolimod alters intrathecal B cell maturation in multiple sclerosis patients
2020-04-20

Abstract Background : B cells are postulated to play multiple roles in the pathogenesis of multiple sclerosis (MS) including pathogenic antibody production, antigen-presentation and pro-inflammatory cytokine secretion. Natalizumab and fingolimod are effective MS therapies that disrupt lymphocyte migration but exert differential effects on B cell maturation and trafficking. Herein, we investigated their effects on peripheral blood and cerebrospinal fluid (CSF) B cell repertoires. Methods : Paired CSF and peripheral blood (PB) lymphocytes were collected from MS patients at baseline and after 6 months of treatment with fingolimod (n = 4) or natalizumab (n = 4). B cell subsets including naïve, CD27+ memory, CD27-IgD- double-negative B cells and plasmablasts were collected by FACS and their respective heavy-chain variable region (VH) repertoires assessed by next generation deep sequencing (Illumina MiSeq). Results : Treatment with fingolimod lead to a distinct contraction of the PB B cell pool whereas natalizumab resulted in an expansion of circulating PB B cells. In contrast, CSF B cell numbers remained stable under treatment with fingolimod but decreased following natalizumab therapy. Clonal overlap between CSF and peripheral blood B cells was reduced following natalizumab treatment (-24% reduction of clonal groups) but remained stable with fingolimod therapy. Lineage analyses of CSF B cell repertoires at baseline and following therapy revealed large, clonally expanded B cell clusters in natalizumab-treated MS patients but no intrathecal clonal expansion following fingolimod therapy. Conclusions : Our findings suggest that natalizumab treatment diminishes the exchange of peripheral and intrathecal B cells but does not impact intrathecal clonal expansion. In contrast, fingolimod treatment fails to alter B cell exchange across the blood-brain-barrier but affects intrathecal clonal expansion. Sphingosine-1 phosphate receptor inhibition may impact MS disease progression by inhibiting intrathecal germinal center activity .
Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson's disease
2020-04-20

Neuroinflammation is one of the hallmarks of Parkinson's disease (PD) and may contribute to midbrain dopamine (DA) neuron degeneration. Recent studies link chronic inflammation with failure to resolve early inflammation, a process operated by specialized pro-resolving mediators, including resolvins. However, the effects of stimulating the resolution of inflammation in PD - to modulate disease progression - still remain unexplored. Here we show that rats overexpressing human α-synuclein (Syn) display altered DA neuron properties, reduced striatal DA outflow and motor deficits prior to nigral degeneration. These early alterations are coupled with microglia activation and perturbations of inflammatory and pro-resolving mediators, namely IFN-γ and resolvin D1 (RvD1). Chronic and early RvD1 administration in Syn rats prevents central and peripheral inflammation, as well as neuronal dysfunction and motor deficits. We also show that endogenous RvD1 is decreased in human patients with early-PD. Our results suggest there is an imbalance between neuroinflammatory and pro-resolving processes in PD.
Data for "A systematic evaluation of interneuron morphology representations for cell type discrimination"
2020-04-20

data_v1.1 contains all the data to reproduce the figures of the publication <em>A systematic evaluation of interneuron morphology representations for cell type discrimination (</em>https://doi.org/10.1101/591370<em>).</em> statistic_descriptions.csv : links each feature's statistic_id with a short description classification: This folder holds the multi-class and the pairwise classification performances of all feature representations (relevant for figure 4 and figure 5). It also holds the pickled multi-class models trained on morphometric statistics which coefficients are visualized in figure S5. embedding_data: This folder holds all the data used for the t-SNE visualizations of figure 8 and S4. features: This folder holds all computed feature representations of each data set and each modality (full, axon, dendrite). Features are indexed by a statistic id. Some example features are shown in figure 2. Careful, this folder is large (~6GB)! reconstructions: This folder contains all the neural reconstructions used for figure 1. final morphologies: contains all pre-processed reconstructions used in this study.