H2A.Z deposition by SWR1C involves multiple ATP-dependent steps

The histone variant H2A.Z is a conserved feature of nucleosomes flanking protein-coding genes. Deposition of H2A.Z requires ATP-dependent replacement of nucleosomal H2A by a chromatin remodeler related to the multi-subunit enzyme, yeast SWR1C. How these enzymes use ATP to promote this nucleosome editing reaction remains unclear. Here we use single-molecule and ensemble methodologies to identify three ATP-dependent phases in the H2A.Z deposition reaction. Real-time analysis of single nucleosome remodeling events reveals an initial, priming step that occurs after ATP addition that likely involves transient DNA unwrapping from the nucleosome. Priming is followed by rapid loss of histone H2A, which is subsequently released from the H2A.Z nucleosomal product. Surprisingly, the rates of both priming and the release of the H2A/H2B dimer are sensitive to ATP concentration. This complex reaction pathway provides multiple opportunities to regulate the timely and accurate deposition of H2A.Z at key genomic locations.

Visualization of Speech Perception Analysis via Phoneme Alignment: A Pilot Study

Objective: Speech tests assess the ability of people with hearing loss to comprehend speech with a hearing aid or cochlear implant. The tests are usually at the word or sentence level. However, few tests analyze errors at the phoneme level. So, there is a need for an automated program to visualize in real time the accuracy of phonemes in these tests.Method: The program reads in stimulus-response pairs and obtains their phonemic representations from an open-source digital pronouncing dictionary. The stimulus phonemes are aligned with the response phonemes via a modification of the Levenshtein Minimum Edit Distance algorithm. Alignment is achieved via dynamic programming with modified costs based on phonological features for insertion, deletions and substitutions. The accuracy for each phoneme is based on the F1-score. Accuracy is visualized with respect to place and manner (consonants) or height (vowels). Confusion matrices for the phonemes are used in an information transfer analysis of ten phonological features. A histogram of the information transfer for the features over a frequency-like range is presented as a phonemegram.Results: The program was applied to two datasets. One consisted of test data at the sentence and word levels. Stimulus-response sentence pairs from six volunteers with different degrees of hearing loss and modes of amplification were analyzed. Four volunteers listened to sentences from a mobile auditory training app while two listened to sentences from a clinical speech test. Stimulus-response word pairs from three lists were also analyzed. The other dataset consisted of published stimulus-response pairs from experiments of 31 participants with cochlear implants listening to 400 Basic English Lexicon sentences via different talkers at four different SNR levels. In all cases, visualization was obtained in real time. Analysis of 12,400 actual and random pairs showed that the program was robust to the nature of the pairs.Conclusion: It is possible to automate the alignment of phonemes extracted from stimulus-response pairs from speech tests in real time. The alignment then makes it possible to visualize the accuracy of responses via phonological features in two ways. Such visualization of phoneme alignment and accuracy could aid clinicians and scientists.

Breaking up the play: The relationship between legal stops and winning in team handball

The purpose of this study was to examine the relationship between legal stops and winning in team handball. Real-time analysis was performed on all games played in the Icelandic elite division for both males and females (regular season and playoffs) between 2017–2021 (854 games [570 male games, 284 female games], 32,392 legal stops in total). Legal stops were assessed as any physical action by a defensive player that resulted in the stop of play, without the defensive player being penalized or the offensive player receiving a 7-meter throw. The results from a multinomial logistic regression analysis indicated that legal stops were significantly associated with winning games in the male league. No statistically significant relationship was found between illegal stops and game outcome for either sex. However, 2-minute suspensions were found to be positively associated with winning in the male league.

Real Time SPR Assessment of the Structural Changes of Adaptive Dynamic Constitutional Frameworks as a New Route for Sensing

Cross linked gold-dynamic constitutional frameworks (DCFs) are functional materials of potential relevance for biosensing applications, given their adaptivity and high responsivity against various external stimuli (such as pH, temperature) or specific interactions with biomolecules (enzymes or DNA) via internal constitutional dynamics. However, characterization and assessment of their dynamic conformational changes in response to external stimuli has never been reported. This study proves the capability of Surface Plasmon Resonance (SPR) assays to analyse the adaptive structural modulation of a functional matrix encompassing 3D gold-dynamic constitutional frameworks (Au-DCFs) when exposed to pH variations, as external stimuli. We analyse Au-DCFs formed from Au nanoparticles, (AuNP) connected through constitutionally dynamic polymers, dynamers, with multiple functionalities. For increased generality of this proof-of-concept assay, Au-DCFs, involving DCFs designed from 1,3,5-benzene-tricarbaldehyde (BTA) connecting centres and polyethylene glycol (PEG) connectors, are covalently attached to standard SPR sensing chips (Au nanolayers, carboxyl terminated or with carboxymethyl dextran, CMD top-layer) and analysed using state-of-the art SPR instrumentation. The SPR effects of the distance from the Au-DCFs matrix to the Au nanolayer of the sensing chip, as well as of Au-DCFs thickness were investigated. This study reveals the SPR response, augmented by the AuNP, to the conformational change, i.e., shrinkage, of the dynamer and AuNP matrix when decreasing the pH, and provides an unexplored insight into the sensing applicability of SPR real-time analysis of adaptive functional materials.

Remote Patient Monitoring for Healthcare

Remote patient monitoring involves the collection of data from wearable sensors that typically requires analysis in real time. The real-time analysis of data streaming continuously to a server challenges data mining algorithms that have mostly been developed for static data residing in central repositories. Remote patient monitoring also generates huge data sets that present storage and management problems. Although virtual records of every health event throughout an individual's lifespan known as the electronic health record are rapidly emerging, few electronic records accommodate data from continuous remote patient monitoring. These factors combine to make data analytics with continuous patient data very challenging. In this chapter, benefits for data analytics inherent in the use of standards for clinical concepts for remote patient monitoring is presented. The openEHR standard that describes the way in which concepts are used in clinical practice is well suited to be adopted as the standard required to record meta-data about remote monitoring. The claim is advanced that this is likely to facilitate meaningful real time analyses with big remote patient monitoring data. The point is made by drawing on a case study involving the transmission of patient vital sign data collected from wearable sensors in an Indian hospital.

Human-Computer Interaction With Big Data Analytics

Big Data has been playing a vital role in almost all environments such as healthcare, education, business organizations and scientific research. Big data analytics requires advanced tools and techniques to store, process and analyze the huge volume of data. Big data consists of huge unstructured data that require advance real-time analysis. Thus, nowadays many of the researchers are interested in developing advance technologies and algorithms to solve the issues when dealing with big data. Big Data has gained much attention from many private organizations, public sector and research institutes. This chapter provides an overview of the state-of-the-art algorithms for processing big data, as well as the characteristics, applications, opportunities and challenges of big data systems. This chapter also presents the challenges and issues in human computer interaction with big data analytics.