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Jennifer K Parker,1 Richard Gu,1 Gregory A Estrera,1 Betsy Kirkpatrick,2 Dusten T Rose,3 Despoina AI Mavridou,1,4 Kristin E Mondy,5 Bryan W Davies1,4 1Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA; 2Austin Public Health, City of Austin, Austin, TX, USA; 3Department of Pharmacy, Ascension Seton, Dell Seton Medical Center at The University of Texas, Austin, TX, USA; 4John Ring LaMontagne Center for Infectious Diseases, The University of Texas at Austin, Austin, TX, USA; 5Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, Austin, TX, USACorrespondence: Bryan W Davies, Email bwdavies@utexas.eduPurpose: Carbapenem-resistant Enterobacterales (CRE) are subject to intense global monitoring in an attempt to maintain awareness of prevalent and emerging resistance mechanisms and to inform treatment and infection prevention strategies. CRE and extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales are not usually examined collectively in regards to their shared pool of resistance determinants. Here, we genetically and phenotypically assess clinical isolates of CRE and extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales in the growing region of Central Texas, where CRE are emergent and occurrence of non-carbapenemase-producing-CRE (non-CP-CRE) infections is increasing.Methods: CRE (n=16) and ESBL-producing Enterobacterales (n=116) isolates were acquired from a regional hospital in Central Texas between December 2018 and January 2020. Isolates were assessed genetically and phenotypically using antibiotic susceptibility testing, targeted PCR, and whole genome sequencing.Results: CRE infections are increasing in incidence in Central Texas, and Klebsiella pneumoniae is causing the majority of these infections. Moreover, K. pneumoniae sequence type (ST) 307 is commonly found among both non-CP-CRE and EBSL-producing strains. Isolates carry similar plasmids harboring the gene for the ESBL CTX-M-15 and belong to the global lineage, rather than the Texas lineage, of ST307. Antibiotic resistance profiles, sequence data, and clinical records suggest that porin mutations may promote the transition of ST307 isolates from ESBL-producing to non-CP-CRE. In addition to antibiotic resistance mechanisms, several CRE isolates harbor active colicinogenic plasmids, which might influence the competitiveness of these bacteria during patient colonization.Conclusion: K. pneumoniae of the global ST307 lineage is circulating in Central Texas and is responsible for both non-CP CRE and ESBL-producing Enterobacterales infections. Enhanced surveillance is needed to understand the possible routes for the emergence of non-CP-CRE from EBSL-producing strains.Keywords: beta-lactam, Klebsiella, colicin, genetics, carbapenemase

This paper investigates the second language (L2) acquisition of the Turkish category Ad tamlaması (AT). AT consists an umbrella term which is encountered in Turkish grammars and L2-Turkish coursebooks to refer to three forms of Nominal Syntagmatic Sets (NSS), namely a) N-(n)In N-(s)I(n), b) N N-(s)I(n) and c) N N-(y) . This paper is trying to examine whether the apparently formal similarity of these 3 Nominal Syntagmatic Sets Ad Tamlaması (NSS-AT) in Turkish can be correlated with a respective degree of ease in L2 acquisition and simultaneity in L2 teaching or not. The main aim of this paper is to delineate the differences of these three NSS forms by testing them upon 12 morpho-syntactic criteria. The test results will show how much syntactically analytic and semantically transparent each of these sets is. We will conclude that the formal differentiation of the 3 NSS types does not always correspond with functional- semantic differentiation, which has implications on the difficulties these forms create in L2-learners. We will show that in the L2 learning process of the 3 NSS-AT forms, we expect a learning step ahead in the analytic N-(n)In N-(s)I(n) form compared to non-analytic compounds such as the N N-(s)I(n) form and more blurred cases such as the N N-(y) form, which shares properties of both Noun Phrases (NPs) and compounds. From a didactic scope, we come to assume that the traditional interconnection of the three NSS-Ad Tamlaması forms in Turkish L2-teaching and L2-learning methods should be put aside and rather give its place in alternative more anti-holistic approaches which would uncover the hidden syntactic properties of the 3 forms rather than stress the similarities between them.

The third harmonic generation (THG) of graphite layers on paper substrate upon excitation with intense (up to 100 kV cm(-1)) narrowband terahertz (THz) pulses is studied. Highest THG efficiencies are comparable with those of chemical vapor deposition-grown single-layer graphene. Samples are hand drawn, using commercially available pencils. The THG response shows high sensitivity regarding the hatching direction relative to the THz polarization orientation. Using Raman spectroscopy, the occurrence of graphene-like structures in the samples is confirmed. The findings demonstrate the feasibility of virtually no-cost and easy-to-fabricate materials for THz nonlinear optics.

This article introduces the Emteq’s OCOsense™ smart glasses equipped with a novel non-contact OCO™ sensor technology for measuring facial muscle activation and expressions based on high resolution tracking of skin movement. We demonstrate that the OCO™ sensor technology based on optomyography is a sensitive and accurate approach for assessing skin movement in 3 dimensions, providing a means for measuring the facial expressions used to assess emotional valence such as smile, frown, and eyebrow raise. We propose that glasses-based optomyography sensing has the potential to herald a paradigm shift in real-world facial expression monitoring, thus enabling real-time emotional analytics with healthcare and research applications.

Mitochondrial ADP/ATP carriers import ADP into the mitochondrial matrix and export ATP to the cytosol to fuel cellular processes. Structures of the inhibited cytoplasmic- and matrix-open states have confirmed an alternating access transport mechanism, but the molecular details of substrate binding remain unresolved. Here, we evaluate the role of the solvent-exposed residues of the translocation pathway in the process of substrate binding. We identify the main binding site, comprising three positively charged and a set of aliphatic and aromatic residues, which bind ADP and ATP in both states. Additionally, there are two pairs of asparagine/arginine residues on opposite sides of this site that are involved in substrate binding in a state-dependent manner. Thus, the substrates are directed through a series of binding poses, inducing the conformational changes of the carrier that lead to their translocation. The properties of this site explain the electrogenic and reversible nature of adenine nucleotide transport.

CuO nanowires were grown on Cu foils at 600 °C, coated with Cu and converted into Cu3N/Cu2O core–shell nanowires under NH3:H2 at 400 °C. The structural and optical properties are described in detail as well as its potential for energy applications.

Peptide macrocycles are a rapidly emerging class of therapeutic, yet the design of their structure and activity remains challenging. This is especially true for those with β-hairpin structure due to weak folding properties and a propensity for aggregation. Here, we use proteomic analysis and common antimicrobial features to design a large peptide library with macrocyclic β-hairpin structure. Using an activity-driven high-throughput screen, we identify dozens of peptides killing bacteria through selective membrane disruption and analyze their biochemical features via machine learning. Active peptides contain a unique constrained structure and are highly enriched for cationic charge with arginine in their turn region. Our results provide a synthetic strategy for structured macrocyclic peptide design and discovery while also elucidating characteristics important for β-hairpin antimicrobial peptide activity.

Raman, XRD and TEM characterization of Cu3N/Cu2O nanowires

Purpose. Implementation of a useful genetic diagnosis for the clinical management of patients with astrocytic tumors. Methods. We investigated 314 prospectively recruited diffuse astrocytic tumours by applying the cIMPACT-NOW Update 3 signature. Results. The cIMPACT-NOW Update 3 (cIMPACT 3+) markers, i.e. alterations of TERT promoter, EGFR, and/or chromosome 7 and 10, characterized 98.5% of IDH-wt cases. Interestingly, it was also found in 57.5% of IDH-mut cases. According to the genomic profile, four genetic subgroups could be distinguished: 1) IDH-wt/cIMPACT 3-negative (=4); 2) IDH-mut/cIMPACT 3-negative (n=14); 3) IDH-mut/cIMPACT 3+ (n=20); and 4) IDH-wt/cIMPACT 3+ (n=276). Multivariate analysis confirmed that IDH1/2 mutations confer a favorable prognosis (IDH-wt, HR 2.91 95%, CI 1.40-6.05), and validated the prognostic value of the cIMPACT 3+ signature. Conclusions. To accurately identify relevant prognostic categories, overcoming the limitations of histopathology and immunohistochemistry, molecular-cytogenetic analyses must be fully integrated into the diagnostic work-up of astrocytic tumors.

Assessing pain levels in real-world conditions, such as during active surgery, can be challenging. Self-reports, often considered globally as ‘ground-truth’ can be unreliable, episodic and ill-suited to routine monitoring or use with non-verbal patients. Lately, physiological measurements have been explored as an objective method for assessing the symptoms of pain increase on the body. We investigated the effects of pain (high pain) using facial mask – emteqPRO, equipped with seven facial electromyographic (fEMG) sensors.Our aims were to: (i) investigate the efficacy of continuous physiological monitoring within surgery at a hospital environment, and (ii) to produce initial findings and show how pain increase affects the data from fEMG sensors.

Anonymized survey responses published with the 2022 paper ''A reliable and robust online validation method for creating a novel 3D Affective Virtual Environment and Event Library (AVEL) "'

The Type VI secretion system (T6SS) is a bacterial nanomachine that delivers toxic effectors to kill competitors or subvert some of their key functions. Here, we use transposon directed insertion-site sequencing to identify T6SS toxins associated with the H1-T6SS, one of the three T6SS machines found in Pseudomonas aeruginosa. This approach identified several putative toxin-immunity pairs, including Tse8-Tsi8. Full characterization of this protein pair demonstrated that Tse8 is delivered by the VgrG1a spike complex into prey cells where it targets the transamidosome, a multiprotein complex involved in protein synthesis in bacteria that lack either one, or both, of the asparagine and glutamine transfer RNA synthases. Biochemical characterization of the interactions between Tse8 and the transamidosome components GatA, GatB and GatC suggests that the presence of Tse8 alters the fine-tuned stoichiometry of the transamidosome complex, and in vivo assays demonstrate that Tse8 limits the ability of prey cells to synthesize proteins. These data expand the range of cellular components targeted by the T6SS by identifying a T6SS toxin affecting protein synthesis and validate the use of a transposon directed insertion site sequencing-based global genomics approach to expand the repertoire of T6SS toxins in T6SS-encoding bacteria., L.M.N. was supported by Medical Research Council (MRC) Grant MR/N023250/1 and a Marie Curie Fellowship (PIIF-GA-2013-625318). A.F. was supported by MRC Grants MR/K001930/1 and MR/N023250/1 and Biotechnology and Biological Sciences Research Council (BBSRC) Grant BB/N002539/1. R.C.D.F. and D.A.I.M. were supported by the MRC Career Development Award MR/M009505/1. D.A.-J. acknowledges support by the MINECO Contract CTQ2016-76941-R, Fundación Biofísica Bizkaia, the Basque Excellence Research Centre (BERC) program and IT709-13 of the Basque Government, and Fundación BBVA. M.A.S.-P. was supported by the MINECO under the “Juan de la Cierva Postdoctoral program” (position FJCI-2015-25725).

This paper considers the challenging problem of establishing deadlock freedom for message-passing processes using behavioral type systems. In particular, we consider the case of processes that implement session types by communicating asynchronously in cyclic process networks. We present APCP, a typed process framework for deadlock freedom which supports asynchronous communication, delegation, recursion, and a general form of process composition that enables specifying cyclic process networks. We discuss the main decisions involved in the design of APCP and illustrate its expressiveness and flexibility using several examples., Comment: In Proceedings ICE 2021, arXiv:2109.14908. arXiv admin note: text overlap with arXiv:2101.09038

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders of the central nervous system, which predominantly affects patients’ motor functions, movement, and stability. Monitoring movement in patients with PD is crucial for inferring motor state fluctuations throughout daily life activities, which aids in disease progression analysis and assessing how patients respond to medications over time. In recent years, there has been an increase in the usage of wearable sensors for PD symptom monitoring. In this study, we present a preliminary analysis of smart glasses equipped with IMU sensors to provide objective information on the motor state in patients with PD. Data were collected from seven Parkinson’s patients with varying levels of symptom severity. The patients performed the Timed-Up-and-Go (TUG) Test while wearing IMU-equipped glasses. Our analysis indicates that smart glasses can provide information about patients’ gait that can be used to assess the severity level of the PD as measured by two standardized questionnaires. Furthermore, patient-specific clusters can be easily detected in the sensor data, hinting at the development of personalized models for patient-specific monitoring of symptom progression. Therefore, smart glasses have the potential to be used as an unobtrusive and continuous screening tool for PD patients’ gait, enhancing medical assessment and treatment.CCS CONCEPTS • Applied computing • Life and medical sciences • Health informaticsACM Reference FormatFirst Author’s Name, Initials, and Last Name, Second Author’s Name, Initials, and Last Name, and Third Author’s Name, Initials, and Last Name. 2022. The Title of the Paper: ACM Conference Proceedings Manuscript Submission Template: This is the subtitle of the paper, this document both explains and embodies the submission format for authors using Word. In Woodstock ‘18: ACM Symposium on Neural Gaze Detection, June 03–05, 2018, Woodstock, NY. ACM, New York, NY, USA, 10 pages. NOTE: This block will be automatically generated when manuscripts are processed after acceptance.

This paper investigates the second language (L2) acquisition of the Turkish category Ad tamlaması (AT). AT consists an umbrella term which is encountered in Turkish grammars and L2-Turkish coursebooks to refer to three forms of Nominal Syntagmatic Sets (NSS), namely a) N-(n)In N-(s)I(n), b) N N-(s)I(n) and c) N N-(y) . This paper is trying to examine whether the apparently formal similarity of these 3 Nominal Syntagmatic Sets Ad Tamlaması (NSS-AT) in Turkish can be correlated with a respective degree of ease in L2 acquisition and simultaneity in L2 teaching or not. The main aim of this paper is to delineate the differences of these three NSS forms by testing them upon 12 morpho-syntactic criteria. The test results will show how much syntactically analytic and semantically transparent each of these sets is. We will conclude that the formal differentiation of the 3 NSS types does not always correspond with functional- semantic differentiation, which has implications on the difficulties these forms create in L2-learners. We will show that in the L2 learning process of the 3 NSS-AT forms, we expect a learning step ahead in the analytic N-(n)In N-(s)I(n) form compared to non-analytic compounds such as the N N-(s)I(n) form and more blurred cases such as the N N-(y) form, which shares properties of both Noun Phrases (NPs) and compounds. From a didactic scope, we come to assume that the traditional interconnection of the three NSS-Ad Tamlaması forms in Turkish L2-teaching and L2-learning methods should be put aside and rather give its place in alternative more anti-holistic approaches which would uncover the hidden syntactic properties of the 3 forms rather than stress the similarities between them.

Background Depression is the most common cause of emotional disorder in older adults causing functional impairment and leading to lower quality of life (QOL). The aim of the study was to investigate the prevalence of depression, measure the perceived QOL and evaluate the impact of depression on life quality of older people in the community. Methods We conducted a cross-sectional study in older people, enrolled in open day care centers and other healthcare facilities. To all participants the Greek validated version of the Geriatric Depression Scale (GDS-15) was applied to screen for depressive symptoms and the EQ-5D-5L scale to estimate their self-reported health status. Results A total of 634 seniors participated in the study, 53% were females, mean age 78 years. 45.6% of the participants showed moderate to severe depression. Those who suffered from at least two chronic diseases (75.6%) were more likely to develop moderate or severe depressive symptoms compared to those with only one (19.3%) or none (2.2%) chronic disease. Increased risk of depression was observed in people with Parkinson’s disease (56.5%), mental illness (47.1%), respiratory disease (40%) and stroke (35.1%). Regarding the EQ-5D-5L scale, 72% reported slight to extreme anxiety or depression, 68.2% slight to extreme pain or discomfort, 59.8% slight to extreme problems in performing usual activities, 59.8% in mobility and 40.1% in self-care, respectively. Significant differences were found between people with or without depression. Specifically, participants who reported slight to severe problems in all five domains of the EQ-5D-5L, showed higher levels of depression in the GDS-15. Conclusions Our results revealed that elderly with depressive symptoms have a lower quality of life. Given the mutual relationship between chronic diseases, lower life quality and depression, assessment of depressive symptoms are needed in elderly population, mainly in people with multiple chronic diseases. Key messages • Depression can be a predictor of poorer quality of life in older population.

Molecular recognition is of central importance in biology. The molecular determinants shaping recognition of one protein domain by another are incompletely understood, especially in the context of the complex function of molecular machines. Here, we combine NMR experiments and molecular dynamics simulations to elucidate the determinants of recognition of the C-terminal (cDsbD) domain of the transmembrane reductant conductor DsbD by its cognate partner, the N-terminal domain of the protein (nDsbD). As part of the natural cycle of this oxidoreductase, which effectively transfers electrons from the cytoplasm to the periplasm of Gram-negative bacteria, cDsbD and nDsbD toggle between oxidised and reduced states, something that modulates the affinity of the domains for each other and prevents otherwise unproductive reactions. We find that the redox state of cDsbD determines the dissociation rate of cDsbD-nDsbD complexes. Molecular dynamics simulations demonstrate how the redox-state of the active site determines the stability of inter-domain hydrogen bonds and thus the dissociation rate. AlphaFold modelling and atomistic molecular dynamics simulations of full-length DsbD in a realistic bacterial membrane again highlights the close proximity of the periplasmic domains and the importance of tuning the strength of the interactions of the periplasmic domains to enable electron transfer to cognate periplasmic partners such as CcmG. Our AlphaFold models are consistent with in vivo functional assays of DsbD mutants, which together help to reveal for the first-time a putative binding site for thioredoxin on the cytoplasmic side of DsbD.

The discovery of penicillin by Alexander Fleming marked a new era for modern medicine, allowing not only the treatment of infectious diseases, but also the safe performance of life-saving interventions, like surgery and chemotherapy. Unfortunately, resistance against penicillin, as well as more complex β-lactam antibiotics, has rapidly emerged since the introduction of these drugs in the clinic, and is largely driven by a single type of extra-cytoplasmic proteins, hydrolytic enzymes called β-lactamases. While the structures, biochemistry and epidemiology of these resistance determinants have been extensively characterized, their biogenesis, a complex process including multiple steps and involving several fundamental biochemical pathways, is rarely discussed. In this review, we provide a comprehensive overview of the journey of β-lactamases, from the moment they exit the ribosomal channel until they reach their final cellular destination as folded and active enzymes.

Using a novel wearable surface electromyography (sEMG), we investigated induced affective states by measuring the activation of facial muscles traditionally associated with positive (left/right orbicularis and left/right zygomaticus) and negative expressions (the corrugator muscle). In a sample of 38 participants that watched 25 affective videos in a virtual reality environment, we found that each of the three variables examined—subjective valence, subjective arousal, and objective valence measured via the validated video types (positive, neutral, and negative)—sEMG amplitude varied significantly depending on video content. sEMG aptitude from “positive muscles” increased when participants were exposed to positively valenced stimuli compared with stimuli that was negatively valenced. In contrast, activation of “negative muscles” was elevated following exposure to negatively valenced stimuli compared with positively valenced stimuli. High arousal videos increased muscle activations compared to low arousal videos in all the measured muscles except the corrugator muscle. In line with previous research, the relationship between sEMG amplitude as a function of subjective valence was V-shaped.

Antibiotics are the cornerstone of modern medicine, but their effectiveness is threatened by the growing problem of antibiotic resistance. Recent research has identified a new strategy with the potential to restore the effectiveness of a range of currently used antibiotics, including drugs of last resort.

Cu3N layers with a thickness of 40 nm were deposited by reactive sputtering using Ar: 10% N2 and 100% N2, after which they were annealed under NH3/H2 between 300 and 500 °C. These exhibited distinc...

This paper describes the development and validation of 3D Affective Virtual environments and Event Library (AVEL) for affect induction in Virtual Reality (VR) settings with an online survey; a cost-effective method for remote stimuli validation which has not been sufficiently explored. Three virtual office-replica environments were designed to induce negative, neutral and positive valence. Each virtual environment also had several affect inducing events/objects. The environments were validated using an online survey containing videos of the virtual environments and pictures of the events/objects. They survey was conducted with 67 participants. Participants were instructed to rate their perceived levels of valence and arousal for each virtual environment (VE), and separately for each event/object. They also rated their perceived levels of presence for each VE, and they were asked how well they remembered the events/objects presented in each VE. Finally, an alexithymia questionnaire was administered at the end of the survey. User ratings were analysed and successfully validated the expected affect and presence levels of each VE and affect ratings for each event/object. Our results demonstrate the effectiveness of the online validation of VE material in affective and cognitive neuroscience and wider research settings as a good scientific practice for future affect induction VR studies.

Novel computing paradigms, e.g., the Cloud, introduce new requirements with regard to access control such as utilization of historical information and continuity of decision. However, these concepts may introduce an additional level of complexity to the underpinning model, rendering its definition and verification a cumbersome and prone to errors process. Using a formal language to specify a model and formally verify it may lead to a rigorous definition of the interactions amongst its components, and the provision of formal guarantees for its correctness. In this paper, we consider a case study where we specify a formal model in TLA $$^+$$ for both a policy-neutral and policy-specific UseCON usage control model. Through that, we anticipate to shed light in the analysis and verification of usage control models and policies by sharing our experience when using TLA $$^+$$ specific tools.

Mitochondrial ADP/ATP carriers catalyse the equimolar exchange of ADP and ATP across the mitochondrial inner membrane, providing metabolic energy for the cell. Crystal structures of the inhibited cytoplasmic-open and matrix-open states support an alternating access mechanism, involving a cytoplasmic and a matrix gate. However, the molecular nature of substrate binding remains unresolved. Substrate binding is concomitant with the structural movements required for translocation, because substrate binding and release provides the free energy changes for the disruption and formation of the gates. The aim of this project was to provide experimental evidence for the residues that are involved in the substrate binding process. For this purpose, all conserved, solvent-accessible residues between the boundaries of the two gates were mutated to alanine, creating a set of 36 variants. A combination of functional complementation, thermostability and transport assays consistently identified five residues (K30, R88, R197, R246 and R287) to be critical for substrate binding. The Ala variants of these residues did not complement growth of an Aac-deficient strain, abolished the concentration-dependent response to substrate, that is observed for the wild-type protein, and had no transport activity. These residues are located roughly in the middle of the central cavity. Around them, another six residues (N85, N96, L135, V138, G192 and Y196) were found to contribute to the binding process. The variants of these residues did not or partially complement growth of the Aac-deficient strain, presented with significantly reduced substrate-induced thermostability shifts compared to the wild-type protein and were either inactive or had altered transport properties. Residues K30, R88, L135, V138, G192, Y196 and R287 cluster together and are accessible with similar conformers in both conformational states, thus forming the main binding site. Residues N96/R197 and N85/R246 form two pairs located on the cytoplasmic and matrix side of the main site and have conformers that change in a state-dependent manner. Hence, they may be involved in the initial binding and guiding of the substrates to the main site and then in their release to the other side of the membrane, inducing conformational changes. The obtained results provide a plausible mechanism for substrate binding, demonstrate that there is a single binding site for ADP and ATP, explain the reversibility of transport and the importance of charge neutralisation in presence of a membrane potential. Results also show that the size and hydrophobicity of the binding pocket are key for the nucleotide base selection.

Virtual Reality (VR) enables the simulation of ecologically validated scenarios, which are ideal for studying behaviour in controllable conditions. Physiological measures captured in these studies provide a deeper insight into how an individual responds to a given scenario. However, the combination of the various biosensing devices presents several challenges, such as efficient time synchronisation between multiple devices, replication between participants and settings, as well as managing cumbersome setups. Additionally, important salient facial information is typically covered by the VR headset, requiring a different approach to facial muscle measurement. These challenges can restrict the use of these devices in laboratory settings. This paper describes a solution to this problem. More specifically, we introduce the emteqPRO system which provides an all-in-one solution for the collection of physiological data through a multi-sensor array built into the VR headset. EmteqPRO is a ready to use, flexible sensor platform enabling convenient, heterogenous, and multimodal emotional research in VR. It enables the capture of facial muscle activations, heart rate features, skin impedance, and movement data—important factors for the study of emotion and behaviour. The platform provides researchers with the ability to monitor data from users in real-time, in co-located and remote set-ups, and to detect activations in physiology that are linked to arousal and valence changes. The SDK (Software Development Kit), developed specifically for the Unity game engine enables easy integration of the emteqPRO features into VR environments.Code available at: (https://github.com/emteqlabs/emteqvr-unity/releases)

Breathing rate is considered one of the fundamental vital signs and a highly informative indicator of physiological state. Given that the monitoring of heart activity is less complex than the monitoring of breathing, a variety of algorithms have been developed to estimate breathing activity from heart activity. However, estimating breathing rate from heart activity outside of laboratory conditions is still a challenge. The challenge is even greater when new wearable devices with novel sensor placements are being used. In this paper, we present a novel algorithm for breathing rate estimation from photoplethysmography (PPG) data acquired from a head-worn virtual reality mask equipped with a PPG sensor placed on the forehead of a subject. The algorithm is based on advanced signal processing and machine learning techniques and includes a novel quality assessment and motion artifacts removal procedure. The proposed algorithm is evaluated and compared to existing approaches from the related work using two separate datasets that contains data from a total of 37 subjects overall. Numerous experiments show that the proposed algorithm outperforms the compared algorithms, achieving a mean absolute error of 1.38 breaths per minute and a Pearson’s correlation coefficient of 0.86. These results indicate that reliable estimation of breathing rate is possible based on PPG data acquired from a head-worn device.

Chromothripsis is a mitotic catastrophe that arises from multiple double strand breaks and incorrect re-joining of one or a few chromosomes. We report on incidence, distribution, and features of chromothriptic events in T-cell acute lymphoblastic leukemias (T-ALL). SNP array was performed in 103 T-ALL (39 ETP/near ETP, 59 non-ETP, and 5 with unknown stage of differentiation), including 38 children and 65 adults. Chromothripsis was detected in 11.6% of all T-ALL and occurred only in adult cases with an immature phenotype (12/39 cases; 30%). It affected 1 to 4 chromosomes, and recurrently involved chromosomes 1, 6, 7, and 17. Abnormalities of genes typically associated with T-ALL were found at breakpoints of chromothripsis. In addition, it gave rise to new/rare alterations, such as, the SFPQ::ZFP36L2 fusion, reported in pediatric T-ALL, deletions of putative suppressors, such as IKZF2 and CSMD1, and amplification of the BCL2 gene. Compared to negative cases, chromothripsis positive T-ALL had a significantly higher level of MYCN expression, and a significant downregulation of RGCC, which is typically induced by TP53 in response to DNA damage. Furthermore we identified mutations and/or deletions of DNA repair/genome stability genes in all cases, and an association with NUP214 rearrangements in 33% of cases.

This paper explores the potential of combining different isotope systems from different tissues to improve resolution when reconstructing breastfeeding and weaning practices (BWP) in archaeology. Additionally, we tested whether changes in diet can be detected in deciduous teeth. Rib collagen samples from 22 infants/children from the archaeological site of Bacuranao I (Mayabeque, Cuba) were processed for nitrogen (δ15N) and carbon (δ13Cco) stable isotopes and assessed using a Bayesian model (WARN). In addition, enamel of 48 teeth from 30 infants/children were analyzed for oxygen (δ18Oen) and carbon (δ13Cen) stable isotopes. Data revealed that the timing of weaning cannot be characterized precisely by analyzing either δ18O or δ15N. While a depletion in both δ15N and δ13Cco is only evident after one year, the WARN model suggested that the weaning process started at around 3 months and ended around 1.7 years. Most teeth were enriched in δ18Oen compared to deciduous incisors, suggesting a breastfeeding signal. However, a high variability in δ18O was found between similar teeth from the same individuals. Higher enrichment in δ18Oen, and variability, was observed in tissues formed during the first six months of life. A δ13C enrichment of 1.0‰ was observed among deciduous teeth and ribs. While most individuals enriched in δ15N showed enrichment in δ13C, the δ18O values were more variable. Our data suggests that stable isotopes of deciduous teeth, especially δ13Cen, can be used to detect changes in diet during the weaning process. It is also possible that the δ18O enrichment observed in M1 is influenced by the effects of cooking techniques on weaning foods. The combination of multiple isotope systems and tissues overcome some of the limitations posed by single tissue approaches.

The emergence of blockchains and smart contracts has renewed interest in electrical cyberphysical systems, especially transactive energy systems. To address the associated challenges, we present TRANSAX, a blockchain-based transactive energy system that provides an efficient, safe, and privacy-preserving market built on smart contracts.

Long-term exposure of Mytilus galloprovincialis to temperatures beyond 26°C triggers mussel mortality. The present study aimed to integratively illustrate the correlation between intermediary metabolism, hsp gene expression, and oxidative stress-related proteins in long-term thermally stressed Mytilus galloprovincialis and whether they are affected by thermal stress magnitude and duration. We accordingly evaluated the gene expression profiles, in the posterior adductor muscle (PAM) and the mantle, concerning heat shock protein 70 and 90 ( hsp70 and hsp90), and the antioxidant defense indicators Mn-SOD, Cu/Zn-SOD, catalase, glutathione S-transferase, and the metallothioneins mt-10 and mt-20. Moreover, we determined antioxidant enzyme activities, oxidative stress through lipid peroxidation, and activities of intermediary metabolism enzymes. The pattern of changes in relative mRNA expression levels indicate that mussels are able to sense thermal stress even when exposed to 22°C and before mussel mortality is initiated. Data indicate a close correlation between the magnitude and duration of thermal stress with lipid peroxidation levels and changes in the activity of antioxidant enzymes and the enzymes of intermediary metabolism. The gene expression and increase in the activities of antioxidant enzymes support a scenario, according to which exposure to 24°C might trigger reactive oxygen species (ROS) production, which is closely correlated with anaerobic metabolism under hypometabolic conditions. Increase and maintenance of oxidative stress in conjunction with energy balance disturbance seem to trigger mussel mortality after long-term exposure at temperatures beyond 26°C. Eventually, in the context of preparation for oxidative stress, certain hypotheses and models are suggested, integrating the several steps of cellular stress response.

We present a system for sensing and reconstructing facial expressions of the virtual reality (VR) head-mounted display (HMD) user. The HMD occludes a large portion of the user's face, which makes most existing facial performance capturing techniques intractable. To tackle this problem, a novel hardware solution with electromyography (EMG) sensors being attached to the headset frame is applied to track facial muscle movements. For realistic facial expression recovery, we first reconstruct the user's 3D face from a single image and generate the personalized blendshapes associated with seven facial action units (AUs) on the most emotionally salient facial parts (ESFPs). We then utilize pre-processed EMG signals for measuring activations of AU-coded facial expressions to drive pre-built personalized blendshapes. Since facial expressions appear as important nonverbal cues of the subject's internal emotional states, we further investigate the relationship between six basic emotions - anger, disgust, fear, happiness, sadness and surprise, and detected AUs using a fern classifier. Experiments show the proposed system can accurately sense and reconstruct high-fidelity common facial expressions while providing useful information regarding the emotional state of the HMD user.

Lysosomal storage diseases (LSDs) are rare to extremely rare monogenic disorders. Their incidence, however, has probably been underestimated owing to their complex clinical manifestations. Sialidosis is a prototypical LSD inherited as an autosomal recessive trait and caused by mutations in the NEU1 gene that result in a deficiency of alpha-N-acetyl neuraminidase 1 (NEU1). Two basic forms of this disease, type I and type II, are known. The dysmorphic type II form features LSD symptoms including congenital hydrops, dysmorphogenetic traits, hepato-splenomegaly and severe intellectual disability. The diagnosis is more challenging in the normosomatic type I forms, whose clinical findings at onset include ocular defects, ataxia and generalized myoclonus. Here we report the clinical, biochemical and molecular analysis of five patients with sialidosis type I. Two patients presented novel NEU1 mutations. One of these patients was compound heterozygous for two novel NEU1 missense mutations: c.530A>T (p.Asp177Val) and c.1010A>G (p.His337Arg), whereas a second patient was compound heterozygous for a known mutation and a novel c.839G>A (p.Arg280Gln) mutation. We discuss the impact of these new mutations on the structural properties of NEU1. We also review available clinical reports of patients with sialidosis type I, with the aim of identifying the most frequent initial clinical manifestations and achieving more focused diagnoses.

OBJECTIVE: The mitochondrial pyruvate carrier (MPC) has emerged as a promising drug target for metabolic disorders, including non-alcoholic steatohepatitis and diabetes, metabolically dependent cancers and neurodegenerative diseases. A range of structurally diverse small molecule inhibitors have been proposed but the nature of their interaction with MPC is not understood. Moreover, the composition of the functional human MPC is still debated. The goal of this study was to characterize the human MPC protein in vitro, to understand the chemical features that determine binding of structurally diverse inhibitors and to develop novel higher affinity ones.METHODS: We have recombinantly expressed and purified human MPC hetero-complexes and have studied the composition, transport and inhibitor binding properties by establishing in vitro transport assays, high throughput thermostability shift assays and pharmacophore modeling.RESULTS: We have determined that the functional unit of human MPC is a hetero-dimer. We have compared all different classes of MPC inhibitors to find that three closely arranged hydrogen bond acceptors followed by an aromatic ring are shared characteristics of all inhibitors and represent the minimal requirement for high potency. We also demonstrate that high affinity binding is not attributed to covalent bond formation with MPC cysteines, as previously proposed. Following the basic pharmacophore properties, we identify 14 new inhibitors of MPC, one outperforming compound UK5099 by tenfold. Two of them are the commonly prescribed drugs entacapone and nitrofurantoin, suggesting an off-target mechanism associated with their adverse effects.CONCLUSION: This work defines the composition of human MPC and the essential MPC inhibitor characteristics. In combination with the functional assays we describe, this new understanding will accelerate the development of clinically relevant MPC modulators.

Cu3N layers prepared by annealing, under NH3 O2 flow, of Cu sputtered on Si, fused SiO2, and soda lime glass were studied by Raman and N K edge Near Edge X ray Absorption Fine Structure NEXAFS spectroscopy. The annealing temperatures were ranging from 300 to 800 C. Benefiting from resonance effects on the Raman peak intensities when different excitation wavelengths are used, the contribution in the Raman signal of copper oxides, which provide peaks lying close to those of Cu3N, is more easily discriminated. The formation of Cu2O surface oxide is observed in almost all the samples even for annealing at low temperatures. CuO is generally formed at higher temperatures with the onset depending on the amount of O2 in the NH3 O2 mixture. However, high temperature is necessary to grow larger crystallites, as it is deduced from the decrease in the width of the high frequency Raman peak at ca. 650 cm amp; 8722;1 of Cu3N, in accordance with Scanning Electron Microscopy observations. The formation of CuO is accompanied by the creation of N2 trapped in the sample, which is directly detected by the NEXAFS measurements. N2 is most probably formed by the N atoms originating from the dissociation of the Cu N bonds

Denna studie behandlar hur pedagoger förhåller sig till flerspråkighet och brytning i förskoleverksamheten tillika hur alla deltagare i förskolans kontext det vill säga barn förskollärare, rektorer, vårdnadshavare och barnskötare interagerar för att stimulera en kvalitativ lärande miljö som främjar flerspråkiga barn i sin språkutveckling. Denna studie är kvalitativ i sin form med strukturerade intervjuer. Vi utgår från Lev Vygotskys pedagogiska teorier alltså sociokulturella teori där de centrala begrepp som studien behandlar är transspråkande, scaffolding, medierade redskap samt kollegialt lärande. Enligt tidigare forskning samt det empiri vi lyckats samla in för denna studie har resultat visat bland annat att flerspråkighet upplevs verka positivt för de barn som har brister i det svenska språket därför det främjar språkkunskaperna. Brytning verkar inte heller vara ett hinder i barnens språkutveckling sålunda personalen behärskar det svenska språket och kan interagera med alla aktörer i verksamheten då detta kan resultera till en kvalitativ lärande där barnen ska vara i centrum.