bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient adherence to rivaroxaban in deep vein thrombosis, a cohort study in Switzerland: quantitative results
Authors: Dotta-Celio Jennifer , Alatri Adriano , Locatelli Isabella , Salvi Monique , Bugnon Olivier , Schneider Marie-Paule , Mazzolai Lucia
Published: November 2019

BackgroundDirect oral anticoagulants (DOACs) have the advantage of being administered orally at a fixed dose without laboratory monitoring, in contrast to the frequent international normalized ratio measurements used to adjust for vitamin K antagonists dosing. Rivaroxaban, has a short half-life. The anticoagulation effect rapidly decreases if medication adherence is suboptimal.ObjectiveThe purpose of this quantitative study (called RIVA) is to longitudinally describe adherence to rivaroxaban (implementation and persistence) in patients with deep vein thrombosis (DVT).SettingThe community pharmacy of the Center for Primary Care and Public Health (Unisanté), University of Lausanne, Switzerland in collaboration with the angiology division of the Lausanne University Hospital (CHUV).MethodsThis is an observational study. Patients received rivaroxaban for 3 or 6 months: 15 mg twice a day during the first 3 weeks and then 20 mg once a day until the end of the treatment. Adherence was measured using electronic monitoring. Implementation and adherence were modelled using a generalized estimating equation model. Persistence was represented using a Kaplan–Meier survival curve.Main outcome measureMedication adherence (implementation and persistence).ResultsThirty-one consecutive patients were included (68% male, mean age: 47 years old). The collected adherence data consisted of 57 inter-visit phases, 2899 electronic monitoring openings and a median follow-up of 92 days (IQR: 87; 100). Implementation to rivaroxaban was initially high [96.3 (92.8; 98.1)] but decreased during the first 3 weeks, until it reached 89.3 (76.0; 95.6). After the switch from twice a day 15 mg to a once a day 20 mg regimen, implementation increased again and remained stable [95.4 (92.2; 97.3)] for 90 days. Four patients who experienced adverse events discontinued the treatment before the end of the study and were considered non-persistent (clinically appropriate discontinuation).ConclusionAdherence to rivaroxaban in deep vein trombosis is high in persistent patients. Discontinuation is related to rivaroxaban adverse effects/toxicity. Implementation should be reinforced during the twice a day-phase, and this first 3-week experience should help patients and healthcare professionals choose the best timing for the once a day phase.
Numerical simulation of trans-critical flows in open channels using a FVM scheme
Authors: Ghezelsofloo Abbas Ali
Published: November 2019

The present study makes efforts to simulate the behavior of fully developed stationary shocks, caused by the incidence of supercritical flow with a cross-barrier in an open channel. The numerical solution of nonlinear governing shallow flow equations has been implemented by the application of a second-order Roe TVD scheme. The obtained results from numerical experiment are compared with some measured in a laboratory setup. It can be deduced by comparison of the flow depths in numerical and measured experiments in three different cases of cross-barrier width of 6, 12 and 16 cm that the numerical scheme of Roe is a robust and capable method for simulation of complicated stationary shocks in shallow water flow.
Are Canadian professors teaching the skills and knowledge students need to prevent plagiarism?
Authors: Peters Martine , Cadieux Alain
Published: November 2019

Max 150 words. If possible, please submit your abstract in both English and French.

When writing an assignment, most students start by searching for information online, which they integrate in their writing and conclude by producing a bibliography for the sources used. They use their informational, writing and referencing skills to do this as well as refer to their plagiarism knowledge to make sure their text is exempt from plagiarism. In this paper, we examined which skills and knowledge students feel the need to further develop in university to prevent plagiarism in their assignments. Professors were also questioned as to their perceptions of their students’ skills development during their pre-university studies. Questionnaires were administered in six Quebec Universities to students (n = 1170) and professors (n = 279). Results show that students feel the need for more training while professors expect students to have already mastered the skills and knowledge to prevent plagiarism. Recommendations are made on how to implement better training for students through a program approach.

Lors de la rédaction d’un devoir, la plupart des étudiants universitaires commencent par chercher des informations en ligne, qu’ils intègrent dans leur rédaction et terminent en produisant une bibliographie des sources utilisées. Ils utilisent leurs compétences informationnelles, rédactionnelles, et de référencement documentaire et se réfèrent à leurs connaissances en matière de plagiat pour s’assurer que leur texte en soit exempt. Dans cet article, nous avons examiné les compétences et les connaissances que les étudiants ressentent le besoin de développer davantage à l’université pour prévenir le plagiat dans leurs travaux. Les professeurs ont également été interrogés sur leur perception du développement des compétences de leurs étudiants durant leurs études pré-universitaires. Des questionnaires ont été administrés dans six universités québécoises à des étudiants (n = 1170) et à des professeurs (n = 279). Les résultats montrent que les étudiants ressentent le besoin d’une formation plus poussée alors que les professeurs s’attendent à ce que les étudiants maîtrisent déjà les compétences et les connaissances nécessaires pour prévenir le plagiat. Des recommandations sont formulées sur la façon de mettre en œuvre une meilleure formation pour les étudiants par le biais d’une approche-programme.
Exploring the efficacy of housing alternatives for adults with an acquired brain or spinal injury: A systematic review
Authors: Wright Courtney J. , Colley Jacinta , Kendall Elizabeth
Published: November 2019

Objective:

Housing for people with acquired brain injury (ABI) or spinal cord injury (SCI) remains a significant issue in Australia and internationally. This review examined the current research evidence regarding the efficacy of housing alternatives for adults with ABI or SCI in relation to four principal outcomes of interest: the person’s (1) community integration/participation, (2) independence, (3) psychosocial well-being and (4) quality of life. The review also sought to identify how the reported efficacy of the housing alternatives might be impacted by individual factors.

Method:

For this systematic review, quantitative empirical, peer-reviewed research published after 1 January 2003 was sought. Ten journal articles met the eligibility criteria. None of the included studies comprised an adult SCI sample.

Results:

The research identified lower levels of community integration/participation, independence, psychosocial well-being and quality of life for adults (particularly younger adults) with ABI living in ‘structured settings’ (i.e., residential care) compared to those living in ‘home-like’ environments (i.e., private homes) and ‘disability-specific’ settings (i.e., shared supported accommodation, group homes, foster care homes, cluster units).

Conclusion:

More research is needed to compare ‘home-like’ and ‘disability-specific’ settings, and individual housing models more generally (i.e., living at home with friends vs with family vs living in shared supported accommodation vs living in residential care). This review identified a number of limitations in the current evidence base and several important directions for future research. Policymakers, architects, designers, builders, developers, funding agencies, international researchers as well as people with ABI or SCI and their families may benefit from the findings of this review.
Developing a text messaging-based smoking cessation intervention for young smokers experiencing homelessness
Authors: Tucker Joan S. , Linnemayr Sebastian , Pedersen Eric R. , Shadel William G. , Zutshi Rushil , Mendoza-Graf Alexandra
Published: November 2019

Introduction

Cigarette smoking is highly prevalent among young people experiencing homelessness, and many of these smokers are motivated to quit. However, there is a lack of readily available cessation services for this population, which is highly mobile and can be challenging to engage in services.

Aims

We describe the development of a smoking cessation text messaging intervention (TMI) for homeless youth who are interested in quitting smoking.

Methods

Participants were 18–25 years old and recruited from drop-in centers serving homeless youth. Three focus groups (N = 18) were conducted with smokers to refine the TMI content, and a separate sample of smokers (N = 8) provided feedback on the TMI after using it for 1 week. Survey data assessed the TMI's acceptability and feasibility.

Results

Participants generally rated the TMI as helpful and relevant, and nearly all had cell phone plans that included unlimited texting and were able to view TMI content with few difficulties. Qualitative feedback on strengths/limitations of the TMI in terms of content, tone, and delivery parameters was used to finalize the TMI for a future evaluation.

Conclusions

Results suggest that a TMI is a feasible and acceptable option for young people experiencing homelessness who are interested in quitting smoking.
How can we play together? Temporal inconsistencies in neural coding of music
Authors: Vickhoff Björn
Published: November 2019

If sensory organs encode environment, this code must be decoded to perception. The currently dominant theory of perception – predictive coding – assumes a “Bayesian decoder,” a probability function, which will present (to whom?) an optimal guess, given previous encodings of the environment – old codes testing new codes. Such a process would delay perception noticeably. This is inconsistent with the perception of music, which for several reasons must be direct.
Codes, functions, and causes: A critique of Brette's conceptual analysis of coding
Authors: Barack David , Jaegle Andrew
Published: November 2019

Brette argues that coding as a concept is inappropriate for explanations of neurocognitive phenomena. Here, we argue that Brette's conceptual analysis mischaracterizes the structure of causal claims in coding and other forms of analysis-by-decomposition. We argue that analyses of this form are permissible and conceptually coherent and offer essential tools for building and developing models of neurocognitive systems like the brain.
Neural codes – Necessary but not sufficient for understanding brain function
Authors: Schultz Simon R. , Gava Giuseppe P.
Published: November 2019

Brains are information processing systems whose operational principles ultimately cannot be understood without resource to information theory. We suggest that understanding how external signals are represented in the brain is a necessary step towards employing further engineering tools (such as control theory) to understand the information processing performed by brain circuits during behaviour.
Codes, communication and cognition
Authors: Harnad Stevan
Published: November 2019

Brette criticizes the notion of neural coding because it seems to entail that neural signals need to “decoded” by or for some receiver in the head. If that were so, then neural coding would indeed be homuncular (Brette calls it “dualistic”), requiring an entity to decipher the code. But I think Brette's plea to think instead in terms of complex, interactive causal throughput is preaching to the converted. Turing (not Shannon) has already shown the way. In any case, the metaphor of neural coding has little to do with the symbol grounding problem.
U.S. Food and Drug Administration anticancer drug approval trends from 2016 to 2018 for lung, colorectal, breast, and prostate cancer
Authors: Ribeiro Tatiane Bomfim , Ribeiro Adalton , Rodrigues Luíza de Oliveira , Harada Guilherme , Nobre Moacyr Roberto Cuce
Published: November 2019

Objective

This paper aims to describe the clinical and regulatory aspects of new drugs and indications that were approved for lung, breast, prostate, and colorectal cancer, from 2016 to 2018, in order to provide health technology assessment trends in oncology.

Methods

Data were collected from the US Food and Drug Administration (FDA) online database for new medications and indications approved for the above-mentioned types of cancer. Data regarding clinical study characteristics and regulatory information were collected.

Results

From 2016 to 2018, 53 percent of the FDA approvals of new drugs and indications for the most incident cancers were for oral protein kinase inhibitor monotherapy for advanced lung cancer. Since 2018, four drugs were approved as tumor-agnostic therapies. A biomarker was included in 72 percent of indications, and 58 percent of approvals were for targeted therapies, potentially heralding an end to research into conventional cytotoxic agents. A special designation for faster approval was granted in 78 percent of new approvals. The majority of the studies were open label randomized controlled trials (RCTs) (44 percent), followed by blind RCTs, single-arm clinical trials, and cohort studies. Only 14 percent of studies used overall survival as the primary end point; the vast majority used surrogate end points, and did not use patient-important outcomes. Three biosimilars were approved in the period.

Conclusion

Advanced lung cancer therapy, mainly targeted drugs, accounted for 53 percent of approvals. Special designations for faster approval were used in 78 percent of FDA approvals, and four drugs were approved for tumor-agnostic treatment—a new form of approval.
Structural dissymmetrization of optically anisotropic Grs64±1Adr36±1Sps2grandite from Meka Presedla (Kopaonik Mt., Serbia)
Authors: Tančić Pavle , Kremenović Aleksandar , Vulić Predrag
Published: November 2019

In this paper, grandite core with Grs64±1Adr36±1Sps2composition was crystallographically studied. This core represents zone A of the macroscopically visible five A–E zones of the optically anisotropic Grs58–64Adr36–42Sps2grandite. The applied procedure includes the detailed analysis of the powder diffraction patterns, and the Rietveld refinements of the crystal structures in a series of 18 space groups and two mixtures, which were followed by the comparative analysis of theR-values, site occupancy factors, and the bond lengths and angles. Synthesis of all of the presented results allows us to undoubtedly conclude that studied grandite is not cubic, neither as monophase nor as multiple phases in a mixture. Namely, it was established that structural dissymmetrization occurred and that it crystallized in the disordered rhombohedral$R\bar{3}c$or orthorhombicFdddspace groups, whereby the first one is more probable. Beside the established lower symmetry of the studied grandite, which could be treated as the primary cause, the residual strain is also not excluded as the second possible cause for its slight optical anisotropy.
Food insecurity is associated with suboptimal sleep quality, but not sleep duration, among low-income Head Start children of pre-school age
Authors: Na Muzi , Eagleton Sally G , Jomaa Lamis , Lawton Kristen , Savage Jennifer S
Published: November 2019

Objective:

To examine the association between food insecurity and child sleep outcomes and to investigate whether parent psychosocial factors mediate such associations.

Design:

Cross-sectional study. Usual wake time and bedtime, bedtime routine and sleep quality were reported by parents using the adapted Brief Infant Sleep Questionnaire. Food insecurity was assessed using the eighteen-item US Department of Agriculture Household Food Security Module. Parent psychosocial factors, including perceived stress, parenting self-efficacy and depressive symptomology, were assessed using validated scales. Multivariable logistic regression models were performed to determine the association between food insecurity and sleep outcomes controlling for potential confounders. Mediation analyses and Sobel tests were applied to test the mediating effect of psychosocial factors.

Setting:

Head Start pre-school classrooms in four regions across central Pennsylvania, USA.

Participants:

Low-income children of pre-school age (n 362) and their caregivers.

Results:

Prevalence of household, adult and child food insecurity was 37·3, 31·8 and 17·7 %, respectively. Food security status at any level was not associated with child sleep duration or bedtime routine. Child food insecurity, but not household or adult food insecurity, was associated with 2·25 times increased odds (95 % CI 1·11, 4·55) of poor child sleep quality in the adjusted model. Perceived stress, self-efficacy and depressive symptomology mediated less than 2 % of the observed effect (all Sobel test P > 0·6).

Conclusion:

Food insecurity, particularly at the child level, is a potential modifiable risk factor for reducing sleep-related health disparities in early childhood. Future studies are needed to explore the plausible mechanisms underlying the associations between food insecurity and adverse child sleep outcomes.
Estuarine Responses to Long‐Term Changes in Inlets, Morphology, and Sea Level Rise
Authors: Mulligan Ryan P. , Mallinson David J. , Clunies Gregory J. , Rey Alexander , Culver Stephen J. , Zaremba Nick , Leorri Eduardo , Mitra Siddhartha
Published: November 2019

Pamlico Sound, a large back‐barrier estuary in North Carolina, is under threat of climate change due to increased storm activity and sea level rise. The response of this system is investigated by considering what has already happened during changes in sea level over the late Holocene epoch. The hydrodynamic changes that occurred in response to geomorphic evolution are simulated using a 3‐D numerical model for four distinct “time‐slice” scenarios. To accomplish this, the present‐day bathymetry was obtained from a high‐resolution digital elevation model, and paleobathymetric grids were developed from sediment cores and seismic observations. Using the same hydrodynamic forcing for each geomorphic scenario, the models are compared to assess the combined response to: different inlets connecting the back‐barrier estuary to the ocean, changes in basin geomorphology due to sedimentation, and sea level rise. The results indicate that these factors have a considerable effect on hydrodynamics, waves, and salinity in the estuary. The time‐averaged tidal ranges were up to 3 times as high for the past environments in comparison with present‐day water level elevations, and maximum current velocities were over 3 times higher in regions close to paleo‐inlets. The simulations for each time slice suggest that the salinity distribution in Pamlico Sound is strongly influenced by the hydraulic connectivity with other estuaries and the number and size of tidal inlets through the barrier island system. The results indicate that changes to barrier systems induce strong, nonuniform, and complex responses in back‐barrier estuaries with regime shifts in hydrodynamic energy and water mass properties.
Assessing Models for Pacific Absolute Plate and Plume Motions
Authors: Wessel Paul , Conrad Clinton P.
Published: November 2019

Absolute plate motion (APM) models derived from hot spot trails must satisfy trail geometries, ages, and paleolatitudes, which requires modeling explicit plume motions. Models lacking plume motions or derived independently from seamounts must also fit these data, provided the implicit plume motions are geodynamically reasonable. We evaluate eight Pacific APM models; three have explicitly modeled plume motions. Seven derive from seamount age progressions; one is a geodynamic model driven by slab pull and ridge push. Using the long‐lived Hawaii‐Emperor and Louisville chains, we derive implicit motions of Hawaii and Louisville plumes for models lacking explicit estimates and compare them with observed paleolatitudes. Inferred plume motions are plausible given rheological constraints on mantle flow, but rates vary considerably and not all models fit the data well. One potential endmember model predicts no APM direction change at 50 Ma, which best explains trails and paleolatitudes, minimizes predicted rotation of Pacific‐Farallon ridge and assumes no true polar motion, yet its implicit plume drift is inconsistent with global circulation models. Alternatively, a global moving hot spot model yields acceptable fits to geometry and ages, implies a major APM change at 50 Ma, but requires significant true polar wander to explain observed paleolatitudes. The inherent inconsistency between age progressions and paleolatitudes may be reconciled by true polar wander, yet questions remain about the accuracy of age progressions for older sections of the Emperor and Louisville chains, the independent geologic evidence for an APM change at 50 Ma, and the uniqueness and relevance of true polar wander estimates.
Atmospheric Water Transport to the Endorheic Tibetan Plateau and Its Effect on the Hydrological Status in the Region
Authors: Li Ying , Su Fengge , Chen Deliang , Tang Qiuhong
Published: November 2019

The endorheic Tibetan Plateau (ETP), which consists of all the endorheic basins of the Tibetan Plateau (TP), has exhibited an overall mass gain in recent decades. However, the role played by atmospheric water (AW) transport on the hydrological status over the ETP is poorly understood. In this study, the AW source to the ETP was tracked with the Water Accounting Model‐2 layers (WAM‐2) and AW transport to the ETP through its boundaries was quantified, with three reanalysis products (ERA‐I, MERRA‐2, and JRA‐55) during 1979/1980–2015. It is found that total AW input to the ETP is about 13–25%, 59–71%, 10–13%, and 3–7% of mean annual totals in spring, summer, autumn, and winter, respectively. At annual scales, the AW source from land (52–54%) dominates the AW contribution to the ETP, while local recycling of AW over the ETP accounts for about 17–22% of the mean annual total AW contribution. Increased precipitation over the ETP during 1979–2015 was mostly attributed to the significantly increased AW contribution from the Indian Ocean, especially from increased AW inputs transported from the western and southern boundaries in summer. Comparisons between the AW budget and terrestrial water storage changes indicate that the AW budget change over the ETP modulated the variations of terrestrial water storage change during 2002–2014 and annual lake mass change during 1989–2015.
MATRIEX imaging: multiarea two-photon real-time in vivo explorer
Authors: Yang Mengke , Zhou Zhenqiao , Zhang Jianxiong , Jia Shanshan , Li Tong , Guan Jiangheng , Liao Xiang , Leng Bing , Lyu Jing , Zhang Kuan , Li Min , Gong Yan , Zhu Zhiming , Yan Junan , Zhou Yi , Liu Jian K , Varga Zsuzsanna , Konnerth Arthur , Tang Yuguo , Gao Jinsong , Chen Xiaowei , Jia Hongbo
Published: November 2019

Two-photon laser scanning microscopy has been extensively applied to study in vivo neuronal activity at cellular and subcellular resolutions in mammalian brains. However, the extent of such studies is typically confined to a single functional region of the brain. Here, we demonstrate a novel technique, termed the multiarea two-photon real-time in vivo explorer (MATRIEX), that allows the user to target multiple functional brain regions distributed within a zone of up to 12 mm in diameter, each with a field of view (FOV) of ~200 μm in diameter, thus performing two-photon Ca2+ imaging with single-cell resolution in all of the regions simultaneously. For example, we demonstrate real-time functional imaging of single-neuron activities in the primary visual cortex, primary motor cortex and hippocampal CA1 region of mice in both anesthetized and awake states. A unique advantage of the MATRIEX technique is the configuration of multiple microscopic FOVs that are distributed in three-dimensional space over macroscopic distances (>1 mm) both laterally and axially but that are imaged by a single conventional laser scanning device. In particular, the MATRIEX technique can be effectively implemented as an add-on optical module for an existing conventional single-beam-scanning two-photon microscope without requiring any modification to the microscope itself. Thus, the MATRIEX technique can be readily applied to substantially facilitate the exploration of multiarea neuronal activity in vivo for studies of brain-wide neural circuit function with single-cell resolution.
Automated optimized parameters for T-distributed stochastic neighbor embedding improve visualization and analysis of large datasets
Authors: Belkina Anna C. , Ciccolella Christopher O. , Anno Rina , Halpert Richard , Spidlen Josef , Snyder-Cappione Jennifer E.
Published: November 2019

Accurate and comprehensive extraction of information from high-dimensional single cell datasets necessitates faithful visualizations to assess biological populations. A state-of-the-art algorithm for non-linear dimension reduction, t-SNE, requires multiple heuristics and fails to produce clear representations of datasets when millions of cells are projected. We develop opt-SNE, an automated toolkit for t-SNE parameter selection that utilizes Kullback-Leibler divergence evaluation in real time to tailor the early exaggeration and overall number of gradient descent iterations in a dataset-specific manner. The precise calibration of early exaggeration together with opt-SNE adjustment of gradient descent learning rate dramatically improves computation time and enables high-quality visualization of large cytometry and transcriptomics datasets, overcoming limitations of analysis tools with hard-coded parameters that often produce poorly resolved or misleading maps of fluorescent and mass cytometry data. In summary, opt-SNE enables superior data resolution in t-SNE space and thereby more accurate data interpretation.
The art of using t-SNE for single-cell transcriptomics
Authors: Kobak Dmitry , Berens Philipp
Published: November 2019

Single-cell transcriptomics yields ever growing data sets containing RNA expression levels for thousands of genes from up to millions of cells. Common data analysis pipelines include a dimensionality reduction step for visualising the data in two dimensions, most frequently performed using t-distributed stochastic neighbour embedding (t-SNE). It excels at revealing local structure in high-dimensional data, but naive applications often suffer from severe shortcomings, e.g. the global structure of the data is not represented accurately. Here we describe how to circumvent such pitfalls, and develop a protocol for creating more faithful t-SNE visualisations. It includes PCA initialisation, a high learning rate, and multi-scale similarity kernels; for very large data sets, we additionally use exaggeration and downsampling-based initialisation. We use published single-cell RNA-seq data sets to demonstrate that this protocol yields superior results compared to the naive application of t-SNE.
Automated sequence design of 2D wireframe DNA origami with honeycomb edges
Authors: Jun Hyungmin , Wang Xiao , Bricker William P. , Bathe Mark
Published: November 2019

Wireframe DNA origami has emerged as a powerful approach to fabricating nearly arbitrary 2D and 3D geometries at the nanometer-scale. Complex scaffold and staple routing needed to design wireframe DNA origami objects, however, render fully automated, geometry-based sequence design approaches essential for their synthesis. And wireframe DNA origami structural fidelity can be limited by wireframe edges that are composed only of one or two duplexes. Here we introduce a fully automated computational approach that programs 2D wireframe origami assemblies using honeycomb edges composed of six parallel duplexes. These wireframe assemblies show enhanced structural fidelity from electron microscopy-based measurement of programmed angles compared with identical geometries programmed using dual-duplex edges. Molecular dynamics provides additional theoretical support for the enhanced structural fidelity observed. Application of our top-down sequence design procedure to a variety of complex objects demonstrates its broad utility for programmable 2D nanoscale materials.
Two-tiered enforcement of high-fidelity DNA ligation
Authors: Tumbale Percy P. , Jurkiw Thomas J. , Schellenberg Matthew J. , Riccio Amanda A. , O’Brien Patrick J , Williams R. Scott
Published: November 2019

DNA ligases catalyze the joining of DNA strands to complete DNA replication, recombination and repair transactions. To protect the integrity of the genome, DNA ligase 1 (LIG1) discriminates against DNA junctions harboring mutagenic 3′-DNA mismatches or oxidative DNA damage, but how such high-fidelity ligation is enforced is unknown. Here, X-ray structures and kinetic analyses of LIG1 complexes with undamaged and oxidatively damaged DNA unveil that LIG1 employs Mg2+-reinforced DNA binding to validate DNA base pairing during the adenylyl transfer and nick-sealing ligation reaction steps. Our results support a model whereby LIG1 fidelity is governed by a high-fidelity (HiFi) interface between LIG1, Mg2+, and the DNA substrate that tunes the enzyme to release pro-mutagenic DNA nicks. In a second tier of protection, LIG1 activity is surveilled by Aprataxin (APTX), which suppresses mutagenic and abortive ligation at sites of oxidative DNA damage.
Simulating quantum many-body dynamics on a current digital quantum computer
Authors: Smith Adam , Kim M. S. , Pollmann Frank , Knolle Johannes
Published: November 2019

Universal quantum computers are potentially an ideal setting for simulating many-body quantum dynamics that is out of reach for classical digital computers. We use state-of-the-art IBM quantum computers to study paradigmatic examples of condensed matter physics—we simulate the effects of disorder and interactions on quantum particle transport, as well as correlation and entanglement spreading. Our benchmark results show that the quality of the current machines is below what is necessary for quantitatively accurate continuous-time dynamics of observables and reachable system sizes are small comparable to exact diagonalization. Despite this, we are successfully able to demonstrate clear qualitative behaviour associated with localization physics and many-body interaction effects.
Production of recombinant soluble dimeric C-type lectin-like receptors of rat natural killer cells
Authors: Vaněk Ondřej , Celadova Petra , Skořepa Ondřej , Bláha Jan , Kalousková Barbora , Dvorská Anna , Poláchová Edita , Pucholtová Helena , Kavan Daniel , Pompach Petr , Hofbauerová Kateřina , Kopecký Vladimír , Mesci Aruz , Voigt Sebastian , Carlyle James R.
Published: November 2019

Working at the border between innate and adaptive immunity, natural killer (NK) cells play a key role in the immune system by protecting healthy cells and by eliminating malignantly transformed, stressed or virally infected cells. NK cell recognition of a target cell is mediated by a receptor “zipper” consisting of various activating and inhibitory receptors, including C-type lectin-like receptors. Among this major group of receptors, two of the largest rodent receptor families are the NKR-P1 and the Clr receptor families. Although these families have been shown to encode receptor-ligand pairs involved in MHC-independent self-nonself discrimination and are a target for immune evasion by tumour cells and viruses, structural mechanisms of their mutual recognition remain less well characterized. Therefore, we developed a non-viral eukaryotic expression system based on transient transfection of suspension-adapted human embryonic kidney 293 cells to produce soluble native disulphide dimers of NK cell C-type lectin-like receptor ectodomains. The expression system was optimized using green fluorescent protein and secreted alkaline phosphatase, easily quantifiable markers of recombinant protein production. We describe an application of this approach to the recombinant protein production and characterization of native rat NKR-P1B and Clr-11 proteins suitable for further structural and functional studies.
Holocene Critical Zone dynamics in an Alpine catchment inferred from a speleothem multiproxy record: disentangling climate and human influences
Authors: Regattieri Eleonora , Zanchetta Giovanni , Isola Ilaria , Zanella Elena , Drysdale Russell N. , Hellstrom John C. , Zerboni Andrea , Dallai Luigi , Tema Evdokia , Lanci Luca , Costa Emanuele , Magrì Federico
Published: November 2019

Disentangling the effects of climate and human impact on the long-term evolution of the Earth Critical Zone is crucial to understand the array of its potential responses to the ongoing Global Change. This task requires natural archives from which local information about soil and vegetation can be linked directly to climate parameters. Here we present a high-resolution, well-dated, speleothem multiproxy record from the SW Italian Alps, spanning the last ~10,000 years of the present interglacial (Holocene). We correlate magnetic properties and the carbon stable isotope ratio to soil stability and pedogenesis, whereas the oxygen isotope composition is interpreted as primarily related to precipitation amount, modulated at different timescales by changes in precipitation source and seasonality. During the 9.7-2.8 ka period, when anthropic pressure over the catchment was scarce, intervals of enhanced soil erosion are related to climate-driven vegetation contractions and occurred during drier periods. Immediately following the onset of the Iron Age (ca. 2.8 ka), by contrast, periods of enhanced soil erosion coincided with a wetter climate. We propose that the observed changes in the soil response to climate forcing were related to early anthropogenic manipulations of Earth’s surface, which made the ECZ more sensitive to climate oscillations.
A Partial Correlation Screening Approach for Controlling the False Positive Rate in Sparse Gaussian Graphical Models
Authors: Lafit Ginette , Tuerlinckx Francis , Myin-Germeys Inez , Ceulemans Eva
Published: November 2019

Gaussian Graphical Models (GGMs) are extensively used in many research areas, such as genomics, proteomics, neuroimaging, and psychology, to study the partial correlation structure of a set of variables. This structure is visualized by drawing an undirected network, in which the variables constitute the nodes and the partial correlations the edges. In many applications, it makes sense to impose sparsity (i.e., some of the partial correlations are forced to zero) as sparsity is theoretically meaningful and/or because it improves the predictive accuracy of the fitted model. However, as we will show by means of extensive simulations, state-of-the-art estimation approaches for imposing sparsity on GGMs, such as the Graphical lasso, ℓ1regularized nodewise regression, and joint sparse regression, fall short because they often yield too many false positives (i.e., partial correlations that are not properly set to zero). In this paper we present a new estimation approach that allows to control the false positive rate better. Our approach consists of two steps: First, we estimate an undirected network using one of the three state-of-the-art estimation approaches. Second, we try to detect the false positives, by flagging the partial correlations that are smaller in absolute value than a given threshold, which is determined through cross-validation; the flagged correlations are set to zero. Applying this new approach to the same simulated data, shows that it indeed performs better. We also illustrate our approach by using it to estimate (1) a gene regulatory network for breast cancer data, (2) a symptom network of patients with a diagnosis within the nonaffective psychotic spectrum and (3) a symptom network of patients with PTSD.
Secure dynamic multiparty quantum private comparison
Authors: Abulkasim Hussein , Farouk Ahmed , Hamad Safwat , Mashatan Atefeh , Ghose Shohini
Published: November 2019

We propose a feasible and efficient dynamic multiparty quantum private comparison protocol that is fully secure against participant attacks. In the proposed scheme, two almost-dishonest third parties generate two random keys and send them to all participants. Every participant independently encrypts their private information with the encryption keys and sends it to the third parties. The third parties can analyze the equality of all or some participants’ secrets without gaining access to the secret information. New participants can dynamically join the protocol without the need for any additional conditions in the protocol. We provide detailed correctness and security analysis of the proposed protocol. Our security analysis of the proposed protocol against both inside and outside attacks proves that attackers cannot extract any secret information.
Long-term monitoring in a microfluidic system to study tumour spheroid response to chronic and cycling hypoxia
Authors: Grist Samantha M. , Nasseri S. Soroush , Laplatine Loïc , Schmok Jonathan C. , Yao Dickson , Hua Jessica , Chrostowski Lukas , Cheung Karen C.
Published: November 2019

We demonstrate the application of a microfluidic platform combining spatiotemporal oxygen control and long-term microscopy monitoring to observe tumour spheroid response to hypoxia. The platform is capable of recreating physiologically-relevant low and cycling oxygen levels not attainable in traditional cell culture environments, while image-based monitoring visualizes cell response to these physiologically-relevant conditions. Monitoring spheroid cultures during hypoxic exposure allows us to observe, for the first time, that spheroids swell and shrink in response to time-varying oxygen profiles switching between 0% and 10% O2; this swelling-shrinkage behaviour appears to be driven by swelling of individual cells within the spheroids. We also apply the system to monitoring tumour models during anticancer treatment under varying oxygen conditions. We observe higher uptake of the anticancer agent doxorubicin under a cycling hypoxia profile than under either chronic hypoxia or in vitro normoxia, and the two-photon microscopy monitoring facilitated by our system also allows us to observe heterogeneity in doxorubicin uptake within spheroids at the single-cell level. Combining optical sectioning microscopy with precise spatiotemporal oxygen control and 3D culture opens the door for a wide range of future studies on microenvironmental mechanisms driving cancer progression and resistance to anticancer therapy. These types of studies could facilitate future improvements in cancer diagnostics and treatment.
Spatiotemporal perturbations in paced finger tapping suggest a common mechanism for the processing of time errors
Authors: López Sabrina Laura , Laje Rodrigo
Published: November 2019

Paced finger tapping is a sensorimotor synchronization task where a subject has to keep pace with a metronome while the time differences (asynchronies) between each stimulus and its response are recorded. A usual way to study the underlying error correction mechanism is to perform unexpected temporal perturbations to the stimuli sequence. An overlooked issue is that at the moment of a temporal perturbation two things change: the stimuli period (a parameter) and the asynchrony (a variable). In terms of experimental manipulation, it would be desirable to have separate, independent control of parameter and variable values. In this work we perform paced finger tapping experiments combining simple temporal perturbations (tempo step change) and spatial perturbations with temporal effect (raised or lowered point of contact). In this way we decouple the parameter-and-variable confounding, performing novel perturbations where either the parameter or the variable changes. Our results show nonlinear features like asymmetry and are compatible with a common error correction mechanism for all types of asynchronies. We suggest taking this confounding into account when analyzing perturbations of any kind in finger tapping tasks but also in other areas of sensorimotor synchronization, like music performance experiments and paced walking in gait coordination studies.
Histopathology Feature Mining and Association with Hyperspectral Imaging for the Detection of Squamous Neoplasia
Authors: Lu Guolan , Wang Dongsheng , Qin Xulei , Muller Susan , Little James V. , Wang Xu , Chen Amy Y. , Chen Georgia , Fei Baowei
Published: November 2019

Hyperspectral imaging (HSI) is a noninvasive optical modality that holds promise for early detection of tongue lesions. Spectral signatures generated by HSI contain important diagnostic information that can be used to predict the disease status of the examined biological tissue. However, the underlying pathophysiology for the spectral difference between normal and neoplastic tissue is not well understood. Here, we propose to leverage digital pathology and predictive modeling to select the most discriminative features from digitized histological images to differentiate tongue neoplasia from normal tissue, and then correlate these discriminative pathological features with corresponding spectral signatures of the neoplasia. We demonstrated the association between the histological features quantifying the architectural features of neoplasia on a microscopic scale, with the spectral signature of the corresponding tissue measured by HSI on a macroscopic level. This study may provide insight into the pathophysiology underlying the hyperspectral dataset.
Revealing the respiratory system of the coffee berry borer (Hypothenemus hampei; Coleoptera: Curculionidae: Scolytinae) using micro-computed tomography
Authors: Alba-Tercedor Javier , Alba-Alejandre Ignacio , Vega Fernando E.
Published: November 2019

The coffee berry borer (Hypothenemus hampei) is the most economically important insect pest of coffee globally. Micro-computed tomography (micro-CT) was used to reconstruct the respiratory system of this species for the first time; this is the smallest insect (ca. 2 mm long) for which this has been done to date. Anatomical details of the spiracles and tracheal tubes are described, images presented, and new terms introduced. The total volume and the relationship between tracheal lumen diameter, length and volume are also presented. The total length of the tracheal tubes are seventy times the length of the entire animal. Videos and a 3D model for use with mobile devices are included as supplementary information; these could be useful for future research and for teaching insect anatomy to students and the public in general.
Quantitative approach to realization of ultrasonic grain refinement of Al-7Si-2Cu-1Mg alloy
Authors: Kim Soo-Bae , Cho Young-Hee , Jo Min-Su , Jung Jae-Gil , Lee Young-Kook , Lee Jung-Moo
Published: November 2019

Ultrasonic melt treatment (UST) was applied to Al-7Si-2Cu-1Mg melt at various temperatures of 620, 650, 700 and 785 °C. MgAl2O4 particles which were often found to be densely populated along oxide films, became effectively dispersed and well-wetted by UST. Transmission electron microscopy work combined with crystallography analysis clearly indicates that MgAl2O4 particles can act as α-Al nucleation site with the aid of UST. However, with UST, grain refinement occurred only at temperature of 620 °C and the grain size increased from 97 to 351 μm with increase of melt temperature to 785 °C for UST. In quantitative analysis of grain size and MgAl2O4 particle diameter, it was found that ultrasonic de-agglomeration decreased mean particle size of the MgAl2O4 particles, significantly reducing size from 1.2 to 0.4 μm when temperature increased from 620 to 785 °C. Such a size reduction with increased number of MgAl2O4 particles does not always guarantee grain refinement. Thus, in this work, detailed condition for achieving grain refinement by UST is discussed based on quantitative measurement. Furthermore, we tried to suggest the most valid grain refinement mechanism among the known mechanisms by investigation of the relationship between grain size and particle size with variation of melt temperature.
Cardiac mitochondrial plasticity and thermal sensitivity in a fish inhabiting an artificially heated ecosystem
Authors: Pichaud Nicolas , Ekström Andreas , Breton Sophie , Sundström Fredrik , Rowinski Piotr , Blier Pierre U. , Sandblom Erik
Published: November 2019

Some evidence suggests that cardiac mitochondrial functions might be involved in the resilience of ectotherms such as fish to environmental warming. Here, we investigated the effects of acute and chronic changes in thermal regimes on cardiac mitochondrial plasticity and thermal sensitivity in perch (Perca fluviatilis) from an artificially heated ecosystem; the “Biotest enclosure” (~25 °C), and from an adjacent area in the Baltic Sea with normal temperatures (reference, ~16 °C). We evaluated cardiac mitochondrial respiration at assay temperatures of 16 and 25 °C, as well as activities of lactate dehydrogenase (LDH) and citrate synthase (CS) in Biotest and reference perch following 8 months laboratory-acclimation to either 16 or 25 °C. While both populations exhibited higher acute mitochondrial thermal sensitivity when acclimated to their natural habitat temperatures, this sensitivity was lost when Biotest and reference fish were acclimated to 16 and 25 °C, respectively. Moreover, reference fish displayed patterns of metabolic thermal compensation when acclimated to 25 °C, whereas no changes were observed in Biotest perch acclimated to 16 °C, suggesting that cardiac mitochondrial metabolism of Biotest fish expresses local adaptation. This study highlights the adaptive responses of cardiac mitochondria to environmental warming, which can impact on fish survival and distribution in a warming climate.
Access site complications following Impella-supported high-risk percutaneous coronary interventions
Authors: Johannsen Laura , Mahabadi Amir A. , Totzeck Matthias , Krueger Andrea , Jánosi Rolf Alexander , Rassaf Tienush , Al-Rashid Fadi
Published: November 2019

Mechanical circulatory support (MCS) devices are increasingly used to provide hemodynamic stability for patients with severe coronary artery disease, comorbidities, and/or impaired hemodynamics during high-risk percutaneous coronary interventions (PCI). Vascular access site complications, particularly those due to the use of large-bore sheaths, may limit outcomes in these patients. The aim of this study was to investigate the incidence and predictors of vascular complications in protected high-risk PCIs. Therefore, we included patients undergoing high-risk PCI with an Impella device from January 2016 to August 2018. Vascular complications were graded according to ‘Valve Academic Research Consortium-2’, a definition routinely used in transcatheter valve implantation procedures. In total, 61 patients (mean age 72 ± 11 years, 79% male, SYNTAX score 33 ± 7) were included, and angiographic- and fluoroscopic-guided vascular access was used for Impella implantation in all patients. Major vascular complications occurred in 5 male patients (8%). All major vascular complications were treated conservatively without the need for surgical intervention, and only one patient received a transfusion of three erythrocyte concentrates. Regression analysis revealed that patients with peripheral arterial disease of the lower extremities are at higher risk of major vascular complications. In conclusion, the utilization of Impella using a standardized protocol for angiographic- and fluoroscopic-guided vascular access was associated with a low rate of vascular complications.