bluuebunny/crossref_metadata_2025 huggingface dataset:
Algebraic Flame Surface Density Modelling of High Pressure Turbulent Premixed Bunsen Flames
Authors: Rasool R. , Chakraborty N. , Klein M.
Published: April 2020

Performance of representative algebraic flame surface density (FSD) models have been a-priori assessed based on a direct numerical simulation database consisting of four turbulent premixed Bunsen flames at four different pressure levels. Results indicate that for a given resolution of the flame front, the considered algebraic FSD closures perform in a qualitatively similar manner irrespective of pressure variation. However, for a given computational mesh, the performance deteriorates as flame thickness decreases with increasing pressure. Additionally, the contribution of the subgrid scale surface-filtered density-weighted tangential diffusion component of the displacement speed tends to increase with pressure increment, further complicating the modelling of FSD. Further analysis also indicate that the inner cut-off scale normalized by the thermal flame thickness increases with increasing pressure, possibly due to the presence of Darrieus–Landau instability which is more likely to occur at higher pressure due to a larger ratio of hydrodynamic length scale to thermal flame thickness.
Mouse single oocyte imaging by MALDI-TOF MS for lipidomics
Authors: Bodzon-Kulakowska Anna , Arena Roberta , Mielczarek Przemyslaw , Hartman Kinga , Kozoł Paulina , Gibuła-Tarlowska Ewa , Wrobel Tomasz P. , Gąsior Łukasz , Polański Zbigniew , Ptak Grazyna E. , Suder Piotr
Published: April 2020

Reproductive cells are a very special kind of material for the analysis. Depending on the species, their dimensions allow for the application of mass spectrometry imaging-based techniques to receive a reasonable data for interpretation of their condition without any additional sample preparation steps, except for typical sample preparation characteristic for IMS protocols. A comparison between lipid profiles of oocytes could answer the question of the overall quality of the cells in the function of time or conditions of storage. Even tiny differences in the lipid profiles, but still detectable by bioinformatic analysis, could be crucial for the estimation of the conditions of the cells in various stages of development or aging. In our study, MALDI-TOF/TOF MSI was used to analyze and visualize the single oocytes. We deposited the cells on the transparent indium-tin-oxide (ITO) glass and marked their positions, which allowed for the fast localization of the cells and precise laser targeting in the ion source. We also optimized the usage of different MALDI matrices and different approaches. The proposed way of measurement allows analyzing quite a significant quantity of oocytes in a reasonably short time. During the analysis, the lipid composition of the single cell was successfully estimated in a conventional usage of the MALDI ion source, and the localization of lipids was confirmed by imaging mass spectrometry (IMS) analysis. The observed quantity of the lipids allowed for the application of the LIFT™ technique to obtain MS/MS spectra sufficient for lipids’ unambiguous identification. We hope that our idea of the oocyte analysis will help to elucidate chemical changes that accompany different processes in which oocytes are involved. There could be such fascinating phenomena as the oocyte maturation, changes in the lipid components during their storage, and much more.
“For Me, the Anorexia is Just a Symptom, and the Cause is the Autism”: Investigating Restrictive Eating Disorders in Autistic Women
Authors: Brede Janina , Babb Charli , Jones Catherine , Elliott Mair , Zanker Cathy , Tchanturia Kate , Serpell Lucy , Fox John , Mandy Will
Published: April 2020

Autistic women are overrepresented among people in treatment for Anorexia Nervosa (AN). The current study aimed to: (1) better understand how AN develops and persists in autistic individuals from the perspective of autistic women, parents and healthcare professionals; (2) derive a theoretical model of restrictive eating difficulties in autism. We conducted 44 semi-structured interviews and used Thematic Analysis to identify patterns of meaning across the data. Themes related to sensory sensitivities, social interaction and relationships, sense of self and identity, difficulties with emotions, thinking styles, and a need for control and predictability. We developed a model of potential autism-specific mechanisms underlying restrictive eating difficulties. This study generated novel insights, which have the potential to inform treatment adaptations following empirical testing.
Low impact of two LED colors on nocturnal insect abundance and bat activity in a peri-urban environment
Authors: Bolliger Janine , Hennet Tom , Wermelinger Beat , Blum Stephan , Haller Jörg , Obrist Martin K.
Published: April 2020

Artificial light at night (ALAN) is an important driver of change in ecological environments of the 21th century. We investigated the impact on nocturnal insect abundance and bat activity of two LED light colors (warm-white 2700 K, cold-white 6500 K) in a peri-urban environment. Bat activity (predominantly Pipistrellus pipistrellus) was largely driven by prey availability (insects), while insect abundance was responsive to nightly weather conditions (precipitation, temperature). Thus, both insects and bats were not differentially responsive to cold-white or warm-white LEDs. These findings are largely in contrast with literature, particularly for insects. However, as most published experiments on ALAN were conducted in areas that were lit solely for the purpose of the experiment, we would like to bring forward that (1) adaptation to environmental constraints may play a role in peri-urban environments that have been exposed to ALAN for many decades; or (2) impacts of cold-white LEDs on nocturnal insects may be lower than expected, because nocturnal insects adapted to low-light conditions may be put off by cold white light sources (6500 K).
Behavioural and Electrophysiological Responses of Female Anopheles gambiae Mosquitoes to Volatiles from a Mango Bait
Authors: Meza Felician C. , Roberts Joe M. , Sobhy Islam S. , Okumu Fredros O. , Tripet Frederic , Bruce Toby J. A.
Published: April 2020

Attractive Toxic Sugar Baits (ATSB) are used in a “lure-and-kill” approach for management of the malaria vector Anopheles gambiae, but the active chemicals were previously unknown. Here we collected volatiles from a mango, Mangifera indica, juice bait which is used in ATSBs in Tanzania and tested mosquito responses. In a Y-tube olfactometer, female mosquitoes were attracted to the mango volatiles collected 24–48 h, 48–72 h and 72–96 h after preparing the bait but volatiles collected at 96–120 h were no longer attractive. Volatile analysis revealed emission of 23 compounds in different chemical classes including alcohols, aldehydes, alkanes, benzenoids, monoterpenes, sesquiterpenes and oxygenated terpenes. Coupled GC-electroantennogram (GC-EAG) recordings from the antennae of An. gambiae showed robust responses to 4 compounds: humulene, (E)-caryophyllene, terpinolene and myrcene. In olfactometer bioassays, mosquitoes were attracted to humulene and terpinolene. (E)-caryophyllene was marginally attractive while myrcene elicited an avoidance response with female mosquitoes. A blend of humulene, (E)-caryophyllene and terpinolene was highly attractive to females (P < 0.001) when tested against a solvent blank. Furthermore, there was no preference when this synthetic blend was offered as a choice against the natural sample. Our study has identified the key compounds from mango juice baits that attract An. gambiae and this information may help to improve the ATSBs currently used against malaria vectors.
Evaluating for Differences by Race/Ethnicity in the Association Between Income and Gambling Disorder
Authors: Day Brendan , Rosenthal Geoffrey , Adetunji Fiyinfolu , Monaghan Andrea , Scheele Christina , Tracy J. Kathleen
Published: April 2020

Multiple studies show an increased prevalence of gambling disorder among African Americans compared to whites. However, few studies take an analytic approach to understanding differences in risk factors by race/ethnicity. Income is inversely associated with gambling disorder; we hypothesized that this association would vary by race/ethnicity. The main objective was to evaluate whether the association between income and gambling disorder varies by race/ethnicity. With data from the baseline visit of a prospective cohort study, Prevention and Etiology of Gambling Addiction Study in the United States, we used multivariable logistic regression analysis to determine whether the association between income and gambling disorder varies by race/ethnicity. 1164 participants were included in the final analyses. Measures included: demographics (age, sex, race/ethnicity, education, employment, annual household income), veteran status, marital status, homelessness, smoking, substance abuse, alcohol abuse, marijuana use, and lifetime gambling disorder diagnosis as derived from Alcohol Use Disorder and Associated Disabilities Interview Schedule. There was no evidence of effect modification by race/ethnicity in the association between income and gambling disorder (global p value = 0.17). Income was associated with increased odds of gambling disorder, but only for those with low income (< $15,000; OR 2.27, 95% CI 1.46, 3.53). There was no evidence that the effect of income on gambling disorder varies by race/ethnicity. For all race/ethnicities combined, low income was associated with significantly increased odds of gambling disorder (OR 2.27, 95% CI 1.46, 3.53). Further research is needed to better understand racial/ethnic differences in gambling disorder.
Persistent organic pollutants in wood fiber–contaminated sediments from the Baltic Sea
Authors: Dahlberg Anna-Karin , Apler Anna , Vogel Lisa , Wiberg Karin , Josefsson Sarah
Published: April 2020

Purpose

Many coastal areas in the Baltic Sea are contaminated with wood fiber and pollutants from pulp and paper industries. These anthropogenic, organic-rich, sediments (fiberbanks) have not been characterized and knowledge about their role as secondary sources for dispersal of persistent organic pollutants (POPs) is limited. Hence, the aim of this study was to elucidate the fate of POPs and the relationships between sorption (KD and KTOC), sediment type, and compound hydrophobicity (KOW) in fiber-contaminated sediments.

Materials and methods

Paired sediment and pore water samples (n = 24 sites) from three fiber-contaminated areas, located in the Ångermanälven river estuary in northern Sweden, were analyzed for POPs (viz. PCBs, DDT, and HCB) in sediment types representing different fiber content (i.e., fiberbanks, fiber-rich sediments, and natural less fiber impacted sediments). The freely dissolved concentration in sediment pore water was determined by sediment-polyoxymethylene (POM) partitioning. Instrumental analysis was performed using gas chromatography coupled to a triple quadrupole mass spectrometer (GC-MS/MS).

Results and discussion

Higher levels of total organic carbon (TOC) were found in the fiberbank sediment (range 8.6–37%) than in fiber-rich sediment (range 2.0–6.5%) and more natural sediment (range 2.0–2.9%). The sediment concentrations of POPs (dry weight basis) were also found to be significantly (p < 0.05) elevated in fiberbanks compared to the other sediment types. The fraction of DDD (48–66% of Σ6DDX) was larger in fiberbanks than in the other sediment types, likely due to anoxic conditions favoring reductive dechlorination of DDT. When sediment levels were normalized to TOC, HCB displayed similar levels across sediment type, suggesting a more diffuse source pattern than for PCB and DDT. Although significantly higher sorption (KD) of POPs was observed in fiberbanks, pore water levels were still elevated due to high bulk concentrations.

Conclusions

This study shows that fiberbanks are coastal hot spots for POPs in the Baltic Sea and that the levels are of ecotoxicological concern. Although the POPs are more strongly sorbed (KD) to this type of organic rich sediment, the high pore water concentrations in fiberbanks compared to the other sediment types investigated show that the risk of contaminant dispersal via pore water is elevated for fiberbanks.
Corona-Krise
Authors: Scherr Albert
Published: April 2020

Der Beitrag setzt sich mit der Frage auseinander, was den gesellschaftlichen Reaktionen auf die Ausbreitung des Coronavirus zu Grunde liegt. In einer sozialwissenschaftlichen Perspektive wird argumentiert, dass diese nicht zureichend als zwangsläufige politische Konsequenz aus Einsichten der medizinischen Virenforschung verstanden werden können, sondern auch als Folge einer fundamentalen kulturellen Verunsicherung in den Blick zu nehmen sind. Aufgezeigt wird zudem die nationalistische Rahmung der politischen Reaktionen. Abschließend wird darauf auf die Gefahr hingewiesen, dass das, was in einem deklarierten temporären Ausnahmezustand gesellschaftlich durchsetzbar ist, auch unter anderen Bedingungen aktualisiert werden könnte.
Five Years Beyond Sendai—Can We Get Beyond Frameworks?
Authors: Wisner Ben
Published: April 2020

The Sendai Framework for Disaster Risk Reduction 2015–2030 (SFDRR) and its implementation is evaluated after its first five years. A dozen questions that the author and a colleague used in their evaluation of the Hyogo Framework for Action 2005–2015 (HFA) are repeated. Improvements are noted in relation to possible coherence and alignment with other components of the Post-2015 Agenda, especially as regards climate change and urban disasters as well as the higher visibility of civil society and women, and also regarding the specificity of targets and monitoring of governments’ successes. Nevertheless, the overall conclusion is that both the HFA and the SFDRR fail to deal with root causes of disaster. A new, radically proactive leadership role is suggested for the United Nations Office for Disaster Risk Reduction in partnership with civil society in identifying and warning all engaged in Post-2015 Agenda activities of possible creation of new risk by agenda implementation activities, especially for the poor and already-marginalized.
Student perspectives on competency-based portfolios: Does a portfolio reflect their competence development?
Authors: Pool Andrea Oudkerk , Jaarsma A. Debbie C. , Driessen Erik W. , Govaerts Marjan J. B.
Published: April 2020

Introduction Portfolio-based assessments require that learners’ competence development is adequately reflected in portfolio documentation. This study explored how students select and document performance data in their portfolios and how they perceive these data to be representative for their competence development.

Methods Students uploaded performance data in a competency-based portfolio. During one clerkship period, twelve students also recorded an audio diary in which they reflected on experiences and feedback that they perceived to be indicants of their competence development. Afterwards, these students were interviewed to explore the extent to which the performance documentation in the portfolio corresponded with what they considered illustrative evidence of their development. The interviews were analyzed using thematic analysis.

Results Portfolios provide an accurate but fragmented picture of student development. Portfolio documentation was influenced by tensions between learning and assessment, student beliefs about the goal of portfolios, student performance evaluation strategies, the learning environment and portfolio structure.

Discussion This study confirms the importance of taking student perceptions into account when implementing a competency-based portfolio. Students would benefit from coaching on how to select meaningful experiences and performance data for documentation in their portfolios. Flexibility in portfolio structure and requirements is essential to ensure optimal fit between students’ experienced competence development and portfolio content.
QTY Code-designed Water-soluble Fc-fusion Cytokine Receptors Bind to their Respective Ligands
Authors: Hao Shilei , Jin David , Zhang Shuguang , Qing Rui
Published: April 2020

Cytokine release syndrome (CRS), or ‘cytokine storm’, is the leading side effect during chimeric antigen receptor (CAR)-T therapy that is potentially life-threatening. It also plays a critical role in viral infections such as Coronavirus Disease 2019 (COVID-19). Therefore, efficient removal of excessive cytokines is essential for treatment. We previously reported a novel protein modification tool called the QTY code, through which hydrophobic amino acids Leu, Ile, Val and Phe are replaced by Gln (Q), Thr (T) and Tyr (Y). Thus, the functional detergent-free equivalents of membrane proteins can be designed. Here, we report the application of the QTY code on six variants of cytokine receptors, including interleukin receptors IL4Rα and IL10Rα, chemokine receptors CCR9 and CXCR2, as well as interferon receptors IFNγR1 and IFNλR1. QTY-variant cytokine receptors exhibit physiological properties similar to those of native receptors without the presence of hydrophobic segments. The receptors were fused to the Fc region of immunoglobulin G (IgG) protein to form an antibody-like structure. These QTY code-designed Fc-fusion receptors were expressed in Escherichia coli and purified. The resulting water-soluble fusion receptors bind to their respective ligands with Kd values affinity similar to isolated native receptors. Our cytokine receptor–Fc-fusion proteins potentially serve as an antibody-like decoy to dampen the excessive cytokine levels associated with CRS and COVID-19 infection.
Dietrich Bonhoeffer's Letter to Mahatma Gandhi
Authors: GREEN CLIFFORD
Published: April 2020

This first publication of the newly-found letter to Gandhi from Dietrich Bonhoeffer is a window into his thinking in the early 1930s, a time of personal formation and of resistance to National Socialism. Western Christianity needed ‘a Christian peace movement’, and Bonhoeffer wanted to learn from Gandhi's movement ‘the meaning of Christian life, of real community life, of truth and love in reality’. The letter includes Bonhoeffer's critique of Western culture and the Church in Europe and America, his hopes for a Church regenerated by the Sermon on the Mount, and his appreciation and critique of Karl Barth
Atmospheric Scientists Show Resilience in the Face of Lockdowns
Authors: Palmer Jane
Published: April 2020

As businesses, schools, and entire cities shut down to prevent the spread of the coronavirus, scientists have been forced to adapt to radically altered working conditions and data collection techniques.
Pharmacological inhibition of mTOR attenuates replicative cell senescence and improves cellular function via regulating the STAT3-PIM1 axis in human cardiac progenitor cells
Authors: Park Ji Hye , Lee Na Kyoung , Lim Hye Ji , Ji Seung taek , Kim Yeon-Ju , Jang Woong Bi , Kim Da Yeon , Kang Songhwa , Yun Jisoo , Ha Jong seong , Kim Hyungtae , Lee Dongjun , Baek Sang Hong , Kwon Sang-Mo
Published: April 2020

The mammalian target of rapamycin (mTOR) signaling pathway efficiently regulates the energy state of cells and maintains tissue homeostasis. Dysregulation of the mTOR pathway has been implicated in several human diseases. Rapamycin is a specific inhibitor of mTOR and pharmacological inhibition of mTOR with rapamycin promote cardiac cell generation from the differentiation of mouse and human embryonic stem cells. These studies strongly implicate a role of sustained mTOR activity in the differentiating functions of embryonic stem cells; however, they do not directly address the required effect for sustained mTOR activity in human cardiac progenitor cells. In the present study, we evaluated the effect of mTOR inhibition by rapamycin on the cellular function of human cardiac progenitor cells and discovered that treatment with rapamycin markedly attenuated replicative cell senescence in human cardiac progenitor cells (hCPCs) and promoted their cellular functions. Furthermore, rapamycin not only inhibited mTOR signaling but also influenced signaling pathways, including STAT3 and PIM1, in hCPCs. Therefore, these data reveal a crucial function for rapamycin in senescent hCPCs and provide clinical strategies based on chronic mTOR activity.
Biological sex classification with structural MRI data shows increased misclassification in transgender women
Authors: Flint Claas , Förster Katharina , Koser Sophie A. , Konrad Carsten , Zwitserlood Pienie , Berger Klaus , Hermesdorf Marco , Kircher Tilo , Nenadic Igor , Krug Axel , Baune Bernhard T. , Dohm Katharina , Redlich Ronny , Opel Nils , Arolt Volker , Hahn Tim , Jiang Xiaoyi , Dannlowski Udo , Grotegerd Dominik
Published: April 2020

Transgender individuals (TIs) show brain-structural alterations that differ from their biological sex as well as their perceived gender. To substantiate evidence that the brain structure of TIs differs from male and female, we use a combined multivariate and univariate approach. Gray matter segments resulting from voxel-based morphometry preprocessing of N = 1753 cisgender (CG) healthy participants were used to train (N = 1402) and validate (20% holdout N = 351) a support-vector machine classifying the biological sex. As a second validation, we classified N = 1104 patients with depression. A third validation was performed using the matched CG sample of the transgender women (TW) application sample. Subsequently, the classifier was applied to N = 26 TW. Finally, we compared brain volumes of CG-men, women, and TW-pre/post treatment cross-sex hormone treatment (CHT) in a univariate analysis controlling for sexual orientation, age, and total brain volume. The application of our biological sex classifier to the transgender sample resulted in a significantly lower true positive rate (TPR-male = 56.0%). The TPR did not differ between CG-individuals with (TPR-male = 86.9%) and without depression (TPR-male = 88.5%). The univariate analysis of the transgender application-sample revealed that TW-pre/post treatment show brain-structural differences from CG-women and CG-men in the putamen and insula, as well as the whole-brain analysis. Our results support the hypothesis that brain structure in TW differs from brain structure of their biological sex (male) as well as their perceived gender (female). This finding substantiates evidence that TIs show specific brain-structural alterations leading to a different pattern of brain structure than CG-individuals.
Cerebrospinal fluid endocannabinoid levels in Gilles de la Tourette syndrome
Authors: Müller-Vahl Kirsten R. , Bindila Laura , Lutz Beat , Musshoff Frank , Skripuletz Thomas , Baumgaertel Charlotte , Sühs Kurt-Wolfram
Published: April 2020

Gilles de la Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by the presence of motor and vocal tics as well as psychiatric comorbidities such as attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), depression, and anxiety. The underlying cause of the disease is still unknown, but several lines of evidence suggest a paramount role of the dopaminergic system. Based on the clinical observation that cannabis-based medicine including cannabis and delta-9-tetrahydrocannabinol (THC, dronabinol) may improve TS, alternatively, an involvement of the endocannabinoid system (ECS) has been suggested. In this study we measured cerebrospinal fluid (CSF) levels of the two most important endocannabinoids “N”-arachidonoylethanolamine (AEA, anandamide) and 2-arachidonoylglycerol (2-AG), the endocannabinoid-like molecule palmitoyl ethanolamide (PEA), and the lipid arachidonic acid (AA) in a sample of adult patients with TS (n = 20) compared with controls (n = 19) using liquid-liquid lipid extraction and simultaneous quantification by liquid chromatography multiple reaction monitoring (LC/MRM). CSF levels of AEA (p = 0.0018), 2-AG (p = 0.0003), PEA (p = 0.02), and AA (p < 0.0001) were significantly increased in TS compared with controls. Levels of 2-AG correlated with the severity of comorbid ADHD (p < 0.01). This is the first study, demonstrating alterations in the ECS suggesting an involvement of this system in the pathophysiology of TS. It can be speculated that elevated endocannabinoid levels either represent secondary changes in order to compensate for alterations in other neurotransmitter systems such as the dopaminergic system, are simply an epiphenomenon or, alternatively, represent the primary cause of TS.
High cell densities favor lysogeny: induction of an H20 prophage is repressed by quorum sensing and enhances biofilm formation in Vibrio anguillarum
Authors: Tan Demeng , Hansen Mads Frederik , de Carvalho Luís Nunes , Røder Henriette Lyng , Burmølle Mette , Middelboe Mathias , Lo Svenningsen Sine
Published: April 2020

Temperate ϕH20-like phages are repeatedly identified at geographically distinct areas as free phage particles or as prophages of the fish pathogen Vibrio anguillarum. We studied mutants of a lysogenic isolate of V. anguillarum locked in the quorum-sensing regulatory modes of low (ΔvanT) and high (ΔvanO) cell densities by in-frame deletion of key regulators of the quorum-sensing pathway. Remarkably, we find that induction of the H20-like prophage is controlled by the quorum-sensing state of the host, with an eightfold increase in phage particles per cell in high-cell-density cultures of the quorum-sensing-deficient ΔvanT mutant. Comparative studies with prophage-free strains show that biofilm formation is promoted at low cell density and that the H20-like prophage stimulates this behavior. In contrast, the high-cell-density state is associated with reduced prophage induction, increased proteolytic activity, and repression of biofilm. The proteolytic activity may dually function to disperse the biofilm and as a quorum-sensing-mediated antiphage strategy. We demonstrate an intertwined regulation of phage-host interactions and biofilm formation, which is orchestrated by host quorum-sensing signaling, suggesting that increased lysogeny at high cell density is not solely a strategy for phages to piggy-back the successful bacterial hosts but is also a host strategy evolved to take control of the lysis-lysogeny switch to promote host fitness.
Highly efficient blue organic light-emitting diodes based on carbene-metal-amides
Authors: Conaghan Patrick J. , Matthews Campbell S. B. , Chotard Florian , Jones Saul T. E. , Greenham Neil C. , Bochmann Manfred , Credgington Dan , Romanov Alexander S.
Published: April 2020

Carbene-metal-amides are soluble and thermally stable materials which have recently emerged as emitters in high-performance organic light-emitting diodes. Here we synthesise carbene-metal-amide photoemitters with CF3-substituted ligands to show sky-blue to deep-blue photoluminescence from charge-transfer excited states. We demonstrate that the emission colour can be adjusted from blue to yellow and observe that the relative energies of charge transfer and locally excited triplet states influence the performance of the deep-blue emission. High thermal stability and insensitivity to aggregation-induced luminescence quenching allow us to fabricate organic light-emitting diodes in both host-free and host-guest architectures. We report blue devices with a peak external quantum efficiency of 17.3% in a host-free emitting layer and 20.9% in a polar host. Our findings inform the molecular design of the next generation of stable blue carbene-metal-amide emitters.
Automatic diagnosis of the 12-lead ECG using a deep neural network
Authors: Ribeiro Antônio H. , Ribeiro Manoel Horta , Paixão Gabriela M. M. , Oliveira Derick M. , Gomes Paulo R. , Canazart Jéssica A. , Ferreira Milton P. S. , Andersson Carl R. , Macfarlane Peter W. , Meira Wagner , Schön Thomas B. , Ribeiro Antonio Luiz P.
Published: April 2020

The role of automatic electrocardiogram (ECG) analysis in clinical practice is limited by the accuracy of existing models. Deep Neural Networks (DNNs) are models composed of stacked transformations that learn tasks by examples. This technology has recently achieved striking success in a variety of task and there are great expectations on how it might improve clinical practice. Here we present a DNN model trained in a dataset with more than 2 million labeled exams analyzed by the Telehealth Network of Minas Gerais and collected under the scope of the CODE (Clinical Outcomes in Digital Electrocardiology) study. The DNN outperform cardiology resident medical doctors in recognizing 6 types of abnormalities in 12-lead ECG recordings, with F1 scores above 80% and specificity over 99%. These results indicate ECG analysis based on DNNs, previously studied in a single-lead setup, generalizes well to 12-lead exams, taking the technology closer to the standard clinical practice.
Membrane mediated toppling mechanism of the folate energy coupling factor transporter
Authors: Faustino Ignacio , Abdizadeh Haleh , Souza Paulo C. T. , Jeucken Aike , Stanek Weronika K. , Guskov Albert , Slotboom Dirk J. , Marrink Siewert J.
Published: April 2020

Energy coupling factor (ECF) transporters are responsible for the uptake of micronutrients in bacteria and archaea. They consist of an integral membrane unit, the S-component, and a tripartite ECF module. It has been proposed that the S-component mediates the substrate transport by toppling over in the membrane when docking onto an ECF module. Here, we present multi-scale molecular dynamics simulations and in vitro experiments to study the molecular toppling mechanism of the S-component of a folate-specific ECF transporter. Simulations reveal a strong bending of the membrane around the ECF module that provides a driving force for toppling of the S-component. The stability of the toppled state depends on the presence of non-bilayer forming lipids, as confirmed by folate transport activity measurements. Together, our data provide evidence for a lipid-dependent toppling-based mechanism for the folate-specific ECF transporter, a mechanism that might apply to other ECF transporters.
Identification of a phosphorylation site on Ulk1 required for genotoxic stress-induced alternative autophagy
Authors: Torii Satoru , Yamaguchi Hirofumi , Nakanishi Akira , Arakawa Satoko , Honda Shinya , Moriwaki Kenta , Nakano Hiroyasu , Shimizu Shigeomi
Published: April 2020

Alternative autophagy is an autophagy-related protein 5 (Atg5)-independent type of macroautophagy. Unc51-like kinase 1 (Ulk1) is an essential initiator not only for Atg5-dependent canonical autophagy but also for alternative autophagy. However, the mechanism as to how Ulk1 differentially regulates both types of autophagy has remained unclear. In this study, we identify a phosphorylation site of Ulk1 at Ser746, which is phosphorylated during genotoxic stress-induced alternative autophagy. Phospho-Ulk1746 localizes exclusively on the Golgi and is required for alternative autophagy, but not canonical autophagy. We also identify receptor-interacting protein kinase 3 (RIPK3) as the kinase responsible for genotoxic stress-induced Ulk1746 phosphorylation, because RIPK3 interacts with and phosphorylates Ulk1 at Ser746, and loss of RIPK3 abolishes Ulk1746 phosphorylation. These findings indicate that RIPK3-dependent Ulk1746 phosphorylation on the Golgi plays a pivotal role in genotoxic stress-induced alternative autophagy.
Conserved in-ovo cranial ossification sequences of extant saurians allow estimation of embryonic dinosaur developmental stages
Authors: Chapelle Kimberley E. J. , Fernandez Vincent , Choiniere Jonah N.
Published: April 2020

Dinosaur embryos are among the rarest of fossils, yet they provide a unique window into the palaeobiology of these animals. Estimating the developmental stage of dinosaur embryos is hindered by the lack of a quantitative method for age determination, by the scarcity of material, and by the difficulty in visualizing that material. Here we present the results of a broad inquiry, using 3D reconstructions from X-ray computed tomography data, into cranial ossification sequences in extant saurian taxa and in well-preserved embryos of the early branching sauropodomorph dinosaur Massospondylus carinatus. Our findings support deep-time conservation of cranial ossification sequences in saurians including dinosaurs, allowing us to develop a new method for estimating the relative developmental percentage of embryos from that clade. We also observe null-generation teeth in the Massospondylus carinatus embryos which get resorbed or shed before hatching, similar to those of geckos. These lines of evidence allow us to confidently estimate that the Massospondylus carinatus embryos are only approximately 60% through their incubation period, much younger than previously hypothesized. The overall consistency of our results with those of living saurians indicates that they can be generalized to other extinct members of that lineage, and therefore our method provides an independent means of assessing the developmental stage of extinct, in-ovo saurians.
Direct evidence of Neanderthal fibre technology and its cognitive and behavioral implications
Authors: Hardy B. L. , Moncel M.-H. , Kerfant C. , Lebon M. , Bellot-Gurlet L. , Mélard N.
Published: April 2020

Neanderthals are often considered as less technologically advanced than modern humans. However, we typically only find faunal remains or stone tools at Paleolithic sites. Perishable materials, comprising the vast majority of material culture items, are typically missing. Individual twisted fibres on stone tools from the Abri du Maras led to the hypothesis of Neanderthal string production in the past, but conclusive evidence was lacking. Here we show direct evidence of fibre technology in the form of a 3-ply cord fragment made from inner bark fibres on a stone tool recovered in situ from the same site. Twisted fibres provide the basis for clothing, rope, bags, nets, mats, boats, etc. which, once discovered, would have become an indispensable part of daily life. Understanding and use of twisted fibres implies the use of complex multi-component technology as well as a mathematical understanding of pairs, sets, and numbers. Added to recent evidence of birch bark tar, art, and shell beads, the idea that Neanderthals were cognitively inferior to modern humans is becoming increasingly untenable.
Nanofabrication of Isoporous Membranes for Cell Fractionation
Authors: Sabirova Ainur , Pisig Florencio , Rayapuram Naganand , Hirt Heribert , Nunes Suzana P.
Published: April 2020

Cell fractionations and other biological separations frequently require several steps. They could be much more effectively done by filtration, if isoporous membranes would be available with high pore density, and sharp pore size distribution in the micro- and nanoscale. We propose a combination of two scalable methods, photolithography and dry reactive ion etching, to fabricate a series of polyester membranes with isopores of size 0.7 to 50 μm and high pore density with a demonstrated total area of 38.5 cm2. The membranes have pore sizes in the micro- and submicro-range, and pore density 10-fold higher than track-etched analogues, which are the only commercially available isoporous polymeric films. Permeances of 220,000 L m−2 h−1bar−1 were measured with pore size 787 nm. The method does not require organic solvents and can be applied to many homopolymeric materials. The pore reduction from 2 to 0.7 μm was obtained by adding a step of chemical vapor deposition. The isoporous system was successfully demonstrated for the organelle fractionation of Arabidopsis homogenates and could be potentially extended to other biological fractionations.
Metabolomic and transcriptomic profiling reveals the alteration of energy metabolism in oyster larvae during initial shell formation and under experimental ocean acidification
Authors: Liu Zhaoqun , Zhang Yukun , Zhou Zhi , Zong Yanan , Zheng Yan , Liu Chang , Kong Ning , Gao Qiang , Wang Lingling , Song Linsheng
Published: April 2020

Marine bivalves secrete calcified shells to protect their soft bodies from predation and damages, which is of great importance for their survival, and for the safety of the coastal ecosystem. In recent years, larval shell formation of marine bivalves has been severely affected by ocean acidification (OA), and previous study indicated that OA might affect such process by disrupting endogenous energy metabolism. Developmental stages from trochophore to D-shape larvae are extremely important for initial shell formation in oyster since a calcified shell was formed to cover the chitin one. In the present study, metabolomic and transcriptomic approaches were employed to investigate the energy metabolism of oyster larvae during initial shell (prodissoconch I, PDI shell) formation and under experimental OA treatment. Totally 230 chemical compounds were identified from the present dataset, most of which were highly expressed in the “middle” stage (early D-shape larvae) which was critical for PDI shell formation since a calcified shell was formed to cover the chitin one. Several compounds such as glucose, glutarylcarnitine (C5), β-hydroxyisovaleroylcarnitine, 5-methylthioadenosine (MTA), myristoleate (14:1n5) and palmitoleate (16:1n7) were identified, which were involved in energy metabolic processes including amino acid oxidation, glycolysis, pentose phosphate pathway and fatty acid metabolism. In addition, mRNA expressions of genes related to protein metabolism, glycolysis, lipid degradation, calcium transport and organic matrix formation activities were significantly down-regulated upon experimental OA. These results collectively suggested that formation of the initial shell in oyster larvae required endogenous energy coming from amino acid oxidation, glycolysis, pentose phosphate pathway and fatty acid metabolism. These metabolic activities could be severely inhibited by experimental OA, which might alter the allocation of endogenous energy. Insufficient endogenous energy supply then suppressed the mobilization of calcium and resulted in a failure or delay in PDI shell formation.
Synthesis, biological activity and molecular modeling study of novel 1,2,4-triazolo[4,3-b][1,2,4,5]tetrazines and 1,2,4-triazolo[4,3-b][1,2,4]triazines
Authors: El-Reedy Ahmed A. M. , Soliman N. K.
Published: April 2020

Different novel 1,2,4-triazolo[4,3-b][1,2,4,5]tetrazines and 1,2,4-triazolo[4,3-b][1,2,4]triazines have been obtained from heterocyclization of 3-substituted-4-amino-5-substituted-amino-1,2,4-triazoles (3a-d) and 3-substituted-4-amino-5-hydrazino-1,2,4-triazoles (9a,b) with (α and β) bifunctional compounds like chloromethyl biphenyl-phosphanoxide, pyruvic acid, phenacyl bromide, diethyl oxalate, triethyl orthoformate, triethyl phosphite, fluorinated benzaldehydes, carbon disulfide and ethyl chloroformate under different experimental settings. Fourier transformer infrared analysis (FTIR), Proton nuclear magnetic resonance (1H NMR) and 13C nuclear magnetic resonance (13C NMR), as well as that of the mass spectral data, were used as the appropriate characterization techniques for the chemical structures of all newly synthesized compounds. The newly prepared compounds were examined as an anti-inflammatory, antibacterial agents (against E. coli (Escherichia coli) and P. aeruginosa (Pseudomonas aeruginosa) as examples for Gram-negative bacteria and S. aureus (Staphylococcus aureus) as examples for Gram-positive bacteria), as well as antifungal (against C. albicans (Candida albicans)) agents. The newly prepared compound showed high antibacterial, antifungal, and anti-inflammatory activities in comparing with the commercial antibiotics Indomethacin, Nalidixic acid, Imipenem, and Nystatin. Docking of the most active compounds was performed depending on the results of antibacterial screening and the anti-inflammatory assay.
Synthesis of mesoporous silica post-loaded by methyl eugenol as an environment-friendly slow-release bio pesticide
Authors: Chen Huayao , Chen Lishen , Shen Zhichuan , Zhou Hongjun , Hao Li , Xu Hua , Zhou Xinhua
Published: April 2020

Salicylaldimine, furfuralimine and benzaldehyde imine were adopted to modify mesoporous silica (MCM) respectively denoted as Sal-MCM, Fur-MCM and Ben-MCM before loading methyl eugenol (Me) for pesticide delivery. Me was adsorbed by Schiff base mesoporous silica without destructing regular hexagonal pore structure verified by the characterization results. DSC result implied that Me in amorphous state which was distributed in the pores of the mesoporous silica. The loading content of Me-Sal-MCM, Me-Fur-MCM and Me-Ben-MCM 67.89%, 73.34% and 73.84% which was higher than Me-MCM without modification (67.35%).Because the electrostatic interaction and π-π interaction between Schiff base and Me strengthened the adsorption capacity of the carrier. And the electrostatic interaction played a more important role in interaction between Me and Schiff base modified mesoporous silica. As a result, Schiff base modified sustained release system also has significantly longer sustained release time with a sequence of Me-Sal-MCM > Me-Ben-MCM > Me-Fur-MCM in release speed in negative correlation with the electric potential sequence. The behaviors of their sustained release performance can be fitted by First order kinetic model before Schiff base modification. After modification, their sustained release behaviors were consistent with Korsmeyer-Peppas equation with non-Fickian diffusion mechanism indicating that main impact on the release process after modification was no longer mainly controlled by the difference of the concentration. Finally, the highest lure rate of the modified MCM (Me-Fur-MCM) equals to the 73% of the pure Me due to its highest BET surface area and strongest interaction with Me among the three Schiff base modified samples. Therefore, the environment-friendly slow-release bio pesticide with long service life was prepared to reduce the damage on the environment caused by pesticide.
Network Systems Pharmacology-Based Mechanism Study on the Beneficial Effects of Vitamin D against Psychosis in Alzheimer’s Disease
Authors: Fan Peihao , Qi Xiguang , Sweet Robert A. , Wang Lirong
Published: April 2020

Alzheimer’s disease (AD) is a chronic neurodegenerative disease with significant financial costs and negative impacts on quality of life. Psychotic symptoms, i.e., the presence of delusions and/or hallucinations, is a frequent complication of AD. About 50% of AD patients will develop psychotic symptoms (AD with Psychosis, or AD + P) and these patients will experience an even more rapid cognitive decline than AD patients without psychosis (AD-P). In a previous analysis on medication records of 776 AD patients, we had shown that use of Vitamin D was associated with delayed time to psychosis in AD patients and Vitamin D was used more by AD-P than AD + P patients. To explore the potential molecular mechanism behind our findings, we applied systems pharmacology approaches to investigate the crosstalk between AD and psychosis. Specifically, we built protein-protein interaction (PPI) networks with proteins encoded by AD- and psychosis-related genes and Vitamin D-perturbed genes. Using network analysis we identified several high-impact genes, including NOTCH4, COMT, CACNA1C and DRD3 which are related to calcium homeostasis. The new findings highlight the key role of calcium-related signaling pathways in AD + P development and may provide a new direction and facilitate hypothesis generation for future drug development.
Looking to recognise: the pre-eminence of semantic over sensorimotor processing in human tool use
Authors: Federico Giovanni , Brandimonte Maria A.
Published: April 2020

Alongside language and bipedal locomotion, tool use is a characterizing activity of human beings. Current theories in the field embrace two contrasting approaches: “manipulation-based” theories, which are anchored in the embodied-cognition view, explain tool use as deriving from past sensorimotor experiences, whereas “reasoning-based” theories suggest that people reason about object properties to solve everyday-life problems. Here, we present results from two eye-tracking experiments in which we manipulated the visuo-perceptual context (thematically consistent vs. inconsistent object-tool pairs) and the goal of the task (free observation or looking to recognise). We found that participants exhibited reversed tools’ visual-exploration patterns, focusing on the tool’s manipulation area under thematically consistent conditions and on its functional area under thematically inconsistent conditions. Crucially, looking at the tools with the aim of recognising them produced longer fixations on the tools’ functional areas irrespective of thematic consistency. In addition, tools (but not objects) were recognised faster in the thematically consistent conditions. These results strongly support reasoning-based theories of tool use, as they indicate that people primarily process semantic rather than sensorimotor information to interact with the environment in an agent’s consistent-with-goal way. Such a pre-eminence of semantic processing challenges the mainstream embodied-cognition view of human tool use.
Toxicology of Heavy Metals to Subsurface Lithofacies and Drillers during Drilling of Hydrocarbon Wells
Authors: Okoro Emmanuel E. , Okolie Amarachi G. , Sanni Samuel E. , Omeje Maxwell
Published: April 2020

This study investigates the toxicological effects of heavy metals on lithofacies of the subsurface in a drilled hydrocarbon well as well as, to the drilling crew and people in an environment. The pollution levels of selected heavy metals were considered alongside their ecological effects during dry and wet seasons. The health hazard potential of human exposures to the metals, were estimated in terms of intensity and time using the USEPA recommended model. The heavy metal concentration for each layer decreased across the lithofacies as follows; Layer 5> Layer 4> Layer 3> Layer 2> Layer 1. The average concentrations of the heavy metals present in the samples obtained from the formation zone, varied significantly and decreased in the order of Al> Zn> Ni> Pb> Cr> Cu> Cd> As> Hg. The highest concentration of Al, Cu, and Zn in this present study were within the maximum allowable limits whereas, those of As, Cd, Hg and Ni were all above their maximum allowable limits. Among the transition metals analysed, the maximum mean daily dose of Pb (9.18 × 10−6 mg/kg/d) and Cr (1.42 × 10−6 mg/kg/d) were confirmed susceptible to human carcinogens and environmental toxins. The estimated hazard quotient shows that the dermal pathway is the most likely route via which the drilling crew and people in the environment can get contaminated. The cancer risk values for the Pb (7.72 × 10−4), Cd (1.35 × 10−1), Ni (9.97 × 10−3), As (1.50 × 10−1) and Cr (3.16 × 10−3) are all above the acceptable values. The cancer risk contribution for each metal was in the order of As> Cd> Ni> Cr> Pb. Layer 5 had the maximum Geo-accumulation index for the heavy metals considered. This higher Geo-accumulation index noted at the depth in Layer 5 may be attributed to the effect of water basin with turbidity currents, deltas, and shallow marine sediment deposits with storm impacted conditions. Also, the pollution from lead (Pb) in the dry season was maximum with an Igeo value> 5 for all the lithofacies considered because of the low background concentration of the metal. During the wet season, the heavy metal pollution rate was moderate for Zn whereas, it was extremely polluted with respect to Pb. The ecological risk potential of Pb shows that the associated ecological risks range from 536 – 664 in the wet season (i.e. extremely strong) and 2810 – 3480 in dry season (extremely strong). The high level of Pb pollution found in the area at such shallow depth may be due to the sedimentary folds possibly caused by the full spectrum of metamorphic rocks and primary flow structures at shallow depths. This was used to identify the environmental sensitivities of the heavy metals during the dry and wet seasons.