bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluid Flow Simulations of a Large-Scale Borehole Leakage Experiment
Authors: Klose Tim , Chaparro M. Carme , Schilling Frank , Butscher Christoph , Klumbach Steffen , Blum Philipp
Published: November 2020

Borehole leakage is a common and complex issue. Understanding the fluid flow characteristics of a cemented area inside a borehole is crucial to monitor and quantify the wellbore integrity as well as to find solutions to minimise existing leakages. In order to improve our understanding of the flow behaviour of cemented boreholes, we investigated experimental data of a large-scale borehole leakage tests by means of numerical modelling using three different conceptual models. The experiment was performed with an autoclave system consisting of two vessels bridged by a cement-filled casing. After a partial bleed-off at the well-head, a sustained casing pressure was observed due to fluid flow through the cement–steel composite. The aim of our simulations is to investigate and quantify the permeability of the cement–steel composite. From our model results, we conclude that the flow occurred along a preferential flow path at the cement–steel interface. Thus, the inner part of the cement core was impermeable during the duration of the experiment. The preferential flow path can be described as a highly permeable and highly porous area with an aperture of about $$5\,\upmu \mathrm{m}$$

5

μ
m

and a permeability of $$3 \cdot 10^{-12}\,\mathrm{m}^{2}$$

3
·

10

-
12

m

2

(3 Darcy). It follows that the fluid flow characteristics of a cemented area inside a borehole cannot be described using one permeability value for the entire cement–steel composite. Furthermore, it can be concluded that the quality of the cement and the filling process regarding the cement–steel interface is crucial to minimize possible well leakages.
Soil Amendment with Biochar, Hydrochar and Compost Mitigates the Accumulation of Emerging Pollutants in Rocket Salad Plants
Authors: Parlavecchia Marco , Carnimeo Claudia , Loffredo Elisabetta
Published: November 2020

The uptake of organic pollutants by agricultural plants and their accumulation in edible parts cause serious health problems to animals and humans. In this study, we used carbon-rich materials, such as biochar (BC), hydrochar (HC), and green compost (GC), to reduce the absorption and accumulation of three pesticides, imidacloprid (IMI), boscalid (BOS), and metribuzin (MET) and two endocrine disruptors, 4-tert-octylphenol (OP) and bisphenol A (BPA), in rocket salad plants (Eruca vesicariaL.). After an experimental period of 35 days, compared to unamended soil, the addition of BC, HC, and GC significantly reduced chemical phytotoxicity, increasing the elongation of the aerial plant parts by 26, 25, and 39%, respectively, whereas GC increased the fresh biomass by 21%. The assessment of residual chemicals in both soil and plant tissues indicated that any amendment was very effective in enhancing the retention of all compounds in soil, thus reducing their uptake by plants. Averagely for the five compounds, the reduction of plant absorption followed the trend BC > HC > GC. In particular, the presence of BC decreased the chemical residues in the plants from a minimum of 71% (IMI) to a maximum of 91% (OP). The overall results obtained encourage the incorporation in soil of C-rich materials, especially BC, to protect leafy food plants from the absorption and toxicity of organic pollutants of a wide range of hydrophobicity, with relevant benefits for consumers.
Saybolt color prediction for condensates and light crude oils
Authors: Leam Jia Jia , Khor Cheng Seong , Dass Sarat C.
Published: November 2020

Saybolt color determination is one of the techniques used to evaluate the quality of petroleum products as an indicator of the degree of refinement. As color is a property readily observed by operators, conventional procedures require operators to determine Saybolt color either through direct visual observation or through Saybolt chromometers. These methods are subjective due to the variability in perception of colors across different observers and may be influenced by external factors such as the level of illuminance. Digital oil color analyzers, on the other hand, cost almost four times as much as Saybolt chromometers. An alternative approach to color measurement is to develop a correlation model between Saybolt color with the physical and chemical properties of condensates and light crude oils from Malaysian oil and gas fields. This work applies several multiple linear regression techniques (such as stepwise regression) performed both manually and using the R software (version 3.6.1) to obtain statistically significant results. The step, regsubsets and glmulti functions from R are explored to develop the correlation model which predicts Saybolt color using only identified key properties, overcoming the possible drawbacks associated with conventional laboratory analysis. The models developed through these different techniques are analyzed and compared based on criteria indicated through the coefficient of multiple determination, R2 and F-tests to infer on suitable regression approaches. Results obtained from these regression methods for models with and without interaction terms report deviations of less than 5% for 75% of the samples used for validation.
Surgical management of oncologic patient during and after the COVID-19 outbreak: practical recommendations from the Italian society of Surgical Oncology
Authors:   SICO (Italian Society of Surgical Oncology), Cavaliere Davide , Parini Dario , Marano Luigi , Cipriani Federica , Di Marzo Francesco , Macrì Antonio , D’Ugo Domenico , Roviello Franco , Gronchi Alessandro
Published: November 2020

The recent outbreak of COVID-19 in Italy caused a limitation of the resources of the health system, which necessarily led to their rationalization in the critical phase (phase 1) and a reorganization of the system in the following phase (phase 2). The Italian Society of Oncological Surgery–SICO has drafted these practical recommendations, calibrated on the most recent scientific literature and taking into account current health regulations and common sense. Surgical activity during phase 1 and 2 should follow a dynamic model, considering architectural structures, hospital mission, organizational models. Surgical delay should not affect oncological prognosis. However, COVID-19-positive cancer patients should be postponed until the infection is cured. The patients to consider more carefully before delaying surgery are those who have completed neoadjuvant therapy, patients with high biological aggressiveness tumors or without therapeutic alternatives. The multidisciplinary discussions are fundamental for sharing clinical decisions; videoconference meetings are preferable and use of telemedicine for follow-up is recommended. Especially in phase 1, maximum effort must be made to reduce the spread of the pandemic. Prefer intra-corporeal rather than open anastomosis during laparoscopy and mechanical rather than hand-sewn anastomosis in open surgery. Consider PPE for caregivers during stoma management. Minimal invasive surgery is not discouraged, because there is little evidence for augmented risk. Specific procedures have to be followed and use of energy devices has to be limited. Training programs with COVID-19 + patients are not recommended. All staff in OR should be trained with specific courses on specific PPE use. Differentiate recommendations are presented for every district cancer. Surgical oncology during phase 2 should be guaranteed by individual and distinct protocols and pathways between cancer patients and COVID-19 + patients with resources specifically addressed to the two distinct kind of patients to limit diagnostic/therapeutic interferences or slowdowns. These recommendations are based on currently available evidence about management of oncologic patients during COVID-19 pandemic, were endorsed by the SICO Executive Board, and are considered suitable for nationwide diffusion. They will be subject to updates and revisions in case of new and relevant scientific acquisitions.
Kriemhilds Widerfahrnis: Hagens letzte Finte
Authors: Serfas Günther
Published: November 2020

Der finale Dialog zwischen Kriemhild und Hagen in der Schlussszene der 39. Aventiure im Nibelungenlied – von der Forschung bis heute irreführend als »2. Hortforderungsszene« bezeichnet – wird als eine psychologisch basierte Finte Hagens gedeutet, die nicht nur eine individuelle Innensphäre der Figur Kriemhilds verifiziert, sondern zugleich das furiose Ende der burgundischen Nibelungen kohärent motiviert. Das Nibelungenlied erscheint in diesem Kontext als literarisches Zeugnis eines zeitgenössischen Ringens um politische Stabilität und traditionelle Wertvorstellungen, das besonders über die Figurenrolle Dietrichs im Spannungsfeld heroischer Gewaltverherrlichung und höfischer Interessenwahrung problematisiert ist.
Rethinking Vaccine Development as an Integral Part of Preparedness in the European Health Union
Authors: RIZZI Marco
Published: November 2020

This opinion piece puts forward a critique of the policy and regulatory frameworks governing vaccines, understood as tools to confront pandemic and epidemic diseases (PEDs). Vaccines being the universally recognised prime method of prevention, immunisation campaigns and vaccine research and development (R&D) could reasonably be expected to feature prominently in any policy and/or strategic document addressing emerging health threats. Yet, vaccination occupies a relatively subsidiary role, with a prevalent focus on risk management mechanisms. This piece outlines the main characteristics of preparedness frameworks and looks at vaccine development in the course of PED outbreaks in the recent past, concluding that the COVID-19 pandemic calls for a paradigm shift in vaccine R&D, which should become integral to public health preparedness.
Detection of polymorphic simple-sequence repeat markers that show linkage to a novel sugarcane brown rust disease resistance gene in resistant and susceptible genetic pools
Authors: Li Jie , Wang Xiao-Yan , Shan Hong-Li , Zhang Rong-Yue , Wang Chan-Mi , Cang Xiao-Yan , Li Wen-Feng , Yin Jiong , Luo Zhi-Ming , Huang Ying-Kun
Published: November 2020

Sugarcane brown rust, caused by Puccinia melanocephala, is one of the main diseases of sugarcane in China. The identification and discovery of new resistance genes have important theoretical and practical significance for preventing outbreaks of brown rust and ensuring the sustainable production of sugarcane. To screen for polymorphic simple-sequence repeat (SSR) molecular markers for localization of brown rust resistance genes, we used two populations that are suitable for genetic linkage map construction and mapping of new resistance genes to construct resistant and susceptible genetic pools. We then screened 449 pairs of primers to identify polymorphic SSR markers in the parental lines and the resistant/susceptible genetic pools. The results showed that 25 pairs of primers directed amplification of polymorphic DNA fragments between the parents of the cross combination ‘Yuetang 03-393’ × ‘ROC 24’, and 16 pairs of primers amplified polymorphic fragments between the parents of the cross combination ‘Liucheng 03-1137’ × ‘Dezhe 93-88’. Four pairs of primers (SMC236CG, SCESSR0928, SCESSR0636 and SCESSR2551) amplified polymorphic DNA fragments between the parental lines and the resistant/susceptible genetic pools in ‘Yuetang 03-393’ × ‘ROC 24’. The results of this study will establish a solid foundation for the mapping of new brown rust resistance genes, genetic linkage map construction and the development of closely-associated molecular markers in sugarcane.
The Rorschach As a Window Into Past Traumas During Therapeutic Assessment
Authors: de Villemor-Amaral Anna Elisa , Finn Stephen E.
Published: November 2020

Abstract. In this article, the authors discuss how the Rorschach can be useful in certain Therapeutic Assessments (TAs) by creating an opening for clients to report and discuss past traumatic events that have not previously been resolved. Two case examples are presented. In the first, a 31-year-old woman sought psychological help to understand why she was so afraid all the time, why she did not know what was best for her, and why she was so influenced by others’ opinions. The client saw many disturbing percepts in the Rorschach and was very unsettled afterward. During an extended inquiry she revealed an extensive history of physical and sexual abuse that she had put out of her mind and never told anyone about previously. Talking about her trauma with the assessor helped her understand why she was struggling. In the second case, a 35-year-old woman experienced a flashback when presented with Card X to finding her father after his suicide when she was 8 years old. The client had not previously recalled the details of this event, which were verified by family members. Retrieving this memory helped the client understand her family better and resolve problems she had in her adult romantic relationships. We believe there are essential elements that permit such therapeutic events to occur: (1) the power of the Rorschach to access split-off affects and memories, (2) the secure relationship created in TA that allows for traumatic material to emerge safely, (3) the technique of scaffolding in TA that helps locate clients’ growing edge, and (4) how client–assessor collaboration creates an intersubjective field in which nonlinear healing events may occur.
The Use of Collaborative/Therapeutic Assessment With Oppositional Defiant Disorder
Authors: del Carmen Espinoza María
Published: November 2020

Abstract. The aim of the present single case study was to demonstrate the effectiveness of a therapeutic evaluation model (CTA) used for 4 years with a teenage girl (13–17 years of age) with oppositional defiant disorder (ODD). Clinical evaluations using autobiography as well as the Millon Adolescent Clinic Inventory, House–Tree–Person Drawing, and Rorschach test (Comprehensive System) were conducted at each of four time points: 13, 14, 15, and 17 years of age. An average of four evaluation sessions were carried out at each time point following feedback of the results to the client, reflections about her experience with the evaluation process and with results obtained were requested in writing. Progressive findings reveal a gradual decrease in ODD markers and increasing sophistication, organization, and realism in the configuration of the drawings. The Rorschach test gradually indicated a decrease in aggression content and improvement in the quality of responses. In conclusion, the longitudinal design used in the case shows a strengthening of the self, a notable decrease in oppositional defiant behavior, and an adaptation and adjustment to reality as expected for a young woman of the client’s age.
Alfvénic Thermospheric Upwelling in a Global Geospace Model
Authors: Hogan Benjamin , Lotko William , Pham Kevin
Published: November 2020

Motivated by low‐altitude cusp observations of small‐scale (~1 km) field‐aligned currents (SSFACs) interpreted as ionospheric Alfvén resonator modes, we have investigated the effects of Alfvén wave energy deposition on thermospheric upwelling and the formation of air density enhancements in and near the cusp. Such density enhancements were commonly observed near 400 km altitude by the CHAMP satellite. They are not predicted by empirical thermosphere models, and they are well correlated with the observed SSFACs. A parameterized model for the altitude dependence of the Alfvén wave electric field, constrained by CHAMP data, has been developed and embedded in the Joule heating module of the National Center for Atmospheric Research (NCAR) Coupled Magnetosphere‐Ionosphere‐Thermosphere (CMIT) model. The CMIT model was then used to simulate the geospace response to an interplanetary stream interaction region (SIR) that swept past Earth on 26–27 March 2003. CMIT diagnostics for the thermospheric mass density at 400 km altitude show (1) CMIT without Alfvénic Joule heating usually underestimates CHAMP's orbit‐average density; inclusion of Alfvénic heating modestly improves CMIT's orbit‐average prediction of the density (by a few %), especially during the more active periods of the SIR event. (2) The improvement in CMIT's instantaneous density prediction with Alfvénic heating included is more significant (up to 15%) in the vicinity of the cusp heating region, a feature that the MSIS empirical thermosphere model misses for this event. Thermospheric density changes of 20–30% caused by the cusp‐region Alfvénic heating sporadically populate the polar region through the action of corotation and neutral winds.
Changes in health-related quality of life among older adults aging with long-term spinal cord injury
Authors: Jörgensen Sophie , Costa Andersson Maria Valentina , Lexell Jan
Published: November 2020

Study design

Cross-sectional and longitudinal.

Objectives

To (i) describe health-related quality of life (HRQoL) and changes over 6 years in older adults aging with long-term spinal cord injury (SCI) and (ii) investigate how changes in HRQoL are associated with age, gender, and injury characteristics.

Setting

Community in southern Sweden.

Methods

From the initial 123 participants (years 2011–2012) in the Swedish Aging with Spinal Cord Injury Study (SASCIS), 77 individuals (32% women, C1-L3, AIS A–D, median age 66 years, median time since injury 31 years, 30% complete injuries) were assessed 6 years later. HRQoL was rated with the Spinal Cord Injury Quality of Life Questionnaire (SCI QL-23). Associations were investigated using multivariable linear regression analyses.

Results

The median rating of global QoL (scale range 0–100) was relatively high at both assessments (67 and 83, respectively). There was a large variability in all HRQoL-domains and no significant changes over 6 years. As compared to an AIS D injury, a tetraplegia AIS A–C injury and tetraplegia and paraplegia AIS A–C injuries were associated with positive change in depressive symptoms and global QoL, respectively.

Conclusions

Older adults aging with long-term SCI show large variations in all HRQoL-domains and have the potential to maintain a high and stable level of HRQoL over time. Persons with AIS D injuries may need increased attention to mitigate negative changes in depressive symptoms and global QoL. Further studies are needed to identify modifiable factors associated with changes in HRQoL in older adults aging with long-term SCI.
Disruption of estradiol regulation of orexin neurons: a novel mechanism in excessive ventilatory response to CO2 inhalation in a female rat model of panic disorder
Authors: Tenorio-Lopes Luana , Fournier Stéphanie , Henry Mathilde S. , Bretzner Frédéric , Kinkead Richard
Published: November 2020

Panic disorder (PD) is ~2 times more frequent in women. An excessive ventilatory response to CO2 inhalation is more likely during the premenstrual phase. While ovarian hormones appear important in the pathophysiology of PD, their role remains poorly understood as female animals are rarely used in pre-clinical studies. Using neonatal maternal separation (NMS) to induce a “PD-like” respiratory phenotype, we tested the hypothesis that NMS disrupts hormonal regulation of the ventilatory response to CO2 in female rats. We then determined whether NMS attenuates the inhibitory actions of 17-β estradiol (E2) on orexin neurons (ORX). Pups were exposed to NMS (3 h/day; postnatal day 3–12). The ventilatory response to CO2-inhalation was tested before puberty, across the estrus cycle, and following ovariectomy. Plasma E2 and hypothalamic ORXA were measured. The effect of an ORX1 antagonist (SB334867; 15 mg/kg) on the CO2 response was tested. Excitatory postsynaptic currents (EPSCs) were recorded from ORX neurons using whole-cell patch-clamp. NMS-related increase in the CO2 response was observed only when ovaries were functional; the largest ventilation was observed during proestrus. SB334867 blocked this effect. NMS augmented levels of ORXA in hypothalamus extracts. EPSC frequency varied according to basal plasma E2 levels across the estrus cycle in controls but not NMS. NMS reproduces developmental and cyclic changes of respiratory manifestations of PD. NMS disrupts the inhibitory actions of E2 on the respiratory network. Impaired E2-related inhibition of ORX neurons during proestrus is a novel mechanism in respiratory manifestations of PD in females.
Polyelectrolyte interactions enable rapid association and dissociation in high-affinity disordered protein complexes
Authors: Sottini Andrea , Borgia Alessandro , Borgia Madeleine B. , Bugge Katrine , Nettels Daniel , Chowdhury Aritra , Heidarsson Pétur O. , Zosel Franziska , Best Robert B. , Kragelund Birthe B. , Schuler Benjamin
Published: November 2020

Highly charged intrinsically disordered proteins can form complexes with very high affinity in which both binding partners fully retain their disorder and dynamics, exemplified by the positively charged linker histone H1.0 and its chaperone, the negatively charged prothymosin α. Their interaction exhibits another surprising feature: The association/dissociation kinetics switch from slow two-state-like exchange at low protein concentrations to fast exchange at higher, physiologically relevant concentrations. Here we show that this change in mechanism can be explained by the formation of transient ternary complexes favored at high protein concentrations that accelerate the exchange between bound and unbound populations by orders of magnitude. Molecular simulations show how the extreme disorder in such polyelectrolyte complexes facilitates (i) diffusion-limited binding, (ii) transient ternary complex formation, and (iii) fast exchange of monomers by competitive substitution, which together enable rapid kinetics. Biological polyelectrolytes thus have the potential to keep regulatory networks highly responsive even for interactions with extremely high affinities.
Low SARS-CoV-2 seroprevalence in blood donors in the early COVID-19 epidemic in the Netherlands
Authors: Slot Ed , Hogema Boris M. , Reusken Chantal B. E. M. , Reimerink Johan H. , Molier Michel , Karregat Jan H. M. , IJlst Johan , Novotný Věra M. J. , van Lier René A. W. , Zaaijer Hans L.
Published: November 2020

The world is combating an ongoing COVID-19 pandemic with health-care systems, society and economies impacted in an unprecedented way. It is unclear how many people have contracted the causative coronavirus (SARS-CoV-2) unknowingly and are asymptomatic. Therefore, reported COVID-19 cases do not reflect the true scale of outbreak. Here we present the prevalence and distribution of antibodies to SARS-CoV-2 in a healthy adult population of the Netherlands, which is a highly affected country, using a high-performance immunoassay. Our results indicate that one month into the outbreak (i) the seroprevalence in the Netherlands was 2.7% with substantial regional variation, (ii) the hardest-hit areas showed a seroprevalence of up to 9.5%, (iii) the seroprevalence was sex-independent throughout age groups (18–72 years), and (iv) antibodies were significantly more often present in younger people (18–30 years). Our study provides vital information on the extent of exposure to SARS-CoV-2 in a country where social distancing is in place.
Exceptional non-Hermitian topological edge mode and its application to active matter
Authors: Sone Kazuki , Ashida Yuto , Sagawa Takahiro
Published: November 2020

Topological materials exhibit edge-localized scattering-free modes protected by their nontrivial bulk topology through the bulk-edge correspondence in Hermitian systems. While topological phenomena have recently been much investigated in non-Hermitian systems with dissipations and injections, the fundamental principle of their edge modes has not fully been established. Here, we reveal that, in non-Hermitian systems, robust gapless edge modes can ubiquitously appear owing to a mechanism that is distinct from bulk topology, thus indicating the breakdown of the bulk-edge correspondence. The robustness of these edge modes originates from yet another topological structure accompanying the branchpoint singularity around an exceptional point, at which eigenvectors coalesce and the Hamiltonian becomes nondiagonalizable. Their characteristic complex eigenenergy spectra are applicable to realize lasing wave packets that propagate along the edge of the sample. We numerically confirm the emergence and the robustness of the proposed edge modes in the prototypical lattice models. Furthermore, we show that these edge modes appear in a model of chiral active matter based on the hydrodynamic description, demonstrating that active matter can exhibit an inherently non-Hermitian topological feature. The proposed general mechanism would serve as an alternative designing principle to realize scattering-free edge current in non-Hermitian devices, going beyond the existing frameworks of non-Hermitian topological phases.
Mus81-Mms4 endonuclease is an Esc2-STUbL-Cullin8 mitotic substrate impacting on genome integrity
Authors: Waizenegger Anja , Urulangodi Madhusoodanan , Lehmann Carl P. , Reyes Teresa Anne Clarisse , Saugar Irene , Tercero José Antonio , Szakal Barnabas , Branzei Dana
Published: November 2020

The Mus81-Mms4 nuclease is activated in G2/M via Mms4 phosphorylation to allow resolution of persistent recombination structures. However, the fate of the activated phosphorylated Mms4 remains unknown. Here we find that Mms4 is engaged by (poly)SUMOylation and ubiquitylation and targeted for proteasome degradation, a process linked to the previously described Mms4 phosphorylation cycle. Mms4 is a mitotic substrate for the SUMO-Targeted Ubiquitin ligase Slx5/8, the SUMO-like domain-containing protein Esc2, and the Mms1-Cul8 ubiquitin ligase. In the absence of these activities, phosphorylated Mms4 accumulates on chromatin in an active state in the next G1, subsequently causing abnormal processing of replication-associated recombination intermediates and delaying the activation of the DNA damage checkpoint. Mus81-Mms4 mutants that stabilize phosphorylated Mms4 have similar detrimental effects on genome integrity. Overall, our findings highlight a replication protection function for Esc2-STUbL-Cul8 and emphasize the importance for genome stability of resetting phosphorylated Mms4 from one cycle to another.
Molecular structure and interactions within amyloid-like fibrils formed by a low-complexity protein sequence from FUS
Authors: Lee Myungwoon , Ghosh Ujjayini , Thurber Kent R. , Kato Masato , Tycko Robert
Published: November 2020

Protein domains without the usual distribution of amino acids, called low complexity (LC) domains, can be prone to self-assembly into amyloid-like fibrils. Self-assembly of LC domains that are nearly devoid of hydrophobic residues, such as the 214-residue LC domain of the RNA-binding protein FUS, is particularly intriguing from the biophysical perspective and is biomedically relevant due to its occurrence within neurons in amyotrophic lateral sclerosis, frontotemporal dementia, and other neurodegenerative diseases. We report a high-resolution molecular structural model for fibrils formed by the C-terminal half of the FUS LC domain (FUS-LC-C, residues 111-214), based on a density map with 2.62 Å resolution from cryo-electron microscopy (cryo-EM). In the FUS-LC-C fibril core, residues 112-150 adopt U-shaped conformations and form two subunits with in-register, parallel cross-β structures, arranged with quasi-21 symmetry. All-atom molecular dynamics simulations indicate that the FUS-LC-C fibril core is stabilized by a plethora of hydrogen bonds involving sidechains of Gln, Asn, Ser, and Tyr residues, both along and transverse to the fibril growth direction, including diverse sidechain-to-backbone, sidechain-to-sidechain, and sidechain-to-water interactions. Nuclear magnetic resonance measurements additionally show that portions of disordered residues 151-214 remain highly dynamic in FUS-LC-C fibrils and that fibrils formed by the N-terminal half of the FUS LC domain (FUS-LC-N, residues 2-108) have the same core structure as fibrils formed by the full-length LC domain. These results contribute to our understanding of the molecular structural basis for amyloid formation by FUS and by LC domains in general.
A convolutional neural network segments yeast microscopy images with high accuracy
Authors: Dietler Nicola , Minder Matthias , Gligorovski Vojislav , Economou Augoustina Maria , Joly Denis Alain Henri Lucien , Sadeghi Ahmad , Chan Chun Hei Michael , Koziński Mateusz , Weigert Martin , Bitbol Anne-Florence , Rahi Sahand Jamal
Published: November 2020

The identification of cell borders (‘segmentation’) in microscopy images constitutes a bottleneck for large-scale experiments. For the model organismSaccharomyces cerevisiae, current segmentation methods face challenges when cells bud, crowd, or exhibit irregular features. We present a convolutional neural network (CNN) named YeaZ, the underlying training set of high-quality segmented yeast images (>10 000 cells) including mutants, stressed cells, and time courses, as well as a graphical user interface and a web application (www.quantsysbio.com/data-and-software) to efficiently employ, test, and expand the system. A key feature is a cell-cell boundary test which avoids the need for fluorescent markers. Our CNN is highly accurate, including for buds, and outperforms existing methods on benchmark images, indicating it transfers well to other conditions. To demonstrate how efficient large-scale image processing uncovers new biology, we analyze the geometries of ≈2200 wild-type and cyclin mutant cells and find that morphogenesis control occurs unexpectedly early and gradually.
Author Correction: Activation of subnanometric Pt on Cu-modified CeO2 via redox-coupled atomic layer deposition for CO oxidation
Authors: Liu Xiao , Jia Shuangfeng , Yang Ming , Tang Yuanting , Wen Yanwei , Chu Shengqi , Wang Jianbo , Shan Bin , Chen Rong
Published: November 2020

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-19663-3.
Phenotypic variation of transcriptomic cell types in mouse motor cortex
Authors: Scala Federico , Kobak Dmitry , Bernabucci Matteo , Bernaerts Yves , Cadwell Cathryn René , Castro Jesus Ramon , Hartmanis Leonard , Jiang Xiaolong , Laturnus Sophie , Miranda Elanine , Mulherkar Shalaka , Tan Zheng Huan , Yao Zizhen , Zeng Hongkui , Sandberg Rickard , Berens Philipp , Tolias Andreas S.
Published: November 2020

Cortical neurons exhibit extreme diversity in gene expression as well as in morphological and electrophysiological properties1,2. Most existing neural taxonomies are based on either transcriptomic3,4 or morpho-electric5,6 criteria, as it has been technically challenging to study both aspects of neuronal diversity in the same set of cells7. Here we used Patch-seq8 to combine patch-clamp recording, biocytin staining, and single-cell RNA sequencing of more than 1,300 neurons in adult mouse primary motor cortex, providing a morpho-electric annotation of almost all transcriptomically defined neural cell types. We found that, although broad families of transcriptomic types (those expressing Vip, Pvalb, Sst and so on) had distinct and essentially non-overlapping morpho-electric phenotypes, individual transcriptomic types within the same family were not well separated in the morpho-electric space. Instead, there was a continuum of variability in morphology and electrophysiology, with neighbouring transcriptomic cell types showing similar morpho-electric features, often without clear boundaries between them. Our results suggest that neuronal types in the neocortex do not always form discrete entities. Instead, neurons form a hierarchy that consists of distinct non-overlapping branches at the level of families, but can form continuous and correlated transcriptomic and morpho-electrical landscapes within families.
County-level CO2 emissions and sequestration in China during 1997–2017
Authors: Chen Jiandong , Gao Ming , Cheng Shulei , Hou Wenxuan , Song Malin , Liu Xin , Liu Yu , Shan Yuli
Published: November 2020

With the implementation of China’s top-down CO2 emissions reduction strategy, the regional differences should be considered. As the most basic governmental unit in China, counties could better capture the regional heterogeneity than provinces and prefecture-level city, and county-level CO2 emissions could be used for the development of strategic policies tailored to local conditions. However, most of the previous accounts of CO2 emissions in China have only focused on the national, provincial, or city levels, owing to limited methods and smaller-scale data. In this study, a particle swarm optimization-back propagation (PSO-BP) algorithm was employed to unify the scale of DMSP/OLS and NPP/VIIRS satellite imagery and estimate the CO2 emissions in 2,735 Chinese counties during 1997–2017. Moreover, as vegetation has a significant ability to sequester and reduce CO2 emissions, we calculated the county-level carbon sequestration value of terrestrial vegetation. The results presented here can contribute to existing data gaps and enable the development of strategies to reduce CO2 emissions in China.
Extracellular vesicles from amyloid-β exposed cell cultures induce severe dysfunction in cortical neurons
Authors: Beretta Chiara , Nikitidou Elisabeth , Streubel-Gallasch Linn , Ingelsson Martin , Sehlin Dag , Erlandsson Anna
Published: November 2020

Alzheimer’s disease (AD) is characterized by a substantial loss of neurons and synapses throughout the brain. The exact mechanism behind the neurodegeneration is still unclear, but recent data suggests that spreading of amyloid-β (Aβ) pathology via extracellular vesicles (EVs) may contribute to disease progression. We have previously shown that an incomplete degradation of Aβ42 protofibrils by astrocytes results in the release of EVs containing neurotoxic Aβ. Here, we describe the cellular mechanisms behind EV-associated neurotoxicity in detail. EVs were isolated from untreated and Aβ42 protofibril exposed neuroglial co-cultures, consisting mainly of astrocytes. The EVs were added to cortical neurons for 2 or 4 days and the neurodegenerative processes were followed with immunocytochemistry, time-lapse imaging and transmission electron microscopy (TEM). Addition of EVs from Aβ42 protofibril exposed co-cultures resulted in synaptic loss, severe mitochondrial impairment and apoptosis. TEM analysis demonstrated that the EVs induced axonal swelling and vacuolization of the neuronal cell bodies. Interestingly, EV exposed neurons also displayed pathological lamellar bodies of cholesterol deposits in lysosomal compartments. Taken together, our data show that the secretion of EVs from Aβ exposed cells induces neuronal dysfunction in several ways, indicating a central role for EVs in the progression of Aβ-induced pathology.
Context aware deep learning for brain tumor segmentation, subtype classification, and survival prediction using radiology images
Authors: Pei Linmin , Vidyaratne Lasitha , Rahman Md Monibor , Iftekharuddin Khan M.
Published: November 2020

A brain tumor is an uncontrolled growth of cancerous cells in the brain. Accurate segmentation and classification of tumors are critical for subsequent prognosis and treatment planning. This work proposes context aware deep learning for brain tumor segmentation, subtype classification, and overall survival prediction using structural multimodal magnetic resonance images (mMRI). We first propose a 3D context aware deep learning, that considers uncertainty of tumor location in the radiology mMRI image sub-regions, to obtain tumor segmentation. We then apply a regular 3D convolutional neural network (CNN) on the tumor segments to achieve tumor subtype classification. Finally, we perform survival prediction using a hybrid method of deep learning and machine learning. To evaluate the performance, we apply the proposed methods to the Multimodal Brain Tumor Segmentation Challenge 2019 (BraTS 2019) dataset for tumor segmentation and overall survival prediction, and to the dataset of the Computational Precision Medicine Radiology-Pathology (CPM-RadPath) Challenge on Brain Tumor Classification 2019 for tumor classification. We also perform an extensive performance evaluation based on popular evaluation metrics, such as Dice score coefficient, Hausdorff distance at percentile 95 (HD95), classification accuracy, and mean square error. The results suggest that the proposed method offers robust tumor segmentation and survival prediction, respectively. Furthermore, the tumor classification results in this work is ranked at second place in the testing phase of the 2019 CPM-RadPath global challenge.
Characterization of the ExoU activation mechanism using EPR and integrative modeling
Authors: Tessmer Maxx H. , DeCero Samuel A. , del Alamo Diego , Riegert Molly O. , Meiler Jens , Frank Dara W. , Feix Jimmy B.
Published: November 2020

ExoU, a type III secreted phospholipase effector of Pseudomonas aeruginosa, serves as a prototype to model large, dynamic, membrane-associated proteins. ExoU is synergistically activated by interactions with membrane lipids and ubiquitin. To dissect the activation mechanism, structural homology was used to identify an unstructured loop of approximately 20 residues in the ExoU amino acid sequence. Mutational analyses indicate the importance of specific loop amino acid residues in mediating catalytic activity. Engineered disulfide cross-links show that loop movement is required for activation. Site directed spin labeling EPR and DEER (double electron–electron resonance) studies of apo and holo states demonstrate local conformational changes at specific sites within the loop and a conformational shift of the loop during activation. These data are consistent with the formation of a substrate-binding pocket providing access to the catalytic site. DEER distance distributions were used as constraints in RosettaDEER to construct ensemble models of the loop in both apo and holo states, significantly extending the range for modeling a conformationally dynamic loop.
Measuring dissolution profiles of single controlled-release drug pellets
Authors: Bhakta Heran C. , Lin Jessica M. , Grover William H.
Published: November 2020

Many solid-dose oral drug products are engineered to release their active ingredients into the body at a certain rate. Techniques for measuring the dissolution or degradation of a drug product in vitro play a crucial role in predicting how a drug product will perform in vivo. However, existing techniques are often labor-intensive, time-consuming, irreproducible, require specialized analytical equipment, and provide only “snapshots” of drug dissolution every few minutes. These limitations make it difficult for pharmaceutical companies to obtain full dissolution profiles for drug products in a variety of different conditions, as recommended by the US Food and Drug Administration. Additionally, for drug dosage forms containing multiple controlled-release pellets, particles, beads, granules, etc. in a single capsule or tablet, measurements of the dissolution of the entire multi-particle capsule or tablet are incapable of detecting pellet-to-pellet variations in controlled release behavior. In this work, we demonstrate a simple and fully-automated technique for obtaining dissolution profiles from single controlled-release pellets. We accomplished this by inverting the drug dissolution problem: instead of measuring the increase in the concentration of drug compounds in the solution during dissolution (as is commonly done), we monitor the decrease in the buoyant mass of the solid controlled-release pellet as it dissolves. We weigh single controlled-release pellets in fluid using a vibrating tube sensor, a piece of glass tubing bent into a tuning-fork shape and filled with any desired fluid. An electronic circuit keeps the glass tube vibrating at its resonance frequency, which is inversely proportional to the mass of the tube and its contents. When a pellet flows through the tube, the resonance frequency briefly changes by an amount that is inversely proportional to the buoyant mass of the pellet. By passing the pellet back-and-forth through the vibrating tube sensor, we can monitor its mass as it degrades or dissolves, with high temporal resolution (measurements every few seconds) and mass resolution (700 nanogram resolution). As a proof-of-concept, we used this technique to measure the single-pellet dissolution profiles of several commercial controlled-release proton pump inhibitors in simulated stomach and intestinal contents, as well as comparing name-brand and generic formulations of the same drug. In each case, vibrating tube sensor data revealed significantly different dissolution profiles for the different drugs, and in some cases our method also revealed differences between different pellets from the same drug product. By measuring any controlled-release pellets, particles, beads, or granules in any physiologically-relevant environment in a fully-automated fashion, this method can augment and potentially replace current dissolution tests and support product development and quality assurance in the pharmaceutical industry.
A birdstrike risk assessment model and its application at Ordos Airport, China
Authors: Hu Yuanyuan , Xing Pu , Yang Fan , Feng Gang , Yang Guisheng , Zhang Zhengwang
Published: November 2020

Birdstrikes are an important threat to aviation safety. A standardized, scientific process for assessing birdstrike risk could prevent accidents, thereby improving the flight safety and reducing economic losses. However, China currently lacks a unified birdstrike risk assessment system. Here, we propose and validate a new model for assessing birdstrike risk in order to fill that need. The model consists of two elements. First, empirical data are collected on the occurrence of birds at the airport and in a surrounding 8 km buffer. Second, each species is evaluated with a risk assessment matrix that takes into account the number of birds, weight, flight altitude, a tendency to cluster, and range of activity. These five factors allow each species to be divided into one of three risk levels: high danger (level 3), moderate danger (level 2) and low danger (level 1). We propose corresponding birdstrike prevention measures for each level. We apply this method to the civil aviation airport in Ordos, China. We found that 20 of the 118 species of birds in and around the airport were high danger birds (level 3). To validate this process, we compared these species with records of birdstrike accidents in a database maintained by the Civil Aviation Administration of China (CAAC) for 2007–2016. We found that 42% of the species we identified as high risk had been involved in at least one birdstrike accident, and that the remaining 58% belonged to families that appeared in the database. The high degree of overlap gives us high confidence in the practicality of our risk assessment model, which is based on the risk management concept of ISO 31000. Critically, this new model and method for predicting bird strike risk can be replicated at other airports around the world, even where no extensive records have been kept of past birdstrikes.
Profile of circulating microRNAs in myalgic encephalomyelitis and their relation to symptom severity, and disease pathophysiology
Authors: Nepotchatykh Evguenia , Elremaly Wesam , Caraus Iurie , Godbout Christian , Leveau Corinne , Chalder Lynda , Beaudin Catherine , Kanamaru Emi , Kosovskaia Renata , Lauzon Shawn , Maillet Yanick , Franco Anita , Lascau-Coman Viorica , Bouhanik Saadallah , Gaitan Yaned Patricia , Li Dawei , Moreau Alain
Published: November 2020

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic disease, rooted in multi-system dysfunctions characterized by unexplained debilitating fatigue. Post-exertional malaise (PEM), defined as the exacerbation of the patient's symptoms following minimal physical or mental stress, is a hallmark of ME/CFS. While multiple case definitions exist, there is currently no well-established biomarkers or laboratory tests to diagnose ME/CFS. Our study aimed to investigate circulating microRNA expression in severely ill ME/CFS patients before and after an innovative stress challenge that stimulates PEM. Our findings highlight the differential expression of eleven microRNAs associated with a physiological response to PEM. The present study uncovers specific microRNA expression signatures associated with ME/CFS in response to PEM induction and reports microRNA expression patterns associated to specific symptom severities. The identification of distinctive microRNA expression signatures for ME/CFS through a provocation challenge is essential for the elucidation of the ME/CFS pathophysiology, and lead to accurate diagnoses, prevention measures, and effective treatment options.
Human pericentromeric tandemly repeated DNA is transcribed at the end of oocyte maturation and is associated with membraneless mitochondria-associated structures
Authors: Dobrynin M. A. , Korchagina N. M. , Prjibelski A. D. , Shafranskaya D. , Ostromyshenskii D. I. , Shunkina K. , Stepanova I. , Kotova A. V. , Podgornaya O. I. , Enukashvily N. I.
Published: November 2020

Most of the human genome is non-coding. However, some of the non-coding part is transcriptionally active. In humans, the tandemly repeated (TR) pericentromeric non-coding DNA—human satellites 2 and 3 (HS2, HS3)—are transcribed in somatic cells. These transcripts are also found in pre- and post-implantation embryos. The aim of this study was to analyze HS2/HS3 transcription and cellular localization of transcripts in human maturating oocytes. The maternal HS2/HS3 TR transcripts transcribed from both strands were accumulated in the ooplasm in GV-MI oocytes as shown by DNA–RNA FISH (fluorescence in-situ hybridization). The transcripts’ content was higher in GV oocytes than in somatic cumulus cells according to real-time PCR. Using bioinformatics analysis, we demonstrated the presence of polyadenylated HS2 and HS3 RNAs in datasets of GV and MII oocyte transcriptomes. The transcripts shared a high degree of homology with HS2, HS3 transcripts previously observed in cancer cells. The HS2/HS3 transcripts were revealed by a combination of FISH and immunocytochemical staining within membraneless RNP structures that contained DEAD-box helicases DDX5 and DDX4. The RNP structures were closely associated with mitochondria, and are therefore similar to membraneless bodies described previously only in oogonia. These membraneless structures may be a site for spatial sequestration of RNAs and proteins in both maturating oocytes and cancer cells.
Alterations in detrusor contractility in rat model of bladder cancer
Authors: Philyppov Igor B. , Sotkis Ganna V. , Rock Aurelien , Roudbaraki Morad , Bonnal Jean-Louis , Mauroy Brigitte , Prevarskaya Natalia , Shuba Yaroslav M.
Published: November 2020

Urinary incontinence of idiopathic nature is a common complication of bladder cancer, yet, the mechanisms underlying changes in bladder contractility associated with cancer are not known. Here by using tensiometry on detrusor smooth muscle (DSM) strips from normal rats and rats with bladder cancer induced by known urothelial carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), we show that bladder cancer is associated with considerable changes in DSM contractility. These changes include: (1) decrease in the amplitude and frequency of spontaneous contractions, consistent with the decline of luminal pressures during filling, and detrusor underactivity; (2) diminution of parasympathetic DSM stimulation mainly at the expense of m-cholinergic excitatory transmission, suggestive of difficulty in bladder emptying and weakening of urine stream; (3) strengthening of TRPV1-dependent afferent limb of micturition reflex and TRPV1-mediated local contractility, promoting urge incontinence; (4) attenuation of stretch-dependent, TRPV4-mediated spontaneous contractility leading to overflow incontinence. These changes are consistent with the symptomatic of bladder dysfunction in bladder cancer patients. Considering that BBN-induced urothelial lesions in rodents largely resemble human urothelial lesions at least in their morphology, our studies establish for the first time underlying reasons for bladder dysfunction in bladder cancer.