bluuebunny/crossref_metadata_2025 huggingface dataset:
High-resolution Digital Surface Model of the 2021 eruption deposit of Cumbre Vieja volcano, La Palma, Spain
Authors: Civico Riccardo , Ricci Tullio , Scarlato Piergiorgio , Taddeucci Jacopo , Andronico Daniele , Del Bello Elisabetta , D’Auria Luca , Hernández Pedro A. , Pérez Nemesio M.
Published: July 2022

Identifying accurate topographic variations associated with volcanic eruptions plays a key role in obtaining information on eruptive parameters, volcano structure, input data for volcano processes modelling, and civil protection and recovery actions. The 2021 eruption of Cumbre Vieja volcano is the largest eruptive event in the recorded history for La Palma Island. Over the course of almost 3 months, the volcano produced profound morphological changes in the landscape affecting both the natural and the anthropic environment over an area of tens of km2. We present the results of a UAS (Unoccupied Aircraft System) survey consisting of >12,000 photographs coupled with Structure-from-Motion photogrammetry that allowed us to produce a very-high-resolution (0.2 m/pixel) Digital Surface Model (DSM). We characterised the surface topography of the newly formed volcanic landforms and produced an elevation difference map by differencing our survey and a pre-event surface, identifying morphological changes in detail. The present DSM, the first one with such a high resolution to our knowledge, represents a relevant contribution to both the scientific community and the local authorities.
Effect of cytokine-induced alterations in extracellular matrix composition on diabetic retinopathy-relevant endothelial cell behaviors
Authors: Giblin Meredith J. , Ontko Cayla D. , Penn John S.
Published: July 2022

Retinal vascular basement membrane (BM) thickening is an early structural abnormality of diabetic retinopathy (DR). Recent studies suggest that BM thickening contributes to the DR pathological cascade; however, much remains to be elucidated about the exact mechanisms by which BM thickening develops and subsequently drives other pathogenic events in DR. Therefore, we undertook a systematic analysis to understand how human retinal microvascular endothelial cells (hRMEC) and human retinal pericytes (hRP) change their expression of key extracellular matrix (ECM) constituents when treated with diabetes-relevant stimuli designed to model the three major insults of the diabetic environment: hyperglycemia, dyslipidemia, and inflammation. TNFα and IL-1β caused the most potent and consistent changes in ECM expression in both hRMEC and hRP. We also demonstrate that conditioned media from IL-1β-treated human Müller cells caused dose-dependent, significant increases in collagen IV and agrin expression in hRMEC. After narrowing our focus to inflammation-induced changes, we sought to understand how ECM deposited by hRMEC and hRP under inflammatory conditions affects the behavior of naïve hRMEC. Our data demonstrated that diabetes-relevant alterations in ECM composition alone cause both increased adhesion molecule expression by and increased peripheral blood mononuclear cell (PBMC) adhesion to naïve hRMEC. Taken together, these data demonstrate novel roles for inflammation and pericytes in driving BM pathology and suggest that inflammation-induced ECM alterations may advance other pathogenic behaviors in DR, including leukostasis.
Factors associated with the differential distribution of cetaceans linked with deep habitats in the Western Mediterranean Sea
Authors: Torreblanca Estefanía , Báez José-Carlos , Real Raimundo , Macías David , García-Barcelona Salvador , Ferri-Yañez Francisco , Camiñas Juan-Antonio
Published: July 2022

Deep-habitat cetaceans are generally difficult to study, leading to a limited knowledge of their population. This paper assesses the differential distribution patterns of three deep-habitat cetaceans (Sperm whale—Physeter macrocephalus,Risso’s dolphin—Grampus griseus &Cuvier’s beaked whale—Ziphius cavirostris). We used data of 842 opportunistic sightings of cetaceans in the western Mediterranean sea. We inferred environmental and spatio-temporal factors that affect their distribution. Binary logistic regression models were generated to compare the presence of deep-habitat cetaceans with the presence of other cetacean species in the dataset. Then, the favourability function was applied, allowing for comparison between all the models. Sperm whale and Risso’s dolphin presence was differentially favoured by the distance to towns in the eastern part of the western Mediterranean sea. The differential distribution of sperm whale was also influenced by the stability of SST, and that of the Risso’s dolphin by lower mean salinity and higher mean Chlorophyll A concentration. When modelling the three deep-habitat cetaceans (including Cuvier’s beaked whale), the variable distance to towns had a negative influence on the presence of any of them more than it did to other cetaceans, being more favourable far from towns, so this issue should be further investigated.
Global economic costs of herpetofauna invasions
Authors: Soto Ismael , Cuthbert Ross N. , Kouba Antonín , Capinha César , Turbelin Anna , Hudgins Emma J. , Diagne Christophe , Courchamp Franck , Haubrock Phillip J.
Published: July 2022

Biological invasions by amphibian and reptile species (i.e. herpetofauna) are numerous and widespread, having caused severe impacts on ecosystems, the economy and human health. However, there remains no synthesised assessment of the economic costs of these invasions. Therefore, using the most comprehensive database on the economic costs of invasive alien species worldwide (InvaCost), we analyse the costs caused by invasive alien herpetofauna according to taxonomic, geographic, sectoral and temporal dimensions, as well as the types of these costs. The cost of invasive herpetofauna totaled at 17.0 billion US$ between 1986 and 2020, divided split into 6.3 billion US$ for amphibians, 10.4 billion US$ for reptiles and 334 million US$ for mixed classes. However, these costs were associated predominantly with only two species (brown tree snake Boiga irregularis and American bullfrog Lithobates catesbeianus), with 10.3 and 6.0 billion US$ in costs, respectively. Costs for the remaining 19 reported species were relatively minor (< 0.6 billion US$), and they were entirely unavailable for over 94% of known invasive herpetofauna worldwide. Also, costs were positively correlated with research effort, suggesting research biases towards well-known taxa. So far, costs have been dominated by predictions and extrapolations (79%), and thus empirical observations for impact were relatively scarce. The activity sector most affected by amphibians was authorities-stakeholders through management (> 99%), while for reptiles, impacts were reported mostly through damages to mixed sectors (65%). Geographically, Oceania and Pacific Islands recorded 63% of total costs, followed by Europe (35%) and North America (2%). Cost reports have generally increased over time but peaked between 2011 and 2015 for amphibians and 2006 to 2010 for reptiles. A greater effort in studying the costs of invasive herpetofauna is necessary for a more complete understanding of invasion impacts of these species. We emphasise the need for greater control and prevention policies concerning the spread of current and future invasive herpetofauna.
Chronic intermittent hypoxia, a hallmark of obstructive sleep apnea, promotes 4T1 breast cancer development through endothelin-1 receptors
Authors: Minoves Mélanie , Kotzki Sylvain , Hazane-Puch Florence , Lemarié Emeline , Bouyon Sophie , Vollaire Julien , Gonthier Brigitte , Pépin Jean-Louis , Josserand Véronique , Briançon-Marjollet Anne , Godin-Ribuot Diane
Published: July 2022

The association between obstructive sleep apnea (OSA) and cancer is still debated and data are scarce regarding the link between OSA and breast cancer progression. Since conclusive epidemiological studies require large sample sizes and sufficient duration of exposure before incident cancer occurrence, basic science studies represent the most promising approach to appropriately address the topic. Here we assessed the impact of intermittent hypoxia (IH), the major hallmark of OSA, on the development of breast cancer and explored the specific involvement of the endothelin signaling pathway. Original in vitro and in vivo models were used where 3D-spheroids or cultures of murine 4T1 breast cancer cells were submitted to IH cycles, and nude NMRI mice, orthotopically implanted with 4T1 cells, were submitted to chronic IH exposure before and after implantation. The role of the endothelin-1 in promoting cancer cell development was investigated using the dual endothelin receptor antagonist, macitentan. In vitro exposure to IH significantly increased 4T1 cell proliferation and migration. Meta-analysis of 4 independent in vivo experiments showed that chronic IH exposure promoted tumor growth, assessed by caliper measurement (overall standardized mean difference: 1.00 [0.45–1.55], p < 0.001), bioluminescence imaging (1.65 [0.59–2.71]; p < 0.01) and tumor weight (0.86 [0.31–1.41], p < 0.01), and enhanced metastatic pulmonary expansion (0.77 [0.12–1.42]; p = 0.01). Both in vitro and in vivo tumor-promoting effects of IH were reversed by macitentan. Overall, these findings demonstrate that chronic intermittent hypoxia exposure promotes breast cancer growth and malignancy and that dual endothelin receptor blockade prevents intermittent hypoxia-induced tumor development.
Water activated disposable paper battery
Authors: Poulin Alexandre , Aeby Xavier , Nyström Gustav
Published: July 2022

We developed a disposable paper battery aiming to reduce the environmental impact of single-use electronics for applications such as point of care diagnosis, smart packaging and environmental sensing. The battery uses Zinc as a biodegradable metal anode, graphite as a nontoxic cathode material and paper as a biodegradable substrate. To facilitate additive manufacturing, we developed electrodes and current collector inks that can be stencil printed on paper to create water-activated batteries of arbitrary shape and size. The battery remains inactive until water is provided and absorbed by the paper substrate, taking advantage of its natural wicking behavior. Once activated, a single cell provides an open circuit potential of 1.2 V and a peak power density of 150 µW/cm2at 0.5 mA. As a proof of concept, we fabricated a two cell battery and used it to power an alarm clock and its liquid crystal display.
Systematic screening and validation of reliable reference genes for qRT-PCR analysis in Okra (Abelmoschus esculentus L.)
Authors: Zhang Jing-Rong , Feng Yuan-Yuan , Yang Ma-Jin , Xiao Yu , Liu Yu-Shan , Yuan Yuan , Li Zhen , Zhang Yan , Zhuo Ming , Zhang Jun , Li Cai-Xia
Published: July 2022

Quantitative real-time polymerase chain reaction (qRT-PCR) is a sensitive and widely used technique for quantifying gene expression levels, and its accuracy depends on the reference genes used for data normalization. To date, no reference gene has been reported in the nutritious and functional vegetable okra (Abelmoschus esculentus L.). Herein, 11 candidates of reference genes were selected and evaluated for their expression stability in okra in different tissues at different developmental stages by using three software algorithms (geNorm, NormFinder, BestKeeper) and a web-based tool (RefFinder). Among them, eukaryotic initiation factor 4 alpha (eIF4A) and protein phosphatase 2A (PP2A) showed the highest stability, while TUA5 had the lowest stability. The combined usage of these two most stable reference genes was sufficient to normalize gene expression in okra. Then, the above results were further validated by normalizing the expression of the cellulose synthase gene CesA4. This work provides appropriate reference genes for transcript normalization in okra, which will facilitate subsequent functional gene research on this vegetable crop.
The psychophysiological mechanisms of real-world time experience
Authors: Ogden Ruth S. , Dobbins Chelsea , Slade Kate , McIntyre Jason , Fairclough Stephen
Published: July 2022

Our sense of time is fallible, often resulting in the sensation of time flying by quickly or dragging slowly. It has been suggested that changes in sympathetic (SNS) and parasympathetic nervous system (PNS) activity may influence the perceived passage of time, however this proposition has never been tested during real-world temporal experience. The current study directly tested the relationship between the passage of time and SNS–PNS activity in the real-world. Sixty-seven participants completed a normal day’s activities whilst wearing sensors to capture electrocardiography (ECG), electrodermal activity (EDA) and movement. They also provided hourly rating of the subjective speed at which time was passing. Results revealed that greater SNS activity (e.g., increased heart rate, frequency of phasic skin conductance response) was associated with time passing more quickly. PNS activity was not related to time experience. Whilst the findings support previous suggestions that changes in physiological arousal are associated with distortions to the passage of time, the effects are small and other factors are likely to contribute to real-world temporal experience.
Clinical and neurophysiological effects of central thalamic deep brain stimulation in the minimally conscious state after severe brain injury
Authors: Arnts Hisse , Tewarie Prejaas , van Erp Willemijn S. , Overbeek Berno U. , Stam Cornelis J. , Lavrijsen Jan C. M. , Booij Jan , Vandertop William P. , Schuurman Rick , Hillebrand Arjan , van den Munckhof Pepijn
Published: July 2022

Deep brain stimulation (DBS) of the central thalamus is an experimental treatment for restoration of impaired consciousness in patients with severe acquired brain injury. Previous results of experimental DBS are heterogeneous, but significant improvements in consciousness have been reported. However, the mechanism of action of DBS remains unknown. We used magnetoencephalography to study the direct effects of DBS of the central thalamus on oscillatory activity and functional connectivity throughout the brain in a patient with a prolonged minimally conscious state. Different DBS settings were used to improve consciousness, including two different stimulation frequencies (50 Hz and 130 Hz) with different effective volumes of tissue activation within the central thalamus. While both types of DBS resulted in a direct increase in arousal, we found that DBS with a lower frequency (50 Hz) and larger volume of tissue activation was associated with a stronger increase in functional connectivity and neural variability throughout the brain. Moreover, this form of DBS was associated with improvements in visual pursuit, a reduction in spasticity, and improvement of swallowing, eight years after loss of consciousness. However, after DBS, all neurophysiological markers remained significantly lower than in healthy controls and objective increases in consciousness remained limited. Our findings provide new insights on the mechanistic understanding of neuromodulatory effects of DBS of the central thalamus in humans and suggest that DBS can re-activate dormant functional brain networks, but that the severely injured stimulated brain still lacks the ability to serve cognitive demands.
Task-independent metrics of computational hardness predict human cognitive performance
Authors: Franco Juan Pablo , Doroc Karlo , Yadav Nitin , Bossaerts Peter , Murawski Carsten
Published: July 2022

The survival of human organisms depends on our ability to solve complex tasks in the face of limited cognitive resources. However, little is known about the factors that drive the complexity of those tasks. Here, building on insights from computational complexity theory, we quantify the computational hardness of cognitive tasks using a set of task-independent metrics related to the computational resource requirements of individual instances of a task. We then examine the relation between those metrics and human behavior and find that they predict both time spent on a task as well as accuracy in three canonical cognitive tasks. Our findings demonstrate that performance in cognitive tasks can be predicted based on generic metrics of their inherent computational hardness.
Sialylated and sulfated N-Glycans in MDCK and engineered MDCK cells for influenza virus studies
Authors: Byrd-Leotis Lauren , Jia Nan , Matsumoto Yasuyuki , Lu Dongli , Kawaoka Yoshihiro , Steinhauer David A. , Cummings Richard D.
Published: July 2022

The Madin-Darby canine kidney (MDCK) cell line is an in vitro model for influenza A virus (IAV) infection and propagation. MDCK-SIAT1 (SIAT1) and humanized MDCK (hCK) cell lines are engineered MDCK cells that express N-glycans with elevated levels of sialic acid (Sia) in α2,6-linkage (α2,6-Sia) that are recognized by many human IAVs. To characterize the N-glycan structures in these cells and the potential changes compared to the parental MDCK cell line resulting from engineering, we analyzed the N-glycans from these cells at different passages, using both mass spectrometry and specific lectin and antibody binding. We observed significant differences between the three cell lines in overall complex N-glycans and terminal galactose modifications. MDCK cells express core fucosylated, bisected complex-type N-glycans at all passage stages, in addition to expressing α2,6-Sia on short N-glycans and α2,3-Sia on larger N-glycans. By contrast, SIAT1 cells predominantly express α2,6-Sia glycans and greatly reduced level of α2,3-Sia glycans. Additionally, they express bisected, sialylated N-glycans that are scant in MDCK cells. The hCK cells exclusively express α2,6-Sia glycans. Unexpectedly, hCK glycoproteins bound robustly to the plant lectin MAL-1, indicating α2,3-Sia glycans, but such binding was not Sia-dependent and closely mirrored that of an antibody that recognizes glycans with terminal 3-O-sulfate galactose (3-O-SGal). The 3-O-SGal epitope is highly expressed in N-glycans on multiple hCK glycoproteins. These results indicate vastly different N-glycomes between MDCK cells and the engineered clones that could relate to IAV infectivity.
AutoComBat: a generic method for harmonizing MRI-based radiomic features
Authors: Carré Alexandre , Battistella Enzo , Niyoteka Stephane , Sun Roger , Deutsch Eric , Robert Charlotte
Published: July 2022

The use of multicentric data is becoming essential for developing generalizable radiomic signatures. In particular, Magnetic Resonance Imaging (MRI) data used in brain oncology are often heterogeneous in terms of scanners and acquisitions, which significantly impact quantitative radiomic features. Various methods have been proposed to decrease dependency, including methods acting directly on MR images, i.e., based on the application of several preprocessing steps before feature extraction or the ComBat method, which harmonizes radiomic features themselves. The ComBat method used for radiomics may be misleading and presents some limitations, such as the need to know the labels associated with the “batch effect”. In addition, a statistically representative sample is required and the applicability of a signature whose batch label is not present in the train set is not possible. This work aimed to compare a priori and a posteriori radiomic harmonization methods and propose a code adaptation to be machine learning compatible. Furthermore, we have developed AutoComBat, which aims to automatically determine the batch labels, using either MRI metadata or quality metrics as inputs of the proposed constrained clustering. A heterogeneous dataset consisting of high and low-grade gliomas coming from eight different centers was considered. The different methods were compared based on their ability to decrease relative standard deviation of radiomic features extracted from white matter and on their performance on a classification task using different machine learning models. ComBat and AutoComBat using image-derived quality metrics as inputs for batch assignment and preprocessing methods presented promising results on white matter harmonization, but with no clear consensus for all MR images. Preprocessing showed the best results on the T1w-gd images for the grading task. For T2w-flair, AutoComBat, using either metadata plus quality metrics or metadata alone as inputs, performs better than the conventional ComBat, highlighting its potential for data harmonization. Our results are MRI weighting, feature class and task dependent and require further investigations on other datasets.
Virtual product development process for reducing noise, vibration, and harshness of vehicle based on substructuring and artificial neural network
Authors: Kim Yongdae , Jeong Un-Chang
Published: July 2022

In this study, virtual product development method for reducing vibration and noise is proposed for designing at the concept development stage of a vehicle. To this end, the vibration characteristics of the system are predicted through the Lagrange-multiplier frequency-based substructuring technique. The concepts of contact, blocked and transmitted force, and force transmissibility were used for determining the improvement subsystem or combination of subsystems when using the modular platform. Moreover, after the subsystems to be improved were determined, Artificial Neural Network was used as a method of predicting vibration characteristics according to the change of design variables. To verify this, the prediction of the blocked force was performed by changing the young’s modulus of the simplified substructure. Finally, the reduction in response was confirmed by applying the blocked force of the simplified subframe to the simplified structure, and a vehicle development process using a database at the concept setting stage is proposed.
RETRACTED ARTICLE: Optical and structural properties of Sn and Ag-doped PbS/PVA nanocomposites synthesized by chemical bath deposition
Authors: Fatemi Ali , Tohidi Tavakkol , Jamshidi-Galeh Kazem , Rasouli Milad , Ostrikov Kostya
Published: July 2022

In this work, Sn and Ag doped PbS/PVA nanocomposites, in three different concentrations were successfully prepared using the low-cost and simple method of chemical bath deposition (CBD). X-ray diffraction patterns confirmed the formation of the PbS cubic phase in all of the nanocomposites. FE-SEM images showed that PbS NPs are cubic in shape and the doping can alter the shape of grains. DLS analysis applied for solution NPs exhibited a 175 nm size distribution for PbS NPs and decreased by doping Ag and Sn to almost 100 nm and 110 nm, respectively. Optical absorption spectra showed the blue phenomena and the band gaps of Sn: PbS/PVA and Ag: PbS/PVA nanocomposites increased with adding Sn and Ag from 3.08 eV for pure PVA/PbS to 3.33 eV for Sn doped and 3.43 eV for Ag-doped samples. The nonlinear refractive index is decreased from 0.55 m2 W−1 for pure PVA/PbS to 0.11 m2 W−1 and 0.13 m2 W−1 for Sn and Ag-doped samples, respectively. Hence, doping Ag and Sn enhanced the optical sensitivity issue of nanocomposites and raised the optical resistivity. Collectively, our results can be useful in the design of linear and nonlinear optical devices such as sensors and optical switches and limiters.
Staphylococcus aureus increases platelet reactivity in patients with infective endocarditis
Authors: Polzin Amin , Dannenberg Lisa , M’Pembele René , Mourikis Philipp , Naguib David , Zako Saif , Helten Carolin , Petzold Tobias , Levkau Bodo , Hohlfeld Thomas , Barth Mareike , Zeus Tobias , Sixt Stephan , Huhn Ragnar , Akhyari Payam , Lichtenberg Artur , Kelm Malte , Hoffmann Till
Published: July 2022

Thromboembolism is frequent in infective endocarditis (IE). However, the optimal antithrombotic regimen in IE is unknown.Staphylococcus aureus(SA) is the leading cause of IE. First studies emphasize increased platelet reactivity by SA. In this pilot study, we hypothesized that platelet reactivity is increased in patients with SA− IE, which could be abrogated by antiplatelet medication. We conducted a prospective, observatory, single-center cohort study in 114 patients with IE, with four cohorts: (1) SA coagulase positive IE without aspirin (ASA) medication, (2) coagulase negative IE without ASA, (3) SA coagulase positive IE with ASA, (4) coagulase negative IE with ASA. Platelet function was measured by Multiplate electrode aggregometry, blood clotting by ROTEM thromboelastometry. Bleeding events were assessed according to TIMI classification. In ASA-naïve patients, aggregation with ADP was increased with coag. pos. IE (coagulase negative: 39.47 ± 4.13 AUC vs. coagulase positive: 59.46 ± 8.19 AUC, p = 0.0219). This was abrogated with ASA medication (coagulase negative: 42.4 ± 4.67 AUC vs. coagulase positive: 45.11 ± 6.063 AUC p = 0.7824). Aspirin did not increase bleeding in SA positive patients. However, in SA negative patients with aspirin, red blood cell transfusions were enhanced. SA coagulase positive IE is associated with increased platelet reactivity. This could be abrogated by aspirin without increased bleeding risk. The results of this pilot study suggest that ASA might be beneficial in SA coagulase positive IE. This needs to be confirmed in clinical trials.
Synthesis of Candida Antarctica Lipase B (CALB) enzyme-powered magnetite nanomotor based on PCL/Chitosan Janus nanostructure
Authors: Mafakheri Fariba , Khoee Sepideh
Published: July 2022

In this work, we report the design and synthesis of internal energy-driven Janus nanomotors (JNMs), which are composed of certain reactive materials that are capable of converting chemical energy in the backbone of nanomotors into kinetic energy. For this purpose, superparamagnetic iron oxide nanoparticles (SPIONs) with the anisotropic surface were obtained via a Pickering emulsion. Modified chitosan (as hydrophilic polymer) and functionalized polycaprolactone (as hydrophobic domain) were covalently linked to the surface of bi-functional SPIONs to produce Janus nanoparticles (JNPs). Then, the CALB enzyme was loaded in the PCL hemisphere of JNPs to form the Janus nanomotor. When nanomotors are placed in the phosphate-buffered saline solution, the driving force for motion is provided by the decomposition of polyester into monomers and oligomers on one side of the JNMs. The trajectories of the nanomotors were recorded under different circumstances by a video microscope and analyzed by the mean squared displacement. The results show that the velocity of JNMs increases with an increasing percentage of the loaded enzyme. In addition, the diffusion coefficient enhances up to 87.67% in compared with nanoparticles without enzyme. Controlling the motion direction of JNMs by an external magnetic field is also possible, due to the presence of SPIONs.
Casein-assisted enhancement of the compressive strength of biocemented sand
Authors: Miyake Masato , Kim Daehyun , Hata Toshiro
Published: July 2022

As a soil biomineralization process, casein-assisted enzyme-induced carbonate precipitation (EICP) yielded biocemented specimens with significantly higher compressive strength than specimens cemented by regular or skim-milk-assisted EICP treatments. The compound concentration and curing strategy of casein-assisted EICP were experimentally optimized to maximize the compressive strength of precipitates with low calcium carbonate content. Under the optimized EICP conditions (0.893 M urea, 0.581 M CaCl2, 2.6 g/L urease enzyme, and 38.87 g/L casein), the unconfined compressive strengths reached 2 MPa. The scanning electron micrographs of selected samples provided microscopic evidence that EICP treatments assisted using skim milk and casein impart distinctive strength-enhancement mechanisms. The ammonium ions released from urea hydrolysis created an alkaline environment that makes casein dissociated into the pore water. As the casein-containing pore water became more viscous, the increased contact area with particles facilitated the precipitation of co-bound CaCO3 minerals and casein in the pore water. Casein was identified as a more efficient assisting agent than skim milk for low-level CaCO3 precipitation by EICP treatment.
Persistent popliteal lymphatic muscle cell coverage defects despite amelioration of arthritis and recovery of popliteal lymphatic vessel function in TNF-Tg mice following anti-TNF therapy
Authors: Kenney H. Mark , Peng Yue , Bell Richard D. , Wood Ronald W. , Xing Lianping , Ritchlin Christopher T. , Schwarz Edward M.
Published: July 2022

While rheumatoid arthritis patients and tumor necrosis factor transgenic (TNF-Tg) mice with inflammatory-erosive arthritis display lymphatic drainage deficits, the mechanisms responsible remain unknown. As ultrastructural studies of joint-draining popliteal lymphatic vessels (PLVs) in TNF-Tg mice revealed evidence of lymphatic muscle cell (LMC) damage, we aimed to evaluate PLV-LMC coverage in TNF-Tg mice. We tested the hypothesis that alpha smooth muscle actin (αSMA)+ PLV-LMC coverage decreases with severe inflammatory-erosive arthritis, and is recovered by anti-TNF therapy facilitated by increased PLV-LMC turnover during amelioration of joint disease. TNF-Tg mice with established disease received anti-TNF monoclonal antibody (mAb) or placebo IgG isotype control mAb therapy (n = 5) for 6-weeks, while wild-type (WT) littermates (n = 8) received vehicle (PBS). Bromodeoxyuridine (BrdU) was also administered daily during the treatment period to monitor PLV-LMC turnover. Effective anti-TNF therapy was confirmed by longitudinal assessment of popliteal lymph node (PLN) volume via ultrasound, PLV contraction frequency via near-infrared imaging of indocyanine green, and ankle bone volumes via micro-computed tomography (micro-CT). Terminal knee micro-CT, and ankle and knee histology were also performed. PLVs were immunostained for αSMA and BrdU to evaluate PLV-LMC coverage and turnover, respectively, via whole-mount fluorescent microscopy. Anti-TNF therapy reduced PLN volume, increased talus and patella bone volumes, and reduced tarsal and knee synovial areas compared to placebo treated TNF-Tg mice (p < 0.05), as expected. Anti-TNF therapy also increased PLV contraction frequency at 3-weeks (from 0.81 ± 1.0 to 3.2 ± 2.0 contractions per minute, p < 0.05). However, both anti-TNF and placebo treated TNF-Tg mice exhibited significantly reduced αSMA+ PLV-LMC coverage compared to WT (p < 0.05). There was no correlation of αSMA+ PLV-LMC coverage restoration with amelioration of inflammatory-erosive arthritis. Similarly, there was no difference in PLV-LMC turnover measured by BrdU labeling between WT, TNF-Tg placebo, and TNF-Tg anti-TNF groups with an average of < 1% BrdU+ PLV-LMCs incorporated per week. Taken together these results demonstrate that PLV-LMC turnover in adult mice is limited, and that recovery of PLV function during amelioration of inflammatory-erosive arthritis occurs without restoration of αSMA+ LMC coverage. Future studies are warranted to investigate the direct and indirect effects of chronic TNF exposure, and the role of proximal inflammatory cells on PLV contractility.
HER2-low breast cancer shows a lower immune response compared to HER2-negative cases
Authors: van den Ende Nadine S. , Smid Marcel , Timmermans Annemieke , van Brakel Johannes B. , Hansum Tim , Foekens Renée , Trapman Anita M. A. C. , Heemskerk-Gerritsen Bernadette A. M. , Jager Agnes , Martens John W. M. , van Deurzen Carolien H. M.
Published: July 2022

Currently, the human epidermal growth factor receptor 2 (HER2) status of breast cancer is classified dichotomously as negative or positive to select patients for HER2-targeted therapy. However, with the introduction of novel treatment options, it is important to get more insight in the biology of cancers with low HER2 expression. Therefore, we studied several clinicopathologic characteristics in relation to the level of HER2 expression (HER2- versus HER2low). We used a well-documented cohort of breast cancer patients (n = 529), with available tissue microarrays and Affymetrix mRNA expression data. HER2 status was scored as negative (immunohistochemistry 0) or low (immunohistochemistry 1 + or 2 + without amplification). We associated HER2 status with several clinicopathologic characteristics, gene-expression data and survival, stratified for estrogen receptor (ER) status. Overall, breast cancers were scored as HER2- (n = 429) or HER2low (n = 100). Within the ER+ cohort (n = 305), no significant associations were found between the HER2 groups and clinicopathologic features. However, HER2low tumors showed several differentially expressed genes compared to HER2- cases, including genes that are associated with worse outcome and depletion of immunity. In ER- cases (n = 224), HER2low status was significantly associated with increased regional nodal positivity, lower density of tumor infiltrating lymphocyte and a lower protein expression of Ki-67 and EGFR compared to HER2- cases. After multivariate analysis, only density of tumor infiltrating lymphocytes remained significantly associated with HER2low status (P = 0.035). No difference in survival was observed between HER2low and HER2- patients, neither in the ER+ nor ER- cohort. In conclusion, our data suggests that HER2low breast cancer is associated with a lower immune response compared to HER2- breast cancer.
Thickness and defect dependent electronic, optical and thermoelectric features of $$\hbox {WTe}_2$$
Authors: Ozdemir Ilkay , Holleitner Alexander W. , Kastl Christoph , Aktürk Olcay Üzengi
Published: July 2022

Transition metal dichalcogenides (TMDs) receive significant attention due to their outstanding electronic and optical properties. In this study, we investigate the electronic, optical, and thermoelectric properties of single and few layer $$\hbox {WTe}_2$$

WTe
2

in detail utilizing first-principles methods based on the density functional theory (DFT). Within the scope of both PBE and HSE06 including spin orbit coupling (SOC), the simulations predict the electronic band gap values to decrease as the number of layers increases. Moreover, spin-polarized DFT calculations combined with the semi-classical Boltzmann transport theory are applied to estimate the anisotropic thermoelectric power factor (Seebeck coefficient, S) for $$\hbox {WTe}_2$$

WTe
2

in both the monolayer and multilayer limit, and S is obtained below the optimal value for practical applications. The optical absorbance of $$\hbox {WTe}_2$$

WTe
2

monolayer is obtained to be slightly less than the values reported in literature for 2H TMD monolayers of $$\hbox {MoS}_2$$

MoS
2

, $$\hbox {MoSe}_2$$

MoSe
2

, and $$\hbox {WS}_2$$

WS
2

. Furthermore, we simulate the impact of defects, such as vacancy, antisite and substitution defects, on the electronic, optical and thermoelectric properties of monolayer $$\hbox {WTe}_2$$

WTe
2

. Particularly, the Te-$$\hbox {O}_2$$

O
2

substitution defect in parallel orientation yields negative formation energy, indicating that the relevant defect may form spontaneously under relevant experimental conditions. We reveal that the electronic band structure of $$\hbox {WTe}_2$$

WTe
2

monolayer is significantly influenced by the presence of the considered defects. According to the calculated band gap values, a lowering of the conduction band minimum gives rise to metallic characteristics to the structure for the single Te(1) vacancy, a diagonal Te line defect, and the Te(1)-$$\hbox {O}_2$$

O
2

substitution, while the other investigated defects cause an opening of a small positive band gap at the Fermi level. Consequently, the real ($$\varepsilon _1(\omega )$$

ε
1

(
ω
)

) and imaginary ($$\varepsilon _2(\omega )$$

ε
2

(
ω
)

) parts of the dielectric constant at low frequencies are very sensitive to the applied defects, whereas we find that the absorbance (A) at optical frequencies is less significantly affected. We also predict that certain point defects can enhance the otherwise moderate value of S in pristine $$\hbox {WTe}_2$$

WTe
2

to values relevant for thermoelectric applications. The described $$\hbox {WTe}_2$$

WTe
2

monolayers, as functionalized with the considered defects, offer the possibility to be applied in optical, electronic, and thermoelectric devices.
A digital alkali spin maser
Authors: Ingleby Stuart , Griffin Paul , Dyer Terry , Mrozowski Marcin , Riis Erling
Published: July 2022

Self-oscillating atomic magnetometers, in which the precession of atomic spins in a magnetic field is driven by resonant modulation, offer high sensitivity and dynamic range. Phase-coherent feedback from the detected signal to the applied modulation creates a resonant spin maser system, highly responsive to changes in the background magnetic field. Here we show a system in which the phase condition for resonant precession is met by digital signal processing integrated into the maser feedback loop. This system uses a modest chip-scale laser and mass-produced dual-pass caesium vapour cell and operates in a 50 $$\mu $$
μ
T field, making it a suitable technology for portable measurements of the geophysical magnetic field. We demonstrate a Cramér-Rao lower bound-limited resolution of 50 fT at 1 s sampling cadence, and a sensor bandwidth of 10 kHz. This device also represents an important class of atomic system in which low-latency digital processing forms an integral part of a coherently-driven quantum system.
Modeling the spatial distribution of Culicoides species (Diptera: Ceratopogonidae) as vectors of animal diseases in Ethiopia
Authors: Fetene Eyerusalem , Teka Getachew , Dejene Hana , Mandefro Deresegn , Teshome Tsedale , Temesgen Dawit , Negussie Haileleul , Mulatu Tesfaye , Jaleta Megarsa Bedasa , Leta Samson
Published: July 2022

Culicoides biting midges (Diptera: Ceratopogonidae) are the major vectors of bluetongue, Schmallenberg, and African horse sickness viruses. This study was conducted to survey Culicoides species in different parts of Ethiopia and to develop habitat suitability for the major Culicoides species in Ethiopia. Culicoides traps were set in different parts of the country from December 2018 to April 2021 using UV light Onderstepoort traps and the collected Culicoides were sorted to species level. To develop the species distribution model for the two predominant Culicoides species, namely Culicoides imicola and C. kingi, an ensemble modeling technique was used with the Biomod2 package of R software. KAPPA True skill statistics (TSS) and ROC curve were used to evaluate the accuracy of species distribution models. In the ensemble modeling, models which score TSS values greater than 0.8 were considered. Negative binomialregression models were used to evaluate the relationship between C. imicola and C. kingi catch and various environmental and climatic factors. During the study period, a total of 9148 Culicoides were collected from 66 trapping sites. Of the total 9148, 8576 of them belongs to seven species and the remaining 572 Culicoides were unidentified. The predominant species was C. imicola (52.8%), followed by C. kingi (23.6%). The abundance of these two species was highly influenced by the agro-ecological zone of the capture sites and the proximity of the capture sites to livestock farms. Climatic variables such as mean annual minimum and maximum temperature and mean annual rainfall were found to influence the catch of C. imicola at the different study sites. The ensemble model performed very well for both species with KAPPA (0.9), TSS (0.98), and ROC (0.999) for C. imicola and KAPPA (0.889), TSS (0.999), and ROC (0.999) for C. kingi. Culicoides imicola has a larger suitability range compared to C. kingi. The Great Rift Valley in Ethiopia, the southern and eastern parts of the country, and the areas along the Blue Nile and Lake Tana basins in northern Ethiopia were particularly suitable for C. imicola. High suitability for C. kingi was found in central Ethiopia and the Southern Nations, Nationalities and Peoples Region (SNNPR). The habitat suitability model developed here could help researchers better understand where the above vector-borne diseases are likely to occur and target surveillance to high-risk areas.
Connexin43 represents an important regulator for Sertoli cell morphology, Sertoli cell nuclear ultrastructure, and Sertoli cell maturation
Authors: Staggenborg Sarah , Koch Rüdiger , Rode Kristina , Hüneke Hanna , Tiedje Louiza , Wirth Gudrun , Langeheine Marion , Blume Ines , Rohn Kerstin , Wrede Christoph , Pfarrer Christiane , Brehm Ralph
Published: July 2022

The Sertoli cell (SC)-specific knockout (KO) of connexin43 (Cx43) was shown to be an effector of multiple histological changes in tubular morphology, resulting in germ cell loss through to a Sertoli-cell-only (SCO) phenotype and vacuolated seminiferous tubules containing SC-clusters. Our present study focused on the effects of Cx43 loss on SC ultrastructure. Using serial block-face scanning electron microscopy (SBF-SEM), we could confirm previous results. Ultrastructural analysis of Sertoli cell nuclei (SCN) revealed that these appear in clusters with a phenotype resembling immature/proliferating SCs in KO mice. Surprisingly, SCs of fertile wild type (WT) mice contained SCN with a predominantly smooth surface instead of deep indentations of the nuclear envelope, suggesting that these indentations do not correlate with germ cell support or spermatogenesis. SBF-SEM facilitated the precise examination of clustered SCs. Even if the exact maturation state of mutant SCs remained unclear, our study could detect indications of cellular senescence as well as immaturity, emphasising that Cx43 affects SC maturation. Moreover, Sudan III staining and transmission electron microscopy (TEM) demonstrated an altered lipid metabolism in SCs of Cx43 deficient mice.
Spatio-temporal photolysis rate profiles of UV254 irradiated toluene
Authors: El-Tawargy Ahmed S.
Published: July 2022

The volatile organic compound (VOC) toluene is irradiated with a 254 nm UV source. The studied sample (1 mL) of toluene is equipped in a sealed quartz cuvette and inserted in one of the Michelson interferometer’s arms. During a UV254 irradiation of 1 h, the variation in the toluene’s refractive index profiles are monitored as a movement of Michelson interference fringes. These interferograms are recorded and digitally analyzed to produce their phase map distributions and, hence, reconstructing the refractive index profiles which are expressing the toluene’s photolysis behavior. With increasing the UV254 irradiation time, the toluene’s refractive index profiles exhibit both temporal and spatial decrease due to the production of benzyl radicals and the consequent oxidation of these radicals. The spatio-temporal refractive index and photolysis rate profiles of toluene are reconstructed and discussed.
Interpersonal neural synchrony when predicting others’ actions during a game of rock-paper-scissors
Authors: Kayhan E. , Nguyen T. , Matthes D. , Langeloh M. , Michel C. , Jiang J. , Hoehl S.
Published: July 2022

As members of a social species, we spend most of our time interacting with others. In interactions, we tend to mutually align our behavior and brain responses to communicate more effectively. In a semi-computerized version of the Rock-Paper-Scissors game, we investigated whether people show enhanced interpersonal neural synchronization when making explicit predictions about others’ actions. Across four experimental conditions, we measured the dynamic brain activity using the functional near-infrared spectroscopy (fNIRS) hyperscanning method. Results showed that interpersonal neural synchrony was enhanced when participants played the game together as they would do in real life in comparison to when they played the game on their own. We found no evidence of increased neural synchrony when participants made explicit predictions about others’ actions. Hence, neural synchrony may depend on mutual natural interaction rather than an explicit prediction strategy. This study is important, as it examines one of the presumed functions of neural synchronization namely facilitating predictions.
Phenotypic, metabolic, and biogenesis properties of human stem cell-derived cerebellar spheroids
Authors: Hua Timothy , Liu Chang , Kiran Sonia , Gray Kelly , Jung Sunghoon , Meckes David G. , Li Yan , Sang Qing-Xiang Amy
Published: July 2022

Human cerebellum consists of high density and complexity of neurons. Thus, it is challenging to differentiate cerebellar-like organoids with similar cellular markers and function to the human brain. Our previous study showed that the combination of retinoic acid (RA), Wingless/integrated (Wnt) activator, and Sonic Hedgehog (SHH) activator promotes cerebellar differentiation from human induced pluripotent stem cells (hiPSCs). This study examined phenotypic, metabolic, and biogenesis in early cerebellar development. Cerebellum spheroids were differentiated from human iPSK3 cells. During day 7–14, RA and Wnt activator CHIR99021 were used and SHH activator purmorphamine (PMR) was added later to promote ventralization. Gene expression for early cerebellar layer markers, metabolism, and extracellular vesicle (EV) biogenesis were characterized. Zinc-induced neurotoxicity was investigated as a proof-of-concept of neurotoxicity study. Flow cytometry results showed that there was no significant difference in NEPH3, PTF1A, OLIG2, and MATH1 protein expression between RCP (RA-CHIR-PMR) versus the control condition. However, the expression of cerebellar genes for the molecular layer (BHLE22), the granule cell layer (GABRB2, PAX6, TMEM266, KCNIP4), the Bergmann glial cells (QK1, DAO), and the Purkinje cell layer (ARHGEF33, KIT, MX1, MYH10, PPP1R17, SCGN) was significantly higher in the RCP condition than the control. The shift in metabolic pathways toward glycolysis was observed for RCP condition. The EV biogenesis marker expression was retained. Mild zinc-induced neurotoxicity may exist when zinc exposure exceeds 1.0 µM. RCP treatment can promote specific cerebellar-like differentiation from hiPSCs indicated by gene expression of early cerebellar markers and regionally enriched genes. The higher cerebellar marker expression is accompanied by the elevated glycolysis with the retained EV biogenesis. This study should advance the understanding of biomarkers during early cerebellar development for cerebellum organoid engineering and neurotoxicity study.
Ecological niche models for the assessment of site suitability of sea cucumbers and sea urchins in China
Authors: Sun Jiangnan , Yu Yushi , Zhao Zihe , Yin Donghong , Chang Yaqing , Zhao Chong
Published: July 2022

In the present study, the maximum entropy model (MaxEnt) based on the data of sea surface temperature (SST) and published information was used to assess the site suitability for the aquaculture expansion of the sea cucumberApostichopus japonicusand the sea urchinStrongylocentrotus intermediusin China. According to the current assessment, the coastal areas of Hebei province and Tianjin have great prospects forA. japonicusaquaculture, while is currently being underutilized. In the south, more than 94% of the coastal areas in Zhejiang, Fujian, and Guangdong provinces are suitable for the growth ofA. japonicusfor six months, especially the coastal areas of Lianjiang, Changle, Fuqing and Putian in Fujian province. The water temperatures in more than 94% of China's coastal areas are higher than 25 °C in July and August, which probably results in the mortality ofS. intermediusin aquaculture. This clearly indicates that high water temperature is the bottleneck ofS. intermediusaquaculture and well explains the limited expansion of this commercially important exotic species since the introduction in 1989. We suggest a new aquaculture model ofS. intermediusthat extends the seed production to November to avoid the mass mortality in summer. In the south, 64% of coastal areas in Zhejiang and Fujian provinces are suitable for the transplantation ofS. intermediusto the south. The present study suggests the ecological niche model MaxEnt based on the data of SST and published information as a new tool for the assessment of the site suitability of sea cucumbers and sea urchins in China. This provides new insights into the aquaculture expansion of native and exotic species.