bluuebunny/crossref_metadata_2025 huggingface dataset:
Some Illustrations of Large Tectonically Driven Climate Changes in Earth History
Authors: Ramstein G. , Godderis Y. , Donnadieu Y. , Sepulchre P. , Fluteau F. , Zhang Z. , Zhang R. , Su B. , Jiang D. , Schuster M. , Besse J.
Published: November 2019

A century ago, the pioneering book published in 1924 Die Klimate der geologischen Vorzeit explained by plate motion the evolution of vegetation revealed in sedimentary records. Nevertheless, they did not invoke climate changes. In the second part of the 20th century, the intricate relationship between tectonics, long‐term carbon cycle, and climate was depicted by Walker (1981). Since these major steps, climate modeling of the Earth system kept on improving and including more and more components and processes to enable the investigation of deep time periods using general circulation model that can account for atmosphere and ocean dynamics. Here we illustrate long but drastic climate changes clearly related with tectonics, through three different examples: (1) the crucial role of paleogeography (continental distribution) to explain the drawdown of atmospheric carbon dioxide and the huge glaciation associated that occurred during the Neoproterozoic period; (2) the shrinkage of large epicontinental Paratethys that covered a large part of Eastern Europe and Western Asia and its impact on both monsoonal systems (African and Asian) since 40 Ma; and (3) the large impact of mountain range uplifts since Eocene both in Asia (Tibetan Plateau and Himalaya) and in Africa (buildup of the rift), on atmosphere and ocean dynamics. These studies not only allow for testing the ability of Earth system models to capture long‐term changes of Earth climate, but they also pinpoint the pivotal role tectonics played in shaping the long‐term evolution of atmospheric CO2 and monsoon patterns.
Spatial Characteristics Reveal the Reactive Transport of Radium Isotopes (224Ra, 223Ra, and 228Ra) in an Intertidal Aquifer
Authors: Liu Yi , Jiao Jiu Jimmy , Mao Rong , Luo Xin , Liang Wenzhao , Robinson Clare E.
Published: November 2019

This study presents high‐resolution two‐dimensional distributions of radium isotopes in the shallow intertidal aquifer of Tolo Harbor, Hong Kong, illustrating the importance of salinity, groundwater residence time, and tidal flushing and mixing in controlling radium behavior in the system. The activities of radium isotopes are low in the fresh groundwater zone with activities increasing in the transition zone (1 < salinity < 25) due to desorption of radium from sediment surface coatings. In the high salinity zone (salinity > 25), the activities of radium isotopes increase with depth due to tidal flushing and mixing of the recirculating seawater in the shallow aquifer as well as increasing residence time with depth. The dissolved radium isotopes are identified to be in disequilibrium in shallow intertidal aquifer based on radium isotopic ratios and observed depletion of dissolved radium isotopes compared to the theoretical mixing line between the equilibrium activity and fresh groundwater. The influence of continuous tidal flushing of the shallow intertidal aquifer on radium is revealed, and shallow sediments are observed to have less total exchangeable radium isotopes than deeper in the aquifer. A new one‐dimensional reactive transport model that considers a depth‐dependent production rate is applied to simulate the vertical distribution of radium isotopes in the intertidal aquifer as seawater infiltrates the beach. Using least squares fitting of the model to field data, the vertical infiltration seepage velocity is estimated to be ~0.5 m/day, and the dimensionless adsorption partition coefficient of radium isotopes (K) is 350. This agrees well with K values (202–365) calculated using an adsorption/desorption model as well as measured values (266 in February and 205 in April). Based on the spatial distribution of radium isotopes and flow patterns in the intertidal aquifer, groundwater in Ra disequilibrium zone is recommended as the endmember for tide‐ or wave‐driven submarine groundwater discharge (SGD) that has shallow flow paths, and groundwater in Ra equilibrium zone is recommended as endmember for seasonally driven or density‐driven SGD that has deep flow paths.
Silencing of long noncoding RNA HOXA11-AS inhibits the Wnt signaling pathway via the upregulation of HOXA11 and thereby inhibits the proliferation, invasion, and self-renewal of hepatocellular carcinoma stem cells
Authors: Guo Jun-Cheng , Yang Yi-Jun , Zheng Jin-Fang , Zhang Jian-Quan , Guo Min , Yang Xiang , Jiang Xiang-Ling , Xiang Li , Li You , Ping Huang , Zhuo Liu
Published: November 2019

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths, but its molecular mechanisms are not yet well characterized. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, including that of HCC. However, the role of homeobox A11 antisense (HOXA11-AS) in determining HCC stem cell characteristics remains to be explained; hence, this study aimed to investigate the effects of HOXA11-AS on HCC stem cell characteristics. Initially, the expression patterns of HOXA11-AS and HOXA11 in HCC tissues, cells, and stem cells were determined. HCC stem cells, successfully sorted from Hep3B and Huh7 cells, were transfected with short hairpin or overexpression plasmids for HOXA11-AS or HOXA11 overexpression and depletion, with an aim to study the influences of these mediators on the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo. Additionally, the potential relationship and the regulatory mechanisms that link HOXA11-AS, HOXA11, and the Wnt signaling pathway were explored through treatment with Dickkopf-1 (a Wnt signaling pathway inhibitor). HCC stem cells showed high expression of HOXA11-AS and low expression of HOXA11. Both HOXA11-AS silencing and HOXA11 overexpression suppressed the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo, as evidenced by the decreased expression of cancer stem cell surface markers (CD133 and CD44) and stemness-related transcription factors (Nanog, Sox2, and Oct4). Moreover, silencing HOXA11-AS inactivated the Wnt signaling pathway by decreasing the methylation level of the HOXA11 promoter, thereby inhibiting HCC stem cell characteristics. Collectively, this study suggested that HOXA11-AS silencing exerts an antitumor effect, suppressing HCC development via Wnt signaling pathway inactivation by decreasing the methylation level of the HOXA11 promoter.
Extracting more light for vertical emission: high power continuous wave operation of 1.3-μm quantum-dot photonic-crystal surface-emitting laser based on a flat band
Authors: Lu Huan-Yu , Tian Si-Cong , Tong Cun-Zhu , Wang Li-Jie , Rong Jia-Min , Liu Chong-Yang , Wang Hong , Shu Shi-Li , Wang Li-Jun
Published: November 2019

For long distance optical interconnects, 1.3-μm surface-emitting lasers are key devices. However, the low output power of several milliwatts limits their application. In this study, by introducing a two-dimensional photonic-crystal and using InAs quantum dots as active materials, a continuous-wave, 13.3-mW output power, 1.3-μm wavelength, room-temperature surface-emitting laser is achieved. In addition, such a device can be operated at high temperatures of up to 90 °C. The enhanced output power results from the flat band structure of the photonic crystal and an extra feedback mechanism. Surface emission is realized by photonic crystal diffraction and thus the distributed Bragg reflector is eliminated. The proposed device provides a means to overcome the limitations of low-power 1.3-μm surface-emitting lasers and increase the number of applications thereof.
Dual phases of crystalline and electronic structures in the nanocrystalline perovskite CsPbBr3
Authors: Whitcher T. J. , Gomes L. C. , Zhao D. , Bosman M. , Chi X. , Wang Y. , Carvalho A. , Hui H. K. , Chang Q. , Breese M. B. H. , Castro Neto A. H. , Wee A. T. S. , Sun H. D. , Chia E. E. M. , Rusydi A.
Published: November 2019

Inorganic perovskites have recently attracted much attention as promising new nanocrystalline materials that have interesting fundamental phenomena and great potential in several applications. Herein, we reveal unusual structural and electronic changes in nanocrystalline cesium lead bromide (CsPbBr3) as a function of temperature using high-resolution spectroscopic ellipsometry, high-resolution transmission electron microscopy and terahertz spectroscopy measurements supported by first-principles calculations. New dual phases of crystalline and electronic structures are observed due to the nanocrystalline nature of the material. Interestingly, a change in the electronic structure occurs below 150 K, and the rate at which the nanocrystal transitions from the tetragonal to orthorhombic phase is found to be nonlinear with temperature. Our results show the importance of the charge and lattice interplay in determining the dual phases and fundamental properties of nanocrystalline materials.
Interplay between α2-chimaerin and Rac1 activity determines dynamic maintenance of long-term memory
Authors: Lv Li , Liu Yunlong , Xie Jianxin , Wu Yan , Zhao Jianjian , Li Qian , Zhong Yi
Published: November 2019

Memory consolidation theory suggests that once memory formation has been completed, memory is maintained at a stable strength and is incapable of further enhancement. However, the current study reveals that even long after formation, contextual fear memory could be further enhanced. Such unexpected enhancement is possible because memory is dynamically maintained at an intermediate level that allows for bidirectional regulation. Here we find that both Rac1 activation and expression of α2-chimaerin are stimulated by single-trial contextual fear conditioning. Such sustained Rac1 activity mediates reversible forgetting, and α2-chimaerin acts as a memory molecule that reverses forgetting to sustain memory through inhibition of Rac1 activity during the maintenance stage. Therefore, the balance between activated Rac1 and expressed α2-chimaerin defines dynamic long-term memory maintenance. Our findings demonstrate that consolidated memory maintains capacity for bidirectional regulation.
Spatial control over catalyst positioning on biodegradable polymeric nanomotors
Authors: Toebes B. Jelle , Cao F. , Wilson Daniela A.
Published: November 2019

Scientists over the world are inspired by biological nanomotors and try to mimic these complex structures. In recent years multiple nanomotors have been created for various fields, such as biomedical applications or environmental remediation, which require a different design both in terms of size and shape, as well as material properties. So far, only relatively simple designs for synthetic nanomotors have been reported. Herein, we report an approach to create biodegradable polymeric nanomotors with a multivalent design. PEG-PDLLA (poly(ethylene glycol)-b-poly(D,L-lactide)) stomatocytes with azide handles were created that were selectively reduced on the outside surface by TCEP (tris(2-carboxyethyl)phosphine) functionalized beads. Thereby, two different functional handles were created, both on the inner and outer surface of the stomatocytes, providing spatial control for catalyst positioning. Enzymes were coupled on the inside of the stomatocyte to induce motion in the presence of fuel, while fluorophores and other molecules can be attached on the outside.
Thermally activated delayed fluorescence with 7% external quantum efficiency from a light-emitting electrochemical cell
Authors: Lundberg Petter , Tsuchiya Youichi , Lindh E. Mattias , Tang Shi , Adachi Chihaya , Edman Ludvig
Published: November 2019

We report on light-emitting electrochemical cells, comprising a solution-processed single-layer active material and air-stabile electrodes, that exhibit efficient and bright thermally activated delayed fluorescence. Our optimized devices delivers a luminance of 120 cd m−2 at an external quantum efficiency of 7.0%. As such, it outperforms the combined luminance/efficiency state-of-the art for thermally activated delayed fluorescence light-emitting electrochemical cells by one order of magnitude. For this end, we employed a polymeric blend host for balanced electrochemical doping and electronic transport as well as uniform film formation, an optimized concentration (<1 mass%) of guest for complete host-to-guest energy transfer at minimized aggregation and efficient emission, and an appropriate concentration of an electrochemically stabile electrolyte for desired doping effects. The generic nature of our approach is manifested in the attainment of bright and efficient thermally activated delayed fluorescence emission from three different light-emitting electrochemical cells with invariant host:guest:electrolyte number ratio.
Glycerol-3-phosphate mediates rhizobia-induced systemic signaling in soybean
Authors: Shine M. B. , Gao Qing-ming , Chowda-Reddy R. V. , Singh Asheesh K. , Kachroo Pradeep , Kachroo Aardra
Published: November 2019

Glycerol-3-phosphate (G3P) is a well-known mobile regulator of systemic acquired resistance (SAR), which provides broad spectrum systemic immunity in response to localized foliar pathogenic infections. We show that G3P-derived foliar immunity is also activated in response to genetically-regulated incompatible interactions with nitrogen-fixing bacteria. Using gene knock-down we show that G3P is essential for strain-specific exclusion of non-desirable root-nodulating bacteria and the associated foliar pathogen immunity in soybean. Grafting studies show that while recognition of rhizobium incompatibility is root driven, bacterial exclusion requires G3P biosynthesis in the shoot. Biochemical analyses support shoot-to-root transport of G3P during incompatible rhizobia interaction. We describe a root-shoot-root signaling mechanism which simultaneously enables the plant to exclude non-desirable nitrogen-fixing rhizobia in the root and pathogenic microbes in the shoot.
Causative role of PDLIM2 epigenetic repression in lung cancer and therapeutic resistance
Authors: Sun Fan , Li Liwen , Yan Pengrong , Zhou Jingjiao , Shapiro Steven D. , Xiao Gutian , Qu Zhaoxia
Published: November 2019

Most cancers are resistant to anti-PD-1/PD-L1 and chemotherapy. Herein we identify PDLIM2 as a tumor suppressor particularly important for lung cancer therapeutic responses. While PDLIM2 is epigenetically repressed in human lung cancer, associating with therapeutic resistance and poor prognosis, its global or lung epithelial-specific deletion in mice causes increased lung cancer development, chemoresistance, and complete resistance to anti-PD-1 and epigenetic drugs. PDLIM2 epigenetic restoration or ectopic expression shows antitumor activity, and synergizes with anti-PD-1, notably, with chemotherapy for complete remission of most lung cancers. Mechanistically, through repressing NF-κB/RelA and STAT3, PDLIM2 increases expression of genes involved in antigen presentation and T-cell activation while repressing multidrug resistance genes and cancer-related genes, thereby rendering cancer cells vulnerable to immune attacks and therapies. We identify PDLIM2-independent PD-L1 induction by chemotherapeutic and epigenetic drugs as another mechanism for their synergy with anti-PD-1. These findings establish a rationale to use combination therapies for cancer treatment.
Synthesizing multi-phonon quantum superposition states using flux-mediated three-body interactions with superconducting qubits
Authors: Kounalakis Marios , Blanter Yaroslav M. , Steele Gary A.
Published: November 2019

Massive mechanical resonators operating at the quantum scale can enable a large variety of applications in quantum technologies as well as fundamental tests of quantum theory. Of crucial importance in that direction is both their integrability into state-of-the-art quantum platforms as well as the ability to prepare them in generic quantum states using well-controlled high-fidelity operations. Here, we propose a scheme for controlling a radio-frequency mechanical resonator at the quantum scale using two superconducting transmon qubits that can be integrated on the same chip. Specifically, we consider two qubits coupled via a capacitor in parallel to a superconducting quantum interference device (SQUID), which has a suspended mechanical beam embedded in one of its arms. Following a theoretical analysis of the quantum system, we find that this configuration, in combination with an in-plane magnetic field, can give rise to a tuneable three-body interaction in the single-photon strong-coupling regime, while enabling suppression of the stray qubit-qubit coupling. Using state-of-the-art parameters and qubit operations at single-excitation levels, we numerically demonstrate the possibility of ground-state cooling as well as high-fidelity preparation of mechanical quantum states and qubit-phonon entanglement, i.e. states having negative Wigner functions and obeying non-classical correlations. Our work significantly extends the quantum control toolbox of radio-frequency mechanical resonators and may serve as a promising architecture for integrating such mechanical elements with transmon-based quantum processors.
Cambridge quantum network
Authors: Dynes J. F. , Wonfor A. , Tam W. W. -S. , Sharpe A. W. , Takahashi R. , Lucamarini M. , Plews A. , Yuan Z. L. , Dixon A. R. , Cho J. , Tanizawa Y. , Elbers J. -P. , Greißer H. , White I. H. , Penty R. V. , Shields A. J.
Published: November 2019

Future-proofing current fibre networks with quantum key distribution (QKD) is an attractive approach to combat the ever growing breaches of data theft. To succeed, this approach must offer broadband transport of quantum keys, efficient quantum key delivery and seamless user interaction, all within the existing fibre network. However, quantum networks to date either require dark fibres and/or offer bit rates inadequate for serving a large number of users. Here we report a city wide high-speed metropolitan QKD network—the Cambridge quantum network—operating on fibres already populated with high-bandwidth data traffic. We implement a robust key delivery layer to demonstrate essential network operation, as well as enabling encryption of 100 Gigabit per second (Gbps) simultaneous data traffic with rapidly refreshed quantum keys. Network resilience against link disruption is supported by high-QKD link rates and network link redundancy. We reveal that such a metropolitan network can support tens of thousands of users with key rates in excess of 1 kilobit per second (kbps) per user. Our result hence demonstrates a clear path for implementing quantum security in metropolitan fibre networks.
Prediction Model of Organic Molecular Absorption Energies based on Deep Learning trained by Chaos-enhanced Accelerated Evolutionary algorithm
Authors: Li Mengshan , Lian Suyun , Wang Fan , Zhou Yanying , Chen Bingsheng , Guan Lixin , Wu Yan
Published: November 2019

As an important physical property of molecules, absorption energy can characterize the electronic property and structural information of molecules. Moreover, the accurate calculation of molecular absorption energies is highly valuable. Present linear and nonlinear methods hold low calculation accuracies due to great errors, especially irregular complicated molecular systems for structures. Thus, developing a prediction model for molecular absorption energies with enhanced accuracy, efficiency, and stability is highly beneficial. By combining deep learning and intelligence algorithms, we propose a prediction model based on the chaos-enhanced accelerated particle swarm optimization algorithm and deep artificial neural network (CAPSO BP DNN) that possesses a seven-layer 8-4-4-4-4-4-1 structure. Eight parameters related to molecular absorption energies are selected as inputs, such as a theoretical calculating value Ec of absorption energy (B3LYP/STO-3G), molecular electron number Ne, oscillator strength Os, number of double bonds Ndb, total number of atoms Na, number of hydrogen atoms Nh, number of carbon atoms Nc, and number of nitrogen atoms NN; and one parameter representing the molecular absorption energy is regarded as the output. A prediction experiment on organic molecular absorption energies indicates that CAPSO BP DNN exhibits a favourable predictive effect, accuracy, and correlation. The tested absolute average relative error, predicted root-mean-square error, and square correlation coefficient are 0.033, 0.0153, and 0.9957, respectively. Relative to other prediction models, the CAPSO BP DNN model exhibits a good comprehensive prediction performance and can provide references for other materials, chemistry and physics fields, such as nonlinear prediction of chemical and physical properties, QSAR/QAPR and chemical information modelling, etc.
The Role of Wettability on the Response of a Quartz Crystal Microbalance Loaded with a Sessile Droplet
Authors: Murray Brandon , Narayanan Shankar
Published: November 2019

In this work, the interaction between a sessile droplet’s contact angle and a quartz crystal microbalance (QCM) is elucidated. We differentiate the QCM’s frequency response to changes in the droplet contact area from variations in the dynamic contact angle. This is done by developing a computational model that couples the electrical and mechanical analysis of the quartz substrate with the visco-acoustic behavior of the sessile droplet. From our analysis, we conclude that changes in the contact angle have an effect on the frequency response of the QCM when the droplet height is on the order of the viscous decay length or smaller. On the other hand, changes in the interfacial contact area of the sessile droplets have a significant impact on the frequency response of the QCM regardless of the droplet size.
A Multi-Phasic Perspective of the Intact Permeability of the Heterogeneous Argillaceous Cobourg Limestone
Authors: Selvadurai A. P. S.
Published: November 2019

The Cobourg limestone is a heterogeneous argillaceous rock consisting of lighter nodular regions of calcite and dolomite, interspersed with darker regions composed of calcite, dolomite, quartz and a clay fraction. The intact permeability of the Cobourg limestone is estimated to be in the range of K ∈ (10−23, 10−19) m2. This paper discusses the factors influencing the measurement of the intact permeability of the Cobourg limestone and presents an upscaling approach for estimating this parameter. The procedure first involves the dissection of a cuboidal sample of the rock measuring, 80 mm × 120 mm × 300 mm, into ten 8 mm-thick slabs. Digital imaging and mapping of the larger surfaces of these sections are used to create, from both surface image extrusion and surface image interpolation techniques, the fabric within the dissected regions. The estimated permeabilities of the lighter and darker regions are used in the computational models of the computer-generated fabric to estimate the effective permeability of the rock. These results are complemented by estimates derived from mathematical theories for estimating permeabilities of multiphasic composites.
The Use of Motion Analysis as Particle Biomarkers in Lensless Optofluidic Projection Imaging for Point of Care Urine Analysis
Authors: Kun Jessica , Smieja Marek , Xiong Bo , Soleymani Leyla , Fang Qiyin
Published: November 2019

Urine testing is an essential clinical diagnostic tool. The presence of urine sediments, typically analyzed through microscopic urinalysis or cell culture, can be indicative of many diseases, including bacterial, parasitic, and yeast infections, as well as more serious conditions like bladder cancer. Current urine analysis diagnostic methods are usually centralized and limited by high cost, inconvenience, and poor sensitivity. Here, we developed a lensless projection imaging optofluidic platform with motion-based particle analysis to rapidly detect urinary constituents without the need for concentration or amplification through culture. A removable microfluidics channel ensures that urine samples do not cross contaminate and the lens-free projection video is captured and processed by a low-cost integrated microcomputer. A motion tracking and analysis algorithm is developed to identify and track moving objects in the flow. Their motion characteristics are used as biomarkers to detect different urine species in near real-time. The results show that this technology is capable of detection of red and white blood cells, Trichomonas vaginalis, crystals, casts, yeast and bacteria. This cost-effective device has the potential to be implemented for timely, point-of-care detection of a wide range of disorders in hospitals, clinics, long-term care homes, and in resource-limited regions.
Spontaneous Yawning and its Potential Functions in South American Sea Lions (Otaria flavescens)
Authors: Palagi Elisabetta , Guillén-Salazar Federico , Llamazares-Martín Clara
Published: November 2019

Spontaneous yawning is a widespread behaviour in vertebrates. However, data on marine mammals are scarce. In this study, we tested some hypotheses on the functions of yawning in a captive group of South American sea lions (Otaria flavescens). According to the Dimorphism Hypothesis, species showing low levels of sexual dimorphism in canine size do not show sex differences in yawning distribution; this was supported by our findings, since yawning did not differ between the sexes. Yawning was more frequently performed during resting/sleeping contexts, thus supporting the Drowsiness Hypothesis. Yawning and self-scratching are considered reliable indicators of short-term anxiety in sea lions, since they immediately increased after conflicts both in aggressors and victims (Social Distress Hypothesis supported). In the long-term, yawning was not correlated with individuals’ dominance status, thus showing that anxiety is similarly experienced by dominants and subordinates. The last two findings can be explained by the social competition of this species, that involves individuals independently from their sex, age or ranking status. Therefore, the exposure to frequent stressful events can induce similar levels of anxiety in all the subjects (Resource Inequity Hypothesis supported). In conclusion, spontaneous yawning in sea lions seems to share similar functions with other social mammals, suggesting that this behaviour is a possible plesiomorphic trait.
Induction of HLA-A2 restricted CD8 T cell responses against ApoB100 peptides does not affect atherosclerosis in a humanized mouse model
Authors: Schaftenaar Frank H. , Amersfoort Jacob , Douna Hidde , Kröner Mara J. , Foks Amanda C. , Bot Ilze , Slütter Bram A. , van Puijvelde Gijs H. M. , Drijfhout Jan W. , Kuiper Johan
Published: November 2019

Cardiovascular diseases form the most common cause of death worldwide, with atherosclerosis as main etiology. Atherosclerosis is marked by cholesterol rich lipoprotein deposition in the artery wall, evoking a pathogenic immune response. Characteristic for the disease is the pathogenic accumulation of macrophages in the atherosclerotic lesion, which become foam cells after ingestion of large quantities of lipoproteins. We hypothesized that, by inducing a CD8 T cell response towards lipoprotein derived apolipoprotein-B100 (ApoB100), lesional macrophages, that are likely to cross-present lipoprotein constituents, can specifically be eliminated. Based onin silicomodels for protein processing and MHC-I binding, 6 putative CD8 T cell epitopes derived from ApoB100 were synthesized. HLA-A2 binding was confirmed for all peptides by T2 cell binding assays and recall responses after vaccination with the peptides proved that 5 of 6 peptides could induce CD8 T cell responses. Induction of ApoB100 specific CD8 T cells did not impact plaque size and cellular composition in HLA-A2 and human ApoB100 transgenic LDLr−/−mice. No recall response could be detected in cultures of cells isolated from the aortic arch, which were observed in cell cultures of splenocytes and mesenteric lymph nodes, suggesting that the atherosclerotic environment impairs CD8 T cell activation.
Genetic disorder prenatal diagnosis and pregnancy termination practices among high consanguinity population, Saudi Arabia
Authors: AbdulAzeez Sayed , Al Qahtani Nourah H. , Almandil Noor B. , Al-Amodi Amani M. , Aldakeel Sumayh A. , Ghanem Neda Z. , Alkuroud Deem N. , AlTurki Ameen , AlQattan Quds Abdulhakeem , Alghamdi Abdulrahman , Alhur Norah Fahad , Al Taifi Hatoon Ahmed , Aljofi Halah Egal , Jermy B. Rabindran , Raman Vinoth , Giambona Antonino , Maggio Aurelio , Borgio J. Francis
Published: November 2019

The prevalence of consanguineous marriage and genetic disorders are high in Saudi Arabia. There were records on the practices of Saudis toward prenatal diagnosis (PND) and termination of pregnancy (TOP), however the sample sizes are small. This study has targeted the Saudi Arabian community and family history of genetic disorders to determine the practices toward PND and TOP. The cross-sectional survey was conducted among Saudis (n = 2761) to determine their practices toward reproductive-decision making. Regression analysis was conducted to identify the association of the limiting factors, relative merits and family history on the outcomes. Total of 2507 participants returned completed questionnaire. The practice towards PND (68%) were more favorable than TOP (33%). PND was found to be a good opportunity for early diagnosis and gives parent’s choice. Education, history with affected baby, prior knowledge and religious belief were significant deciding factors of PND and TOP. Down syndrome (n = 161) and sickle cell anemia (n = 152) were commonly available genetic disorder among participant’s family. Respondents with autistic cases in their family have higher acceptance rate for TOP. Non-consanguineous are more willing to consider TOP than consanguineous. Participants with abnormal fetus, aged of > 36 years, married and educated Saudis were more likely consider TOP. Though, religion is the most influencing factor for not accepting TOP, comparatively willingness to PND and TOP have increased recently. Awareness campaigns about PND and TOP may increase the chances of accepting prenatal genetic diagnosis.
Neurophysiological Correlates of Concussion: Deep Learning for Clinical Assessment
Authors: Boshra Rober , Ruiter Kyle I. , DeMatteo Carol , Reilly James P. , Connolly John F.
Published: November 2019

Concussion has been shown to leave the afflicted with significant cognitive and neurobehavioural deficits. The persistence of these deficits and their link to neurophysiological indices of cognition, as measured by event-related potentials (ERP) using electroencephalography (EEG), remains restricted to population level analyses that limit their utility in the clinical setting. In the present paper, a convolutional neural network is extended to capitalize on characteristics specific to EEG/ERP data in order to assess for post-concussive effects. An aggregated measure of single-trial performance was able to classify accurately (85%) between 26 acutely to post-acutely concussed participants and 28 healthy controls in a stratified 10-fold cross-validation design. Additionally, the model was evaluated in a longitudinal subsample of the concussed group to indicate a dissociation between the progression of EEG/ERP and that of self-reported inventories. Concordant with a number of previous studies, symptomatology was found to be uncorrelated to EEG/ERP results as assessed with the proposed models. Our results form a first-step towards the clinical integration of neurophysiological results in concussion management and motivate a multi-site validation study for a concussion assessment tool in acute and post-acute cases.
The MUC5B mucin polymer is dominated by repeating structural motifs and its topology is regulated by calcium and pH
Authors: Hughes Gareth W. , Ridley Caroline , Collins Richard , Roseman Alan , Ford Robert , Thornton David J.
Published: November 2019

The polymeric mucin MUC5B provides the structural and functional framework of respiratory mucus, conferring both viscoelastic and antimicrobial properties onto this vital protective barrier. Whilst it is established that MUC5B forms disulfide-linked linear polymers, how this relates to their packaging in secretory granules, and their molecular form in mucus remain to be fully elucidated. Moreover, the role of the central heavily O-glycosylated mucin domains in MUC5B conformation is incompletely described. Here we have completed a detailed structural analysis on native MUC5B polymers purified from saliva and subsequently investigated how MUC5B conformation is affected by changes in calcium concentration and pH, factors important for mucin intragranular packaging and post-secretory expansion. The results identify that MUC5B has a beaded structure repeating along the polymer axis and suggest that these repeating motifs arise from distinct glycosylation patterns. Moreover, we demonstrate that the conformation of these highly entangled linear polymers is sensitive to calcium concentration and changes in pH. In the presence of calcium (Ca2+, 10 mM) at pH 5.0, MUC5B adopted a compact conformation which was lost either upon removal of calcium with EGTA, or by increasing the pH to 7.4. These results suggest a pathway of mucin collapse to enable intracellular packaging and mechanisms driving mucin expansion following secretion. They also point to the importance of the tight control of calcium and pH during different stages of mucin biosynthesis and secretion, and in the generation of correct mucus barrier properties.
Author Correction: Comparison between chronic hepatitis B patients with untreated immune-tolerant phase vs. those with virological response by antivirals
Authors: Lee Hye Won , Kim Seung Up , Baatarkhuu Oidov , Park Jun Yong , Kim Do Young , Ahn Sang Hoon , Han Kwang-Hyub , Kim Beom Kyung
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Activation of heme oxygenase-1 by Ginkgo biloba extract differentially modulates endothelial and smooth muscle-like progenitor cells for vascular repair
Authors: Wu Tao-Cheng , Chen Jia-Shiong , Wang Chao-Hung , Huang Po-Hsun , Lin Feng-Yen , Lin Liang-Yu , Lin Shing-Jong , Chen Jaw-Wen
Published: November 2019

Vascular progenitors such as endothelial progenitor cells (EPCs) and smooth muscle-like progenitor cells (SMPCs) may play different roles in vascular repair.Ginkgo bilobaextract (GBE) is an exogenous activator of heme oxygenase (HO)-1, which has been suggested to improve vascular repair; however, the detailed mechanisms have yet to be elucidated. This study aimed to investigate whether GBE can modulate different vascular progenitor cells by activating HO-1 for vascular repair. A bone marrow transplantation mouse model was used to evaluate thein vivoeffects of GBE treatment on wire-injury induced neointimal hyperplasia, which is representative of impaired vascular repair. On day 14 of GBE treatment, the mice were subjected to wire injury of the femoral artery to identify vascular reendothelialization. Compared to the mice without treatment, neointimal hyperplasia was reduced in the mice that received GBE treatment for 28 days in a dose-dependent manner. Furthermore, GBE treatment increased bone marrow-derived EPCs, accelerated endothelial recovery, and reduced the number of SMPCs attached to vascular injury sites. The effects of GBE treatment on neointimal hyperplasia could be abolished by co-treatment with zinc protoporphyrin IX, an HO-1 inhibitor, suggesting thein vivorole of HO-1. In thisin vitrostudy, treatment with GBE activated human early and late EPCs and suppressed SMPC migration. These effects were abolished by HO-1 siRNA and an HO-1 inhibitor. Furthermore, GBE induced the expression of HO-1 by activating PI3K/Akt/eNOS signaling in human late EPCs and via p38 pathways in SMPCs, suggesting that GBE can induce HO-1in vitrothrough different molecular mechanisms in different vascular progenitor cells. Accordingly, GBE could activate early and late EPCs, suppress the migration of SMPCs, and improvein vivovascular repair after mechanical injury by activating HO-1, suggesting the potential role of pharmacological HO-1 activators, such as GBE, for vascular protection in atherosclerotic diseases.
Human pleural fluid triggers global changes in the transcriptional landscape of Acinetobacter baumannii as an adaptive response to stress
Authors: Martinez Jasmine , Fernandez Jennifer S. , Liu Christine , Hoard Amparo , Mendoza Anthony , Nakanouchi Jun , Rodman Nyah , Courville Robert , Tuttobene Marisel R. , Lopez Carolina , Gonzalez Lisandro J. , Shahrestani Parvin , Papp-Wallace Krisztina M. , Vila Alejandro J. , Tolmasky Marcelo E. , Bonomo Robert A. , Sieira Rodrigo , Ramirez Maria Soledad
Published: November 2019

Acinetobacter baumannii is a feared, drug-resistant pathogen, characterized by its ability to resist extreme environmental and nutrient-deprived conditions. Previously, we showed that human serum albumin (HSA) can increase foreign DNA acquisition specifically and alter the expression of genes associated with pathogenicity. Moreover, in a recent genome-wide transcriptomic study, we observed that pleural fluid (PF), an HSA-containing fluid, increases DNA acquisition, can modulate cytotoxicity, and control immune responses by eliciting changes in the A. baumannii metabolic profile. In the present work, using more stringent criteria and focusing on the analysis of genes related to pathogenicity and response to stress, we analyzed our previous RNA-seq data and performed phenotypic assays to further explore the impact of PF on A. baumannii’s microbial behavior and the strategies used to overcome environmental stress. We observed that PF triggered differential expression of genes associated with motility, efflux pumps, antimicrobial resistance, biofilm formation, two-component systems (TCSs), capsule synthesis, osmotic stress, and DNA-damage response, among other categories. Phenotypic assays of A. baumannii A118 and two other clinical A. baumannii strains, revealed differences in their responses to PF in motility, biofilm formation, antibiotic susceptibility, osmotic stress, and outer membrane vesicle (OMV) production, suggesting that these changes are strain specific. We conclude that A. baumannii’s pathoadaptive responses is induced by HSA-containing fluids and must be part of this bacterium armamentarium to persist in hostile environments.
GeographicalDifference, Rural-urban Transition and Trend in Stroke Prevalence in China: Findings from a National Epidemiological Survey of Stroke in China
Authors: Ru Xiaojuan , Wang Wenzhi , Sun Haixin , Sun Dongling , Fu Jie , Ge Siqi , Wang Limin , Wang Linhong , Jiang Bin
Published: November 2019

Accurate and up-to-date provincial and regional-level stroke prevalence estimates are important for research planning and targeted strategies for stroke prevention and management. However, recent and comprehensive evaluation is lacking over the past 30 years in China. This study aimed to examine the geographical variations in stroke prevalence based on data from the National Epidemiological Survey of Stroke in China (NESS-China) and demonstrate urban-rural transition and trend over three decades. The stroke prevalence (prevalence day, August 31, 2013) was estimated using the world standard population. The stroke prevalence was 873.4 per 100,000 population, and varied from 218.0 in Sichuan to 1768.9 in Heilongjiang. Stroke prevalence exhibited a noticeable north-south gradient (1097.1, 917.7, and 619.4 in the north, middle, and the south, respectively; P < 0.001) and showed a 2.0-fold, 1.5-fold, and 1.2-fold increase in rural areas in the north, the middle, and the south, respectively, from 1985 to 2013. Overall, stroke prevalence was higher in the rural regions than in the urban (945.4 versus 797.5, P < 0.001) regions. However, the converse was depicted in 12 provinces. A noticeable geographical variation in stroke prevalence was observed and was evolving overtime in China. It is imperative that effective public health policies and interventions be implemented, especially in those regions with higher prevalence.
Parasite induced mortality is context dependent in Atlantic salmon: insights from an individual-based model
Authors: Vollset Knut Wiik
Published: November 2019

An individual-based model was parameterized to explore the impact of a crustacean ectoparasite (sea louse, Lepeophtheirus salmonis & Caligus spp.) on migrating Atlantic salmon smolt. The model explores how environmental and intrinsic factors can modulate the effect of sea lice on survival, growth and maturation of Atlantic salmon at sea. Relative to other effects, the parasite infestation pressure from fish farms and the encounter process emerge as the most important parameters. Although small variations in parasite-induced mortality may be masked by variable environmental effects, episodes of high infestation pressure from fish farms should be observable in wild populations of Atlantic salmon if laboratory studies accurately reflect the physiological effects of sea lice. Increases in temperature in the model negatively influenced fish survival by affecting the development time of the parasite at a rate that was not compensated for by the growth of the host. Discharge from rivers was parameterized to increase migration speed and influenced parasite induced mortality by decreasing time spent in areas with increased infestation pressure. Initial size and growth of the host was inversely related to the impact of the parasite because of size-dependent parasite-induced mortality in the early phase of migration. Overall, the model illustrates how environmental factors modulate effects on the host population by impacting either the parasite load or the relative effect of the parasite. The results suggest that linking population-level effects to parasite infestation pressure across climatic and environmental gradients may be challenging without correctly accounting for these effects.
Longitudinal morphological changes during recovery from brain deformation due to idiopathic normal pressure hydrocephalus after ventriculoperitoneal shunt surgery
Authors: Yamada Shigeki , Ishikawa Masatsune , Yamaguchi Makoto , Yamamoto Kazuo
Published: November 2019

The present study aimed to examine time-dependent change in cerebrospinal fluid distribution and various radiological indices for evaluating shunt effectiveness in patients with idiopathic normal pressure hydrocephalus (iNPH). This study included 54 patients with iNPH who underwent MRI before and after ventriculoperitoneal shunt surgery. The volume of the total ventricles and subarachnoid spaces decreased within 1 month after shunting. However, more than 1 year after shunting, the volume of the total ventricles decreased, whereas that of the total subarachnoid spaces increased. Although cerebrospinal fluid distribution changed considerably throughout the follow-up period, the brain parenchyma expanded only 2% from the baseline brain volume within 1 month after shunting and remained unchanged thereafter. The volume of the convexity subarachnoid space markedly increased. The changing rate of convexity subarachnoid space per ventricle ratio (CVR) was greater than that of any two-dimensional index. The brain per ventricle ratio (BVR), callosal angle and z-Evans index continued gradually changing, whereas Evans index did not change throughout the follow-up period. Both decreased ventricular volume and increased convexity subarachnoid space volume were important for evaluating shunt effectiveness. Therefore, we recommend CVR and BVR as useful indices for the diagnosis and evaluation of treatment response in patients with iNPH.
Author Correction: Collagen XXV promotes myoblast fusion during myogenic differentiation and muscle formation
Authors: Gonçalves Tristan J. M. , Boutillon Florence , Lefebvre Suzie , Goffin Vincent , Iwatsubo Takeshi , Wakabayashi Tomoko , Oury Franck , Armand Anne-Sophie
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Nutritional factors associated with distribution of Mopani Worms in Mopani woodlands in Tsholotsho and Gwanda Districts, Zimbabwe: A comparative survey
Authors: Nunu Wilfred Njabulo , Ncube Buhlebenkosi , Dube Oliver , Mpofu Clever , Ndlovu Brighton , Dzinomwa Tariro , Khumalo Nkosana
Published: November 2019

Mopani worms are abundant in Gwanda and sporadic in Tsholotsho though the two areas have similar climatic conditions. The study sought to determine nutritional factors that could be associated with distribution of Mopani worms in these two districts. Ten sampling points in undisturbed Mopani woodlands were established in each district. Samples were collected and analysed in the lab to determine the levels of crude protein, tannin and natural detergent fibres levels in leaves and pH, Nitrates, Phosphates and Potassium levels in soil and Welch’s test, Wilcoxon-Mann-Whitney, Analysis of Variance and the Bonferroni Confidence Intervals were employed to test for significance in the observed differences. Findings showed differences in tree size and leaf length whilst the differences of all other variables (non-extractible tannis, extractible tannis crude protein levels and natural detergent fibres) relating to leaf sample analysis were not statistically significant. Findings on soil sample analysis pointed out that Gwanda had higher pH, Phosphorus and Potassium levels whilst Nitrates were significantly higher in Tsholotsho. Differences in the tree sizes and leaf sizes of the samples from the two sites show that there could be host selection based on these variables.
Lactation and menstruation shift the vaginal microbiota in captive rhesus monkeys to be more similar to the male urethral microbiota
Authors: Hallmaier-Wacker L. K. , Lüert S. , Roos C. , Knauf S.
Published: November 2019

The vaginal microbiota of nonhuman primates differs substantially from humans in terms of Lactobacillus abundance, overall taxonomic diversity, and vaginal pH. Given these differences, it remains unclear in what way the nonhuman primate genital microbiota protects against pathogens, in particular sexually transmitted infections. Considering the effect that microbiota variations can have on disease acquisition and outcome, we examined endogenous and exogenous factors that influence the urogenital microbiota of male and female captive rhesus monkeys. The male urethral (n = 37) and vaginal (n = 194) microbiota of 11 breeding groups were examined in a cross-sectional study. During lactation and menstruation, the vaginal microbiota becomes significantly more diverse and more similar to the microbes observed in the male urethra. Group association and cage-mate (sexual partners) relationships were additionally associated with significant differences in the urogenital microbiota. Our results demonstrate that microbiota considerations are necessary in order to make informed selection of nonhuman primates as translational animal models.