bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation and Propagation of M2 Internal Tides Modulated by the Kuroshio Northeast of Taiwan
Authors: Chang Hang , Xu Zhenhua , Yin Baoshu , Hou Yijun , Liu Yahao , Li Delei , Wang Yang , Cao Shengshan , Liu Antony K.
Published: March 2019

The variability and energetics of M2 internal tides during their generation and propagation through the Kuroshio flows northeast of Taiwan are investigated using a high‐resolution numerical model. The corrugated continental slopes, particularly the I‐Lan Ridge and Mien‐Hua Canyon, are first identified as the energetic sources of M2 internal tides. The domain‐integrated M2 barotropic‐to‐baroclinic conversion rate under the Kuroshio influence is ~2.35 GW, ~0.9 GW of which is generated at the I‐Lan Ridge, ~0.93 GW at the Mien‐Hua Canyon, and ~0.52 GW at the north shelf. The M2 internal tide generation is influenced by the horizontally varying, zonally tilting stratification associated with the Kuroshio. In this situation, the conversion rate decreases by ~30% at the I‐Lan Ridge but increases to within ~10% at the Mien‐Hua Canyon and north shelf, in comparison to the simulation initiated with horizontal homogeneous stratification. Internal tides from multiple sources interfere to form a three‐dimensional baroclinic field. The interference by the internal tides from the Mien‐Hua Canyon and north shelf is refracted by the Kuroshio and exhibits a mesoscale gyre pattern, which can explain the frequent occurrence of internal solitary waves. An energetic along‐slope tidal beam (TBKC) from the I‐Lan Ridge radiates southward against the northward Kuroshio flows, causing strong vertical displacement, which favorably compares with recently reported field measurements. The M2 internal tide energy dissipates primarily near the source sites, and the remaining energy radiates outward over limited distances. Complex topographic features and background currents enhance the internal tide dissipation, which induces strong, inhomogeneous diapycnal mixing.
Assessing Climate Change Impacts on Human‐Perceived Temperature Extremes and Underlying Uncertainties
Authors: Zhu J. , Wang S. , Huang G.
Published: March 2019

It has been suggested that global warming impacts on human thermal comfort will cause an increase in the heat stress and a decrease in the cold stress in the future. A recent study has shown elevated increases in human‐perceived equivalent temperature (HPET) by using a single index for summer and winter seasons (Li et al., 2018, https://doi.org/10.1038/s41558‐017‐0036‐2). However, they have not considered multiple indices with combined effects on deriving HPET, which can result in large uncertainties in assessing climate change impacts on HPET and related extremes. Therefore, we develop a new framework with high‐resolution projections and an ensemble of 10 indices to quantify the impacts of climate change on HPET and related perceived extremes as well as to address uncertainties in both empirical indices and emission scenarios over China. Our findings reveal that different combinations of climatic variables can lead to two opposite conclusions for both normal and extreme conditions. For example, by using indices only considering the combined effect of temperature and relative humidity, China is projected to have an elevated increase in the HPET and in the frequency of high‐temperature extremes. By taking into account wind speed, the country expects to have the HPET even lower than the surface air temperature and an increase in the frequency of low‐temperature extremes. In addition, the resulting range of HPET due to uncertainty in indices is greater than the uncertainty range derived from different emission scenarios for the entire country. Therefore, it is necessary to conduct a comprehensive assessment that explicitly addresses uncertainties in the HPET in order to improve the robustness and reliability of assessing climate change impacts on human‐perceived temperature extremes.
Gravity Versus Tectonics: The Case of 2016 Amatrice and Norcia (Central Italy) Earthquakes Surface Coseismic Fractures
Authors: Di Naccio D. , Kastelic V. , Carafa M. M. C. , Esposito C. , Milillo P. , Di Lorenzo C.
Published: March 2019

The 2016 central Apennines earthquake sequence was caused by slip on an extensional fault system and resulted in sizable coseismic surface deformation. The most evident effects occurred along the western slope of Mount Vettore, a geologically and morphologically complex mountain ridge. Steep topography and rheological contrasts are known to have strongly controlled the coseismic deformation pattern during a number of different earthquakes that occurred in mountainous areas worldwide. Nevertheless, so far the role of seismically induced slope failures has not been taken into account in the interpretation of the surface fractures caused by the 2016 earthquake sequence. We modeled the static and dynamic slope stability along the western flank of Mount Vettore and in the underlying Piano Grande plain. Combining the slope stability analysis with geomorphic and geological analyses, we show that the coseismic fractures are distributed along the most unstable areas of the western flank of Mount Vettore and can be partly explained by shaking‐induced mechanisms such as gravity‐driven displacement, compaction, and secondary ground failure. Conversely, in the Piano Grande plain the fracture pattern is not affected by topography or rheology contrasts, suggesting that it is positively caused by tectonic faulting. Different processes, such as gravitational and erosional‐depositional phenomena, may contribute to the exposure of fault scarps during both the coseismic and interseismic periods. Attributing the surface deformation entirely to tectonic faulting, especially in complex mountainous terrains such as the Apennines, may lead to an incorrect assessment of fault displacement and fault slip rate and hence of seismic hazard.
Scales of Similarity and Disparity Between Drainage Networks
Authors: Roberts Gareth G.
Published: March 2019

At large scales (
10 km,
1 Ma) drainage networks appear to have a synchronized response to uplift and erosional processes. At smaller scales erosion generates complex landforms. Here, cross wavelet spectral transformation of longitudinal river profiles is performed to develop a framework that unifies these scale‐dependent views of landscape evolution. Distance‐elevation and time‐elevation profiles are transformed using a continuous wavelet approach to determine where signal power resides and appropriate scaling regimes. Cross wavelet spectral power is then calculated to determine scales of similarity and disparity between river channels. Spectral power of rivers draining Angola are compared to lithology, biota, precipitation, and gravity data to examine origins of river shapes and commonalities. Most power and commonalities reside at long wavelengths and timescales (>100 km, >1 Ma). The presence of commonalities between drainage networks is expected for systems in which large signals (e.g., uplift) are forced through random media (e.g., lithology, biota).
Bay of Bengal‐East Asia‐Pacific Teleconnection in Boreal Summer
Authors: Yang Ruowen , Gui Shu , Cao Jie
Published: March 2019

A new teleconnection pattern (the BEAP) across the Bay of Bengal‐East Asia‐Pacific region in boreal summer is revealed in this study using mainly ERA‐Interim reanalysis data from the European Centre for Medium‐Range Weather Forecasts. The BEAP index (BEAPI) is defined as the signed sum of standardized apparent moisture sinks at five centers along the pathway. Correlation analysis of the apparent heat sources and apparent moisture sinks has verified the existence of the BEAP teleconnection. Variations in BEAP can affect precipitation anomalies resulting from the anomalous moisture transport and the antiphase surface temperature variation. Wave flux analysis has verified the Rossby wave propagation route that originates around the central Bay of Bengal and extends across North China to the West Pacific. La Niña‐type sea surface temperature anomalies (SSTAs) appearing simultaneously in the same season can excite a positive BEAP pattern by enhancing convection over the Bay of Bengal, while El Niño‐type SSTAs have the opposite effect. Significant correlation between the BEAPI and the SSTAs can last from early summer to early winter. Numerical experiments confirm the BEAP teleconnection pattern and the associated physical processes.
Environmental filtering determines family-level structure of sulfate-reducing microbial communities in subsurface marine sediments
Authors: Marshall Ian P G , Ren Ge , Jaussi Marion , Lomstein Bente Aa , Jørgensen Bo Barker , Røy Hans , Kjeldsen Kasper U
Published: March 2019

Recent work has shown that subsurface microbial communities assemble by selective survival of surface community members during sediment burial, but it remains unclear to what extent the compositions of the subsurface communities are a product of their founding population at the sediment surface or of the changing geochemical conditions during burial. Here we investigate this question for communities of sulfate-reducing microorganisms (SRMs). We collected marine sediment samples from the upper 3–5 m at four geochemically contrasting sites in the Skagerrak and Baltic Sea and measured SRM abundance (quantitative PCR of dsrB), metabolic activity (radiotracer rate measurements), and community composition (Illumina sequencing of dsrB amplicons). These data showed that SRM abundance, richness, and phylogenetic clustering as determined by the nearest taxon index peaked below the bioturbation zone and above the depth of sulfate depletion. Minimum cell-specific rates of sulfate reduction did not vary substantially between sites. SRM communities at different sites were best distinguished based on their composition of amplicon sequence variants (ASVs), while communities in different geochemical zones were best distinguished based on their composition of SRM families. This demonstrates environmental filtering of SRM communities in sediment while a site-specific fingerprint of the founding community is retained.
Treatment of patients with multiple myeloma progressing on frontline-therapy with lenalidomide
Authors: Moreau Philippe , Zamagni Elena , Mateos Maria-Victoria
Published: March 2019

Over the last years, there has been great progress in the treatment of multiple myeloma with many new agents and combinations having been approved and being now routinely incorporated into treatment strategies. As a result, patients are experiencing benefits in terms of survival and better tolerance. However, the multitude of treatment options also presents a challenge to select the best options tailored to the specific patient situation. Lenalidomide is increasingly being used as part of frontline therapy in newly diagnosed multiple myeloma. This agent is typically administered until disease progression. It is currently unclear, how to best manage patients, who relapse while receiving lenalidomide as part of their frontline treatment. We conducted a review to summarize the available evidence in this setting. Our summary shows that there are very few data from current trials testing new combinations based on carfilzomib, pomalidomide, or daratumumab that address this specific patient population. Our review is aimed to summarize the available evidence to assist treatment decision making and to raise awareness of this lack of data to encourage further analyses and the incorporation of sequencing questions in future trial designs.
Loss of the androgen receptor suppresses intrarenal calcium oxalate crystals deposition via altering macrophage recruitment/M2 polarization with change of the miR-185-5p/CSF-1 signals
Authors: Zhu Wei , Zhao Zhijian , Chou Fuju , Zuo Li , Liu Tongzu , Yeh Shuyuan , Bushinsky David , Zeng Guohua , Chang Chawnshang
Published: March 2019

Crystals can trigger a wide range of kidney injuries that may link to the development of kidney stones. Infiltrating macrophages may influence hyperoxaluria-induced intrarenal calcium oxalate (CaOx) crystals deposition, yet their linkage to sex hormones remains unclear. Here we demonstrated that suppressing the androgen receptor (AR) expression in renal tubular epithelial cells increased the macrophage recruitment/M2 polarization that may result in enhancing the phagocytosis of intrarenal CaOx crystals. Mechanism dissection suggested that AR can suppress macrophage colony-stimulating factor 1 (CSF-1) expression via increasing miRNA-185-5p expression to suppress the M2 macrophage polarization-mediated intrarenal CaOx crystals phagocytosis. The preclinical study using glyoxylate-induced intrarenal CaOx crystals deposition mouse model revealed that renal tubule-specific AR knockout mice have less intrarenal CaOx crystals deposition with more recruited M2 macrophages in the kidney compared with the wild-type mice. Results from the in vivo rat model using hydroxy-l-proline-induced CaOx crystals deposition also demonstrated that targeting the AR with ASC-J9® suppressed the intrarenal CaOx crystals deposition via increasing the renal macrophage recruitment/M2 polarization. Together, results from multiple preclinical studies using multiple in vitro cell lines and in vivo mouse/rat models all demonstrated that targeting the AR with a small molecule ASC-J9® may function via altering macrophage recruitment/M2 polarization to decrease the intrarenal CaOx crystals deposition, a key phenotype seen in many kidney stone disease patients with hyperoxaluria.
Direct reprogramming of epidermal cells toward sweat gland-like cells by defined factors
Authors: Yao Bin , Xie Jiangfan , Liu Nanbo , Hu Tian , Song Wei , Huang Sha , Fu Xiaobing
Published: March 2019

Several studies have reported inducing adult cells into sweat gland-like cells; however, slow transition and low efficiency limit the potential for cell-based treatment. Here, we show that overexpression of the transcription factor FoxC1 was sufficient to reprogram epidermal cells to induced functional sweat gland-like cells (iSGCs). The iSGCs expressing secreting-related genes, had a global gene expression profile between fetal SGCs (P5) and adult SGCs (P28). Moreover, iSGCs transplanted into the burn mice model facilitated wound repair and sweat gland regeneration. We further demonstrated that the Foxc1 upregulated BMP5 transcription and BMP5 is responsible for the cell-type transition. Collectively, this study shows that lineage reprogramming of epidermal cells into iSGCs provides an excellent cell source and a promising regenerative strategy for anhidrosis and hypohidrosis.
Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness
Authors: Shin Vivian Yvonne , Chen Jiawei , Cheuk Isabella Wai -Yin , Siu Man-Ting , Ho Chi-Wang , Wang Xian , Jin Hongchuan , Kwong Ava
Published: March 2019

Triple-negative breast cancer (TNBC) is a malignant subtype of breast cancer with the absence of targeted therapy, resulting in poor prognosis in patients. Chemotherapy remains the mainstay of treatment for TNBC; however, development of drug resistance is the main obstacle for successful treatments. In recent years, long non-coding RNA (lncRNA) has been implicated in multiple biological functions in various diseases, particularly cancers. Accumulating evidence suggested that lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) expression is dysregulated in many human cancers and thus is a useful prognostic marker for cancer patients. Nevertheless, the mechanism of how NEAT1 confers drug resistance in TNBC is still largely unknown. We performed lncRNA profiling by the LncRNA Profiler qPCR Array Kit in normal control (NC) and breast cancers (BC) blood samples and further validated in a larger cohort of samples by qRT-PCR. Gene expression level and localization were investigated by qRT-PCR, western blotting, and immunofluorescence staining. Flow cytometric analysis was carried out to detect cancer stem cells. Functional studies were performed both in vitro and in vivo xenograft model. Among 90 lncRNAs, NEAT1 was highly expressed in the blood samples of breast cancer patients than in NC. In particular, the expression of NEAT1 was higher in TNBC tissues than other subgroups. Functional studies revealed that NEAT1 conferred oncogenic role by regulating apoptosis and cell cycle progression in TNBC cells. We identified that knockdown of NEAT1 sensitized cells to chemotherapy, indicating the involvement in chemoresistance. Importantly, shNEAT1 reduced stem cell populations such as CD44+/CD24−, ALDH+, and SOX2+, implicating that NEAT1 was closely related to cancer stemness in TNBC. Our data highlighted the roles of NEAT1 chemoresistance and cancer stemness, suggesting that it could be used as a new clinical therapeutic target for treating TNBC patients especially those with drug resistance.
Cryo-EM structure of cardiac amyloid fibrils from an immunoglobulin light chain AL amyloidosis patient
Authors: Swuec Paolo , Lavatelli Francesca , Tasaki Masayoshi , Paissoni Cristina , Rognoni Paola , Maritan Martina , Brambilla Francesca , Milani Paolo , Mauri Pierluigi , Camilloni Carlo , Palladini Giovanni , Merlini Giampaolo , Ricagno Stefano , Bolognesi Martino
Published: March 2019

Systemic light chain amyloidosis (AL)  is a life-threatening disease caused by aggregation and deposition of monoclonal immunoglobulin light chains (LC) in target organs. Severity of heart involvement is the most important factor determining prognosis. Here, we report the 4.0 Å resolution cryo-electron microscopy map and molecular model of amyloid fibrils extracted from the heart of an AL amyloidosis patient with severe amyloid cardiomyopathy. The helical fibrils are composed of a single protofilament, showing typical 4.9 Å stacking and cross-β architecture. Two distinct polypeptide stretches (total of 77 residues) from the LC variable domain (Vl) fit the fibril density. Despite Vl high sequence variability, residues stabilizing the fibril core are conserved through different cardiotoxic Vl, highlighting structural motifs that may be common to misfolding-prone LCs. Our data shed light on the architecture of LC amyloids, correlate amino acid sequences with fibril assembly, providing the grounds for development of innovative medicines.
Waveguide-PAINT offers an open platform for large field-of-view super-resolution imaging
Authors: Archetti Anna , Glushkov Evgenii , Sieben Christian , Stroganov Anton , Radenovic Aleksandra , Manley Suliana
Published: March 2019

Super-resolution microscopies based on the localization of single molecules have been widely adopted due to their demonstrated performance and their accessibility resulting from open software and simple hardware. The PAINT method for localization microscopy offers improved resolution over photoswitching methods, since it is less prone to sparse sampling of structures and provides higher localization precision. Here, we show that waveguides enable increased throughput and data quality for PAINT, by generating a highly uniform ~100 × 2000 µm2 area evanescent field for TIRF illumination. To achieve this, we designed and fabricated waveguides optimized for efficient light coupling and propagation, incorporating a carefully engineered input facet and taper. We also developed a stable, low-cost microscope and 3D-printable waveguide chip holder for easy alignment and imaging. We demonstrate the capabilities of our open platform by using DNA-PAINT to image multiple whole cells or hundreds of origami structures in a single field of view.
Axial shielding of Pd(II) complexes enables perfect stereoretention in Suzuki-Miyaura cross-coupling of Csp3 boronic acids
Authors: Lehmann Jonathan W. , Crouch Ian T. , Blair Daniel J. , Trobe Melanie , Wang Pulin , Li Junqi , Burke Martin D.
Published: March 2019

Stereocontrolled Csp3cross-coupling can fundamentally change the types of chemical structures that can be mined for molecular functions. Although considerable progress in achieving the targeted chemical reactivity has been made, controlling stereochemistry in Csp3cross-coupling remains challenging. Here we report that ligand-based axial shielding of Pd(II) complexes enables Suzuki-Miyaura cross-coupling of unactivated Csp3boronic acids with perfect stereoretention. This approach leverages key differences in spatial orientation between competing pathways for stereoretentive and stereoinvertive transmetalation of Csp3boronic acids to Pd(II). We show that axial shielding enables perfectly stereoretentive cross-coupling with a range of unactivated secondary Csp3boronic acids, as well as the stereocontrolled synthesis of xylarinic acid B and all of its Csp3stereoisomers. We expect these ligand design principles will broadly enable the continued search for practical and effective methods for stereospecific Csp3cross-coupling.
An Early Cretaceous enantiornithine (Aves) preserving an unlaid egg and probable medullary bone
Authors: Bailleul Alida M. , O’Connor Jingmai , Zhang Shukang , Li Zhiheng , Wang Qiang , Lamanna Matthew C. , Zhu Xufeng , Zhou Zhonghe
Published: March 2019

Understanding non-crown dinosaur reproduction is hindered by a paucity of directly associated adults with reproductive traces. Here we describe a new enantiornithine, Avimaia schweitzerae gen. et sp. nov., from the Lower Cretaceous Xiagou Formation with an unlaid egg two-dimensionally preserved within the abdominothoracic cavity. Ground-sections reveal abnormal eggshell proportions, and multiple eggshell layers best interpreted as a multi-layered egg resulting from prolonged oviductal retention. Fragments of the shell membrane and cuticle are both preserved. SEM reveals that the cuticle consists of nanostructures resembling those found in neornithine eggs adapted for infection-prone environments, which are hypothesized to represent the ancestral avian condition. The femur preserves small amounts of probable medullary bone, a tissue found today only in reproductively active female birds. To our knowledge, no other occurrence of Mesozoic medullary bone is associated with indications of reproductive activity, such as a preserved egg, making our identification unique, and strongly supported.
Optogenetic stimulation of Gs-signaling in the heart with high spatio-temporal precision
Authors: Makowka Philipp , Bruegmann Tobias , Dusend Vanessa , Malan Daniela , Beiert Thomas , Hesse Michael , Fleischmann Bernd K. , Sasse Philipp
Published: March 2019

The standard technique for investigating adrenergic effects on heart function is perfusion with pharmaceutical agonists, which does not provide high temporal or spatial precision. Herein we demonstrate that the light sensitive Gs-protein coupled receptor JellyOp enables optogenetic stimulation of Gs-signaling in cardiomyocytes and the whole heart. Illumination of transgenic embryonic stem cell-derived cardiomyocytes or of the right atrium of mice expressing JellyOp elevates cAMP levels and instantaneously accelerates spontaneous beating rates similar to pharmacological β-adrenergic stimulation. Light application to the dorsal left atrium instead leads to supraventricular extrabeats, indicating adverse effects of localized Gs-signaling. In isolated ventricular cardiomyocytes from JellyOp mice, we find increased Ca2+ currents, fractional cell shortening and relaxation rates after illumination enabling the analysis of differential Gs-signaling with high temporal precision. Thus, JellyOp expression allows localized and time-restricted Gs stimulation and will provide mechanistic insights into different effects of site-specific, long-lasting and pulsatile Gs activation.
Computational geometry analysis of dendritic spines by structured illumination microscopy
Authors: Kashiwagi Yutaro , Higashi Takahito , Obashi Kazuki , Sato Yuka , Komiyama Noboru H. , Grant Seth G. N. , Okabe Shigeo
Published: March 2019

Dendritic spines are the postsynaptic sites that receive most of the excitatory synaptic inputs, and thus provide the structural basis for synaptic function. Here, we describe an accurate method for measurement and analysis of spine morphology based on structured illumination microscopy (SIM) and computational geometry in cultured neurons. Surface mesh data converted from SIM images were comparable to data reconstructed from electron microscopic images. Dimensional reduction and machine learning applied to large data sets enabled identification of spine phenotypes caused by genetic mutations in key signal transduction molecules. This method, combined with time-lapse live imaging and glutamate uncaging, could detect plasticity-related changes in spine head curvature. The results suggested that the concave surfaces of spines are important for the long-term structural stabilization of spines by synaptic adhesion molecules.
Encapsulation of macrophages enhances their retention and angiogenic potential
Authors: Ludwinski Francesca E. , Patel Ashish S. , Damodaran Gopinath , Cho Jun , Furmston Joanna , Xu Qingbo , Jayasinghe Suwan N. , Smith Alberto , Modarai Bijan
Published: March 2019

Cell therapies to treat critical limb ischaemia have demonstrated only modest results in clinical trials, and this has been partly attributed to poor cell retention following their delivery directly into the ischaemic limb. The aim of this study was to determine whether alginate encapsulation of therapeutic pro-angio/arteriogenic macrophages enhances their retention and ultimately improves limb perfusion. A reproducible GMP-compliant method for generating 300 µm alginate capsules was developed to encapsulate pro-angio/arteriogenic macrophages. Longitudinal analysis revealed no detrimental effect of encapsulation on cell number or viability in vitro, and macrophages retained their pro-angio/arteriogenic phenotype. Intramuscular delivery of encapsulated macrophages into the murine ischaemic hindlimb demonstrated increased cell retention compared with injection of naked cells (P = 0.0001), and that this was associated both enhanced angiogenesis (P = 0.02) and arteriogenesis (P = 0.03), and an overall improvement in limb perfusion (P = 0.0001). Alginate encapsulation of pro-angio/arteriogenic macrophages enhances cell retention and subsequent limb reperfusion in vivo. Encapsulation may therefore represent a means of improving the efficacy of cell-based therapies currently under investigation for the treatment of limb ischaemia.
Proposed U.S. regulation of gene-edited food animals is not fit for purpose
Authors: Van Eenennaam Alison L. , Wells Kevin D. , Murray James D.
Published: March 2019

Dietary DNA is generally regarded as safe to consume, and is a routine ingredient of food obtained from any living organism. Millions of naturally-occurring DNA variations are observed when comparing the genomic sequence of any two healthy individuals of a given species. Breeders routinely select desired traits resulting from this DNA variation to develop new cultivars and varieties of food plants and animals. Regulatory agencies do not evaluate these new varieties prior to commercial release. Gene editing tools now allow plant and animal breeders to precisely introduce useful genetic variation into agricultural breeding programs. The U.S. Department of Agriculture (USDA) announced that it has no plans to place additional regulations on gene-edited plants that could otherwise have been developed through traditional breeding prior to commercialization. However, the U.S. Food and Drug Administration (FDA) has proposed mandatory premarket new animal drug regulatory evaluation for all food animals whose genomes have been intentionally altered using modern molecular technologies including gene editing technologies. This runs counter to U.S. biotechnology policy that regulatory oversight should be triggered by unreasonable risk, and not by the fact that an organism has been modified by a particular process or technique. Breeder intention is not associated with product risk. Harmonizing the regulations associated with gene editing in food species is imperative to allow both plant and animal breeders access to gene editing tools to introduce useful sustainability traits like disease resistance, climate adaptability, and food quality attributes into U.S. agricultural breeding programs.
Remote preparation for single-photon two-qubit hybrid state with hyperentanglement via linear-optical elements
Authors: Jiao Xian-Fang , Zhou Ping , Lv Shu-Xin , Wang Zhi-Yong
Published: March 2019

Linear-optical-based quantum information processing has attached much attention since photon is an ideal medium for transmitting quantum information remotely. Until now, there are some important works in quantum state remote preparation, the method for reconstructing quantum state deterministically via linear optics. However, most of the methods are protocols to prepare single-qubit states remotely via linear-optical elements. In this article, we investigate the methods to prepare two-qubit hybrid states remotely. We present a deterministic remote state preparation scheme for an arbitrary two-qubit hybrid state via a hyperentangled Bell state, resorting to linear-optical elements only. The sender rotates the spatial-mode state and polarization state of the hyperentangled photon respectively in accordance with his knowledge of the two-qubit hybrid state, and the receiver can reconstruct the original two-qubit hybrid state by applying appropriate recovery operations. Moreover, we discuss the remote state preparation scheme for the two-qubit hybrid state via partially hyperentangled Bell state.
Interaction between active particles and quantum vortices leading to Kelvin wave generation
Authors: Giuriato Umberto , Krstulovic Giorgio
Published: March 2019

One of the main features of superfluids is the presence of topological defects with quantised circulation. These objects are known as quantum vortices and exhibit a hydrodynamic behaviour. Nowadays, particles are the main experimental tool used to visualise quantum vortices and to study their dynamics. We use a self-consistent model based on the three-dimensional Gross-Pitaevskii (GP) equation to explore theoretically and numerically the attractive interaction between particles and quantized vortices at very low temperature. Particles are described as localised potentials depleting the superfluid and following Newtonian dynamics. We are able to derive analytically a reduced central-force model that only depends on the classical degrees of freedom of the particle. Such model is found to be consistent with the GP simulations. We then generalised the model to include deformations of the vortex filament. The resulting long-range mutual interaction qualitatively reproduces the observed generation of a cusp on the vortex filament during the particle approach. Moreover, we show that particles can excite Kelvin waves on the vortex filament through a resonance mechanism even if they are still far from it.
Pitx2 cholinergic interneurons are the source of C bouton synapses on brainstem motor neurons
Authors: Rozani Ismini , Tsapara Georgia , Witts Emily C. , Deaville S. James , Miles Gareth B. , Zagoraiou Laskaro
Published: March 2019

Cholinergic neuromodulation has been described throughout the brain and has been implicated in various functions including attention, food intake and response to stress. Cholinergic modulation is also thought to be important for regulating motor systems, as revealed by studies of large cholinergic synapses on spinal motor neurons, called C boutons, which seem to control motor neuron excitability in a task-dependent manner. C boutons on spinal motor neurons stem from spinal interneurons that express the transcription factor Pitx2. C boutons have also been identified on the motor neurons of specific cranial nuclei. However, the source and roles of cranial C boutons are less clear. Previous studies suggest that they originate from Pitx2+ and Pitx2− neurons, in contrast to spinal cord C boutons that originate solely from Pitx2 neurons. Here, we address this controversy using mouse genetics, and demonstrate that brainstem C boutons are Pitx2+ derived. We also identify new Pitx2 populations and map the cholinergic Pitx2 neurons of the mouse brain. Taken together, our data present important new information about the anatomical organization of cholinergic systems which impact motor systems of the brainstem. These findings will enable further analyses of the specific roles of cholinergic modulation in motor control.
Influence of Different Urban Structures on Metal Contamination in Two Metropolitan Cities
Authors: Alharbi Badr H. , Pasha Mohammad J. , Al-Shamsi Mohammed Ahmad S.
Published: March 2019

The influence of urban structures and land use patterns of metropolitan cities on the distribution of contaminants is not well understood. In this study, two metropolitan cities [Jeddah (a typical corridor city) and Madinah (a typical compact city)], featuring different spreading patterns and urban structures, were selected to investigate the contamination level and potential risk caused by metals (i.e., Pb, Zn, Co, Fe, Al, Cr, Cu, Ni, and Mn) associated with urban dust. The findings of this study show that a metropolitan city with a limited variety of activities and a polar center (e.g., Madinah) displays a typical distribution pattern of metals, i.e., concentrations of metals increase gradually toward the center of the city. In contrast, a metropolitan city with multiple major activities (e.g., Jeddah) displays a different distribution pattern, controlled by multiple key actors (e.g., seaports, oil refineries, and desalination/power plants) able to shift the location of highest contamination away from the city center. The above findings are supported by the results of several contamination and health indices. In Jeddah, the highest Pb contamination was found near an oil refinery based on geoaccumulation index (Igeo), contamination factor (CF), enrichment factor (EF), and ecological risk (Ei) values; whereas, the highest Zn contamination was found near a seaport, based on EF, CF, and Ei values. However, in Madinah, the contamination indices indicate that the most contaminated locations are near the city center. The highest non-carcinogenic health risk in Jeddah was found near an oil refinery and in the city center; whereas in Madinah, it was found mainly in the city center. Although there is no significant risk of cancer due to metals associated with dust in the two cities, Cr, representing a health risk contribution of >24%, was the major contributor of non-carcinogenic health risk in the two metropolitan cities.
Transcriptome analysis of rumen epithelium and meta-transcriptome analysis of rumen epimural microbial community in young calves with feed induced acidosis
Authors: Li Wenli , Gelsinger Sonia , Edwards Andrea , Riehle Christina , Koch Daniel
Published: March 2019

Many common management practices used to raise dairy calves while on milk and during weaning can cause rumen acidosis. Ruminal pH has long been used to identify ruminal acidosis. However, few attempts were undertaken to understand the role of prolonged ruminal acidosis on rumen microbial community or host health in young calves long after weaning. Thus, the molecular changes associated with prolonged rumen acidosis in post weaning young calves are largely unknown. In this study, we induced ruminal acidosis by feeding a highly processed, starch-rich diet to calves starting from one week of age through 16 weeks. Rumen epithelial tissues were collected at necropsy at 17 weeks of age. Transcriptome analyses on the rumen epithelium and meta-transcriptome analysis of rumen epimural microbial communities were carried out. Calves with induced ruminal acidosis showed significantly less weight gain over the course of the experiment, in addition to substantially lower ruminal pH in comparison to the control group. For rumen epithelial transcriptome, a total of 672 genes (fold-change, FC ≥ 1.5; adjusted-p≤ 0.05) showed significant differential expression in comparison to control. Biological pathways impacted by these differentially expressed genes included cell signaling and morphogenesis, indicating the impact of ruminal acidosis on rumen epithelium development. rRNA read-based microbial classification indicated significant increase in abundance of several genera in calves with induced acidosis. Our study provides insight into host rumen transcriptome changes associated with prolonged acidosis in post weaning calves. Shifts in microbial species abundance are promising for microbial species-based biomarker development and artificial manipulation. Such knowledge provides a foundation for future more precise diagnosis and preventative management of rumen acidosis in dairy calves.
Genetic differences in host infectivity affect disease spread and survival in epidemics
Authors: Anacleto Osvaldo , Cabaleiro Santiago , Villanueva Beatriz , Saura María , Houston Ross D. , Woolliams John A. , Doeschl-Wilson Andrea B.
Published: March 2019

Survival during an epidemic is partly determined by host genetics. While quantitative genetic studies typically consider survival as an indicator for disease resistance (an individual’s propensity to avoid becoming infected or diseased), mortality rates of populations undergoing an epidemic are also affected by endurance (the propensity of diseased individual to survive the infection) and infectivity (i.e. the propensity of an infected individual to transmit disease). Few studies have demonstrated genetic variation in disease endurance, and no study has demonstrated genetic variation in host infectivity, despite strong evidence for considerable phenotypic variation in this trait. Here we propose an experimental design and statistical models for estimating genetic diversity in all three host traits. Using an infection model in fish we provide, for the first time, direct evidence for genetic variation in host infectivity, in addition to variation in resistance and endurance. We also demonstrate how genetic differences in these three traits contribute to survival. Our results imply that animals can evolve different disease response types affecting epidemic survival rates, with important implications for understanding and controlling epidemics.
Glucose tolerance in Canadian and French cystic fibrosis adult patients
Authors: Reynaud Quitterie , Boudreau Valérie , Touzet Sandrine , Desjardins Katherine , Bourdy Stéphanie Poupon , Blond Emilie , Berthiaume Yves , Rabasa-Lhoret Rémi , Durieu Isabelle
Published: March 2019

Cystic fibrosis (CF)-related diabetes is associated with increased mortality. We analysed the clinical and glycemic profiles of two cohorts of patients treated according to the same guidelines in France and Canada. To investigate incidence differences in phenotypic and glucose abnormalities and to explore the evolution over a 4-year follow-up period, two cohorts of 224 Canadian and 147 French adult CF patients (≥18 years) without treated CF-related diabetes (CFRD) were followed over a 4 year period. In each of these groups, we investigated the longitudinal relationship between glucose tolerance and pulmonary function. An annual 2-hour oral glucose tolerance test was performed: fasting blood glucose (G0) and 2-h blood glucose (G2) were measured. Patients were classified at inclusion according to their glucose tolerance status: Normal glucose tolerant, abnormal glucose tolerant or de novo CFRD. Age, sex ratio and proportion of F508del homozygous patients were not statistically different between both cohorts. Canadian patients had better pulmonary function (median %FEV1 (IQR): 71.0 (55.0–82.0) vs. 64.0 (40.0–78.0), p < 0.001) and greater body mass index (BMI; median BMI in kg/m2) (IQR) 21.1 (19.5–22.8) vs. 19.9 (18.4–21.4), p < 0.001). Glucose values: G0 (5.4 (5.0–5.9) vs. 4.8 (4.5–5.1) mmol/L, p < 0.001) and G2 (7.6 (5.8–9.7) vs. 6.5 (5.2–8.5) mmol/L, p = 0.001) were higher in the Canadian cohort translating into a higher incidence of de novo CFRD diagnosis (19.2 vs. 9.8%, p = 0.003). Decline in FEV1 over time was not different between patients according to glucose tolerance groups. Despite higher glucose levels and incidence of de novo CFRD, Canadian CF patients have a better lung function and a higher BMI than French patients. In spite of these differences between the cohorts, the decline in FEV1 in patients with abnormal glucose tolerance is similar between these groups.
Inhibition of PGE2/EP4 receptor signaling enhances oxaliplatin efficacy in resistant colon cancer cells through modulation of oxidative stress
Authors: Huang Huakang , Aladelokun Oladimeji , Ideta Takayasu , Giardina Charles , Ellis Lee M. , Rosenberg Daniel W.
Published: March 2019

The platinum-based chemotherapeutic agent, oxaliplatin, is used to treat advanced colorectal cancer (CRC). Unfortunately, nearly all patients acquire resistance to oxaliplatin after long-term use, limiting its therapeutic efficacy. Since COX-2 and PGE2 signaling can impact colon cancer cell proliferation and survival, we examined how this pathway was affected in an oxaliplatin resistant colon cancer cell line. PGE2 levels were significantly elevated in oxaliplatin-resistant HT29 cells (OXR) compared to naïve parental HT29 cells (PAR). This increase was associated with elevated COX-2 (17.9-fold; P = 0.008) and reduced 15-hydroxyprostaglandin dehydrogenase (2.9-fold; P < 0.0001) expression. RNAi knockdown of microsomal prostaglandin E synthase-1, the rate-limiting enzyme in PGE2 synthesis, sensitized OXR cells to oxaliplatin. Downstream effects of PGE2 in OXR cells were also examined. Selective inhibition of the EP4 PGE2 receptor by the small molecule inhibitor, L-161,982 enhanced oxaliplatin-induced apoptosis in OXR cells. L-161,982 also reduced expression of the colonic stem cell markers, CD133 and CD44, and inhibited tumor sphere formation. The accumulation of intracellular reactive oxygen species (ROS), a key component of oxaliplatin cytotoxicity, was significantly increased by EP4 inhibition (2.4 -fold; P < 0.0001). Overall, our findings uncover an important role for the COX-2/PGE2/EP4 signaling axis in oxaliplatin resistance via regulation of oxidative stress.
Extensive epigenetic and transcriptomic variability between genetically identical human B-lymphoblastoid cells with implications in pharmacogenomics research
Authors: Ozgyin Lilla , Horvath Attila , Hevessy Zsuzsanna , Balint Balint L.
Published: March 2019

Genotyped human B-lymphoblastoid cell lines (LCLs) are widely used models in mapping quantitative trait loci for chromatin features, gene expression, and drug response. The extent of genotype-independent functional genomic variability of the LCL model, although largely overlooked, may inform association study design. In this study, we use flow cytometry, chromatin immunoprecipitation sequencing and mRNA sequencing to study surface marker patterns, quantify genome-wide chromatin changes (H3K27ac) and transcriptome variability, respectively, among five isogenic LCLs derived from the same individual. Most of the studied LCLs were non-monoclonal and had mature B cell phenotypes. Strikingly, nearly one-fourth of active gene regulatory regions showed significantly variable H3K27ac levels, especially enhancers, among which several were classified as clustered enhancers. Large, contiguous genomic regions showed signs of coordinated activity change. Regulatory differences were mirrored by mRNA expression changes, preferentially affecting hundreds of genes involved in specialized cellular processes including immune and drug response pathways. Differential expression of DPYD, an enzyme involved in 5-fluorouracil (5-FU) catabolism, was associated with variable LCL growth inhibition mediated by 5-FU. The extent of genotype-independent functional genomic variability might highlight the need to revisit study design strategies for LCLs in pharmacogenomics.
Automated segmentation of the corneal endothelium in a large set of ‘real-world’ specular microscopy images using the U-Net architecture
Authors: Daniel Moritz C. , Atzrodt Lisa , Bucher Felicitas , Wacker Katrin , Böhringer Stefan , Reinhard Thomas , Böhringer Daniel
Published: March 2019

Monitoring the density of corneal endothelial cells (CEC) is essential in the management of corneal diseases. Its manual calculation is time consuming and prone to errors. U-Net, a neural network for biomedical image segmentation, has shown promising results in the automated segmentation of images of healthy corneas and good quality. The purpose of this study was to assess its performance in “real-world” CEC images (variable quality, different ophthalmologic diseases). The outcome measures were: precision and recall of the extraction of CEC, correctness of CEC density estimation, detection of ungradable images. A classical approach based on grayscale morphology and water shedding was pursued for comparison. There was good agreement between the automated image analysis and the manual annotation from the U-Net. R-square from Pearson’s correlation was 0.96. Recall of CEC averaged 0.34 and precision 0.84. The U-Net correctly predicted the CEC density in a large set of images of healthy and diseased corneas, including images of poor quality. It robustly ignored image regions with poor visibility of CEC. The classical approach, however, did not provide acceptable results. R-square from Pearson’s correlation with the ground truth was as low as 0.35.
Differential gene expression in response to eCry3.1Ab ingestion in an unselected and eCry3.1Ab-selected western corn rootworm (Diabrotica virgifera virgifera LeConte) population
Authors: Zhao Zixiao , Meihls Lisa N. , Hibbard Bruce E. , Ji Tieming , Elsik Christine G. , Shelby Kent S.
Published: March 2019

Diabrotica virgifera virgifera LeConte, the western corn rootworm (WCR) is one of the most destructive pests in the U.S. Corn Belt. Transgenic maize lines expressing various Cry toxins from Bacillus thuringiensis have been adopted as a management strategy. However, resistance to many Bt toxins has occurred. To investigate the mechanisms of Bt resistance we carried out RNA-seq using Illumina sequencing technology on resistant, eCry3.1Ab-selected and susceptible, unselected, whole WCR neonates which fed on seedling maize with and without eCry3.1Ab for 12 and 24 hours. In a parallel experiment RNA-seq experiments were conducted when only the midgut of neonate WCR was evaluated from the same treatments. After de novo transcriptome assembly we identified differentially expressed genes (DEGs). Results from the assemblies and annotation indicate that WCR neonates from the eCry3.1Ab-selected resistant colony expressed a small number of up and down-regulated genes following Bt intoxication. In contrast, unselected susceptible WCR neonates expressed a large number of up and down-regulated transcripts in response to intoxication. Annotation and pathway analysis of DEGs between susceptible and resistant whole WCR and their midgut tissue revealed genes associated with cell membrane, immune response, detoxification, and potential Bt receptors which are likely related to eCry3.1Ab resistance. This research provides a framework to study the toxicology of Bt toxins and mechanism of resistance in WCR, an economically important coleopteran pest species.