bluuebunny/crossref_metadata_2025 huggingface dataset:
Impacts of Representing Heterogeneous Distribution of Cloud Liquid and Ice on Phase Partitioning of Arctic Mixed‐Phase Clouds with NCAR CAM5
Authors: Zhang Meng , Liu Xiaohong , Diao Minghui , D'Alessandro John J. , Wang Yong , Wu Chenglai , Zhang Damao , Wang Zhien , Xie Shaocheng
Published: November 2019

In this study, we conduct sensitivity experiments with the Community Atmosphere Model version 5 to understand the impact of representing heterogeneous distribution between cloud liquid and ice on the phase partitioning in mixed‐phase clouds through different perturbations on the Wegener‐Bergeron‐Findeisen (WBF) process. In two experiments, perturbation factors that are based on assumptions of pocket structure and the partial homogeneous cloud volume derived from the High‐performance Instrumented Airborne Platform for Environmental Research (HIAPER) Pole‐to‐Pole Observation (HIPPO) campaign are utilized. Alternately, a mass‐weighted assumption is used in the calculation of WBF process to mimic the appearance of unsaturated area in mixed‐phase clouds as the result of heterogeneous distribution. Model experiments are tested in both single column and weather forecast modes and evaluated against data from the U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Program's Mixed‐Phase Arctic Cloud Experiment (M‐PACE) field campaign and long‐term ground‐based multisensor measurements. Model results indicate that perturbations on the WBF process can significantly modify simulated microphysical properties of Arctic mixed‐phase clouds. The improvement of simulated cloud water phase partitioning tends to be linearly proportional to the perturbation magnitude that is applied in the three different sensitivity experiments. Cloud macrophysical properties such as cloud fraction and frequency of occurrence of low‐level mixed‐phase clouds are less sensitive to the perturbation magnitude than cloud microphysical properties. Moreover, this study indicates that heterogeneous distribution between cloud hydrometeors should be treated consistently for all cloud microphysical processes. The model vertical resolution is also important for liquid water maintenance in mixed‐phase clouds.
Assessing the Impact of Urban Hydrological Processes on the Summertime Urban Climate in Nanjing Using the WRF Model
Authors: Wang Xueyuan , Miao Shiguang , Liu Hongnian , Sun Jianning , Zhang Ning , Zou Jun
Published: November 2019

The impacts of urban hydrological processes, such as anthropogenic latent heat (ALH), multilayer green roof systems (GRO), evaporation from impervious surfaces (EIMP), urban irrigation (IRR), and the urban “oasis effect” (OASIS) on regional hydrometeorology in Nanjing, are assessed by the Weather Research and Forecasting Single‐Layer Urban Canopy Models (WRF‐SLUCM). The results show that including all five urban hydrological processes, ALL best improves the prediction of near‐surface meteorology and has the largest correlation coefficients, the smallest root mean square errors, and the most accurate diurnal variations compared with observations. The improvements of ALH, GRO, and OASIS are larger than those of IRR and EIMP. The influence of ALH, GRO, and OASIS is comparable in commercial areas, whereas the influence of OASIS is significantly greater and plays essential roles in low‐intensity residential areas. Therefore, the overall effect of urban hydrological processes is especially large over low‐intensity residential areas, where the ALL case‐simulated monthly mean 2‐m air temperature (surface temperature) is reduced by approximately 1.3 (5.0) °C, the 2‐m specific humidity increases by 0.8 g kg–1, and the sensible heat (latent heat) flux is reduced (increased) at most by 90 W m–2. The changes in the vertical profiles indicate that urban hydrological processes reduce the potential temperature and wind speed, whereas they increase specific humidity over the entire urban boundary layer, leading to a more stable atmospheric conditions, reduced vertical mixing, and weaker convective rolls. These effects could mitigate the intensity of urban heat/dry islands while simultaneously exacerbating low‐level air pollution.
The Role of the Stratosphere in Subseasonal to Seasonal Prediction: 1. Predictability of the Stratosphere
Authors: Domeisen Daniela I.V. , Butler Amy H. , Charlton‐Perez Andrew J. , Ayarzagüena Blanca , Baldwin Mark P. , Dunn‐Sigouin Etienne , Furtado Jason C. , Garfinkel Chaim I. , Hitchcock Peter , Karpechko Alexey Yu. , Kim Hera , Knight Jeff , Lang Andrea L. , Lim Eun‐Pa , Marshall Andrew , Roff Greg , Schwartz Chen , Simpson Isla R. , Son Seok‐Woo , Taguchi Masakazu
Published: November 2019

The stratosphere has been identified as an important source of predictability for a range of processes on subseasonal to seasonal (S2S) time scales. Knowledge about S2S predictability within the stratosphere is however still limited. This study evaluates to what extent predictability in the extratropical stratosphere exists in hindcasts of operational prediction systems in the S2S database. The stratosphere is found to exhibit extended predictability as compared to the troposphere. Prediction systems with higher stratospheric skill tend to also exhibit higher skill in the troposphere. The analysis also includes an assessment of the predictability for stratospheric events, including early and midwinter sudden stratospheric warming events, strong vortex events, and extreme heat flux events for the Northern Hemisphere and final warming events for both hemispheres. Strong vortex events and final warming events exhibit higher levels of predictability as compared to sudden stratospheric warming events. In general, skill is limited to the deterministic range of 1 to 2 weeks. High‐top prediction systems overall exhibit higher stratospheric prediction skill as compared to their low‐top counterparts, pointing to the important role of stratospheric representation in S2S prediction models.
Assessing XMT‐Measurement Variability of Air‐Water Interfacial Areas in Natural Porous Media
Authors: Araujo Juliana B. , Brusseau Mark L.
Published: November 2019

This study investigates the accuracy and reproducibility of air‐water interfacial areas measured with high‐resolution synchrotron X‐ray microtomography (XMT). Columns packed with one of two relatively coarse‐grained monodisperse granular media, glass beads or a well‐sorted quartz sand, were imaged over several years, encompassing changes in acquisition equipment, improved image quality, and enhancements to image acquisition and to processing software. For the glass beads, the specific solid surface area (SSSA‐XMT) of 31.6 ± 1 cm−1 determined from direct analysis of the segmented solid‐phase image data is statistically identical to the independently calculated geometric smooth‐sphere specific solid surface area (GSSA, 32 ± 1 cm−1) and to the measured SSSA (28 ± 3 cm−1) obtained with the N2‐Brunauer, Emmett, and Teller method. The maximum specific air‐water interfacial area (Amax) is 27.4 (±2) cm−1, which compares very well to the SSSA‐XMT, GSSA, and SSSA‐N2‐Brunauer, Emmett, and Teller values. For the sand, the SSSA‐XMT (111 ± 2 cm−1) and GSSA (113 ± 1 cm−1) are similar. The mean Amax is 96 ± 5 cm−1, which compares well to both the SSSA and the GSSA values. The XMT‐SSSA values deviated from the GSSA values by 7–16% for the first four experiments but were essentially identical for the later experiments. This indicates that enhancements in image acquisition and processing improved data accuracy. The Amax values ranged from 74 cm−1 to 101 cm−1, with a coefficient of variation (COV) of 9%. The maximum capillary interfacial area ranged from 12 cm−1 to 19 cm−1, for a COV of 10%. The COVs for both decreased to 5–6% for the latter five experiments. These results demonstrate that XMT imaging provides accurate and reproducible measurements of total and capillary interfacial areas.
A Consistent Approach for Probabilistic Residential Flood Loss Modeling in Europe
Authors: Lüdtke Stefan , Schröter Kai , Steinhausen Max , Weise Laura , Figueiredo Rui , Kreibich Heidi
Published: November 2019

In view of globally increasing flood losses, a significantly improved and more efficient flood risk management and adaptation policy are needed. One prerequisite is reliable risk assessments on the continental scale. Flood loss modeling and risk assessments for Europe are until now based on regional approaches using deterministic depth‐damage functions. Uncertainties associated with the risk estimation are hardly known. To reduce these shortcomings, we present a novel, consistent approach for probabilistic flood loss modeling for Europe, based on the upscaling of the Bayesian Network Flood Loss Estimation MOdel for the private sector, BN‐FLEMOps. The model is applied on the mesoscale in the whole of Europe and can be adapted to regional situations. BN‐FLEMOps is validated in three case studies in Italy, Austria, and Germany. The officially reported loss figures of the past flood events are within the 95% quantile range of the probabilistic loss estimation, for all three case studies. In the Italian, Austrian, and German case studies, the median loss estimate shows an overestimation by 28% (2.1 million euro) and 305% (5.8 million euro) and an underestimation by 43% (104 million euro), respectively. In two of the three case studies, the performance of the model improved, when updated with empirical damage data from the area of interest. This approach represents a step forward in European wide flood risk modeling, since it delivers consistent flood loss estimates and inherently provides uncertainty information. Further validation and tests with respect to adapting the model to different European regions are recommended.
RIG-I-based immunotherapy enhances survival in preclinical AML models and sensitizes AML cells to checkpoint blockade
Authors: Ruzicka Michael , Koenig Lars M. , Formisano Simone , Boehmer Daniel F. R. , Vick Binje , Heuer Eva-M. , Meinl Hanna , Kocheise Lorenz , Zeitlhöfler Marcus , Ahlfeld Julia , Kobold Sebastian , Endres Stefan , Subklewe Marion , Duewell Peter , Schnurr Max , Jeremias Irmela , Lichtenegger Felix S. , Rothenfusser Simon
Published: November 2019

Retinoic acid-inducible gene-I (RIG-I) is a cytoplasmic immune receptor sensing viral RNA. It triggers the release of type I interferons (IFN) and proinflammatory cytokines inducing an adaptive cellular immune response. We investigated the therapeutic potential of systemic RIG-I activation by short 5′-triphosphate-modified RNA (ppp-RNA) for the treatment of acute myeloid leukemia (AML) in the syngeneic murine C1498 AML tumor model. ppp-RNA treatment significantly reduced tumor burden, delayed disease onset and led to complete remission including immunological memory formation in a substantial proportion of animals. Therapy-induced tumor rejection was dependent on CD4+ and CD8+ T cells, but not on NK or B cells, and relied on intact IFN and mitochondrial antiviral signaling protein (MAVS) signaling in the host. Interestingly, ppp-RNA treatment induced programmed death ligand 1 (PD-L1) expression on AML cells and established therapeutic sensitivity to anti-PD-1 checkpoint blockade in vivo. In immune-reconstituted humanized mice, ppp-RNA treatment reduced the number of patient-derived xenografted (PDX) AML cells in blood and bone marrow while concomitantly enhancing CD3+ T cell counts in the respective tissues. Due to its ability to establish a state of full remission and immunological memory, our findings show that ppp-RNA treatment is a promising strategy for the immunotherapy of AML.
Direct growth of ZnO nanowires on civil engineering materials: smart materials for supported photodegradation
Authors: Le Pivert Marie , Poupart Romain , Capochichi-Gnambodoe Martine , Martin Nathan , Leprince-Wang Yamin
Published: November 2019

Photocatalysis is one of the most promising processes for treating air and water pollution. Innovative civil engineering materials for environmental depollution by photocatalysis have already been synthesized by incorporating TiO2 or ZnO nanoparticles in cement. This method suffers from two flaws: first, most of the NPs are incorporated into the cement and useless for photocatalysis; second, rain and wind could spread the potentially carcinogenic nanoparticles from the cement surface into nature. Thus, we propose the efficient synthesis of nontoxic and biocompatible ZnO nanostructures solely onto the surface of commercially available concrete and tiling pavements by a low-cost and low-temperature hydrothermal method. Our samples exhibited enhanced photocatalytic activity for degrading organic dyes in aqueous media, and dye molecules are commonly used in the pharmaceutical, food, and textile industries. Durability studies showed no loss of efficiency after four photocatalysis experiments. Such supported structures, which are easy to implement onto the varying surfaces of commercially available materials, are promising for integration into civil engineering surfaces for environmental depollution in our daily life.
Long non-coding RNA GAS5 acts as proliferation “brakes” in CD133+ cells responsible for tumor recurrence
Authors: Sharma Nikita S. , Gnamlin Prisca , Durden Brittany , Gupta Vineet K. , Kesh Kousik , Garrido Vanessa T. , Dudeja Vikas , Saluja Ashok , Banerjee Sulagna
Published: November 2019

Presence of quiescent, therapy evasive population often described as cancer stem cells (CSC) or tumor initiating cells (TIC) is often attributed to extreme metastasis and tumor recurrence. This population is typically enriched in a tumor as a result of microenvironment or chemotherapy induced stress. The TIC population adapts to this stress by turning on cell cycle arrest programs that is a “fail-safe” mechanism to prevent expansion of malignant cells to prevent further injury. Upon removal of the “stress” conditions, these cells restart their cell cycle and regain their proliferative nature thereby resulting in tumor relapse. Growth Arrest Specific 5 (GAS5) is a long-non-coding RNA that plays a vital role in this process. In pancreatic cancer, CD133+ population is a typical representation of the TIC population that is responsible for tumor relapse. In this study, we show for the first time that emergence of CD133+ population coincides with upregulation of GAS5, that reprograms the cell cycle to slow proliferation by inhibiting GR mediated cell cycle control. The CD133+ population further routed metabolites like glucose to shunt pathways like pentose phosphate pathway, that were predominantly biosynthetic in spite of being quiescent in nature but did not use it immediately for nucleic acid synthesis. Upon inhibiting GAS5, these cells were released from their growth arrest and restarted the nucleic acid synthesis and proliferation. Our study thus showed that GAS5 acts as a molecular switch for regulating quiescence and growth arrest in CD133+ population, that is responsible for aggressive biology of pancreatic tumors.
Chemical compound cinobufotalin potently induces FOXO1-stimulated cisplatin sensitivity by antagonizing its binding partner MYH9
Authors: Li YongHao , Liu Xiong , Lin Xian , Zhao Menyang , Xiao Yanyi , Liu Chen , Liang Zixi , Lin Zelong , Yi Renhui , Tang Zibo , Liu Jiahao , Li Xin , Jiang Qingping , Li Libo , Xie Yinyin , Liu Zhen , Fang Weiyi
Published: November 2019

In this study, we present novel molecular mechanisms by which FOXO1 functions as a tumor suppressor to prevent the pathogenesis of nasopharyngeal carcinoma (NPC). First, we observed that FOXO1 not only controlled tumor stemness and metastasis, but also sensitized NPC cells to cisplatin (DDP) in vitro and in vivo. Mechanistic studies demonstrated that FOXO1-induced miR-200b expression through the GSK3β/β-catenin/TCF4 network-mediated stimulation of ZEB1, which reduced tumor stemness and the epithelial–mesenchymal transition (EMT) signal. Furthermore, we observed FOXO1 interaction with MYH9 and suppression of MYH9 expression by modulating the PI3K/AKT/c-Myc/P53/miR-133a-3p pathway. Decreased MYH9 expression not only reduced its interactions with GSK3β, but also attenuated TRAF6 expression, which then decreased the ubiquitin-mediated degradation of GSK3β protein. Increased GSK3β expression stimulated the β-catenin/TCF4/ZEB1/miR-200b network, which increased the downstream tumor stemness and EMT signals. Subsequently, we observed that chemically synthesized cinobufotalin (CB) strongly increased FOXO1-induced DDP chemosensitivity by reducing MYH9 expression, and the reduction in MYH9 modulated GSK3β/β-catenin and its downstream tumor stemness and EMT signal in NPC. In clinical samples, the combination of low FOXO1 expression and high MYH9 expression indicated the worst overall survival rates. Our studies demonstrated that CB potently induced FOXO1-mediated DDP sensitivity by antagonizing its binding partner MYH9 to modulate tumor stemness in NPC.
Prenatal nicotine sex-dependently alters adolescent dopamine system development
Authors: Dwyer Jennifer B. , Cardenas Anjelica , Franke Ryan M. , Chen YiLing , Bai Yu , Belluzzi James D. , Lotfipour Shahrdad , Leslie Frances M.
Published: November 2019

Despite persistent public health initiatives, many women continue to smoke during pregnancy. Since maternal smoking has been linked to persisting sex-dependent neurobehavioral deficits in offspring, some consider nicotine to be a safer alternative to tobacco during pregnancy, and the use of electronic nicotine delivery systems is on the rise. We presently show, however, that sustained exposure to low doses of nicotine during fetal development, approximating plasma levels seen clinically with the nicotine patch, produces substantial changes in developing corticostriatal dopamine systems in adolescence. Briefly, pregnant dams were implanted on gestational day 4 with an osmotic minipump that delivered either saline (GS) or nicotine (3 mg/kg/day) (GN) for two weeks. At birth, pups were cross-fostered with treatment naïve dams and were handled daily. Biochemical analyses, signaling assays, and behavioral responses to cocaine were assessed on postnatal day 32, representative of adolescence in the rodent. GN treatment had both sex-dependent and sex-independent effects on prefrontal dopamine systems, altering Catechol-O-methyl transferase (COMT)-dependent dopamine turnover in males and norepinephrine transporter (NET) binding expression in both sexes. GN enhanced cocaine-induced locomotor activity in females, concomitant with GN-induced reductions in striatal dopamine transporter (DAT) binding. GN enhanced ventral striatal D2-like receptor expression and G-protein coupling, while altering the roles of D2 and D3 receptors in cocaine-induced behaviors. These data show that low-dose prenatal nicotine treatment sex-dependently alters corticostriatal dopamine system development, which may underlie clinical deficits seen in adolescents exposed to tobacco or nicotine in utero.
Individual differences in human fear generalization—pattern identification and implications for anxiety disorders
Authors: Stegmann Y. , Schiele M. A. , Schümann D. , Lonsdorf T. B. , Zwanzger P. , Romanos M. , Reif A. , Domschke K. , Deckert J. , Gamer M. , Pauli P.
Published: November 2019

Previous research indicates that anxiety disorders are characterized by an overgeneralization of conditioned fear as compared with healthy participants. Therefore, fear generalization is considered a key mechanism for the development of anxiety disorders. However, systematic investigations on the variance in fear generalization are lacking. Therefore, the current study aims at identifying distinctive phenotypes of fear generalization among healthy participants. To this end, 1175 participants completed a differential fear conditioning phase followed by a generalization test. To identify patterns of fear generalization, we used a k-means clustering algorithm based on individual arousal generalization gradients. Subsequently, we examined the reliability and validity of the clusters and phenotypical differences between subgroups on the basis of psychometric data and markers of fear expression. Cluster analysis reliably revealed five clusters that systematically differed in mean responses, differentiation between conditioned threat and safety, and linearity of the generalization gradients, though mean response levels accounted for most variance. Remarkably, the patterns of mean responses were already evident during fear acquisition and corresponded most closely to psychometric measures of anxiety traits. The identified clusters reliably described subgroups of healthy individuals with distinct response characteristics in a fear generalization test. Following a dimensional view of psychopathology, these clusters likely delineate risk factors for anxiety disorders. As crucial group characteristics were already evident during fear acquisition, our results emphasize the importance of average fear responses and differentiation between conditioned threat and safety as risk factors for anxiety disorders.
Idebenone has preventative and therapeutic effects on pulmonary fibrosis via preferential suppression of fibroblast activity
Authors: Sugizaki Toshifumi , Tanaka Ken-ichiro , Asano Teita , Kobayashi Daisuke , Hino Yuuki , Takafuji Ayaka , Shimoda Mikako , Mogushi Kaoru , Kawahara Masahiro , Mizushima Tohru
Published: November 2019

Alveolar epithelial injury induced by reactive oxygen species (ROS) and abnormal collagen production by activated fibroblasts (myofibroblasts) is involved in the onset and exacerbation of idiopathic pulmonary fibrosis (IPF). Compared with alveolar epithelial cells, lung fibroblasts, especially myofibroblasts, exhibit an apoptosis-resistance phenotype (apoptosis paradox) that appears to be involved in IPF pathogenesis. Thus, we screened for chemicals eliciting preferential cytotoxicity of LL29 cells (lung fibroblasts from an IPF patient) compared with A549 cells (human lung alveolar epithelial cell line) from medicines already in clinical use. We identified idebenone, a synthetic analogue of coenzyme Q10 (CoQ10, an antioxidant) that has been used clinically as a brain metabolic stimulant. Idebenone induced cell growth inhibition and cell death in LL29 cells at a lower concentration than in A549 cells, a feature that was not observed for other antioxidant molecules (such as CoQ10) and two IPF drugs (pirfenidone and nintedanib). Administration of idebenone prevented bleomycin-induced pulmonary fibrosis and increased pulmonary ROS levels. Importantly, idebenone also improved pulmonary fibrosis and lung function when administered after the development of fibrosis, whereas administration of CoQ10 similarly prevented bleomycin-induced pulmonary fibrosis, but had no effect after its development. Administration of idebenone, but not CoQ10, suppressed bleomycin-induced increases in lung myofibroblasts. In vitro, treatment of LL29 cells with idebenone, but not CoQ10, suppressed TGF-β–induced collagen production. These results suggest that in addition to antioxidant activity, idebenone exerts inhibitory activity on the function of lung fibroblasts, with the former activity being preventative and the latter therapeutic for bleomycin-induced fibrosis. Thus, we propose that idebenone may be more therapeutically beneficial for IPF patients than current treatments.
Geodynamic evolution of southwestern North America since the Late Eocene
Authors: Bahadori Alireza , Holt William E.
Published: November 2019

Slab rollback, lithospheric body forces, or evolution of plate boundary conditions are strongly debated as possible lithospheric driving mechanisms for Cenozoic extension in southwestern North America. By incorporating paleo-topography, lithospheric structure, and paleo-boundary conditions, we develop a complete geodynamic model that quantifies lithospheric deviatoric stresses and predicts extension and shear history since Late Eocene. We show that lithospheric body forces together with influence of change-over from subduction to transtensional boundary conditions from Late Eocene to Early Miocene were the primary driving factors controlling direction and magnitude of extensional deviatoric stresses that produced topographic collapse. After paleo-highlands collapsed, influence of Pacific-North America plate motion and associated deformation style along the plate boundary became increasingly important from Middle Miocene to present. Smaller-scale convection stress effects from slab rollback and associated mantle flow played only a minor role. However, slab rollback guided deformation rate through introduction of melts and fluids that impacted rheology.
Key drivers of cloud response to surface-active organics
Authors: Lowe S. J. , Partridge D. G. , Davies J. F. , Wilson K. R. , Topping D. , Riipinen I.
Published: November 2019

Aerosol-cloud interactions constitute the largest source of uncertainty in global radiative forcing estimates, hampering our understanding of climate evolution. Recent empirical evidence suggests surface tension depression by organic aerosol to significantly influence the formation of cloud droplets, and hence cloud optical properties. In climate models, however, surface tension of water is generally assumed when predicting cloud droplet concentrations. Here we show that the sensitivity of cloud microphysics, optical properties and shortwave radiative effects to the surface phase are dictated by an interplay between the aerosol particle size distribution, composition, water availability and atmospheric dynamics. We demonstrate that accounting for the surface phase becomes essential in clean environments in which ultrafine particle sources are present. Through detailed sensitivity analysis, quantitative constraints on the key drivers – aerosol particle number concentrations, organic fraction and fixed updraft velocity – are derived for instances of significant cloud microphysical susceptibilities to the surface phase.
Interspecific introgression mediates adaptation to whole genome duplication
Authors: Marburger Sarah , Monnahan Patrick , Seear Paul J. , Martin Simon H. , Koch Jordan , Paajanen Pirita , Bohutínská Magdalena , Higgins James D. , Schmickl Roswitha , Yant Levi
Published: November 2019

Adaptive gene flow is a consequential phenomenon across all kingdoms. Although recognition is increasing, there is no study showing that bidirectional gene flow mediates adaptation at loci that manage core processes. We previously discovered concerted molecular changes among interacting members of the meiotic machinery controlling crossover number upon adaptation to whole-genome duplication (WGD) in Arabidopsis arenosa. Here we conduct a population genomic study to test the hypothesis that adaptation to WGD has been mediated by adaptive gene flow between A. arenosa and A. lyrata. We find that A. lyrata underwent WGD more recently than A. arenosa, suggesting that pre-adapted alleles have rescued nascent A. lyrata, but we also detect gene flow in the opposite direction at functionally interacting loci under the most extreme levels of selection. These data indicate that bidirectional gene flow allowed for survival after WGD, and that the merger of these species is greater than the sum of their parts.
Genetic Characteristics of Korean Patients with Autosomal Dominant Polycystic Kidney Disease by Targeted Exome Sequencing
Authors: Kim Hyunsuk , Park Hayne Cho , Ryu Hyunjin , Kim Hyunho , Lee Hyun-Seob , Heo Jongho , Lee Chung , Kim Nayoung K. D. , Park Woong-Yang , Hwang Young-Hwan , Lee Kyu Beck , Oh Kook-Hwan , Oh Yun kyu , Ahn Curie
Published: November 2019

Autosomal dominant polycystic kidney disease (ADPKD) is one of the main causes of end-stage renal disease (ESRD). Genetic information is of the utmost importance in understanding pathogenesis of ADPKD. Therefore, this study aimed to demonstrate the genetic characteristics of ADPKD and their effects on renal function in 749 Korean ADPKD subjects from 524 unrelated families. Genetic studies of PKD1/2 were performed using targeted exome sequencing combined with Sanger sequencing in exon 1 of the PKD1 gene and a multiple ligation probe assay. The mutation detection rate was 80.7% (423/524 families, 331 mutations) and 70.7% was novel. PKD1 protein-truncating (PKD1-PT) genotype was associated with younger age at diagnosis, larger kidney volume, lower renal function compared to PKD1 non-truncating and PKD2 genotypes. The PKD1 genotype showed earlier onset of ESRD compared to PKD2 genotype (64.9 vs. 72.9 years old, P < 0.001). In frailty model controlled for age, gender, and familial clustering effect, PKD2 genotype had 0.2 times lower risk for reaching ESRD than PKD1-PT genotype (p = 0.037). In conclusion, our results suggest that genotyping can contribute to selecting rapid progressors for new emerging therapeutic interventions among Koreans.
Single-Shot Readout Performance of Two Heterojunction-Bipolar-Transistor Amplification Circuits at Millikelvin Temperatures
Authors: Curry M. J. , Rudolph M. , England T. D. , Mounce A. M. , Jock R. M. , Bureau-Oxton C. , Harvey-Collard P. , Sharma P. A. , Anderson J. M. , Campbell D. M. , Wendt J. R. , Ward D. R. , Carr S. M. , Lilly M. P. , Carroll M. S.
Published: November 2019

High-fidelity single-shot readout of spin qubits requires distinguishing states much faster than the T1 time of the spin state. One approach to improving readout fidelity and bandwidth (BW) is cryogenic amplification, where the signal from the qubit is amplified before noise sources are introduced and room-temperature amplifiers can operate at lower gain and higher BW. We compare the performance of two cryogenic amplification circuits: a current-biased heterojunction bipolar transistor circuit (CB-HBT), and an AC-coupled HBT circuit (AC-HBT). Both circuits are mounted on the mixing-chamber stage of a dilution refrigerator and are connected to silicon metal oxide semiconductor (Si-MOS) quantum dot devices on a printed circuit board (PCB). The power dissipated by the CB-HBT ranges from 0.1 to 1 μW whereas the power of the AC-HBT ranges from 1 to 20 μW. Referred to the input, the noise spectral density is low for both circuits, in the 15 to 30 fA/$$\sqrt{{\bf{Hz}}}$$

Hz

range. The charge sensitivity for the CB-HBT and AC-HBT is 330 μe/$$\sqrt{{\bf{Hz}}}$$

Hz

and 400 μe/$$\sqrt{{\bf{Hz}}}$$

Hz

, respectively. For the single-shot readout performed, less than 10 μs is required for both circuits to achieve bit error rates below 10−3, which is a putative threshold for quantum error correction.
Non-deforestation drivers of fires are increasingly important sources of aerosol and carbon dioxide emissions across Amazonia
Authors: Morgan William T. , Darbyshire Eoghan , Spracklen Dominick V. , Artaxo Paulo , Coe Hugh
Published: November 2019

Deforestation rates have declined substantially across the Brazilian Legal Amazon (BLA) over the period from 2000–2017. However, reductions in fire, aerosol and carbon dioxide have been far less significant than deforestation, even when accounting for inter-annual variability in precipitation. Our observations and analysis support a decoupling between fire and deforestation that has exacerbated forest degradation in the BLA. Basing aerosol and carbon dioxide emissions on deforestation rates, without accounting for forest degradation will bias these important climate and ecosystem-health parameters low, both now and in the future. Recent increases in deforestation rate since 2014 will enhance such degradation, particularly during drought-conditions, increasing emissions of aerosol and greenhouse gases. Given Brazil’s committed Nationally Determined Contribution under the Paris Agreement, failure to account for forest degradation fires will paint a false picture of prior progress and potentially have profound implications for both regional and global climate.
Epigenetic regulation of AURKA by miR-4715-3p in upper gastrointestinal cancers
Authors: Gomaa Ahmed , Peng Dunfa , Chen Zheng , Soutto Mohammed , Abouelezz Khaled , Corvalan Alejandro , El-Rifai Wael
Published: November 2019

Aurora kinase A (AURKA) is frequently overexpressed in several cancers. miRNA sequencing and bioinformatics analysis indicated significant downregulation of miR-4715-3p. We found that miR-4715-3p has putative binding sites on the 3UTR region of AURKA. Upper gastrointestinal adenocarcinoma (UGC) tissue samples and cell models demonstrated significant overexpression of AURKA with downregulation of miR-4715-3p. Luciferase reporter assays confirmed binding of miR-4715-3p on the 3UTR region of AURKA. miR-4715-3p mediated a reduction in AURKA levels leading to G2/M delay, chromosomal polyploidy, and cell death. We also detected a remarkable decrease in GPX4, an inhibitor of ferroptosis, with an increase in cleaved PARP and caspase-3. Inhibition of AURKA using siRNA produced similar results, suggesting a possible link between AURKA and GPX4. Analysis of UGC samples and cell models demonstrated increased methylation levels of several CpG nucleotides upstream of miR-4715-3p. 5-Aza-2′-deoxycytidine induced demethylation of several CpG nucleotides, restoring miR-4715-3p expression, leading to downregulation of AURKA. In conclusion, our data identified a novel epigenetic mechanism mediating silencing of miR-4715-3p and induction of AURKA in UGCs. Inhibition of AURKA or reconstitution of miR-4715-3p inhibited GPX4 and induced cell death, suggesting a link between AURKA and ferroptosis.
Vanadium Phosphorus Oxide/Siliceous Mesostructured Cellular Foams: efficient and selective for sustainable acrylic acid production via condensation route
Authors: Liu Jun , Xu Peiwen , Wang Pengcheng , Xu Zhijia , Feng Xinzhen , Ji Weijie , Au Chak-Tong
Published: November 2019

A new type of supported vanadium phosphorus oxide (VPO) with self-phase regulation was simply fabricated (organic solvent free) for the first time by depositing the specific VPO precursor NH4(VO2)HPO4 onto the Siliceous Mesostructured Cellular Foams (MCF) with controlled activation. The resulting materials were found to be highly efficient and selective for sustainable acrylic acid (AA) plus methyl acrylate (MA) production via a condensation route between acetic acid (HAc) and formaldehyde (HCHO). A (AA + MA) yield of 83.7% (HCHO input-based) or a (AA + MA) selectivity of 81.7% (converted HAc-based) are achievable at 360 °C. The systematic characterizations and evaluations demonstrate a unique surface regulation occurring between the MCF and the NH4(VO2)HPO4 precursor. NH3 release upon activation of NH4(VO2)HPO4 precursor together with adsorption of NH3 by MCF automatically induces partial reduction of V5+ whose content is fine-tunable by the VPO loading. Such a functionalization simultaneously modifies phase constitution and surface acidity/basicity of catalyst, hence readily controls catalytic performance.
Publisher Correction: The effect of attention and working memory on the estimation of elapsed time
Authors: Polti Ignacio , Martin Benoît , van Wassenhove Virginie
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Precise determination of surface band bending in Ga-polar n-GaN films by angular dependent X-Ray photoemission spectroscopy
Authors: Zhao Yanfei , Gao Hongwei , Huang Rong , Huang Zengli , Li Fangsen , Feng Jiagui , Sun Qian , Dingsun An , Yang Hui
Published: November 2019

We present a systematic study of surface band bending in Ga-polar n-GaN with different Si doping concentrations by angular dependent X-ray photoelectron spectroscopy (ADXPS). The binding energies of Ga 3d and N 1 s core levels in n-GaN films increase with increasing the emission angle, i. e., the probing depth, suggesting an upward surface band bending. By fitting the Ga 3d core level spectra at different emission angles and considering the integrated effect of electrostatic potential, the core level energy at the topmost surface layer is well corrected, therefore, the surface band bending is precisely evaluated. For moderately doped GaN, the electrostatic potential can be reflected by the simply linear potential approximation. However, for highly doped GaN samples, in which the photoelectron depth is comparable to the width of the space charge region, quadratic depletion approximation was used for the electrostatic potential to better understand the surface band bending effect. Our work improves the knowledge of surface band bending determination by ADXPS and also paves the way for studying the band bending effect in the interface of GaN based heterostructures.
Modified behavioural tests to detect white matter injury- induced motor deficits after intracerebral haemorrhage in mice
Authors: Chen Weixiang , Xia Min , Guo Chao , Jia Zhengcai , Wang Jie , Li Chengcheng , Li Mingxi , Tang Xiaoqin , Hu Rong , Chen Yujie , Liu Xin , Feng Hua
Published: November 2019

Motor function deficit induced by white matter injury (WMI) is one of the most severe complications of intracerebral haemorrhage (ICH). The degree of WMI is closely related to the prognosis of patients after ICH. However, the current behavioural assessment of motor function used in the ICH mouse model is mainly based on that for ischaemic stroke and lacks the behavioural methods that accurately respond to WMI. Here, a series of easy-to-implement behavioural tests were performed to detect motor deficits in mice after ICH. The results showed that the grip strength test and the modified pole test not only can better distinguish the degree of motor dysfunction between different volumes of blood ICH models than the Basso Mouse Scale and the beam walking test but can also accurately reflect the severity of WMI characterized by demyelination, axonal swelling and the latency of motor-evoked potential delay induced by ICH. In addition, after ICH, the results of grip tests and modified pole tests, rather than the Basso Mouse Scale and the beam walking test, were worse than those observed after intraventricular haemorrhage (IVH), which was used as a model of brain haemorrhage in non-white matter areas. These results indicate that the grip strength test and the modified pole test have advantages in detecting the degree of motor deficit induced by white matter injury after ICH in mice.
Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma
Authors: Poropatich Kate , Paunesku Tatjana , Zander Alia , Wray Brian , Schipma Matthew , Dalal Prarthana , Agulnik Mark , Chen Si , Lai Barry , Antipova Olga , Maxey Evan , Brown Koshonna , Wanzer Michael Beau , Gursel Demirkan , Fan Hanli , Rademaker Alfred , Woloschak Gayle E. , Mittal Bharat B.
Published: November 2019

Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is biologically distinct from HPV-negative HNSCC. Outside of HPV-status, few tumor-intrinsic variables have been identified that correlate to improved survival. As part of exploratory analysis into the trace elemental composition of oropharyngeal squamous cell carcinoma (OPSCC), we performed elemental quanitification by X-ray fluorescence microscopy (XFM) on a small cohort (n = 32) of patients with HPV-positive and -negative OPSCC and identified in HPV-positive cases increased zinc (Zn) concentrations in tumor tissue relative to normal tissue. Subsequent immunohistochemistry of six Zn-binding proteins—zinc-α2-glycoprotein (AZGP1), Lipocalin-1, Albumin, S100A7, S100A8 and S100A9—revealed that only AZGP1 expression significantly correlated to HPV-status (p < 0.001) and was also increased in tumor relative to normal tissue from HPV-positive OPSCC tumor samples. AZGP1 protein expression in our cohort significantly correlated to a prolonged recurrence-free survival (p = 0.029), similar to HNSCC cases from the TCGA (n = 499), where highest AZGP1 mRNA levels correlated to improved overall survival (p = 0.023). By showing for the first time that HPV-positive OPSCC patients have increased intratumoral Zn levels and AZGP1 expression, we identify possible positive prognostic biomarkers in HNSCC as well as possible mechanisms of increased sensitivity to chemoradiation in HPV-positive OPSCC.
Circulating tumor DNA as a prognostic indicator in resectable pancreatic ductal adenocarcinoma: A systematic review and meta-analysis
Authors: Lee Jee-Soo , Rhee Tae-Min , Pietrasz Daniel , Bachet Jean-Baptiste , Laurent-Puig Pierre , Kong Sun-Young , Takai Erina , Yachida Shinichi , Shibata Tatsuhiro , Lee Jung Woo , Park Hyoung-chul , Zang Dae Young , Jeon Kibum , Lee Jiwon , Kim Miyoung , Kim Han-Sung , Kang Hee Jung , Lee Young Kyung
Published: November 2019

Circulating tumor DNA (ctDNA) is a promising prognostic biomarker in various cancers. Due to the high recurrence rate of resectable pancreatic ductal adenocarcinoma (PDAC), effective strategies for prognostic stratification are necessary. Yet, for resectable PDAC, prognostic impact of ctDNA lacks systemic evidence. We sought to investigate the prognostic significance of baseline ctDNA and postoperative ctDNA in patients with resectable PDAC. PubMed, EMBASE, and the Cochrane library were searched up to March 2019. Five studies met the inclusion criteria, and 375 patients were pooled for the meta-analysis. Positive ctDNA significantly indicated poor overall survival (at baseline, hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.13–4.56; postoperative, HR 3.66, 95% CI 1.45–9.28). Patients with detectable ctDNA showed the trend to have higher risk for disease recurrence than those without detectable ctDNA (at baseline, HR 1.96, 95% CI 0.65–5.87; postoperative, HR 2.20, 95% CI 0.99–4.87). The results were consistent regardless of pre- or post-operative ctDNA. There was no significant heterogeneity among the included studies. In conclusion, our meta-analysis revealed that ctDNA, either at baseline or postoperative, might be a useful prognostic biomarker for stratifying risk of death and recurrence in resectable PDAC.
Encapsulation of human limbus-derived stromal/mesenchymal stem cells for biological preservation and transportation in extreme Indian conditions for clinical use
Authors: Damala Mukesh , Swioklo Stephen , Koduri Madhuri A. , Mitragotri Noopur S. , Basu Sayan , Connon Che J. , Singh Vivek
Published: November 2019

Human limbus-derived stromal/mesenchymal stem cells (hLMSC) can be one of the alternatives for the treatment of corneal scars. However, reliable methods of storing and transporting hLMSC remains a serious translational bottleneck. This study aimed to address these limitations by encapsulating hLMSC in alginate beads. Encapsulated hLMSC were kept in transit in a temperature-conditioned container at room temperature (RT) or stored at 4 °C for 3–5 days, which is the likely duration for transporting cells from bench-to-bedside. Non-encapsulated cells were used as controls. Post-storage, hLMSC were released from encapsulation, and viability-assessed cells were plated. After 48 and 96-hours in culture the survival, gene-expression and phenotypic characteristics of hLMSC were assessed. During transit, the container maintained an average temperature of 18.6 ± 1.8 °C, while the average ambient temperature was 31.4 ± 1.2 °C (p = 0.001). Encapsulated hLMSC under transit at RT were recovered with a higher viability (82.5 ± 0.9% and 76.9 ± 1.9%) after 3 (p = 0.0008) and 5-day storage (p = 0.0104) respectively as compared to 4 °C (65.2 ± 1.2% and 64.5 ± 0.8% respectively). Cells at RT also showed a trend towards greater survival-rates when cultured (74.3 ± 2.9% and 67.7 ± 9.8%) than cells stored at 4 °C (54.8 ± 9.04% and 52.4 ± 8.1%) after 3 and 5-days storage (p > 0.2). Non-encapsulated cells had negligible viability at RT and 4 °C. Encapsulated hLMSC (RT and 4 °C) maintained their characteristic phenotype (ABCG2, Pax6, CD90, p63-α, CD45, CD73, CD105, Vimentin and Collagen III). The findings of this study suggest that alginate encapsulation is an effective method of hLMSC preservation offering high cell viability over prolonged durations in transit at RT, therefore, potentially expanding the scope of cell-based therapy for corneal blindness.
Activated Carbons from Hydrochars Prepared in Milk
Authors: Haj Yahia Salwa , Lee Kian Keat , Ayed Brahim , Hedin Niklas , Church Tamara L.
Published: November 2019

Hydrothermal carbonization converts organics in aqueous suspension to a mixture of liquid components and carbon-rich solids (hydrochars), which in turn can be processed into activated carbons. We investigated whether milk could be used as a medium for hydrothermal carbonization, and found that hydrochars prepared from milk, with or without an added fibrous biomass, contained more carbon (particularly aliphatic carbon), less oxygen, and more mineral components than those prepared from fibrous biomass in water. Activated carbons produced from hydrochars generated in milk had lower specific surface areas and CO2 capacities than those from hydrochars formed in water; however, these differences disappeared upon normalizing to the combustible mass of the solid. Thus, in the context of N2 and CO2 uptake on activated carbons, the primary effect of using milk rather than water to form the hydrochar precursor was to contribute inorganic mass that adsorbed little CO2. Nevertheless, some of the activated carbons generated from hydrochars formed in milk had specific CO2 uptake capacities in the normal range for activated carbons prepared by activation in CO2 (here, up to 1.6 mmol g−1 CO2 at 15 kPa and 0 °C). Thus, hydrothermal carbonization could be used to convert waste milk to hydrochars and activated carbons.
Dry-Season Snow Cover Losses in the Andes (18°–40°S) driven by Changes in Large-Scale Climate Modes
Authors: Cordero Raul R. , Asencio Valentina , Feron Sarah , Damiani Alessandro , Llanillo Pedro J. , Sepulveda Edgardo , Jorquera Jose , Carrasco Jorge , Casassa Gino
Published: November 2019

The Andean snowpack is the primary source of water for many communities in South America. We have used Landsat imagery over the period 1986–2018 in order to assess the changes in the snow cover extent across a north-south transect of approximately 2,500 km (18°–40°S). Despite the significant interannual variability, here we show that the dry-season snow cover extent declined across the entire study area at an average rate of about −12% per decade. We also show that this decreasing trend is mainly driven by changes in the El Niño Southern Oscillation (ENSO), especially at latitudes lower than 34°S. At higher latitudes (34°–40°S), where the El Niño signal is weaker, snow cover losses appear to be also influenced by the poleward migration of the westerly winds associated with the positive trend in the Southern Annular Mode (SAM).