bluuebunny/crossref_metadata_2025 huggingface dataset:
H+/O+ Escape Rate Ratio in the Venus Magnetotail and its Dependence on the Solar Cycle
Authors: Persson M. , Futaana Y. , Fedorov A. , Nilsson H. , Hamrin M. , Barabash S.
Published: October 2018

A fundamental question for the atmospheric evolution of Venus is how much water‐related material escapes from Venus to space. In this study, we calculate the nonthermal escape of H+ and O+ ions through the Venusian magnetotail and its dependence on the solar cycle. We separate 8 years of data obtained from the ion mass analyzer on Venus Express into solar minimum and maximum. The average escape of H+ decreased from 7.6 · 1024 (solar minimum) to 2.1 · 1024 s−1 (solar maximum), while a smaller decrease was found for O+: 2.9 · 1024 to 2.0 · 1024 s−1. As a result, the H+/O+ flux ratio decreases from 2.6 to 1.1. This implies that the escape of hydrogen and oxygen could have been below the stoichiometric ratio of water for Venus in its early history under the more active Sun.
Equatorial Intraseasonal Temperature Oscillations in the Lower Thermosphere From SABER
Authors: Vergados Panagiotis , Liu Guiping , Mannucci Anthony J. , Janches Diego
Published: October 2018

We analyze the spatial‐temporal variability of the mesosphere/lower thermosphere (MLT) temperature at ±15N/S over 14 years, using measurements from the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument. We report that during the Madden‐Julian Oscillation season (November–April) the MLT region exhibits temperature variations with dominant periodicities at 40 and 60 days with amplitudes as large as 5.0 K. These intraseasonal oscillations (ISOs) are expressed across all longitudes, having superimposed zonal wave‐like structures that resemble waves 3 and 4 with amplitudes as large as 5.0 K. The cold and warm ISO phases are ubiquitous and repeatable from year to year over the 14‐year satellite record. We show that the MLT ISO exhibits the characteristics of a propagating wave carrying the embedded zonal wave‐like structures. At 20 km an ISO signal also exists with similar characteristics as the MLT ISO, suggesting a potential connection with the lower atmosphere.
Warm Terrestrial Subtropics During the Paleocene and Eocene: Carbonate Clumped Isotope (Δ47) Evidence From the Tornillo Basin, Texas (USA)
Authors: Kelson Julia R. , Watford Dylana , Bataille Clement , Huntington Katharine W. , Hyland Ethan , Bowen Gabriel J.
Published: October 2018

Records of subtropical climate on land from the early Paleogene offer insights into how the Earth system responds to greenhouse climate conditions. Fluvial and floodplain deposits of the Tornillo Basin (Big Bend National Park, Texas, USA) preserve a record of environmental and climatic change of the Paleocene and the early Eocene. We report carbon, oxygen, and clumped isotopic compositions (δ13C, δ18O, and Δ47) of paleosol carbonate nodules from this basin. Mineralogical, geochemical, and thermal modeling evidence suggests that the measured isotopic values preserve primary environmental signals with a summer bias with the exception of data from two nodules reset by local igneous intrusions. The unaltered nodules record Δ47 temperatures of 25 ± 4 and 32 ± 2 °C for the Paleocene and early Eocene nodules, respectively, showing an increase in average summer temperatures of 7 ± 3 °C. Calculations of δ18O of soil water are −2.8 ± 0.7‰ and −0.8 ± 0.4‰ (standard mean ocean water) for the early‐mid‐Paleocene and late Paleocene‐early Eocene, showing an increase of 2.0 ± 0.9‰. The increase in temperature and δ18O values likely relates to a rise in atmospheric pCO2, although we cannot rule out that changes in paleosol texture and regional precipitation patterns also influence the record. Comparison with Δ47 estimates of summer temperature from the Green River and Bighorn Basins (WY) highlights that terrestrial surface temperatures are heterogeneous, and latitudinal temperature gradients on land remain undetermined. Previously published paleoclimate models predict summer temperatures that are 2 to 6 °C higher than our estimate; discrepancies between climate models and proxy data persist at lower latitudes.
The Influence of Cloudiness on Hydrologic Fluctuations in the Mountains of the Western United States
Authors: Sumargo Edwin , Cayan Daniel R.
Published: October 2018

This study investigates snowmelt and streamflow responses to cloudiness variability across the mountainous parts of the western United States. Twenty years (1996–2015) of Geostationary Operational Environmental Satellite‐derived cloud cover indices (CC) with 4‐km spatial and daily temporal resolutions are used as a proxy for cloudiness. The primary driver of nonseasonal fluctuations in daily mean solar insolation is the fluctuating cloudiness. We find that CC fluctuations are related to snowmelt and snow‐fed streamflow fluctuations, to some extent (correlations of <0.5). Multivariate linear regression models of daily snowmelt (MELT) and streamflow (ΔQ) variations are constructed for each month from February to July, when snowmelt is most active. Predictors include CC from five antecedent days up to the current day. The CC‐MELT and CC‐ΔQ associations vary with time and location. The results show the dominance of negative correlations between CC and MELT, exemplifying the cloud‐shading (or clear‐sky) effect on snowmelt. The magnitude of the CC‐MELT association (R2) amounts to 5–61%, typically peaking in May. These associations fade earlier in summer during dry years than wet years, indicating the differing responses of thicker versus thinner snowpack. The CC‐ΔQ association displays a less consistent pattern, with R2 amounting to 2–47%. Nevertheless, MELT and ΔQ fluctuations exhibit spatially extensive patterns of correlations with daily cloudiness anomalies, indicating that the effects of cloudiness often operate over regional spatial scales.
Diffusive Regimes of the Motion of Bed Load Particles in Open Channel Flows at Low Transport Stages
Authors: Cecchetto M. , Tregnaghi M. , Bottacin‐Busolin A. , Tait S. J. , Cotterle L. , Marion A.
Published: October 2018

The stochasticity of fluid and sediment parameters has been identified as a source of diffusion, particularly anomalous diffusion at different temporal and spatial scales of bed load particle trajectories. Data from two sets of flume experiments are presented, one data set has gravel particle trajectories tracked over a limited area and was used in identifying the influence of different shear stress conditions on diffusive processes. A new experiment was performed using spherical particles moving as bed load in an annular flume in order to address concerns about censorship effects caused by the size of the detection window. An annular flume allowed collection of practically uncensored particle trajectories over longer time period than has been previously possible in the laboratory. Three diffusive regimes were observed at distinct stages of particle motion: (i) ballistic regime at the local range; (ii) Fickian diffusion at the intermediate range; (iii) subdiffusion at the global range. Characteristic time scales separate the regimes and correlate with the mean traveling and resting times of particles. Fickian diffusion in the intermediate range is first recognized as a result of the balance between intermittent weak transport and near‐bed turbulence, as first predicted by Nikora et al. (2002, https://doi.org/10.1029/2001WR000513). In the global range, extreme values were observed in the distribution of particle resting times, suggesting that two types of distributions (related to surface motion and vertical mixing) were responsible for the subdiffusion at longer time scales. Diffusion was found to be anisotropic at all stages of particle motion.
Opportunities and Challenges in Computing Fresh Groundwater Discharge to Continental Coastlines: A Multimodel Comparison for the United States Gulf and Atlantic Coasts
Authors: Zhou YaoQuan , Befus Kevin M. , Sawyer Audrey H. , David Cédric H.
Published: October 2018

The fresh component of submarine groundwater discharge (fresh SGD) transports nutrient and contaminant loads from land to sea. Fresh SGD fluxes are poorly known but depend on geology, topography, climate, and land use. Here we assess two general approaches for quantifying the magnitude of fresh SGD over regional to continental scales—water budgets (lumped parameter models) and groundwater flow models—focusing on the U.S. Atlantic and Gulf Coasts as a large‐scale case study. Estimates of fresh SGD fluxes from groundwater flow models are more variable than estimates from water budgets, and both are often less than field‐based estimates. Both approaches predict the volume of fresh SGD within approximately 50% of 12.3 km3/year, in line with previous estimates, and differences are largely driven by hydrographic data inputs. The simplified water budget approach, while computationally cheap, cannot resolve flow paths or continuous flux distributions and may neglect groundwater flow from deep aquifers or distal recharge zones. Conversely, three‐dimensional groundwater flow models can resolve flow paths and fresh SGD contributions from heterogeneous aquifer systems but are computationally expensive and require more parameterization. Ultimately, multiple models and integrated field data are needed to improve our estimates of fresh SGD fluxes over a wide range of scales.
Method of Distributions for Water Hammer Equations With Uncertain Parameters
Authors: Alawadhi Abdulrahman , Boso Francesca , Tartakovsky Daniel M.
Published: October 2018

Water hammer equations (WHE) are routinely used to interpret leak detection tests in pipe networks. Assimilation of pressure data into model predictions is typically done within the probabilistic framework, which treats uncertain model parameters (e.g., initial and boundary conditions, location, and intensity of a leak) as random variables so that solutions of the WHE are given in terms of probability density functions (PDFs) of fluid pressure and velocity. These are usually estimated with computationally expensive Monte Carlo simulations. We use the method of distributions to derive a deterministic equation for the (joint) PDFs of the pressure and flow rate governed by the WHE. This PDF equation employs a closure approximation that ensures the self‐consistency in terms of the mean and variance of the state variables. Our numerical experiments demonstrate the agreement between solutions of the PDF equation and Monte Carlo simulations, and the computational efficiency of the former relative to the latter.
0.04 degree-per-hour MEMS disk resonator gyroscope with high-quality factor (510 k) and long decaying time constant (74.9 s)
Authors: Li Qingsong , Xiao Dingbang , Zhou Xin , Xu Yi , Zhuo Ming , Hou Zhanqiang , He Kaixuan , Zhang Yongmeng , Wu Xuezhong
Published: October 2018

The disk resonator gyroscope is an attractive candidate for high-performance MEMS gyroscopes. This gyroscope consists of a sensor and readout electronics, and the characteristics of the sensor directly determine the performance. For the sensor, a high-quality factor and long decaying time constant are the most important characteristics required to achieve high performance. We report a disk resonator gyroscope with a measured quality factor of 510 k and decaying time constant of 74.9 s, which is a record for MEMS silicon disk resonator gyroscopes, to the best of our knowledge. To improve the quality factor of the DRG, the quality factor improvement mechanism is first analyzed, and based on this mechanism two stiffness-mass decoupled methods, i.e., spoke length distribution optimization and lumped mass configuration design, are proposed and demonstrated. A disk resonator gyroscope prototype is fabricated based on these design strategies, and the sensor itself shows an angle random walk as low as 0.001°/√h, demonstrating true potential to achieve navigation-grade performance. The gyroscope with readout electronics shows an angle random walk of 0.01°/√h and a bias instability of 0.04°/h at room temperature without compensation, revealing that the performance of the gyroscope is severely limited by the readout electronics, which should be further improved. We expect that the quality factor improvement methods can be used in the design of other MEMS gyroscopes and that the newly designed DRG can be further improved to achieve navigation-grade performances for high-end industrial, transportation, aerospace, and automotive applications.
Depletion of ZBTB38 potentiates the effects of DNA demethylating agents in cancer cells via CDKN1C mRNA up-regulation
Authors: Marchal Claire , de Dieuleveult Maud , Saint-Ruf Claude , Guinot Nadège , Ferry Laure , Olalla Saad Sara T. , Lazarini Mariana , Defossez Pierre-Antoine , Miotto Benoit
Published: October 2018

DNA methyltransferase inhibitor (DNMTi) treatments have been used for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and have shown promising beneficial effects in some other types of cancers. Here, we demonstrate that the transcriptional repressor ZBTB38 is a critical regulator of the cellular response to DNMTi. Treatments with 5-azacytidine, or its derivatives decitabine and zebularine, lead to down-regulation of ZBTB38 protein expression in cancer cells, in parallel with cellular damage. The depletion of ZBTB38 by RNA interference enhances the toxicity of DNMTi in cell lines from leukemia and from various solid tumor types. Further we observed that inactivation of ZBTB38 causes the up-regulation of CDKN1C mRNA, a previously described indirect target of DNMTi. We show that CDKN1C is a key actor of DNMTi toxicity in cells lacking ZBTB38. Finally, in patients with MDS a high level of CDKN1C mRNA expression before treatment correlates with a better clinical response to a drug regimen combining 5-azacytidine and histone deacetylase inhibitors. Collectively, our results suggest that the ZBTB38 protein is a target of DNMTi and that its depletion potentiates the toxicity of DNMT inhibitors in cancer cells, providing new opportunities to enhance the response to DNMT inhibitor therapies in patients with MDS and other cancers.
Grading of Atrophic Gastritis is Useful for Risk Stratification in Endoscopic Screening for Gastric Cancer
Authors: Kaji Kyosuke , Hashiba Atsushi , Uotani Chika , Yamaguchi Yasushi , Ueno Toshio , Ohno Kenji , Takabatake Ichiro , Wakabayashi Tokio , Doyama Hisashi , Ninomiya Itasu , Kiriyama Masato , Ohyama Shigekazu , Yoneshima Manabu , Koyama Nobu , Takeda Yasuo , Yasuda Kenji
Published: October 2018

OBJECTIVES:

In order to screen for gastric cancer effectively, its interval should be set according to the risk. This study aimed to determine whether risk stratification is possible using the data obtained from medical examination or endoscopic findings.

METHODS:

First, subjects who underwent both cancer screening and medical examination from 2009 to 2015 and underwent cancer screening once more by 2016 were studied. Data such as the lipid profile and history of smoking obtained during the medical examination, and the grade of atrophy and presence of peptic ulcers were studied using multivariate analysis. Next, subjects who underwent cancer screening twice or more between 2009 and 2015 with or without medical examinations were studied to analyze any correlation between the grade of atrophy and cancer occurrence using univariate analysis. In both studies, the status of Helicobacter pylori (HP) infection was determined.

RESULTS:

In the multivariate analysis, 9378 subjects were included. Aging, advanced atrophy, presence of ulcers, and uric acid levels were identified as risk factors. Among subjects who underwent successful HP eradication therapy, advanced atrophy and aging were observed to be crucial risk factors. In the univariate analysis, there were 12,941 subjects. Gastric cancer occurred more frequently in the more severe atrophy group (P < 0.001). The annual rate of cancer occurrence in the most severe atrophy group was 0.31%, which was approximately thrice as that in the less atrophy group.

CONCLUSIONS:

Risk stratification was possible based on endoscopic examination alone. The interval should be set depending on each case.
Genetic pleiotropy between mood disorders, metabolic, and endocrine traits in a multigenerational pedigree
Authors: Kember Rachel L. , Hou Liping , Ji Xiao , Andersen Lars H. , Ghorai Arpita , Estrella Lisa N. , Almasy Laura , McMahon Francis J. , Brown Christopher , Bućan Maja
Published: October 2018

Bipolar disorder (BD) is a mental disorder characterized by alternating periods of depression and mania. Individuals with BD have higher levels of early mortality than the general population, and a substantial proportion of this is due to increased risk for comorbid diseases. To identify the molecular events that underlie BD and related medical comorbidities, we generated imputed whole-genome sequence data using a population-specific reference panel for an extended multigenerational Old Order Amish pedigree (n = 394), segregating BD and related disorders. First, we investigated all putative disease-causing variants at known Mendelian disease loci present in this pedigree. Second, we performed genomic profiling using polygenic risk scores (PRS) to establish each individual’s risk for several complex diseases. We identified a set of Mendelian variants that co-occur in individuals with BD more frequently than their unaffected family members, including the R3527Q mutation inAPOBassociated with hypercholesterolemia. Using PRS, we demonstrated that BD individuals from this pedigree were enriched for the same common risk alleles for BD as the general population (β = 0.416,p = 6 × 10−4). Furthermore, we find evidence for a common genetic etiology between BD risk and polygenic risk for clinical autoimmune thyroid disease (p = 1 × 10−4), diabetes (p = 1 × 10−3), and lipid traits such as triglyceride levels (p = 3 × 10−4) in the pedigree. We identify genomic regions that contribute to the differences between BD individuals and unaffected family members by calculating local genetic risk for independent LD blocks. Our findings provide evidence for the extensive genetic pleiotropy that can drive epidemiological findings of comorbidities between diseases and other complex traits.
Metallo-polyelectrolytes as a class of ionic macromolecules for functional materials
Authors: Zhu Tianyu , Sha Ye , Yan Jing , Pageni Parasmani , Rahman Md Anisur , Yan Yi , Tang Chuanbing
Published: October 2018

The fields of soft polymers and macromolecular sciences have enjoyed a unique combination of metals and organic frameworks in the name of metallopolymers or organometallic polymers. When metallopolymers carry charged groups, they form a class of metal-containing polyelectrolytes or metallo-polyelectrolytes. This review identifies the unique properties and functions of metallo-polyelectrolytes compared with conventional organo-polyelectrolytes, in the hope of shedding light on the formation of functional materials with intriguing applications and potential benefits. It concludes with a critical perspective on the challenges and hurdles for metallo-polyelectrolytes, especially experimental quantitative analysis and theoretical modeling of ionic binding.
The genetic basis of a social polymorphism in halictid bees
Authors: Kocher Sarah D. , Mallarino Ricardo , Rubin Benjamin E. R. , Yu Douglas W. , Hoekstra Hopi E. , Pierce Naomi E.
Published: October 2018

The emergence of eusociality represents a major evolutionary transition from solitary to group reproduction. The most commonly studied eusocial species, honey bees and ants, represent the behavioral extremes of social evolution but lack close relatives that are non-social. Unlike these species, the halictid bee Lasioglossum albipes produces both solitary and eusocial nests and this intraspecific variation has a genetic basis. Here, we identify genetic variants associated with this polymorphism, including one located in the intron of syntaxin 1a (syx1a), a gene that mediates synaptic vesicle release. We show that this variant can alter gene expression in a pattern consistent with differences between social and solitary bees. Surprisingly, syx1a and several other genes associated with sociality in L. albipes have also been implicated in autism spectrum disorder in humans. Thus, genes underlying behavioral variation in L. albipes may also shape social behaviors across a wide range of taxa, including humans.
Production of hypoallergenic milk from DNA-free beta-lactoglobulin (BLG) gene knockout cow using zinc-finger nucleases mRNA
Authors: Sun Zhaolin , Wang Ming , Han Shiwen , Ma Shuangyu , Zou Zhiyuan , Ding Fangrong , Li Xinrui , Li Ling , Tang Bo , Wang Haiping , Li Ning , Che Huilian , Dai Yunping
Published: October 2018

The whey protein β-lactoglobulin (BLG) is a major milk allergen which is absent in human milk. Here, we for the first time generated DNA-freeBLGbi-allelic knockout cow by zinc-finger nuclease (ZFNs) mRNA and produced BLG-free milk. According to the allergenicity evaluation of BLG-free milk, we found it can trigger lower allergic reaction of Balb/c mice including the rectal temperature drop and the allergen-specific immunoglobulin IgE production; BLG free-milk was easily digested by pepsin at 2 min, while BLG in control milk was still not completely digested after 60 min, and the binding of IgE from cow’s milk allergy (CMA) patients to BLG free-milk was significantly lower than that to the control milk. Meanwhile, the genome sequencing revealed that our animal is free of off-target events. Importantly, editing animal genomes without introducing foreign DNA into cells may alleviate regulatory concerns related to foods produced by genome edited animals. Finally, the ZFNs-mediated targeting in cow could be transmitted through the germline by breeding. These findings will open up unlimited possibilities of modifying milk composition to make it more suitable for human health and also improve the functional properties of milk.
Imatinib reduces non-alcoholic fatty liver disease in obese mice by targeting inflammatory and lipogenic pathways in macrophages and liver
Authors: AlAsfoor Shefaa , Rohm Theresa V. , Bosch Angela J. T. , Dervos Thomas , Calabrese Diego , Matter Matthias S. , Weber Achim , Cavelti-Weder Claudia
Published: October 2018

Macrophages have been recognized as key players in non-alcoholic fatty liver disease (NAFLD). Our aim was to assess whether pharmacological attenuation of macrophages can be achieved by imatinib, an anti-leukemia drug with known anti-inflammatory and anti-diabetic properties, and how this impacts on NAFLD. We analyzed the pro- and anti-inflammatory gene expression of murine macrophages and human monocytes in vitro in the presence or absence of imatinib. In a time-resolved study, we characterized metabolic disease manifestations such as hepatic steatosis, systemic and adipose tissue inflammation as well as lipid and glucose metabolism in obese mice at one and three months of imatinib treatment. Our results showed that imatinib lowered pro-inflammatory markers in murine macrophages and human monocytes in vitro. In obese mice, imatinib reduced TNFα-gene expression in peritoneal and liver macrophages and systemic lipid levels at one month. This was followed by decreased hepatic steatosis, systemic and adipose tissue inflammation and increased insulin sensitivity after three months. As the transcription factor sterol regulatory element-binding protein (SREBP) links lipid metabolism to the innate immune response, we assessed the gene expression of SREBPs and their target genes, which was indeed downregulated in the liver and partially in peritoneal macrophages. In conclusion, targeting both inflammatory and lipogenic pathways in macrophages and liver as shown by imatinib could represent an attractive novel therapeutic strategy for patients with NAFLD.
Functional Analysis of Human Pathological Semen Samples in an Oocyte Cytoplasmic Ex Vivo System
Authors: Amargant Farners , García Désirée , Barragán Montserrat , Vassena Rita , Vernos Isabelle
Published: October 2018

Human fertilization and embryo development involve a wide range of critical processes that determine the successful development of a new organism. Although Assisted Reproduction Technologies (ART) may help solve infertility problems associated to severe male factor, the live birth rate is still low. A high proportion of ART failures occurs before implantation. Understanding the causes for these failures has been difficult due to technical and ethical limitations. Diagnostic procedures on human spermatozoa in particular have been limited to morphology and swimming behaviours while other functional requirements during early development have not been addressed due to the lack of suitable assays. Here, we have established a quantitative system based on the use of Xenopus egg extracts and human spermatozoa. This system provides novel possibilities for the functional characterization of human spermatozoa. Using clinical data we show that indeed this approach offers a set of complementary data for the functional evaluation of spermatozoa from patients.
A Comparative Assessment of Human and Chimpanzee iPSC-derived Cardiomyocytes with Primary Heart Tissues
Authors: Pavlovic Bryan J. , Blake Lauren E. , Roux Julien , Chavarria Claudia , Gilad Yoav
Published: October 2018

Comparative genomic studies in primates have the potential to reveal the genetic and mechanistic basis for human specific traits. These studies may also help us better understand inter-species phenotypic differences that are clinically relevant. Unfortunately, the obvious limitation on sample collection and experimentation in humans and non-human apes severely restrict our ability to perform dynamic comparative studies in primates. Induced pluripotent stem cells (iPSCs), and their corresponding differentiated cells, may provide a suitable alternative system for dynamic comparative studies. Yet, to effectively use iPSCs and differentiated cells for comparative studies, one must characterize the extent to which these systems faithfully represent biological processes in primary tissues. To do so, we compared gene expression data from primary adult heart tissue and iPSC-derived cardiomyocytes from multiple human and chimpanzee individuals. We determined that gene expression in cultured cardiomyocytes from both human and chimpanzee is most similar to that of adult hearts compared to other adult tissues. Using a comparative framework, we found that 50% of gene regulatory differences between human and chimpanzee hearts are also observed between species in cultured cardiomyocytes; conversely, inter-species regulatory differences seen in cardiomyocytes are found significantly more often in hearts than in other primary tissues. Our work provides a detailed description of the utility and limitation of differentiated cardiomyocytes as a system for comparative functional genomic studies in primates.
Coitus-Free Sexual Transmission of Zika Virus in a Mouse Model
Authors: Clancy Chad S. , Van Wettere Arnaud J. , Morrey John D. , Julander Justin G.
Published: October 2018

Zika virus (ZIKV) is an arboviral infection that may be sexually transmitted. The present study aims to determine if accessory sex glands are a potential source of infectious virus and important in sexual transmission. Male interferon type I receptor knockout (Ifnar−/−) mice were challenged subcutaneously with a Puerto Rican ZIKV isolate. Reproductive tissues were harvested seven days after viral challenge and artificial insemination fluid derived from epididymis or homogenized accessory sex glands (seminal plasma) was obtained. Naïve interferon type I and II receptor knockout (AG129) females were pre-treated with progesterone, and inoculated intravaginally with either epididymal flush or seminal plasma from ZIKV-infected males. ZIKV RNA was demonstrated in the artificial insemination fluid and ZIKV antigen was detected in epididymal epithelial cells but not within seminiferous tubules at the time of artificial insemination fluid collection. Peripheral viremia, demonstrated by ZIKV RNA in whole blood samples of females from each challenge group was observed. Infectious virus was present in both epididymal fluid and seminal plasma. These studies provide evidence of passage of virus from epididymal flush and seminal plasma to naïve females via artificial insemination and provides a model for the study of sexual transmission of ZIKV.
Value of serial cervical length measurement in prediction of spontaneous preterm birth in post-conization pregnancy without short mid-trimester cervix
Authors: Wang Liang
Published: October 2018

Serial cervical length (CL) measurement in mid-trimester is recommended in post-conization pregnancy to estimate the risk of spontaneous preterm birth (SPTB). A short mid-trimester cervix (CL < 25 mm) has been considered as a strong predictor for SPTB. However, the low incidence of short cervix limits the utility of mid-trimester CL measurement in prediction of SPTB. A great proportion of women who develop SPTB don’t have a short mid-trimester cervix. Therefore, this study was aimed to investigate the additional value of serial CL measurement in predicting SPTB in addition to detecting short cervix alone. A total of 613 post-conization pregnant women who did not have short mid-trimester cervix between January 2004 and January 2014 were included in this study. Serial CL measurements were taken by transvaginal ultrasound at three timepoints (A: 13 + 0–15 + 6 weeks, B: 16 + 0–18 + 6 weeks, and C: 20 + 0–22 + 6 weeks). Eight parameters were analyzed for predicting SPTB, including CL measurements at different timepoints (CLA, CLB, CLC), the maximum and minimum CL measurements (CLMAX, CLMIN), and the percentage change in CL measurement between different timepoints (%ΔCLAB, %ΔCLBC, %ΔCLAC). After univariate and multivariate analysis, CLMAX and %ΔCLAC were independent variables in predicting SPTB. Lower CLMAX (OR [95%CI]: 0.92 [0.90–0.93]) and higher %ΔCLAC (OR [95%CI]: 1.05 [1.01–1.09]) were related to an increasing risk of SPTB. In conclusion, our study for the first time in literature reported the value of serial CL measurement in prediction of SPTB in post-conization pregnancy without short mid-trimester cervix. In the subpopulation of pregnant women who did not have short mid-trimester cervix, CLMAX and %ΔCLAC were of value in predicting SPTB, which warranted further investigations.
Observational Evidence for Unintentional Weight Loss in All-Cause Mortality and Major Cardiovascular Events: A Systematic Review and Meta-Analysis
Authors: De Stefani Fernanda do Carmo , Pietraroia Priscila Saia , Fernandes-Silva Miguel Morita , Faria-Neto José , Baena Cristina Pellegrino
Published: October 2018

The obesity paradox has been described in several observational cohorts and meta-analysis. However, evidence of the intentionality of weight loss in all-cause deaths and major cardiovascular events (MACE) in prospective cohorts is unclear. We analysed whether involuntary weight loss is associated with increased cardiovascular events and mortality. In a systematic review, we searched multiple electronic databases for observational studies published up to October 2016. Studies reporting risk estimates for unintentional weight loss compared with stable weight in MACE and mortality were included. Fifteen studies met the selection criteria, with a total of 178,644 participants. For unintentional weight loss, we found adjusted risk ratios (RRs) with confidence intervals (CIs) of 1.38 (95% CI: 1.23, 1.53) and 1.17 (95% CI: 0.98, 1.37) for all-cause mortality and MACE, respectively. Participants with comorbidities, overweight and obese populations, and older adults yielded RRs (95% CI) of 1.49 (1.30, 1.68), 1.11 (1.04, 1.18), and 1.81 (1.59, 2.03), respectively. Unintentional weight loss had a significant impact on all-cause mortality. We found no protective effect of being overweight or obese for unintentional weight loss and MACE.
Non-invasive continuous real-time in vivo analysis of microbial hydrogen production shows adaptation to fermentable carbohydrates in mice
Authors: Fernández-Calleja José M. S. , Konstanti Prokopis , Swarts Hans J. M. , Bouwman Lianne M. S. , Garcia-Campayo Vicenta , Billecke Nils , Oosting Annemarie , Smidt Hauke , Keijer Jaap , van Schothorst Evert M.
Published: October 2018

Real time in vivo methods are needed to better understand the interplay between diet and the gastrointestinal microbiota. Therefore, a rodent indirect calorimetry system was equipped with hydrogen (H2) and methane (CH4) sensors. H2 production was readily detected in C57BL/6J mice and followed a circadian rhythm. H2 production was increased within 12 hours after first exposure to a lowly-digestible starch diet (LDD) compared to a highly-digestible starch diet (HDD). Marked differences were observed in the faecal microbiota of animals fed the LDD and HDD diets. H2 was identified as a key variable explaining the variation in microbial communities, with specific taxa (including Bacteroides and Parasutterella) correlating with H2 production upon LDD-feeding. CH4 production was undetectable which was in line with absence of CH4 producers in the gut. We conclude that real-time in vivo monitoring of gases provides a non-invasive time-resolved system to explore the interplay between nutrition and gut microbes in a mouse model, and demonstrates potential for translation to other animal models and human studies.
Quantitative Analysis of a Whole Cardiac Mass Using Dual-Energy Computed Tomography: Comparison with Conventional Computed Tomography and Magnetic Resonance Imaging
Authors: Hong Yoo Jin , Hur Jin , Han Kyunghwa , Im Dong Jin , Suh Young Joo , Lee Hye-Jeong , Kim Young Jin , Choi Byoung Wook
Published: October 2018

It is critical to distinguish between cardiac tumors and thrombi because they require different treatment strategies. Although accurate differentiation of these cardiac masses can be challenging, computed tomography (CT) and magnetic resonance imaging (MRI) are promising tools to improve their diagnosis. This study aimed to assess the diagnostic value of a volume-based quantification strategy using dual-energy CT to differentiate between cardiac tumors and thrombi. We prospectively enrolled 41 patients who had a cardiac mass. All patients underwent electrocardiography gated dual-energy CT. Among them, 28 patients underwent late gadolinium enhancement cardiac MRI. For quantitative analysis, the following parameters of the entire cardiac masses were measured: CT attenuation values in Hounsfield units (HU), iodine concentration (mg/ml), and signal intensity (SI) ratio. A mixed effects model was used to evaluate the significance of differences in mean CT attenuation, mean iodine concentration, and SI ratios between the cardiac tumor and thrombus groups. Diagnostic performance of each parameter was evaluated by constructing a receiver operating characteristics curve. A total of 24 cardiac tumors and 19 cardiac thrombi were analyzed. The mean iodine concentration was significantly higher in tumors than in thrombi (tumors: 2.98 ± 0.23; thrombi: 1.79 ± 0.26, p = 0.002). The diagnostic performance of iodine concentration was better than that of post-contrast HU (area under the curve [AUC]: 0.77 vs. 0.51; p < 0.001), and worse than that of SI ratio (AUC: 0.89; p = 0.04) for differentiation of cardiac tumors and thrombi. Dual-energy CT using volume-based iodine measurements can differentiate between cardiac tumors and thrombi.
1-Oxo-2,2,6,6-tetramethylpiperidinium bromide converts α-H N,N-dialkylhydroxylamines to nitrones via a two-electron oxidation mechanism
Authors: Stoyanovsky Anastas D. , Stoyanovsky Detcho A.
Published: October 2018

Herein we provide experimental proof that 1-oxo-2,2,6,6-tetramethylpiperidinium bromide converts α-H N,N-dialkylhydroxylamines to nitrones via a two-electron oxidation mechanism. The reactions reported are rapid, proceed under mild conditions, and afford nitrones in excellent yields.
Drug Screening of Human GBM Spheroids in Brain Cancer Chip
Authors: Akay Metin , Hite John , Avci Naze Gul , Fan Yantao , Akay Yasemin , Lu Guangrong , Zhu Jay-Jiguang
Published: October 2018

Glioblastoma multiforme (GBM), an extremely invasive and high-grade (grade IV) glioma, is the most common and aggressive form of brain cancer. It has a poor prognosis, with a median overall survival of only 11 months in the general GBM population and 14.6 to 21 months in clinical trial participants with standard GBM therapies, including maximum safe craniotomy, adjuvant radiation, and chemotherapies. Therefore, new approaches for developing effective treatments, such as a tool for assessing tumor cell drug response before drug treatments are administered, are urgently needed to improve patient survival. To address this issue, we developed an improved brain cancer chip with a diffusion prevention mechanism that blocks drugs crossing from one channel to another. In the current study, we demonstrate that the chip has the ability to culture 3D spheroids from patient tumor specimen-derived GBM cells obtained from three GBM patients. Two clinical drugs used to treat GBM, temozolomide (TMZ) and bevacizumab (Avastin, BEV), were applied and a range of relative concentrations was generated by the microfluidic channels in the brain cancer chip. The results showed that TMZ works more effectively when used in combination with BEV compared to TMZ alone. We believe that this low-cost brain cancer chip could be further developed to generate optimal combination of chemotherapy drugs tailored to individual GBM patients.
Fingolimod reduces circulating tight-junction protein levels and in vitro peripheral blood mononuclear cells migration in multiple sclerosis patients
Authors: Annunziata Pasquale , Cioni Chiara , Masi Gianni , Tassi Maristella , Marotta Giuseppe , Severi Sauro
Published: October 2018

There are no data on the effects of fingolimod, an immunomodulatory drug used in treatment of multiple sclerosis (MS), on circulating tight-junction (TJ) protein levels as well as on peripheral blood mononuclear cells (PBMC) migration. Serum TJ protein [occludin (OCLN), claudin-5 (CLN-5) and zonula occludens-1 (ZO-1)] levels, sphingosine-1 phosphate 1 (S1P1) receptor expression on circulating leukocyte populations as well as in vitro PBMC migration were longitudinally assessed in 20 MS patients under 12-months fingolimod treatment and correlated with clinical and magnetic resonance imaging (MRI) parameters. After 12 months of treatment, a significant reduction of mean relapse rate as well as number of active lesions at MRI was found. TJ protein levels significantly decreased and were associated with reduction of S1P1 expression as well as of PBMC in vitro migratory activity. A significant correlation of CLN-5/OCLN ratio with new T2 MRI lesions and a significant inverse correlation of CLN-5/ZO-1 ratio with disability scores were found. These findings support possible in vivo effects of fingolimod on the blood-brain barrier (BBB) functional activity as well as on peripheral cell trafficking that could result in avoiding passage of circulating autoreactive cells into brain parenchyma. Circulating TJ protein levels and respective ratios could be further studied as a novel candidate biomarker of BBB functional status to be monitored in course of fingolimod as well as of other immunomodulatory treatments in MS.
Interactions of momentary thought content and subjective stress predict cortisol fluctuations in a daily life experience sampling study
Authors: Linz R. , Singer T. , Engert V.
Published: October 2018

Daily life stress is an omnipresent phenomenon in modern society. Research has linked prolonged activation of the hypothalamic-pituitary-adrenal axis to psychiatric and somatic diseases. Everyday stressors substantially contribute to these health risks. Despite the notion that the physiological stress response is highly dependent on concurrent psychological processes, investigations associating diurnal cortisol levels with subjective experience have primarily focused on affective states. The impact of everyday cognitive processes including thought content has been largely neglected. To investigate this link, moment-to-moment associations of psychological experience including subjective stress, thought content and affect, and cortisol levels were assessed throughout the daily routines of 289 healthy adult participants. We found that subjective stress interacted with current thought content and affect in predicting cortisol release: more negative and future-directed thoughts were associated with higher cortisol levels after experiencing subjective stress, suggesting an increase in negative future anticipation. Concurrent cortisol rises might reflect proactive coping to adequately prepare for upcoming demands. In the absence of subjective stress, more past-directed thoughts and negative affect were associated with higher cortisol levels. These findings provide evidence for a fundamental link between thought content and daily cortisol activation, and highlight the significant contribution of thought patterns to physiological stress levels.
Novel Hybrid Evolutionary Algorithms for Spatial Prediction of Floods
Authors: Bui Dieu Tien , Panahi Mahdi , Shahabi Himan , Singh Vijay P. , Shirzadi Ataollah , Chapi Kamran , Khosravi Khabat , Chen Wei , Panahi Somayeh , Li Shaojun , Ahmad Baharin Bin
Published: October 2018

Adaptive neuro-fuzzy inference system (ANFIS) includes two novel GIS-based ensemble artificial intelligence approaches called imperialistic competitive algorithm (ICA) and firefly algorithm (FA). This combination could result in ANFIS-ICA and ANFIS-FA models, which were applied to flood spatial modelling and its mapping in the Haraz watershed in Northern Province of Mazandaran, Iran. Ten influential factors including slope angle, elevation, stream power index (SPI), curvature, topographic wetness index (TWI), lithology, rainfall, land use, stream density, and the distance to river were selected for flood modelling. The validity of the models was assessed using statistical error-indices (RMSE and MSE), statistical tests (Friedman and Wilcoxon signed-rank tests), and the area under the curve (AUC) of success. The prediction accuracy of the models was compared to some new state-of-the-art sophisticated machine learning techniques that had previously been successfully tested in the study area. The results confirmed the goodness of fit and appropriate prediction accuracy of the two ensemble models. However, the ANFIS-ICA model (AUC = 0.947) had a better performance in comparison to the Bagging-LMT (AUC = 0.940), BLR (AUC = 0.936), LMT (AUC = 0.934), ANFIS-FA (AUC = 0.917), LR (AUC = 0.885) and RF (AUC = 0.806) models. Therefore, the ANFIS-ICA model can be introduced as a promising method for the sustainable management of flood-prone areas.
Genomic analysis of Acinetobacter baumannii prophages reveals remarkable diversity and suggests profound impact on bacterial virulence and fitness
Authors: Costa Ana Rita , Monteiro Rodrigo , Azeredo Joana
Published: October 2018

The recent nomination by the World Health Organization of Acinetobacter baumannii as the number one priority pathogen for the development of new antibiotics is a direct consequence of its fast evolution of pathogenicity, and in particular of multidrug resistance. While the development of new antibiotics is critical, understanding the mechanisms behind the crescent bacterial antibiotic resistance is equally relevant. Often, resistance and other bacterial virulence elements are contained on highly mobile pieces of DNA that can easily spread to other bacteria. Prophages are one of the mediators of this form of gene transfer, and have been frequently found in bacterial genomes, often offering advantageous features to the host. Here we assess the contribution of prophages for the evolution of A. baumannii pathogenicity. We found prophages to be notably diverse and widely disseminated in A. baumannii genomes. Also remarkably, A. baumannii prophages encode for multiple putative virulence factors that may be implicated in the bacterium’s capacity to colonize host niches, evade the host immune system, subsist in unfavorable environments, and tolerate antibiotics. Overall our results point towards a significant contribution of prophages for the dissemination and evolution of pathogenicity in A. baumannii, and highlight their clinical relevance.
Ionizing radiation induces transgenerational effects of DNA methylation in zebrafish
Authors: Kamstra Jorke H. , Hurem Selma , Martin Leonardo Martin , Lindeman Leif C. , Legler Juliette , Oughton Deborah , Salbu Brit , Brede Dag Anders , Lyche Jan Ludvig , Aleström Peter
Published: October 2018

Ionizing radiation is known to cause DNA damage, yet the mechanisms underlying potential transgenerational effects of exposure have been scarcely studied. Previously, we observed effects in offspring of zebrafish exposed to gamma radiation during gametogenesis. Here, we hypothesize that these effects are accompanied by changes of DNA methylation possibly inherited by subsequent generations. We assessed DNA methylation in F1 embryos (5.5 hours post fertilization) with whole genome bisulfite sequencing following parental exposure to 8.7 mGy/h for 27 days and found 5658 differentially methylated regions (DMRs). DMRs were predominantly located at known regulatory regions, such as gene promoters and enhancers. Pathway analysis indicated the involvement of DMRs related to similar pathways found with gene expression analysis, such as development, apoptosis and cancers, which could be linked to previous observed developmental defects and genomic instability in the offspring. Follow up of 19 F1 DMRs in F2 and F3 embryos revealed persistent effects up to the F3 generation at 5 regions. These results indicate that ionizing radiation related effects in offspring can be linked to DNA methylation changes that partly can persist over generations. Monitoring DNA methylation could serve as a biomarker to provide an indication of ancestral exposures to ionizing radiation.
Fabrication of chitosan/magnetite-graphene oxide composites as a novel bioadsorbent for adsorption and detoxification of Cr(VI) from aqueous solution
Authors: Zhang Bei , Hu Runtao , Sun Dejun , Wu Tao , Li Yujiang
Published: October 2018

By utilizing the synergistic effect of chitosan (CS), magnetite (Fe3O4) particles, and graphene oxide (GO), a series of efficient and eco-friendly chitosan/magnetite-graphene oxide (CS/MGO) composites were fabricated through a facile chemical route. First, Fe3O4 particles were chemically deposited on the surface of GO to fabricate MGO hybrid. Then, chitosan was attached on MGO sheets, assembling to CS/MGO composites. According to the results of characterization, the covalent Fe-O-C bonds, electrostatic attraction, and hydrogen bonding between GO, Fe3O4, and chitosan ensure excellent structural stability and physico-chemical properties. The adsorption of Cr(VI) onto CS/MGO composites was also carried out under various conditions (content of CS, pH, initial concentration, contact time, and temperature). The CS/MGO composites possess high removal capacity for Cr(VI) from aqueous solution. Moreover, results also suggested that the CS/MGO composites had a strong reducing action for Cr(VI). When adsorption occurred, Cr(VI) and Cr(III) were simultaneously removed by CS/MGO composites. In addition, CS/MGO composites could retain good Cr(VI) removal efficiency after reuse over five cycles. CS/MGO composites are expected to have potential applications as easily regenerative bioadsorbents for Cr(VI) polluted water cleanup.