bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractDNA 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

AbstractBipolar 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

AbstractThe 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

AbstractThe 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

AbstractThe 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

AbstractMacrophages 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

AbstractHuman 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

AbstractComparative 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

AbstractZika 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

AbstractSerial 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

AbstractThe 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

AbstractReal 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.