bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance analysis of underwater towing cable based on overset grid
Authors: Liu Xianlong , Lin Zhengcheng , Jiang Aiguo , zhu Linyong
Published: August 2019

The method of overset grid is used to calculate the lift and drag of towing cable at various angles of attack. Compared with the past method, it effectively solves the problem of mesh distortion at high angles of attack. Overset grid is more effective, and most of the grids are formed by regular hexahedron, so the accuracy of calculation is more guaranteed. When calculating the special angle of attack, the cubic spline interpolation method is used to solve the problem.
Simulation study on the mass transport in PCL based on the ciliated dynamic system of the respiratory tract
Authors: Zhu Pengfei , Chen Duanduan , Xu Yuanqing
Published: August 2019

In this paper, a two-dimensional dynamic model of human respiratory cilia is established by immersed boundary-lattice Boltzmann method. In the model, periciliary liquid and mucus layer with different flow characteristics are considered, in which the non-Newtonian fluid in the viscous layer is described by Oldroyd-B model; the area between two layers is dynamically divided by a virtual membrane. By changing the cilium beat amplitude and the depth of periciliary liquid, this paper focuses on the removal of particle impurities by cilium beat. The results show that when the initial position is near the top of cilium, the particle tends to migrate upward to approach the mucus layer. However, if the initial position is near the middle or at lower part of the cilia, most of the particles will not be transferred to the vicinity of mucus layer by the swinging cilium. It is also found that by increasing the beat amplitude of cilia, particles are more likely to approach the mucus layer. By conducting this study, the migration of the particle in periciliary liquid is discussed in detail. The results are significant to help us to know the material transport law of human respiratory tract.
New Development of Flow Field Calibration in the 2.4 m Transonic Wind Tunnel
Authors: Chen Xuekong , Lin Xuedong , Zhang Lin , Liu Guangyuan , Wang Ruibo
Published: August 2019

For the purpose of improving the flow fields of CARDC’s 2.4 m transonic wind tunnel in accuracy, two types of calibrations have been done in this tunnel. One was designing and manufacturing a new centerline pipe in high quality to calibrate the centreline flow, obtaining the accurate Mach number correction relationships and helped to build up new flow fields in accuracy. The other was applying a cone-cylinder model to measure the symmetries of the longitudinal flow fields to simulate the testing articles’ movement in pitching zone. It helped to investigate the detailed information of this flow fields. Based on these, the flow fields in higher accuracy were built up in the full-span model test section. This article presents the method, the process and the results of the calibrations herein.
Simulation and Analysis of Flexible Piezoelectric Beam under Karmen Vortex Street Effect
Authors: Li Haining , Wang Haifeng , Sun Kaili , Guo Xiuyu
Published: August 2019

Recent years, researchers have gradually increased their research efforts on energy harvesters for low power applications. Among them, many piezoelectric energy harvesters have been widely used because of their simple structures, low energy consumption and easy miniaturization. In order to study the energy harvesting with a flexible piezoelectric beam deformed by vortex-induced vibration, this paper takes polyvinylidene fluoride as the piezoelectric beam, and relies on ANSYS simulation software, establishes a fluid-solid-piezoelectric three-field coupling model, and calculates the energy harvesting capacity of piezoelectric beam. The results show that the positive output voltage is 59.763V and the negative output voltage is -67.633V.
The effect of high temperature overalls on body temperature
Authors: Mao Jie
Published: August 2019

When working in a high temperature environment, people need to wear special clothing to avoid burns. High-temperature special clothing can avoid burns and greatly improve the safety of work. In order to design a special garment with high strength and heat insulation and low cost, we built a model by heat conduction equation to simulate the change of human body temperature at a certain temperature. By simulating the body temperature changes in the high temperature environment, it is judged whether the high temperature overalls meet the requirements.
Research on Free Jet Test Technology
Authors: Xu Kao , Zhu Xiaojun , Li Feng
Published: August 2019

Aerodynamic thermal ground test can not completely simulate flight conditions, and there is no simple and clear similarity criterion as aerodynamic test. In practical application, it is often to grasp the local flow characteristics of materials or structures and use ground test equipment to simulate their main thermal environment parameters. Therefore, according to the thermal environment characteristics of different parts of the aircraft, a variety of arc heating test techniques have been developed. For example, free jet test technology has been developed for material test of simplified model and assessment test of small-scale components. It effectively solves some problems of thermal protection test examination.
Research Progress in Signaling Pathways That Regulate Life Span
Authors: Shi Yue , Ding Feng , Zhao Yan
Published: August 2019

Aging is a complex multifactorial biological process shared by all living organisms. It shows a gradual decline in normal physiological function in a time-dependent manner. Various model organisms are used to study the mechanisms of aging, and important discoveries in this area have contributed to the development of new therapies for age-related diseases. In this review, we discuss the important signaling pathways that have been shown to affect longevity, including the insulin/insulin-like growth factor (IGF-1) signaling pathway, the target of rapamycin (TOR) signaling pathway, and the AMP-activated protein kinase (AMPK) signaling pathway, providing a basic understanding of the mechanisms of the aging process.
Justification of the Need and Feasibility of Switching to Renewable Energy Sources for the Implementation of Sustainable Development Principles
Authors: Tyaglov S , Sheveleva A , Guseva T
Published: August 2019

Reduction of the negative impact on the environment, improvement of the energy efficiency, optimization in the structure of the global energy balance and ensuring innovative energy development are important tasks in achieving sustainable development. The aim of this article is to justify the need for the development and feasibility of switching to renewable energy sources (RES) in order to solve the abovementioned issues. In this regard, it is necessary to study the prerequisites for intensifying the process of transition from traditional energy sources made up of renewable ones, analyze their current state and prospects for further development. In addition, it is necessary to identify the necessary measures to stimulate the transition from traditional energy sources to RES. Eventually, the expected results of transition to RES are identified and allow proving the economic, social and environmental efficiency of their use.
PTRF/CAVIN1, regulated by SHC1 through the EGFR pathway, is found in urine exosomes as a potential biomarker of ccRCC
Authors: Zhao Yubo , Wang Yunfei , Zhao Enyang , Tan Yanli , Geng Bo , Kang Chunsheng , Li Xuedong
Published: August 2019

Polymerase I and transcript release factor (PTRF)/Cavin1 regulates RNA polymerase I during transcription and plays a critical role in endocytosis. Abnormal expressions of PTRF were detected in multiple cancers according to increasing research. PTRF has been showed to involve in the formation and secretion of exosomes and can be detected in the exosomes, which suggests that PTRF would be a potential biomarker for diagnosis of clear cell renal cell carcinoma (ccRCC) using urine samples. Approximately 50–90% of ccRCC cases suffered abnormal epidermal growth factor receptor (EGFR), which activates a variety of signaling pathways, including the mitogen-activated protein kinase/extracellular signal-regulated kinase and Phosphoinositide 3-Kinase/Akt pathway. According to bioinformatic analysis of gene expression arrays of kidney clear cell carcinoma from The Cancer Genome Atlas, we found SHC1 was significantly overexpressed in high-grade ccRCC and correlated to poor prognosis, and also SHC1 was annotated in extracellular matrix process, which was regulated by EGFR. Further studies showed that the expression of PTRF was regulated by SHC1 through EGFR-Phosphoinositide 3-Kinase/Akt pathway. PTRF was detected in the exosomes isolated from ccRCC patients' urine and ccRCC cancer cells culture medium. It suggested that the abnormal SHC1-increased PTRF, which is detected in exosomes from urine, would be a potential marker for ccRCC diagnose and treatment.
The Flexible Loop is a New Sweetness Determinant Site of the Sweet-Tasting Protein: Characterization of Novel Sweeter Mutants of the Single-Chain Monellin (MNEI)
Authors: Yang Liu , Zhu Kongkai , Yu Haifeng , Zhang Xinlei , Liu Bo
Published: August 2019

The single-chain monellin (MNEI) displays same sweet potency as the natural monellin protein. To identify critical residues determining its sweetness, residues located at the loops region were selected for mutagenesis analysis. Mutations of positive-charge residues R31, R53, and R82 consistently led to obvious decrease of sweetness, whereas mutations of negative-charge residues resulted in variable sweet potency. Of note, the E50N mutant in the loop region linking the 2 natural chains showed significantly increased sweetness. Mutations of this residue to M or K led to similar effects, in accordance with the so-called wedge model for explanation of the sweet protein–receptor interaction. Homology modeling was carried out with the firstly reported crystal structure of sweet taste receptor (from medaka fish) as the template, and molecular docking and dynamics simulations suggested that flexible conformations of specific residues located in the loops region play essential roles for the interaction with the receptor and the sweetness of the protein. Moreover, obvious additive effects were found for the sweetness as 2 double-site mutants (E50N/Y65R and E2N/E50N) displayed increased sweetness than their single-site mutants. Our results revealed the flexible loop L23 linking the 2 natural chains as a novel sweetness determinant site of the sweet protein monellin and raised a series of new sweeter mutants, which could provide helpful guidance for molecular designing the sweet-tasting proteins.
Neurosyphilis Treatment Outcomes After Intravenous Penicillin G Versus Intramuscular Procaine Penicillin Plus Oral Probenecid
Authors: Dunaway Shelia B , Maxwell Clare L , Tantalo Lauren C , Sahi Sharon K , Marra Christina M
Published: August 2019

Background

Data comparing neurosyphilis treatment regimens are limited.

Methods

Participants were enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis that was conducted at the University of Washington between April 2003 to May 2014. They were diagnosed with syphilis and referred by their providers due to concerns for neurosyphilis. We evaluated 150 people with CSF abnormalities who were treated with either intravenous aqueous penicillin G (PenG) or intramuscular aqueous procaine penicillin G plus oral probenecid (APPG-P). An abnormal CSF diagnosis was defined as a white blood cell (WBC) count >20/µL, a CSF protein reading >50 mg/dL, or a reactive CSF–Venereal Disease Research Laboratory test (VDRL). Hazard ratios for normalization of CSF or serum measures were determined using Cox regression.

Results

In individuals treated with either PenG or APPG-P, CSF WBCs and CSF-VDRL reactivity normalized within 12 months after treatment, while protein normalized more slowly and less completely. There was no relationship between treatment regimen or human immunodeficiency virus (HIV) status and likelihood of normalization of any measure. Among those living with HIV, CSF WBC counts and CSF-VDRL reactivity were more likely to normalize in those treated with antiretrovirals. Unexpectedly, CSF WBCs were more likely to normalize in those with low CD4+ T cell counts. When neurosyphilis was more stringently defined as a reactive CSF-VDRL, the relationship with the CD4+ T cell count remained unchanged.

Conclusions

In the current antiretroviral treatment era, neurosyphilis treatment outcomes are not different for PenG and APPG-P, regardless of HIV status. The relationship between the normalization of CSF WBC counts and CD4+ T cell counts may indicate continued imprecision in neurosyphilis diagnostic criteria, due to HIV-related CSF pleocytosis.
An Informational Theory of Privacy
Authors: Jann Ole , Schottmüller Christoph
Published: August 2019

Privacy of consumers or citizens is often seen as an inefficient information asymmetry. We challenge this view by showing that privacy can increase welfare in an informational sense. It can also improve information aggregation and prevent inefficient statistical discrimination. We show how and when the different informational effects of privacy line up to make privacy efficient or even Pareto-optimal. Our theory can be applied to decide who should have which information and how privacy and information disclosure should be regulated. We discuss applications to online privacy, credit decisions and transparency in government.
Machine learning of clinical variables and coronary artery calcium scoring for the prediction of obstructive coronary artery disease on coronary computed tomography angiography: analysis from the CONFIRM registry
Authors: Al’Aref Subhi J , Maliakal Gabriel , Singh Gurpreet , van Rosendael Alexander R , Ma Xiaoyue , Xu Zhuoran , Alawamlh Omar Al Hussein , Lee Benjamin , Pandey Mohit , Achenbach Stephan , Al-Mallah Mouaz H , Andreini Daniele , Bax Jeroen J , Berman Daniel S , Budoff Matthew J , Cademartiri Filippo , Callister Tracy Q , Chang Hyuk-Jae , Chinnaiyan Kavitha , Chow Benjamin J W , Cury Ricardo C , DeLago Augustin , Feuchtner Gudrun , Hadamitzky Martin , Hausleiter Joerg , Kaufmann Philipp A , Kim Yong-Jin , Leipsic Jonathon A , Maffei Erica , Marques Hugo , Gonçalves Pedro de Araújo , Pontone Gianluca , Raff Gilbert L , Rubinshtein Ronen , Villines Todd C , Gransar Heidi , Lu Yao , Jones Erica C , Peña Jessica M , Lin Fay Y , Min James K , Shaw Leslee J
Published: August 2019

Aims

Symptom-based pretest probability scores that estimate the likelihood of obstructive coronary artery disease (CAD) in stable chest pain have moderate accuracy. We sought to develop a machine learning (ML) model, utilizing clinical factors and the coronary artery calcium score (CACS), to predict the presence of obstructive CAD on coronary computed tomography angiography (CCTA).

Methods and results

The study screened 35 281 participants enrolled in the CONFIRM registry, who underwent ≥64 detector row CCTA evaluation because of either suspected or previously established CAD. A boosted ensemble algorithm (XGBoost) was used, with data split into a training set (80%) on which 10-fold cross-validation was done and a test set (20%). Performance was assessed of the (1) ML model (using 25 clinical and demographic features), (2) ML + CACS, (3) CAD consortium clinical score, (4) CAD consortium clinical score + CACS, and (5) updated Diamond-Forrester (UDF) score. The study population comprised of 13 054 patients, of whom 2380 (18.2%) had obstructive CAD (≥50% stenosis). Machine learning with CACS produced the best performance [area under the curve (AUC) of 0.881] compared with ML alone (AUC of 0.773), CAD consortium clinical score (AUC of 0.734), and with CACS (AUC of 0.866) and UDF (AUC of 0.682), P < 0.05 for all comparisons. CACS, age, and gender were the highest ranking features.

Conclusion

A ML model incorporating clinical features in addition to CACS can accurately estimate the pretest likelihood of obstructive CAD on CCTA. In clinical practice, the utilization of such an approach could improve risk stratification and help guide downstream management.
Comparison of single-nucleotide variants identified by Illumina and Oxford Nanopore technologies in the context of a potential outbreak of Shiga toxin–producing Escherichia coli
Authors: Greig David R , Jenkins Claire , Gharbia Saheer , Dallman Timothy J
Published: August 2019

Background

We aimed to compare Illumina and Oxford Nanopore Technology sequencing data from the 2 isolates of Shiga toxin–producing Escherichia coli (STEC) O157:H7 to determine whether concordant single-nucleotide variants were identified and whether inference of relatedness was consistent with the 2 technologies.

Results

For the Illumina workflow, the time from DNA extraction to availability of results was ~40 hours, whereas with the ONT workflow serotyping and Shiga toxin subtyping variant identification were available within 7 hours. After optimization of the ONT variant filtering, on average 95% of the discrepant positions between the technologies were accounted for by methylated positions found in the described 5-methylcytosine motif sequences, CC(A/T)GG. Of the few discrepant variants (6 and 7 difference for the 2 isolates) identified by the 2 technologies, it is likely that both methodologies contain false calls.

Conclusions

Despite these discrepancies, Illumina and Oxford Nanopore Technology sequences from the same case were placed on the same phylogenetic location against a dense reference database of STEC O157:H7 genomes sequenced using the Illumina workflow. Robust single-nucleotide polymorphism typing using MinION-based variant calling is possible, and we provide evidence that the 2 technologies can be used interchangeably to type STEC O157:H7 in a public health setting.
SNV identification from single-cell RNA sequencing data
Authors: Schnepp Patricia M , Chen Mengjie , Keller Evan T , Zhou Xiang
Published: August 2019

Integrating single-cell RNA sequencing (scRNA-seq) data with genotypes obtained from DNA sequencing studies facilitates the detection of functional genetic variants underlying cell type-specific gene expression variation. Unfortunately, most existing scRNA-seq studies do not come with DNA sequencing data; thus, being able to call single nucleotide variants (SNVs) from scRNA-seq data alone can provide crucial and complementary information, detection of functional SNVs, maximizing the potential of existing scRNA-seq studies. Here, we perform extensive analyses to evaluate the utility of two SNV calling pipelines (GATK and Monovar), originally designed for SNV calling in either bulk or single-cell DNA sequencing data. In both pipelines, we examined various parameter settings to determine the accuracy of the final SNV call set and provide practical recommendations for applied analysts. We found that combining all reads from the single cells and following GATK Best Practices resulted in the highest number of SNVs identified with a high concordance. In individual single cells, Monovar resulted in better quality SNVs even though none of the pipelines analyzed is capable of calling a reasonable number of SNVs with high accuracy. In addition, we found that SNV calling quality varies across different functional genomic regions. Our results open doors for novel ways to leverage the use of scRNA-seq for the future investigation of SNV function.
Surgical treatment of pulmonary oligorecurrence after curative resection for non-small-cell lung cancer
Authors: Han Sung Joon , Cho Sukki , Yum Sungwon , Kim Kwhanmien , Jheon Sanghoon
Published: August 2019

OBJECTIVES

The most appropriate therapeutic strategy for patients with pulmonary oligorecurrence after curative resection of non-small-cell lung cancer (NSCLC) is unclear; therefore, characterizing the results of various treatments for pulmonary oligorecurrence would be valuable. This study compared the prognosis of operative and non-operative treatment for pulmonary oligorecurrence after complete resection of NSCLC.

METHODS

Among 2230 patients from a prospective lung cancer database who underwent surgical resection between 2004 and 2014, 486 patients (22%) experienced recurrence, including 254 with pulmonary recurrence and 102 with pulmonary oligorecurrence (5 or fewer metastatic lesions). Post-recurrence survival (PRS) rates were compared between those who received operative or non-operative treatment, including chemotherapy, radiotherapy, chemoradiotherapy and best supportive care.

RESULTS

Among 102 patients with pulmonary oligorecurrence, 41 patients received operative treatment and 61 received non-operative treatment (34 chemotherapy, 15 radiotherapy, 9 chemoradiotherapy and 3 best supportive care). The patients who received operative treatment were significantly younger at the first operation than those in the non-operative group and had better performance status, lower pathological T stage at the first operation, younger age at recurrence and fewer metastatic lesions. The median PRS was 46.4 months, and the 5-year PRS rates were 67% and 26% in the operative and non-operative groups, respectively. The multivariable analysis revealed that undergoing video-assisted thoracoscopic surgery at the first operation and receiving operative treatment for recurrence were independent prognostic factors for more favourable PRS.

CONCLUSIONS

Operative treatment of pulmonary oligorecurrence after curative resection significantly prolonged the PRS in patients who underwent curative resection for NSCLC.
Precision Medicine and Precision Public Health in the Era of Pathogen Next-Generation Sequencing
Authors: Leguia Mariana , Vila-Sanjurjo Anton , Chain Patrick S G , Berry Irina Maljkovic , Jarman Richard G , Pollett Simon
Published: August 2019

This brief report serves as an introduction to a supplement of the Journal of Infectious Diseases entitled “Next-Generation Sequencing (NGS) Technologies to Advance Global Infectious Disease Research.” We briefly discuss the history of NGS technologies and describe how the techniques developed during the past 40 years have impacted our understanding of infectious diseases. Our focus is on the application of NGS in the context of pathogen genomics. Beyond obvious clinical and public health applications, we also discuss the challenges that still remain within this rapidly evolving field.
Functional Human CD141+ Dendritic Cells in Human Immune System Mice
Authors: Coelho-Dos-Reis Jordana G A , Funakoshi Ryota , Huang Jing , Pereira Felipe Valença , Iketani Sho , Tsuji Moriya
Published: August 2019

Background

For the purpose of studying functional human dendritic cells (DCs) in a humanized mouse model that mimics the human immune system (HIS), a model referred to as HIS mice was established.

Methods

Human immune system mice were made by engrafting NOD/SCID/IL2Rgammanull (NSG) mice with human hematopoietic stem cells (HSCs) following the transduction of genes encoding human cytokines and human leukocyte antigen (HLA)-A2.1 by adeno-associated virus serotype 9 (AAV9) vectors.

Results

Our results indicate that human DC subsets, such as CD141+CD11c+ and CD1c+CD11c+ myeloid DCs, distribute throughout several organs in HIS mice including blood, bone marrow, spleen, and draining lymph nodes. The CD141+CD11c+ and CD1c+CD11c+ human DCs isolated from HIS mice immunized with adenoviruses expressing malaria/human immunodeficiency virus (HIV) epitopes were able to induce the proliferation of malaria/HIV epitopes-specific human CD8+ T cells in vitro. Upregulation of CD1c was also observed in human CD141+ DCs 1 day after immunization with the adenovirus-based vaccines.

Conclusions

Establishment of such a humanized mouse model that mounts functional human DCs enables preclinical assessment of the immunogenicity of human vaccines in vivo.
Living with AI: A Personal Perspective
Authors: Fernando Ransith
Published: August 2019

‘Who is not talking about artificial intelligence?’ asks Ransith Fernando, chair of BCS Sri Lanka. Respectable CIOs are busy adding an AI strategy and road map to make their companies future ready. Most IT students sprinkle a bit of deep learning and some neural networks to make their CVs glow and improve their chances of getting employed.
The IARC Monographs: Updated Procedures for Modern and Transparent Evidence Synthesis in Cancer Hazard Identification
Authors: Samet Jonathan M , Chiu Weihsueh A , Cogliano Vincent , Jinot Jennifer , Kriebel David , Lunn Ruth M , Beland Frederick A , Bero Lisa , Browne Patience , Fritschi Lin , Kanno Jun , Lachenmeier Dirk W , Lan Qing , Lasfargues Gérard , Le Curieux Frank , Peters Susan , Shubat Pamela , Sone Hideko , White Mary C , Williamson Jon , Yakubovskaya Marianna , Siemiatycki Jack , White Paul A , Guyton Kathryn Z , Schubauer-Berigan Mary K , Hall Amy L , Grosse Yann , Bouvard Véronique , Benbrahim-Tallaa Lamia , El Ghissassi Fatiha , Lauby-Secretan Béatrice , Armstrong Bruce , Saracci Rodolfo , Zavadil Jiri , Straif Kurt , Wild Christopher P
Published: August 2019

The Monographs produced by the International Agency for Research on Cancer (IARC) apply rigorous procedures for the scientific review and evaluation of carcinogenic hazards by independent experts. The Preamble to the IARC Monographs, which outlines these procedures, was updated in 2019, following recommendations of a 2018 expert advisory group. This article presents the key features of the updated Preamble, a major milestone that will enable IARC to take advantage of recent scientific and procedural advances made during the 12 years since the last Preamble amendments. The updated Preamble formalizes important developments already being pioneered in the Monographs program. These developments were taken forward in a clarified and strengthened process for identifying, reviewing, evaluating, and integrating evidence to identify causes of human cancer. The advancements adopted include the strengthening of systematic review methodologies; greater emphasis on mechanistic evidence, based on key characteristics of carcinogens; greater consideration of quality and informativeness in the critical evaluation of epidemiological studies, including their exposure assessment methods; improved harmonization of evaluation criteria for the different evidence streams; and a single-step process of integrating evidence on cancer in humans, cancer in experimental animals, and mechanisms for reaching overall evaluations. In all, the updated Preamble underpins a stronger and more transparent method for the identification of carcinogenic hazards, the essential first step in cancer prevention.
The parasite that came in from the cold
Authors: Vidal-Moreso Anna , Gómez-Serrano Maria , Sulleiro Elena , Zarzuela Francesc , Soriano-Arandes Antoni , Espiau María
Published: August 2019

We describe the case of a Russian child with persistent mild eosinophilia in whom intestinal parasitism by Dibothriocephalus latus is finally diagnosed. This cestode is prevalent in circumpolar regions and, therefore, an uncommon finding in International Health units, where care for patients from tropical and subtropical areas is usually provided.
ERECTA receptor-kinases play a key role in the appropriate timing of seed germination under changing salinity
Authors: Nanda Amrit K , El Habti Abdeljalil , Hocart Charles H , Masle Josette
Published: August 2019

Appropriate timing of seed germination is crucial for the survival and propagation of plants, and for crop yield, especially in environments prone to salinity or drought. However, the exact mechanisms by which seeds perceive changes in soil conditions and integrate them to trigger germination remain elusive, especially once the seeds are non-dormant. In this study, we determined that the Arabidopsis ERECTA (ER), ERECTA-LIKE1 (ERL1), and ERECTA-LIKE2 (ERL2) leucine-rich-repeat receptor-like kinases regulate seed germination and its sensitivity to changes in salt and osmotic stress levels. Loss of ER alone, or in combination with ERL1 and/or ERL2, slows down the initiation of germination and its progression to completion, or arrests it altogether under saline conditions, until better conditions return. This function is maternally controlled via the tissues surrounding the embryo, with a primary role being played by the properties of the seed coat and its mucilage. These relate to both seed-coat expansion and subsequent differentiation and to salinity-dependent interactions between the mucilage, subtending seed coat layers and seed interior in the germinating seed. Salt-hypersensitive er105, er105 erl1.2, er105 erl2.1 and triple-mutant seeds also exhibit increased sensitivity to exogenous ABA during germination, and under salinity show an enhanced up-regulation of the germination repressors and inducers of dormancy ABA-insensitive-3, ABA-insensitive-5, DELLA-encoding RGL2, and Delay-Of-Germination-1. These findings reveal a novel role of the ERECTA receptor-kinases in the sensing of conditions at the seed surface and the integration of developmental, dormancy and stress signalling pathways in seeds. They also open novel avenues for the genetic improvement of plant adaptation to changing drought and salinity patterns.
Elevated CO2 alleviates the negative impact of heat stress on wheat physiology but not on grain yield
Authors: Chavan Sachin G , Duursma Remko A , Tausz Michael , Ghannoum Oula
Published: August 2019

Elevated CO2 protects wheat photosynthesis from heat stress damage via increased electron transport and facilitates recovery of photosynthesis and biomass but not the yield due to heat-induced grain abortion.
The density distribution of accreting cosmic filaments as shaped by Kelvin–Helmholtz instability
Authors: Vossberg Ann-Christine E , Cantalupo Sebastiano , Pezzulli Gabriele
Published: August 2019

Cosmic filaments play a crucial role in galaxy evolution, transporting gas from the intergalactic medium into galaxies. However, little is known about the efficiency of this process and whether the gas is accreted in a homogenous or clumpy way. Recent observations suggest the presence of broad gas density distributions in the circumgalactic medium, which could be related to the accretion of filaments. By means of two-dimensional high-resolution hydrodynamical simulations, we explore here the evolution of cold accreting filaments flowing through the hot circumgalactic medium (CGM) of high-z galaxies. We focus on the purely adiabatic case, not including cooling, gravity, or magnetic fields. In particular, we examine the non-linear effects of Kelvin–Helmholtz instability on the development of broad gas density distributions and on the formation of cold, dense clumps. We explore a large parameter space in the filament and perturbation properties, such as filament Mach number, initial perturbation wavelength, and thickness of the interface between the filament and the halo. We find that the time-averaged density distribution of the cold gas is qualitatively consistent with a skewed lognormal probability distribution function plus an additional component in the form of a high-density tail for high Mach numbers. Our results suggest a tight correlation between the accreting velocity and the maximum densities developing in the filament, which is consistent with the variance–Mach number relation for turbulence. Therefore, cosmological accretion could be a viable mechanism to produce turbulence and broad gas density distributions within the CGM.
5-Hydroxymethylcytosine in cord blood and associations of DNA methylation with sex in newborns
Authors: Solomon Olivia , Macisaac Julia L , Tindula Gwen , Kobor Michael S , Eskenazi Brenda , Holland Nina
Published: August 2019

DNA methylation has been widely studied for associations with exposures and health outcomes. Both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks that may function differently to impact gene expression; however, the most commonly used technology to assess methylation for population studies in blood use are the Illumina 450K and EPIC BeadChips, for which the traditional bisulfite conversion does not differentiate 5mC and 5hmC marks. We used a modified protocol originally developed by Stewart et al. to analyse oxidative bisulfite-converted and conventional bisulfite-converted DNA for the same subject in parallel by the EPIC chip, allowing us to isolate the two measures. We measured 5mC and 5hmC in cord blood of 41 newborn participants of the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort and investigated differential methylation of 5mC + 5hmC, isolated 5mC and isolated 5hmC with sex at birth as an example of a biological variable previously associated with DNA methylation. Results showed low levels of 5hmC throughout the epigenome in the cord blood samples in comparison to 5mC. The concordance of autosomal hits between 5mC + 5hmC and exclusive 5mC analyses were low (25%); however, overlap was larger with increased effect size difference. There were 43 autosomal cytosine nucleotide followed by a guanine nucleotide (CpG) sites where 5hmC was associated with sex, 21 of which were unique to 5hmC after adjustment for cell composition. 5hmC only accounts for a small portion of overall methylation in cord blood; however, it has the potential to impact interpretation of combined 5hmC + 5mC studies in cord blood, especially given that effect sizes of differential methylation analyses are often small. Several significant CpG sites were unique to 5hmC, suggesting some functions distinct from 5mC. More studies of genome-wide 5hmC in children are warranted.
Machine learning-based chemical binding similarity using evolutionary relationships of target genes
Authors: Park Keunwan , Ko Young-Joon , Durai Prasannavenkatesh , Pan Cheol-Ho
Published: August 2019

Chemical similarity searching is a basic research tool that can be used to find small molecules which are similar in shape to known active molecules. Despite its popularity, the retrieval of local molecular features that are critical to functional activity related to target binding often fails. To overcome this limitation, we developed a novel machine learning-based chemical binding similarity score by using various evolutionary relationships of binding targets. The chemical similarity was defined by the probability of chemical compounds binding to identical targets. Comprehensive and heterogeneous multiple target-binding chemical data were integrated into a paired data format and processed using multiple classification similarity-learning models with various levels of target evolutionary information. Encoding evolutionary information to chemical compounds through their binding targets substantially expanded available chemical-target interaction data and significantly improved model performance. The output probability of our integrated model, referred to as ensemble evolutionary chemical binding similarity (ensECBS), was effective for finding hidden chemical relationships. The developed method can serve as a novel chemical similarity tool that uses evolutionarily conserved target binding information.
Fail-safe genetic codes designed to intrinsically contain engineered organisms
Authors: Calles Jonathan , Justice Isaac , Brinkley Detravious , Garcia Alexa , Endy Drew
Published: August 2019

One challenge in engineering organisms is taking responsibility for their behavior over many generations. Spontaneous mutations arising before or during use can impact heterologous genetic functions, disrupt system integration, or change organism phenotype. Here, we propose restructuring the genetic code itself such that point mutations in protein-coding sequences are selected against. Synthetic genetic systems so-encoded should fail more safely in response to most spontaneous mutations. We designed fail-safe codes and simulated their expected effects on the evolution of so-encoded proteins. We predict fail-safe codes supporting expression of 20 or 15 amino acids could slow protein evolution to ∼30% or 0% the rate of standard-encoded proteins, respectively. We also designed quadruplet-codon codes that should ensure all single point mutations in protein-coding sequences are selected against while maintaining expression of 20 or more amino acids. We demonstrate experimentally that a reduced set of 21 tRNAs is capable of expressing a protein encoded by only 20 sense codons, whereas a standard 64-codon encoding is not expressed. Our work suggests that biological systems using rationally depleted but otherwise natural translation systems should evolve more slowly and that such hypoevolvable organisms may be less likely to invade new niches or outcompete native populations.
LYAR potentiates rRNA synthesis by recruiting BRD2/4 and the MYST-type acetyltransferase KAT7 to rDNA
Authors: Izumikawa Keiichi , Ishikawa Hideaki , Yoshikawa Harunori , Fujiyama Sally , Watanabe Akira , Aburatani Hiroyuki , Tachikawa Hiroyuki , Hayano Toshiya , Miura Yutaka , Isobe Toshiaki , Simpson Richard J , Li Li , Min Jinrong , Takahashi Nobuhiro
Published: August 2019

Activation of ribosomal RNA (rRNA) synthesis is pivotal during cell growth and proliferation, but its aberrant upregulation may promote tumorigenesis. Here, we demonstrate that the candidate oncoprotein, LYAR, enhances ribosomal DNA (rDNA) transcription. Our data reveal that LYAR binds the histone-associated protein BRD2 without involvement of acetyl-lysine–binding bromodomains and recruits BRD2 to the rDNA promoter and transcribed regions via association with upstream binding factor. We show that BRD2 is required for the recruitment of the MYST-type acetyltransferase KAT7 to rDNA loci, resulting in enhanced local acetylation of histone H4. In addition, LYAR binds a complex of BRD4 and KAT7, which is then recruited to rDNA independently of the BRD2-KAT7 complex to accelerate the local acetylation of both H4 and H3. BRD2 also helps recruit BRD4 to rDNA. By contrast, LYAR has no effect on rDNA methylation or the binding of RNA polymerase I subunits to rDNA. These data suggest that LYAR promotes the association of the BRD2-KAT7 and BRD4-KAT7 complexes with transcription-competent rDNA loci but not to transcriptionally silent rDNA loci, thereby increasing rRNA synthesis by altering the local acetylation status of histone H3 and H4.
Robust gene expression control in human cells with a novel universal TetR aptamer splicing module
Authors: Mol Adam A , Groher Florian , Schreiber Britta , Rühmkorff Ciaran , Suess Beatrix
Published: August 2019

Fine-tuning of gene expression is desirable for a wide range of applications in synthetic biology. In this context, RNA regulatory devices provide a powerful and highly functional tool. We developed a versatile, robust and reversible device to control gene expression by splicing regulation in human cells using an aptamer that is recognized by the Tet repressor TetR. Upon insertion in proximity to the 5′ splice site, intron retention can be controlled via the binding of TetR to the aptamer. Although we were able to demonstrate regulation for different introns, the genomic context had a major impact on regulation. In consequence, we advanced the aptamer to develop a splice device. Our novel device contains the aptamer integrated into a context of exonic and intronic sequences that create and maintain an environment allowing a reliable and robust splicing event. The exon-born, additional amino acids will then be cleaved off by a self-cleaving peptide. This design allows portability of the splicing device, which we confirmed by demonstrating its functionality in different gene contexts. Intriguingly, our splicing device shows a high dynamic range and low basal activity, i.e. desirable features that often prove a major challenge when implementing synthetic biology in mammalian cell lines.
High-resolution mapping of brain vasculature and its impairment in the hippocampus of Alzheimer's disease mice
Authors: Zhang Xiaochuan , Yin Xianzhen , Zhang Jingjing , Li Anan , Gong Hui , Luo Qingming , Zhang Haiyan , Gao Zhaobing , Jiang Hualiang
Published: August 2019

Accumulating evidence indicates the critical importance of cerebrovascular dysfunction in the pathogenesis of Alzheimer's disease (AD). However, systematic comparative studies on the precise brain vasculature of wild-type and AD model mice are still rare. Using an image-optimization method for analysing Micro-Optical Sectioning Tomography (MOST) data, we generated cross-scale whole-brain 3D atlases that cover the entire vascular system from large vessels down to smallest capillaries at submicron resolution, for both wild-type mice and a transgenic (APP/PS1) mouse model of AD. In addition to distinct vascular patterns in different brain regions, we found that the main vessels of the molecular layer of the hippocampal dentate gyrus (DG-ml) undergo abrupt changes in both diameter and branch angle, spreading a unique comb-like pattern of capillaries. By using a quantitative analysis workflow, we identified in the hippocampus of AD mice an overall reduction of the mean vascular diameter, volume fraction and branch angle, with most significant impairment in the DG-ml. In addition, virtual endoscopy revealed irregular morphological features in the vessel lumen of the AD mice, potentially contributing to the impairment of blood flow. Our results demonstrate the capability of high-resolution cross-scale evaluation of brain vasculature and underscore the importance of studying hippocampal microcirculation for understanding AD pathogenesis.
Impact of Acute HIV Infection and Early Antiretroviral Therapy on the Human Gut Microbiome
Authors: Sortino Ornella , Phanuphak Nittaya , Schuetz Alexandra , Ortiz Alexandra M , Chomchey Nitiya , Belkaid Yasmine , Davis Jacquice , Mystakelis Harry A , Quiñones Mariam , Deleage Claire , Ingram Brian , Rerknimitr Rungsun , Pinyakorn Suteeraporn , Rupert Adam , Robb Merlin L , Ananworanich Jintanat , Brenchley Jason , Sereti Irini ,   RV254/SEARCH010 Study Group, Teeratakulpisarn Nipat , Pattanachaiwit Supanit , de Souza Mark , Fletcher James , Kroon Eugene , Tantivitayakul Ponpen , Suttichom Duanghathai , Rattanamanee Somprartthana , Poltavee Kultida , Intasan Jintana , Luekasemsuk Tassanee , Savadsuk Hathairat , Tipsuk Somporn , Puttamsawin Suwanna , Benjapornpong Khunthalee , Ratnaratorn Nisakorn , Eamyoung Patcharin , Ubolyam Sasiwimol , O’Connell Robert , Akapirat Siriwat , Nuntapinit Bessara , Tantibul Nantana , Churikanont Nampueng , Getchalarat Saowanit , Vasan Sandhya , Trichavaroj Rapee , Sajiaweerawan Chayada , Phuang-Ngern Yuwadee , Jongrakthaitae Surat , Sukhumvittaya Suchada , Saetun Putida , Chuenarom Weerawan , Michael Nelson , Turk Ellen , McCullough Corinne , Butterworth Oratai , Milazzo Mark
Published: August 2019

Background

Intestinal microbial dysbiosis is evident in chronic HIV-infected individuals and may underlie inflammation that persists even during antiretroviral therapy (ART). It remains unclear, however, how early after HIV infection gut dysbiosis emerges and how it is affected by early ART.

Methods

Fecal microbiota were studied by 16s rDNA sequencing in 52 Thai men who have sex with men (MSM), at diagnosis of acute HIV infection (AHI), Fiebig Stages 1–5 (F1-5), and after 6 months of ART initiation, and in 7 Thai MSM HIV-uninfected controls. Dysbiotic bacterial taxa were associated with relevant inflammatory markers.

Results

Fecal microbiota profiling of AHI pre-ART vs HIV-uninfected controls showed a mild dysbiosis. Transition from F1-3 of acute infection was characterized by enrichment in pro-inflammatory bacteria. Lower proportions of Bacteroidetes and higher frequencies of Proteobacteria and Fusobacteria members were observed post-ART compared with pre-ART. Fusobacteria members were positively correlated with levels of soluble CD14 in AHI post-ART.

Conclusions

Evidence of gut dysbiosis was observed during early acute HIV infection and was partially restored upon early ART initiation. The association of dysbiotic bacterial taxa with inflammatory markers suggests that a potential relationship between altered gut microbiota and systemic inflammation may also be established during AHI.
The Sublimity of Document
Authors: MacDonald Scott
Published: August 2019

The Sublimity of Document: Cinema as Diorama (Avant-Doc 2) is an international collection of in-depth, substantive interviews with moving-image artists working “avant-doc,” that is, making films that explore the territory between documentary and experimental cinema. The Sublimity of Document follows on MacDonald’s earlier Avant-Doc: Intersections of Documentary and Avant-Garde Cinema (Oxford, 2015), though the focus here is on filmmakers who are committed to document itself, willing to go anywhere on the planet (or within film archives or on the internet) to document what they believe we need to see—regardless of whatever political implications the film experiences they create may have for us. The book uses the early history of the museum habitat diorama of animal life, specifically the Akeley Hall of African Mammals at the American Museum of Natural History, as a way of rethinking both early and modern cinema of document—and especially those recent filmmakers and films devoted to providing a panorama of places and events that viewers might never have opportunities to experience in person. The twenty-seven interviews in The Sublimity of Document are organized panoramically within the volume.
Introduction
Authors: MacDonald Scott
Published: August 2019

The introduction creates a context for a wide range of avant-doc films (that is, films that work in the zone between conventional documentary and what has usually been called “avant-garde” filmmaking), locating these films within the tradition established a century ago by the development of the habitat diorama of animal life, specifically the Akeley Hall of African Mammals at the American Museum of Natural History in New York City. The habitat diorama provides precise documentation of the specifics of animal life that is, insofar as possible, devoid of political argument. The aim of the habitat diorama, and of the films discussed throughout the book, is to be as purely educational as cinema can be: the creator of the habitat dioramas and the film documents discussed provide precise visions of what the makers believe we need to see, in order to understand more of the world around us.
Nikolaus Geyrhalter
Authors: MacDonald Scott
Published: August 2019

This is the first career interview with Austrian documentary filmmaker Nikolaus Geyrhalter, whose films, like those of Fred Wiseman, often focus on cultural institutions, though with a radically different sensibility. Geyrhalter’s most widely known film in the United States is Our Daily Bread (2005), his astonishing documentation of mass food production within the European community. Geyrhalter’s films are visually rigorous and formal—he was a photographer before he turned to filmmaking and is his own cinematographer. His films have explored cultural realities far and wide, from the aftermath of the Balkan wars of the 1990s to the plight of workers laid off from an Austrian factory during the years after the factory closed. His most elaborate film is Elsewhere (2000), a global survey of the edges of modern life and cultural transformation at the moment of the new millennium. The recent Homo Sapiens is a panorama of ruined places and landscapes across the planet at the dawn of the Anthropocene.
Brett Story
Authors: MacDonald Scott
Published: August 2019

This interview surveys the career of Canadian filmmaker Brett Story, from her early attempts to evoke dimensions of modern urban life to her feature The Prison in Twelve Landscapes (2016), a panorama of the ways in which the American prison system is visible and audible outside prison walls and away from the remote prison locations across the country, where criminals are housed. Story finds evidence of the prison system hidden in plain sight in New York City’s Washington Square, at an airport built on the flat top of what was once a coal mine in Eastern Kentucky, at Quicken Loans headquarters in downtown Detroit, where a forest fire is being fought in Marin County, California, at a grocery storeroom in the Bronx, at a kids pocket park in LA, in a quiet town outside of St. Louis, in a radio station in Kentucky, and on buses traveling through the night toward rural New York State towns.