bluuebunny/crossref_metadata_2025 huggingface dataset:
Conductor Sharing Drilling Technique
Authors: Alabbasy Emad Alabbasy , Ahmed Ahmed Khamis , Khaled Khalid Alwahedi , Abdulmohsen Abdulmohsen Al Marzooqi , Majid Majid Hammadi
Published: May 2021

With the objective to drill two wells shared from one conductor with independent wellhead and completion, ADNOC Offshore drilling team pioneered for the first time in Umm Lulu field and ADNOC UAE the Conductor sharing drilling technique. Which is to drill two wells from one single conductor in wellhead tower. Well planning technique drilling 42" hole and run 36" conductor, then install lower male connector and run conductor Down Hole Guide (DHG) assembly to be a guide for both two wells. Land the DHG on the lower male connector. Install upper male connector, which is equipped with two well slots for drilling the two wells. Drilling 1st 16" hole and run 13 3/8" casing and cemented. Skid over second slot and drill second hole 16" and run and cement 13 3/8" casing and carry out top up cement job for both hole up to surface inside 36" conductor. Install casing head housing for each well. Then each well could be drilled as per normal procedures.

Well executing process.

Well challenges:

Drilling large hole 42" hole with 42" bit and BHA.

Run 36" conductor and conductor sharing DHG and keep aligned for accessibility of BHA and casing Nudge 16" hole for both two wells at centre-to-centre distance 8" safely without collision issue.

Run two 13 3/8" casing strings in 36" conductor and cement same up to surface.

Complete drilling well UL-056 from slot A, drilled 12 ¼" hole section to TH-I ABS, run 9 5/8" casing and perform cement job to surface, drilled 6" hole (linerless design) and land in TH II then continued drilling horizontal drain to TD, Run completion and deliver the well. Suspend the other well in slot B at 13 3/8" casing with securing the well with abandonment cap and as per ADNOC offshore policy.
Evaluation of Cement-Casing & Cement-Rock Bond Integrity During Well Operations
Authors: Lamik Abdelfattah , Pittino Gerhard , Prohaska-Marchried Michael , Krishna Ravi , Thonhauser Gerhard , Antretter Thomas
Published: May 2021

This paper presents the results of laboratory static and dynamic tests on casing-cement-rock systems exposed to axial loads under ambient conditions. A new testing method has been developed.

The casing-cement-rock system mostly fails due to tension and shear stresses. In various applications such as HPHT, deep-water, (steam) injection or geothermal wells, the cement-casing bond is exposed to cyclic thermomechanical loads resulting in casing elongation, contraction, expansion and subsequently in cyclic radial and axial stresses at the cement-casing-rock system. Cement is a brittle material which can fail when subjected to repeated application of stresses lesser in magnitude than the statically determined strength. A novel atmospheric test cell has been designed and constructed. In order to achieve the fatigue limits of the cement-casing bond, a set of testing procedures has been established. Several tests are conducted to evaluate de-bonding. The focus on de-bonding is achieved by allowing the casing to move through the test while preventing any cement movement. Thus, when a force is applied in the axial z-direction - either the casing is pulled out (tension) or pushed down (compression) - the casing has enough space to move in both directions. The advantage of this testing method is that different stress ratios can be applied during the test.
Comparative Study of Managed Pressure Drilling Application in Deepwater Gas Wells - Case Study from Offshore Eastern Mediterranean of Egypt
Authors: El-Husseiny Mahmoud Ahmed , Khaled Samir Mohamed , El-Fakharany Taher El-Sebaay , Al-Nadi Yehia Mohamed
Published: May 2021

Although devised in 2003, managed pressure drilling (MPD) has gained widespread popularity in recent years to precisely control the annular pressure profile throughout the wellbore. Due to the relatively high cost and complexity of implementing MPD, some operators still face a challenge deciding whether or not to MPD the well.

In the offshore Mediterranean of Egypt, severe to catastrophic mud losses are encountered while conventionally drilling deepwater wells through cavernous fractured carbonate gas reservoirs with a narrow pore pressure-fracture gradient (PP-FG) window, leading to the risk of not reaching the planned target depth (TD). Furthermore, treating such losses was associated with long non-productive time (NPT), massive volume consumption of cement, and lost-circulation materials (LCM), in addition to well control situations encountered several times due to loss of hydrostatic head during severe losses. Accordingly, the operator decided to abandon the conventional drilling method and implement MPD technology to drill these problematic formations.

In this paper, the application of MPD is to be examined versus the conventional drilling in terms of well control events, NPT, rate of penetration (ROP), mud losses per drilled meter, LCM volume pumped, and drilling operations optimization.

According to the comparative study, MPD application showed a drastic improvement in all drilling performance aspects over the conventional drilling where the mud losses per drilled meter reduced from 19.6 m3/m to 3.7m3/m (123.2 bbl/m to 23.4 bbl/m). In addition to that, a 35% reduction of NPT and also a 35% reduction of LCM pumped, and 67.2 % reduction by volume of cement pumped to cure the mud losses. Moreover, the average mechanical rate of penetration increased by 37.4%. MPD was also credited with eliminating the need for an additional contingent 7" liner which was conventionally used to isolate the thief zone. The MPD ability to precisely control bottom hole pressure during drilling with the integration of MPD early kick detection system enables the rapid response in case of mud loss or kick, eliminating kick-loss cycles, well control events, and drilling flat time to change mud density.

This paper provides an advanced and in-depth study for deep-water drilling problems of a natural gas field in the East Mediterranean and presents a comprehensive analysis of the MPD application with a drilling performance assessment (average ROP, mud losses, LCM and cement volumes, well control events) emphasizing how MPD can offer a practical solution for future drilling of challenging deepwater gas wells.
Integrating the Fully Coupled Geomechanical with Thermodynamics Modeling for the Well Control in High Pressure and Temperature Condition
Authors: Wang Xindong , Ke Xue , Zhang Shuxia , Zhang Cheng , Li Hui , Li Pengfei , Li Zhenchuan , Huang Xingning
Published: May 2021

Drilling operations is risky due to narrow mud weight windows in deep wells. Different type of drilling events and wellbore instability have encountered frequently including inflow, drilling induced tensile fractures (DITF), losses and connection gas etc. As such to mitigate the problems, a robust pore pressure prediction is necessary with requires an understanding of the origins and distribution of overpressures in the area. The technical research process is divided into three steps: pre-drill pore pressure predication (PPP) modelling, real-time monitoring and post-drill validation. Efforts were made to understand the geological settings and temperature model. A pore pressure predication (PPP) model was built by integrating fully coupled geomechanical with thermodynamics modeling. Real-time monitoring information provides references and guidelines for PPP model optimization. During the post-drill stage, the updated PPP model was used to design a mud weight and casing program for the upcoming wells. The study area is located northwestern China, the deep formations that more than 7000 meters are ultra-high temperature (200-220 deg C). Thermal-related secondary pore pressure generating mechanism may become active leading to higher overpressure and difficulties in prediction. For the case study, an empirical relationship of overpressure impact factors versus temperature of sandstone and mudstone was proposed. An accurate PPP model is generated using available well-scale geomechanical model and overpressure impact factors. With an integrating fully coupled PPP model as foundation, the integrated approach helps to reduce serious wellbore instability caused by abnormal formation pressure, wellbore collapse and other complex drilling problems deep wells. A1 well was safely drilled guided by the study result and has no significant wellbore instability issues and has minimum reservoir damage due to optimal mud weight program. These findings will provide reference for overpressure mechanics study of deep wells. The multidisciplinary study results have created value by improving drilling performance and well delivery efficiency. It can also help operator reduce drilling costs and make development plan decisions.
Combining Machine Learning and Classic Drilling Theories to Improve Rate of Penetration Prediction
Authors: Zhang Hongbao , Lu Baoping , Liao Lulu , Bao Hongzhi , Wang Zhifa , Hou Xutian , Mulunjkar Amol , Jin Xin
Published: May 2021

Theoretically, rate of penetration (ROP) model is the basic to drilling parameters design, ROP improvement tools selection and drill time & cost estimation. Currently, ROP modelling is mainly conducted by two approaches: equation-based approach and machine learning approach, and machine learning performs better because of the capacity in high-dimensional and non-linear process modelling. However, in deep or deviated wells, the ROP prediction accuracy of machine learning is always unsatisfied mainly because the energy loss along the wellbore and drill string is non-negligible and it's difficult to consider the effect of wellbore geometry in machine learning models by pure data-driven methods. Therefore, it's necessary to develop robust ROP modelling method for different scenarios.

In the paper, the performance of several equation-based methods and machine learning methods are evaluated by data from 82 wells, the technical features and applicable scopes of different methods are analysed. A new machine learning based ROP modelling method suitable for different well path types was proposed. Integrated data processing pipeline was designed to dealing with data noises, data missing, and discrete variables. ROP effecting factors were analysed, including mechanical parameters, hydraulic parameters, bit characteristics, rock properties, wellbore geometry, etc. Several new features were created by classic drilling theories, such as downhole weight on bit (DWOB), hydraulic impact force, formation heterogeneity index, etc. to improve the efficiency of learning from data. A random forest model was trained by cross validation and hyperparameters optimization methods.

Field test results shows that the model could predict the ROP in different hole sections (vertical, deviated and horizontal) and different drilling modes (sliding and rotating drilling) and the average accuracy meets the requirement of well planning.

A novel data processing and feature engineering workflow was designed according the characteristics of ROP modelling in different well path types. An integrated data-driven ROP modelling and optimization software was developed, including functions of mechanical specific energy analysis, bit wear analysis and predict, 2D & 3D ROP sensitivity analysis, offset wells benchmark, ROP prediction, drilling parameters constraints analysis, cost per meter prediction, etc. and providing quantitative evidences for drilling parameters optimization, drilling tools selection and well time estimation.
Connexin 26 (GJB2) Gene Mutations Linked With Autosomal Recessive Nonsyndromic Sensorineural Hearing Loss in Iraqi Population.
Authors: Al-janabi Anwar Madlool , Ahmmed Habeeb Shuhaib , Alkhafaji Salih Mahdi
Published: May 2021

Objectives: The ARNSHL wasn’t been studied enough in Iraq, this study aimed to detect the prevalence of the three most common mutations of Connexin 26 gene in Iraqi population. This study was conducted in order to detect c.35delG, c.235delC and c.167delT mutations in GJB2 gene, we were employed PCR-RFLP assays.Results: The current case-control study was conducted from January 2018 to January 2020, The study was included 95 deaf patients (55 males and 40 females) their age range between 11-40 years and 21.5 ± 6.3 year (mean ± SD) and 110 healthy control group, their ages range between 10-40 years and 20.1 ± 5.9 year (mean ± SD), these two groups were matched in age and gender. From 95 deaf patients with ARNSHL who were participated in this study, c.35delG was the main frequent mutation encountered with GJB2 gene, The second frequent mutation was c.235delC, None of 95 deaf patients were showed the c.167delT mutation, these variants were not detected in healthy control group which was studied parallel with patients group. Our data conclude that GJB2 c.35delG and c.235delC gene mutations were the main cause of ARNSHL in Iraqi deaf population.
Geophysical Imaging of Yellowstone’s Hydrothermal Plumbing System
Authors: Finn Carol , Bedrosian Paul A. , Holbrook W. , Auken Esben , Bloss Benjamin , Crosbie Jade
Published: May 2021

The authors have requested that this preprint be removed from Research Square.
Chronic Foot Pain and Foot Solutions in Adults from Different Professions: the I-Corps-National Science Foundation Foot Health Survey.
Authors: Mbue Ngozi , Wang Wanyi , Rosario Martin
Published: May 2021

Background

Chronic foot pain (CFP) is a major contributor to sick leave and early retirement among individuals in all professions, especially those whose jobs require prolonged standing, lifting and walking. Current treatment modalities are inadequate in managing CFP. Hence, there is a significant need for new treatment options to manage chronic foot pain. The objectives of this study are i) explore the current state of chronic foot pain; ii) investigate current solutions and treatment options; and iii) explore opportunities for future inventions to address chronic foot pain.
Methods

Between April 2019 and September 2020, our team embarked on an I-Corps-National Science Foundation (NSF) programs in the United States to obtain information from stakeholders. Individualized, open-ended, mostly face-to-face interviews from nurses, athletes, construction and restaurant workers, among others were conducted.
Results

Preliminary data (N = 119) showed that current solutions and treatments for CFP were insufficient in managing moderate to acute pain (mostly pain scale 5 on a scale of 0–10). Those with ≥ 5 pain, changed shoes (63.3%), used shoe inserts, nursing clogs and painkillers (53.3%), and compression stockings (40%), with none reporting effectiveness. Fisher's exact tests were used to examine the relationships between regions (foot, heel and leg) and pain solutions. Regions (foot and heel) and shoe change were significantly related (p = 0.006) with participants using 5–7 pairs of shoes interchangeably, spending approximately $500-$700/year on new shoes. Female nurses 30–40 years experienced the highest foot pain than those younger. No significant differences in nursing and other professions with regards to CFP and solutions.
Conclusions

The majority expressed interest in trying new products to relieve their chronic foot and heel pain. Risk factors for foot pain included prolonged standing, walking, and lifting heavy objects. Current solutions are inadequate for managing moderate to acute foot pain in those who stand for prolonged periods of time on their feet. Innovations are urgently needed to address CFP.
Cerebellar White Matter Abnormalities in Patients with Charcot-Marie-Tooth disease
Authors: Kim Hyeon-Jin , Park Chang-Hyun , Kim Regina Eun-Young , Hwang Sungeun , Choi Yun Seo , Kim Sol-Ah , Yoo Jeong Hyun , Chung Ki Wha , Choi Byung-Ok , Lee Hyang Woon
Published: May 2021

Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous hereditary peripheral neuropathy. Brain volumetry and diffusion tensor imaging (DTI) were performed in CMT patients with PMP22 duplication, MFN2, GJB1, or NEFL mutations to investigate for structural changes of the cerebellum.Volume in cerebellar white matter (WM) was significantly reduced in CMT patients with NEFL mutations. Abnormal DTI findings ​​were observed in the superior, middle, and inferior cerebellar peduncles predominantly in NEFL mutations, and partly in GJB1 mutations. Cerebellar ataxia was more prevalent in the NEFL mutation (72.7%) than GJB1 mutation (9.1%), but not observed in other genotypic subtypes, which indicates that structural cerebellar abnormalities were associated with the presence of cerebellar ataxia. However, NEFL and GJB1 mutations did not affect cerebellar gray matter (GM), and neither cerebellar GM nor WM abnormalities were observed in PMP22 duplication or MFN2 mutations. We found structural evidence of cerebellar WM abnormalities in CMT patients with NEFL and GJB1 mutations and the association between cerebellar WM involvement and cerebellar ataxia in these genetic subtypes, especially in the NEFL subgroup. Therefore, we suggest that neuroimaging such as MRI volumetry or DTI in CMT patients could play an important role in detecting abnormalities of the cerebellar WM.
Time scales for pluton growth, magma chamber formation and super-eruptions
Authors: Sparks Stephen , Zalinge Marit van , Mark Darren , Tremblay Marissa , Keller Brenhin , Cooper Francis , Rust Alison
Published: May 2021

Generation of silicic magmas leads to emplacement of granite plutons, huge explosive volcanic eruptions and physical and chemical zoning of continental and arc crust1-7. While the time scales for silicic magma generation in the deep and middle crust are prolonged8 magma transfer into the upper crust followed by eruption is episodic and can be rapid9-12. Ages of inherited zircons and sanidines from four Miocene ignimbrites in the Central Andes indicate a gap of 4.6 Myr between the start of pluton emplacement and onset of super-eruptions, with a 1 Myr cyclicity. Here we show that inherited sanidine crystals were stored at temperatures <470oC prior to incorporation in the magma. Our observations are explained by silicic melt segregation in a middle crustal hot zone with episodic melt ascent from an unstable layer at the top of the zone with a time scale governed by the rheology of the upper crust. After thermal incubation of the growing batholith, large magma chambers formed in only a few thousand years or less by dyke transport from the hot zone melt layer. Instability and disruption of earlier plutonic rock occurred in a few decades or less just prior to or during super-eruptions.
Investigation of Long Term Hazards of Chemical Weapon Agents in the Environment of Sardasht Area, Iran
Authors: Vaezihir Abdorreza , Pirkhezranian Asra , Sehati Negar , Hosseinzadeh Mohammad Reza , Salehi-Lisar Seyed Yahya , Sanderson Hans
Published: May 2021

The present study aimed to was to investigate the persistence and existence of chemical warfare agents (CWAs) and related dissipation products in the environment. The study area is Sardasht district located in the western borderline of Iran and Iraq in which was subjected to attack with chemical weapons in July 1987 during the Iran-Iraq war. Three types of environmental samples including water, soil and native local plant materials were collected and analyzed. Gas chromatography-mass spectrometry in the electron impact ionization mode has been developed for the separation, screening, identification and qualification of chemicals after the sample preparation methods. In order to validate the applied extraction procedures, ethylene glycol was spiked to some of the samples including groundwater, surface soil, grape and alfalfa plants. All the recoveries were in the range of 83.6–107.4% with the relative standard deviations varying from 4.9–12.4% (n = 3) successfully. The initial results revealed that no trace of related compounds or CWAs was detected in the soil and water samples. However, trace amounts of some degradation products of blistering agents like Mustard gas (HD) and Lewisite were found in a tree wood from a house subjected to chemical attack as well as in barley samples (a mixture of leaves and root) collected from an agricultural field in the area indicating chronic low exposure to the environment and people.
Organogenesis and Sonication-Assisted Agrobacterium-Mediated Transformation of Poplar Roots
Authors: Giovanella Thais Salete , Degenhardt Juliana , Zanella Laudiane Bruna , Filho João Carlos Bespalhok
Published: May 2021

Functional genomics along with genetic transformation and plant regeneration are used to identify genes of interest, comprising essential tools to obtain plants with desired characteristics. In this study, we described an organogenesis and a genetic transformation protocol for Populus tremula x Populus alba clone 717-1B4 using roots. In the organogenesis experiments the PGRs zeatin, BA and kinetin at different concentrations were evaluated. The effect of explant age was evaluated and at 30 days “old” roots (6 months old) showed a higher regeneration rate when compared to “young” roots (2 months old). In the genetic transformation experiments kanamycin concentration, the use of sonication (SAAT), co-cultivation period and explant age were evaluated. Sonication positively affected transformation, while co-cultivation time did not interfere. Regarding explant age, no statistical differences were observed. Quantitative real-time PCR (qPCR) data showed that among the six transgenic plants evaluated, two presented two copies and the others only one copy of the gene. In this study, efficient protocols of organogenesis and genetic transformation for poplar roots are presented with a transformation efficiency of 58%.
Effects of Haze Pollution on Pesticide use by Rice Farmers: Fresh Evidence from Rural Area of China
Authors: Guo Lili , Cao Andi , Huang Minjun , Li Houjian
Published: May 2021

Recently, serious haze pollution has not only threatened the human health and food security, but also seems to have aggravated the unscientific use of pesticides by rice farmers in rural area of China. Using original data on haze pollution across China, combined with rural household survey data collected from 2014 to 2018, we conducted a detailed empirical study on the effects of haze pollution on pesticide use by rice farmers based on the theory of risk aversion. The empirical results revealed that haze pollution with higher levels of PM2.5 positively impacted the use of chemical pesticides in the rice cultivation. More precisely, with 1% increases in PM2.5 concentration, the amount of pesticide application per mu increased by 7.9%, and the average pesticide fee per mu increased by 2.3%, respectively. The results were robust to a series of tests that addressed potential endogeneity concerns, including omitted variable bias, measurement error and reverse causality. We then examined the heterogeneous effects of haze pollution increase on the use of chemical pesticides and found that the effects of haze pollution on the use of chemical pesticides to be weaker for rice farmer with more rice-planting experience, those with smaller cultivated area of rice, however, the effects on the amount of chemical pesticide application per mu to be weaker for those with rice insurance, but the effects on the average chemical pesticide fee per mu to be stronger for those with rice insurance. Our findings provide important policy implications for pesticide risk management in rural areas of developing countries.
Oyster As, Cd, Cu, Hg, Pb and Zn Levels in the Northern South China Sea: Long-term Spatiotemporal Distributions, Interacting Effects, and Risk Assessment to Human Health
Authors: Wang Lifei , Wang Xuefeng , Chen Haigang , Wang Zenghuan , Jia Xiaoping
Published: May 2021

Estuarine and coastal ecosystems are often considered vulnerable due to the complex biogeochemical processes and the human disturbances through a variety of pollution. Among environmental contaminants, heavy metals in estuarine and coastal ecosystems have been of increasing concern in environmental conservation. Long-term exposure to heavy metal contamination, mainly through food and water, could be harmful to human health. It is therefore critical to understand the quantitative comparisons and interacting effects of different heavy metals in common seafood species, such as oysters. This work studied the long-term spatiotemporal trends and health risk assessment of oyster arsenic (As), cadmium (Cd), copper (Cu), mercury (Hg), lead (Pb) and zinc (Zn) levels in the coastal waters of northern South China Sea. Cultured oysters (Crassostrea rivularis) from 23 estuaries and harbors in the coastal areas of northern South China Sea in 1989–2015 were analyzed for the spatiotemporal trends of the six heavy metal levels. Metal pollution index (MPI), target hazard quotient (THQ) and hazard index (HI) were used for quantifying the exposure of the six heavy metals to human health through oyster consumption. Principal component analysis (PCA) was used for assessing the relative importance of the six metals in oyster heavy metal distribution patterns in the northern South China Sea. Overall, the As, Cd, Cu, Hg, Pb and Zn levels in oysters from the northern South China Sea generally declined from 1989 to 2015, stayed relatively high (MPI = 2.42–3.68) during 1989–2000, gradually decreased since 2000, and slightly increased after 2010. Oyster heavy metal levels were highest in the Pearl River Estuary (MPI = 1.20–5.52), followed by west Guangdong and east Guangdong, Guangxi, and Hainan coastal waters. This pattern is probably because economics and industry around the Pearl River Estuary have been growing faster than the other areas of this work in the recent two decades, and it should be taken as a hotspot for the monitoring of seafood safety in southern China. Principal component analysis indicated that Cu, Zn and Cd were the most important metals in the long-term distributions of oyster heavy metal levels in the northern South China Sea. Health risk assessment suggested that the risk of the six heavy metals exposure through oyster consumption were relatively high during 1989–2005 (THQ = 1.01–5.82), significantly decreased since 2005 (THQ < 1), and slightly increased after 2010.
The synergistic coordination of DNA 5-hydroxylmethylcytosine and RNA 5-methycytosine regulates human foetal development
Authors: Han Xiao , Guo Jia , Wang Mengke , Zhang Nan , Ren Jie , Yang Ying , Chi Xu , Chen Yusheng , Yao Huan , Zhao Yongliang , Yang Yun-Gui , Sun Yingpu , Xu Jiawei
Published: May 2021

After implantation, complex and highly specialized molecular events render functionally distinct organ formation, whereas how the epigenome shapes organ-specific development remains to be fully elucidated. Here, Nano-hmC-Seal and RNA bisulfite sequencing (RNA-BisSeq) were performed and the first multilayer landscapes of both DNA 5hmC and RNA m5C epigenome, as well as the accompanying transcriptome were obtained, in the heart, kidney, liver and lung of the human foetuses at 13 − 28 weeks with 123 samples in total. DNA 5hmC plays a consistently leading role, while RNA m5C acts as a dynamic downstream regulatory valve in regulating gene expression with a turning point of 18–19 weeks. Although, these modifications appear to coordinate in general, they also play different roles with regard to specific functions. Our integrated studies illustrate the epigenetic maps during different stages of human foetal organogenesis, which provide a foundation for understanding the in-depth epigenetic mechanisms for early development and birth defects.
Global Disparities of Greenhouse Gases Emission in Agriculture Sector: Panel Club Convergence Analysis
Authors: Akram Vaseem , Ali Jabir
Published: May 2021

A lot has been discussed about the greenhouse gases (GHGs) emissions in the existing studies, the study on the club convergence of GHGs emissions is limited particularly for the agriculture sector. This study tries to investigate the convergence hypothesis across 93 countries spanning 1980–2017. To examine the convergence hypothesis, we implement the novel Phillips and Sul test. Results obtained from this test show the evidence of divergence when we consider all 93 countries as a group. This implies that GHGs across the countries are following different convergence paths. To capture this, we further apply clustering algorithms and results show the existence of five clubs of convergence and one group stating the need for altered the polices at the club level to achieve a single steady-state in GHGs emission. Moreover, our findings recommend that the mitigation policies would be considered the presence of different clubs of regions with different convergence paths in terms of GHGs emissions and account for the distributional effect of transfers across countries.
Altered cfDNA Fragmentation Profile in Hypomethylated Regions as Diagnostic Marker in Breast Cancer
Authors: Wang Jun , Yang Ming , Su Mingyang , Shu Lirong , Wang Hongxian , Wu Xiaoqian , Zhong Guocheng , Tang Zhixiong , Chen Peng , Zhang Shasha , Wang Yun , Yu Li , Gou Deming
Published: May 2021

Backgroud: Breast cancer, the most common malignancy in women, has been proved to have both altered plasma cell-free DNA (cfDNA) methylation and fragmentation profiles, nevertheless, simultaneously detecting both of them for breast cancer diagnosis has never been reported. Moreover, although fragmentation pattern of cfDNA is determined by nuclease digestion of chromatin, structure of which may be affected by DNA methylation, whether cfDNA methylation and fragmentation are biologically related or not still remains unclear.Methods: Improved cfMeDIP-seq were utilized to characterize both cfDNA methylation and fragmentation profiles in 25 plasma samples from both healthy individuals and patients with breast cancer. The feasibility of using cfDNA fragmentation profile in hypo- and hyper- methylated regions as diagnostic markers for breast cancer was evaluated. Results: Mean size of cfDNA fragments ranging from 100 to 220 base pairs (bp) was found to increase from 170.06 (Input libraries) to 173.04 (IP libraries) bp in healthy individuals, which was not observed in patients with breast cancer (170.51 to 170.71 bp). Furthermore, mean size of cfDNA fragments mapped to hypomethylated regions decreased more win patients with breast cancer (4.60 bp, 172.33 bp in hypermethylated regions to 167.73 bp in hypomethylated regions) than healthy individuals (2.87 bp, 174.54 bp in hypermethylated regions to 171.67 bp in hypomethylated regions). The feasibility of using abnormality of short cfDNA fragments ratio in hypomethylated genomic regions for diagnosis of breast cancer in validation cohort was evaluated. 7 out of 11 patients were detected as having breast cancer (63.6% sensitivity), whereas no healthy individuals were mis-detected (100% specificity). Conclusion: We identified enriched short cfDNA fragments after 5mC-immunoprecipitation (IP) in patients with breast cancer, and demonstrated the enriched short cfDNA fragments might originated from hypomethylated genomic regions. Furthermore, we proved the feasibility of using differentially methylated regions (DMRs)-dependent cfDNA fragmentation profile for breast cancer diagnosis.
Cretaceous fire-resistant angiosperms
Authors: Wang Shuo , Shi Chao , Cai Hao-hong , Zhang Hong-rui , Long Xiao-xuan , Tihelka Erik , Song Wei-cai , Feng Qi , Jiang Ri-xin , Cai Chenyang , Lombard Natasha , Li Xiong , Yuan Ji , Zhu Jian-ping , Yang Hui-yu , Liu Xiao-fan , Xiang Qiao-Ping , Zhao Zun-tian , Long Chunlin , Zhang Xianchun , Peng Hua , Li De-Zhu , Schneider Harald , Engel Michael , Wang Yongdong , Spicer Robert
Published: May 2021

Background: Flowering plants (angiosperms) dominate most global ecosystems today, but their rapid Cretaceous diversification has remained poorly understood ever since Darwin referred to it as an ‘abominable mystery’. Although numerous Cretaceous fossil flowers have been discovered in recent years, most are represented by incomplete charcoalified fragments that do not preserve delicate structures such as complete petals and surface textures, which means that their similarity to living forms is often difficult to discern. The scarcity of information about the ecology of early angiosperms makes it difficult to test hypotheses about the drivers of their diversification. Among other factors, frequent fires in the Cretaceous have been postulated as having possibly facilitated the rise of angiosperms. However, to date no early fossil angiosperms displaying fire-adapted traits have been known, making the role of fire in shaping Cretaceous floras uncertain.Results: We report the discovery of two exquisitely preserved fossil flower species, one identical to the inflorescences of the extant crown eudicot genus Phylica and the other recovered as a sister group to Phylica, both preserved as inclusions in Cretaceous amber from northern Myanmar (~99 Ma). These specialized flower structures, named Phylica piloburmensis sp. nov. and Eophylica priscastellata gen. et sp. nov., were adapted to surviving frequent wildfires, providing the earliest evidence of fire-resistance in angiosperms. The fossils suggest that fire was a significant selective force in Cretaceous angiosperm floras and that adaptations to fire resistance in some eudicot clades have been conserved for at least 99 Ma. This morphological stasis encompasses a range of floral characters, including the production of ‘pseudo-flowers’, and characteristic fruit and pollen architecture. Given its morphological distinctiveness, the Eophylica-Phylica clade represents one of the first well-documented angiosperm ‘living fossil’ genera from the Cretaceous. Conclusion: Our study suggests that core eudicots with specialised flower morphology displaying hallmarks of fire resistance and identical to those of the extant south African genus Phylica, had originated by the mid-Cretaceous (~99 Ma). Palaeoenvironmental reconstructions indicate that these plants lived in conditions similar to those of present-day southern Africa where 70% of taxa survive frequent burning, and that fire resistance was probably widespread in the fire-prone Cretaceous. The results also provide new insights into the biogeographic origin of at least one element of the highly endemic Greater Cape Region biodiversity hotspot flora biota.
Quantum Structured Light: Non-classical Spin Texture of Twisted Single-photon Pulses
Authors: Yang Li-Ping , Jacob Zubin
Published: May 2021

Classical structured light with controlled polarization and orbital angular momentum (OAM) of electromagnetic waves has varied applications in optical trapping, bio-sensing, optical communications and quantum simulations. The classical electromagnetic theory of such structured light beams and pulses have advanced significantly over the last two decades. However, a framework for the quantum density of spin and OAM for single-photons remains elusive. Here, we develop a theoretical framework and put forth the concept of quantum structured light for space-time wavepackets at the single-photon level. Our work marks a paradigm shift beyond scalar-field theory as well as the paraxial approximation and can be utilized to study the quantum properties of the spin and OAM of all classes of twisted quantum light pulses. We capture the uncertainty in full three-dimensional (3D) projections of vector spin demonstrating their quantum behavior beyond the conventional concept of classical polarization. Even in laser beams with high OAM along the propagation direction, we predict the existence of large OAM quantum fluctuations in the transverse plane which can be verified experimentally. We show that the spin density generates modulated helical texture beyond the paraxial limit and exhibits distinct statistics for Fock-state vs. coherent-state twisted pulses. We introduce the quantum correlator of photon spin density to characterize the nonlocal spin noise providing a rigorous parallel with fermionic spin noise operators. Our work paves the way for quantum spin-OAM physics in twisted single photon pulses and also opens explorations for new phases of light with long-range spin order.
In Vivo Imaging of Cannabinoid Type 2 Receptors, Functional and Structural Alterations in Mouse Model of Cerebral Ischemia by PET and MRI
Authors: Ni Ruiqing , Herde Adrienne Müller , Haider Ahmed , Keller Claudia , Louloudis Georgios , Vaas Markus , Schibli Roger , Ametamey Simon M. , Klohs Jan , Mu Linjing
Published: May 2021

Background and purposeBrain ischemia is one of the most important pathologies of the central nervous system. Non-invasive molecular imaging methods have the potential to provide critical insights into the temporal dynamics and follow alterations of receptor expression and metabolism in ischemic stroke. The aim of this study was to assess the cannabinoid type 2 receptors (CB2R) levels in transient middle cerebral artery occlusion (tMCAO) mouse models at subacute stage using positron emission tomography (PET) with our novel tracer [18F]RoSMA-18-d6, and structural imaging by magnetic resonance imaging (MRI). MethodsOur recently developed CB2R PET tracer [18F]RoSMA-18-d6 was used for imaging the neuroinflammation at 24 h after reperfusion in tMCAO mice. The RNA expression levels of CB2R and other inflammatory markers were analyzed by quantitative real-time polymerase chain reaction using brain tissues from tMCAO (1 h occlusion) and sham-operated mice. [18F]fluorodeoxyglucose (FDG) was included for evaluation of the cerebral metabolic rate of glucose (CMRglc). In addition, diffusion-weighted imaging and T2-weighted imaging were performed for anatomical reference and delineating the lesion in tMCAO mice. ResultsmRNA expressions of inflammatory markers TNF-a, Iba1, MMP9 and GFAP, CNR2 were increased at 24 h after reperfusion in the ipsilateral compared to contralateral hemisphere of tMCAO mice, while mRNA expression of the neuronal marker MAP-2 was markedly reduced. Reduced [18F]FDG uptake was observed in the ischemic striatum of tMCAO mouse brain at 24 h after reperfusion. Although higher activity of [18F]RoSMA-18-d6 in ex-vivo biodistribution studies and higher standard uptake value ratio (SUVR) were detected in the ischemic ipsilateral compared to contralateral striatum in tMCAO mice, the in-vivo specificity of [18F]RoSMA-18-d6 was confirmed only in the CB2R-rich spleen. ConclusionsThis study revealed an increased [18F]RoSMA-18-d6 measure of CB2R and a reduced [18F]FDG measure of CMRglc in ischemic striatum of tMCAO mice at subacute stage. [18F]RoSMA-18-d6 might be a promising PET tracer for detecting CB2R alterations in animal models of neuroinflammation without neuronal loss.
Identification of Differentially Expressed Genes for Disc Degeneration Using Gene Expression Profiling and Bioinformatics Analysis
Authors: Fan Ning , Yuan Shuo , Hai Yong , Du Peng , Li Jian , Kong Xiaochuan , Zhu Wenyi , Liu Yuzeng , Zang Lei
Published: May 2021

BackgroundInflammatory processes exacerbated by IL-1β are believed to be key mediators of disc degeneration and low back pain. However, the underlying mechanism remains unclear. We performed a bioinformatics analysis to identify the key genes that were differentially expressed between degenerative intervertebral disc cells with and without exposure to interleukin (IL)-1β, and explore the related signaling pathways and interaction networks.MethodsThe microarray data were downloaded from the Gene Expression Omnibus (GSE 27494). Then, analyses of the gene ontology, signaling pathways, and interaction networks for the differentially expressed genes (DEGs) were conducted using tools including the Database for Annotation, Visualization, and Integrated Discovery (DAVID), Metascape, Gene Set Enrichment Analysis (GSEA), Search Tool for the Retrieval of Interacting Genes (STRING), Cytoscape, the Venn method, and packages of the R computing language.ResultsA total of 260 DEGs were identified, including 161 upregulated genes and 99 down-regulated genes. Gene Ontology (GO) annotation analysis showed that these DEGs were mainly associated with the extracellular region, chemotaxis, taxis, cytokine activity, and cytokine receptor binding. A Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis showed that these DEGs were mainly involved in the interactions of cytokine-cytokine receptor interaction, rheumatoid arthritis, tumor necrosis factor (TNF) signaling pathway, salmonella infection, and chemokine signaling pathway. The interaction network analysis indicated that 10 hub genes, including CXCL8, CXCL1, CCL20, CXCL2, CXCL5, CXCL3, CXCL6, C3, PF4, and GPER1 may play key roles in intervertebral disc degeneration.ConclusionsBioinformatic analysis showed that CXCL8 and other 9 key genes may play a role in the development of disc degeneration induced by inflammatory reactions, and can be used to identify the potential therapeutic target genes.
An Improved Picard Iteration Scheme for Simulating Unsaturated Flow in Layered Porous Media
Authors: Zhu S.R. , Wu L.Z. , Li S.H.
Published: May 2021

Picard iteration method is commonly used to obtain numerical solution of unsaturated flow in porous media. However, because the system of linear equations derived from Richards equation is seriously ill-conditioned, Picard iteration has slow convergence rate and low computational efficiency, particularly in layered porous media. In this study, control volume method based on non-uniform nodes is used to discrete Richards equation. To improve the convergence rate of Picard iteration, we combine the non-uniform multigrid correction method with the multistep preprocessing technology. Thus, an improved Picard iteration scheme with multistep preconditioner based on non-uniform multigrid correction method (NMG-MPPI(m)) is proposed to model 1D unsaturated flow in layered porous media. Three test cases were used to verify the proposed schemes. The result shows that the condition number of the coefficient matrix has been greatly reduced using the multistep preconditioner. Numerical results indicate that NMG-MPPI(m) can solve Richards equation at a faster convergence rate, with higher calculation accuracy and good robustness. Compared with conventional Picard iteration, NMG-MPPI(m) shows a very high speed-up ratio. As a result, the improved Picard iteration scheme has good application for simulating unsaturated flow in layered porous media.
Microwave Versus Radiofrequency Ablation for the Treatment of Liver Malignancies: A Randomized Controlled Phase 2 Trial
Authors: Radosevic Aleksandar , Quesada Rita , Serlavos Clara , Sánchez Juan , Zugazaga Ander , Sierra Ana , Coll Susana , Busto Marcos , Aguilar Guadalupe , Flores Daniel , Arce Javier , Maiques José María , García Montserrat , Carrion José Antonio , Visa Laura , Villamonte María , Pueyo Eva , Berjano Enrique , Trujillo Macarena , Sánchez-Velázquez Patricia , Grande Luís , Burdio Fernando
Published: May 2021

Purpose: Microwave (MWA) and radiofrequency ablation (RFA) are main ablative techniques for hepatocellular carcinoma (HCC) and colorectal liver metastasis (MT). This randomized phase 2 clinical trial compares the effectiveness of MWA and RFA in medium-sized liver tumors.Methods: HCC and MT patients with 1.5 to 4 cm tumors suitable for ablation were randomized into MWA or RFA Groups. The primary endpoints were primary technical success (TS) and local tumor progression (LTP) rate after a 2-year follow-up. Secondary endpoints were safety and overall survival. Results: Between June 2015 and April 2020, 82 patients were randomly assigned (41 patients per group). For the per-protocol analysis, three patients were excluded. Median follow-up was 27 months (MWA group) and 23 months (RFA Group). The TS was achieved in 98% (46/47) and 90 % (45/50) (p=0.108), and LTP was observed in 21% (10/47) vs. 12% (6/50) (OR 1.9 [95% CI 0.66-5.3], p=0.238) of tumors in the MWA and RFA Group, respectively. Major complications were found in 5 cases (11%) in the MWA Group vs. 2 cases (4%) in RFA, without statistical significance. MWA created larger ablation zones than RFA (p=0.036).Conclusion: MWA and RFA show similar effectiveness and safety in medium-sized liver tumors (1.5-4 cm).
Integrated Single-cell Bioinformatics Analysis Reveals Intrinsic and Extrinsic Biological Characteristics of Hematopoietic Stem Cell Aging
Authors: Zeng Xiangjun , Li Xia , Shao Mi , Xu Yulin , Shan Wei , Wei Cong , Li Xiaoqing , Wang Limengmeng , Hu Yongxian , Zhao Yanmin , Qian Pengxu , Huang He
Published: May 2021

Hematopoietic stem cell (HSC) aging, which is accompanied by loss of self-renewal capacity, myeloid-biased differentiation and increased risks of hematopoietic malignancies, is an important focus in stem cell research. However, the mechanisms underlying HSC aging have not been fully elucidated. In the present study, we integrated 3 independent single-cell transcriptome datasets of HSCs together and identified Il10ra and Tnfsf14 as two markers of inflammatory and apoptosis-biased aged HSCs. Besides, common differentially expressed genes (DEGs) between young and aged HSCs were identified and further validated by quantitative RT-PCR. Functional enrichment analysis revealed that these DEGs were predominantly involved in the cell cycle and the tumor necrosis factor (TNF) signaling pathway. We further found that the Skp2-induced signaling pathway (Skp2→Cip1→CycA/CDK2→DP-1) contributed to a rapid transition through G1 phase in aged HSCs. In addition, analysis of the extrinsic alterations on HSC aging revealed the increased expression levels of inflammation genes in bone marrow microenvironment. Colony formation unit assays showed that inflammatory cytokines promoted cellular senescence and that blockade of inflammatory pathway markedly rejuvenated aged HSC functions and increased B cell output. Collectively, our study elucidated the biological characteristics of HSC aging, and the genes and pathways we identified could be potential biomarkers and targets for the identification and rejuvenation of aged HSCs.
miR-204-5p Inhibits Cell Proliferation and Induces Cell Apoptosis in Esophageal Squamous Cell Carcinoma by Regulating Nestin
Authors: Zhong Beilong , Lv Weize , Zhang Huayong , Lin Chunxia , Li Fei , Zheng Fangfang , Luo Honghe
Published: May 2021

PurposeThis study aimed to investigate the relationship between miR-204-5p and Nestin in esophageal squamous cell carcinoma (ESCC). MethodsThe expression levels of miR-204-5p and Nestin were tested by quantitative real-time polymerase chain reaction (q-PCR) and Western blotting, respectively. The colony formation assay was used to assess cell proliferation. The flow cytometry and TUNEL assay were used to examine cell apoptosis. Tumorigenesis was evaluated using a murine xenograft tumor model. ResultsESCC tissues and cell lines exhibited decreased miR-204-5p expression and increased Nestin expression, while the opposite results were found in paired para-carcinoma tissues and esophageal epithelial cell lines. The Luciferase reported assay confirmed that Nestin was the direct target of miR-204-5p. In vitro, miR-204-5p inhibited cell proliferation and induced apoptosis through regulating Nestin expression. In vivo, miR-204-5p inhibited xenograft tumor formation. Conclusion﻿In conclusion, these results indicate that miR-204-5p inhibits cell proliferation and induces cell apoptosis in ESCC through regulating Nestin.
Dynamical Analysis of an SEIRS Model With Incomplete Recovery and Relapse on Networks and Its Optimal Vaccination Control
Authors: Zhang Lei , Liu Maoxing , Hou Qiang , Xie Boli
Published: May 2021

For some infectious diseases, such as herpes and tuberculosis, there is incomplete recovery and relapse. These phenomena make them difficult to control. In consequence of this status, an SEIRS epidemic model with incomplete recovery and relapse on networks is established and the global dynamics is studied. The results show that when the basic reproduction number R 0 <=1 the disease-free equilibrium is globally asymptotically stable; when R 0 > 1, the endemic equilibrium is globally asymptotically stable. In addition, in consideration of vaccination control strategy, an SVEIRS model is introduced and the optimal control is solved. At last, the theoretical results are illustrated with numerical simulations.