bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical simulation for water invasion and water control optimization in water drive gas reservoirs
Authors: Xu Xuan , Li Xizhe , Hu Yong , Mei Qingyan , Shi Yu , Jiao Chunyan 
Published: March 2021

AbstractThe development of water drive gas reservoirs (WDGRs) with fractures or strong heterogeneity is severely influenced by water invasion. Accurately simulating the rules of water invasion and drainage gas recovery countermeasures in fractured WDGRs, thereby revealing the mechanism of water invasion and an appropriate development strategy, is important for formulating water management measures and enhancing the recovery of gas reservoirs. In this work, physical simulation methods were proposed to gain a better understanding of water invasion and to optimize the water control of fractured WDGRs. Five groups of experiments were designed and conducted to probe the impacts of the distance between the fractures and the gas well, the drainage position, the drainage timing and the aquifer size on the water invasion and production performance of a gas reservoir. The gas and water production and the internal pressure drop were monitored in real time during the experiments. Based on the above experimental works, a theoretical analysis was conducted to quantitatively evaluate the performance of the gas reservoir recovery via the gas well production performance, water invasion, dynamic pressure drop and residual gas and water distribution analysis. The results show that when the fracture scale was appropriate, a gas well drilled close to a fracture (Experiment 1-3) or a high-permeability formation could also produce gas and achieve drainage efficiently. The recovery factor of Experiment 1-3 reached 62.5%, which was 24.6% and 21.1% higher than those of Experiments 1-1 and 1-2, respectively, which had wells drilled in low-permeability areas. Draining water near an aquifer can effectively inhibit water invasion during the early stage of gas recovery. The setup in Experiment 2-1 effectively inhibited water invasion and avoided the formation of water-sealed volumes of gas to recover 30% more gas than recovered with that of Experiment 1-1 without drainage wells. A shorter distance between the drainage well and the aquifer increased the drainage capacity and decreased the gas production capacity, respectively (Well 2 at Point A vs Point B). A larger aquifer had a lower gas recovery, which reduced the economic benefit. For example, due to an infinitely large aquifer, the reserves in Experiment 4-1 were developed by a single well, the gas recovery was only 33.4%. These research results are expected to be beneficial for the preparation of development plans and the optimization of water control measures for WDGRs.
Differential role of SIRT1/MAPK pathway during cerebral ischemia in rats and humans
Authors: Teertam Sireesh Kumar , Prakash Babu Phanithi 
Published: March 2021

AbstractCerebral ischemia (CI) is a severe cause of neurological dysfunction and mortality. Sirtuin-1 (Silent information regulator family protein 1, SIRT1), an oxidized nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, plays an important role in protection against several neurodegenerative disorders. The present study aims to investigate the protective role of SIRT1 after CI in experimental young and aged rats and humans. Also, the study examines the possible regulatory mechanisms of neuronal death in CI settings. Immunoblotting and immunohistochemistry were used to evaluate changes in the expression of SIRT1, JNK/ERK/MAPK/AKT signaling, and pro-apoptotic caspase-3 in experimental rats and CI patients. The study findings demonstrated that, in aged experimental rats, SIRT1 activation positively influenced JNK and ERK phosphorylation and modulated neuronal survival in AKT-dependent manner. Further, the protection conferred by SIRT1 was effectively reversed by JNK inhibition and increased pro-apoptotic caspase-3 expression. In young experimental rats, SIRT1 activation decreased the phosphorylation of stress-induced JNK, ERK, caspase-3, and increased the phosphorylation of AKT after CI. Inhibition of SIRT1 reversed the protective effect of resveratrol. More importantly, in human patients, SIRT1 expression, phosphorylation of JNK/ERK/MAPK/AKT signaling and caspase-3 were up-regulated. In conclusion, SIRT1 could possibly be involved in the modulation of JNK/ERK/MAPK/AKT signaling pathway in experimental rats and humans after CI.
Tillage and irrigation increase wheat root systems at deep soil layer and grain yields in lime concretion black soil
Authors: Wang Jinfeng , Wang Zhuangzhuang , Gu Fengxu , Liu Huan , Kang Guozhang , Feng Wei , Wang Yonghua , Guo Tiancai 
Published: March 2021

AbstractIn lime concretion black soil, a two-factor (tillage and irrigation) split block experiment from 2015 to 2017 was conducted to identify whether their combination is suitable for the improvement of winter wheat yield and water use efficiency. The main treatments were subsoiling (SS) and rotary tillage (RT), with secondary treatments of three irrigation regimes: no irrigation during the whole growth period (W0), irrigation at jointing stage (W1), and irrigation at both jointing and anthesis stages (W2). In combination with a soil column experiment, the contribution of the root system in different soil layers to yield was clarified. The results indicated that both tillage and irrigation significantly influenced the spatiotemporal distributions of the root systems and yield components, while tillage produced the strongest effect. Compared with RT, SS significantly promoted the root penetration and delayed root senescence in deep soil layers. With increasing soil depth, each root configuration parameter (dry root weight density, DRWD; root length density, RLD; root surface area per unit area, RSA; root volume per unit area, RV) gradually decreased, and the peak appearance times of each root parameter in RT and three parameters (RLD, RSA and RV) in SS were postponed from heading to anthesis and from anthesis to filling stage, respectively. The average post-peak attenuation values at soil layers from 60 to 100 cm in W1 were less than those in W0 and W2. SSW1 generated the highest grain yields, with an average increase of 31.88% compared with the yield in RTW0. Root systems at three soil layers (0–40 cm, 40–80 cm and below 80 cm) differentially contributed to grain yields with 78.32%, 12.09% and 9.59%, respectively. The growth peak of the deep root system in SSW1 was postponed to the filling stage, and the post-peak attenuation declining rates were also slowed. Therefore, SSW1 is an effective cultivation method improving grain yields and water use efficiency in lime concretion black soil.
Death agonist antibody against TRAILR2/DR5/TNFRSF10B enhances birinapant anti-tumor activity in HPV-positive head and neck squamous cell carcinomas
Authors: An Yi , Jeon Jun , Sun Lillian , Derakhshan Adeeb , Chen Jianhong , Carlson Sophie , Cheng Hui , Silvin Christopher , Yang Xinping , Van Waes Carter , Chen Zhong 
Published: March 2021

AbstractHead and neck squamous cell carcinomas (HNSCC) induced by human papillomavirus (HPV) have increased recently in the US. However, the distinct alterations of molecules involved in the death pathways and drug effects targeting inhibitor of apoptosis proteins (IAPs) have not been extensively characterized in HPV(+) HNSCC cells. In this study, we observed the distinct genomic and expression alterations of nine genes involved in cell death in 55% HNSCC tissues, which were associated with HPV status, tumor staging, and anatomic locations. Expression of four genes was statistically correlated with copy number variation. A panel of HPV(+) HNSCC lines showed abundant TRAILR2 and IAP1 protein expression, but were not sensitive to IAP inhibitor birinapant alone, while combinatory treatment with TNFα or especially TRAIL enhanced this drug sensitivity. The death agonistic TRAILR2 antibody alone showed no cell inhibitory effects, whereas its combination with birinapant and/or TRAIL protein demonstrated additive or synergistic effects. We observed predominantly late apoptosis mode of cell death after combinatorial treatments, and pan-caspase (ZVAD) and caspase-8 (ZIETD) inhibitors attenuated treatment-induced cell death. Our genomic and expression data-driven study provides a framework for identifying relevant combinatorial therapies targeting death pathways in HPV(+) HNSCC and other squamous cancer types.
Regulation of cardiomyocyte DNA damage and cell death by the type 2A protein phosphatase regulatory protein alpha4
Authors: Cowan Jonathan , Longman Michael R. , Snabaitis Andrew K. 
Published: March 2021

AbstractThe type 2A protein phosphatase regulatory protein alpha4 (α4) constitutes an anti-apoptotic protein in non-cardiac tissue, however it’s anti-apoptotic properties in the heart are poorly defined. To this end, we knocked down α4 protein expression (α4 KD) using siRNA in cultured H9c2 cardiomyocytes and confirmed the lack of DNA damage/cell death by TUNEL staining and MTT assay. However, α4 KD did increase the phosphorylation of p53 and ATM/ATR substrates, decreased the expression of poly ADP-ribose polymerase and associated fragments. Expression of anti-apoptotic proteins Bcl-2 and Bcl-xL was reduced, whereas expression of pro-apoptotic BAX protein did not change. Alpha4 KD reduced basal H2AX Ser139 phosphorylation, whereas adenoviral-mediated re-expression of α4 protein following α4 KD, restored basal H2AX phosphorylation at Ser139. The sensitivity of H9c2 cardiomyocytes to doxorubicin-induced DNA damage and cytotoxicity was augmented by α4 KD. Adenoviral-mediated overexpression of α4 protein in ARVM increased PP2AC expression and augmented H2AX Ser139 phosphorylation in response to doxorubicin. Furthermore, pressure overload-induced heart failure was associated with reduced α4 protein expression, increased ATM/ATR protein kinase activity, increased H2AX expression and Ser139 phosphorylation. Hence, this study describes the significance of altered α4 protein expression in the regulation of DNA damage, cardiomyocyte cell death and heart failure.
Strain-induced modulation of temperature characteristics in ferrimagnetic Tb–Fe films
Authors: Ota Shinya , Van Thach Pham , Awano Hiroyuki , Ando Akira , Toyoki Kentaro , Kotani Yoshinori , Nakamura Tetsuya , Koyama Tomohiro , Chiba Daichi 
Published: March 2021

AbstractThis study investigates the effect of strain on the compensation temperature of ferrimagnetic Tb–Fe films formed on a flexible substrate. The compensation temperature is determined by the anomalous Hall measurement, and an application of 1.2% tensile strain reduces the compensation temperature by 12 K. X-ray magnetic circular dichroism reveals that approximately 5% of Fe magnetic moment and approximately 1% of Tb magnetic moment are reduced by an application of 0.9% tensile strain at the room temperature. To understand the greater reduction in Fe magnetization compared with that in Tb and the compensation temperature reduction simultaneously, a model applying molecular field theory is analyzed. Changes in three types of exchange coupling between Fe and Tb atoms are speculated to be caused by the strain.
A multi-phase deep CNN based mitosis detection framework for breast cancer histopathological images
Authors: Sohail Anabia , Khan Asifullah , Wahab Noorul , Zameer Aneela , Khan Saranjam 
Published: March 2021

AbstractThe mitotic activity index is a key prognostic measure in tumour grading. Microscopy based detection of mitotic nuclei is a significant overhead and necessitates automation. This work proposes deep CNN based multi-phase mitosis detection framework “MP-MitDet” for mitotic nuclei identification in breast cancer histopathological images. The workflow constitutes: (1) label-refiner, (2) tissue-level mitotic region selection, (3) blob analysis, and (4) cell-level refinement. We developed an automatic label-refiner to represent weak labels with semi-sematic information for training of deep CNNs. A deep instance-based detection and segmentation model is used to explore probable mitotic regions on tissue patches. More probable regions are screened based on blob area and then analysed at cell-level by developing a custom CNN classifier “MitosRes-CNN” to filter false mitoses. The performance of the proposed “MitosRes-CNN” is compared with the state-of-the-art CNNs that are adapted to cell-level discrimination through cross-domain transfer learning and by adding task-specific layers. The performance of the proposed framework shows good discrimination ability in terms of F-score (0.75), recall (0.76), precision (0.71) and area under the precision-recall curve (0.78) on challenging TUPAC16 dataset. Promising results suggest good generalization of the proposed framework that can learn characteristic features from heterogenous mitotic nuclei.
Intranuclear birefringent inclusions in paraffin sections by polychromatic polarization microscopy
Authors: Vitkunaite Aiste , Laurinaviciene Aida , Plancoulaine Benoit , Rasmusson Allan , Levenson Richard , Shribak Michael , Laurinavicius Arvydas 
Published: March 2021

AbstractIntranuclear birefringent inclusions (IBI) found in various cell types in paraffin-embedded tissue sections have long been considered to be a tissue processing artifact, although an association with biological processes has been suggested. We applied polychromatic polarization microscopy to image their spatial organization. Our study provides evidence that IBI are caused by liquid paraffin-macromolecular crystals formed during paraffin-embedding procedures within cells and potentially reflect an active transcriptional status.
Triangulating evidence from longitudinal and Mendelian randomization studies of metabolomic biomarkers for type 2 diabetes
Authors: Porcu Eleonora , Gilardi Federica , Darrous Liza , Yengo Loic , Bararpour Nasim , Gasser Marie , Marques-Vidal Pedro , Froguel Philippe , Waeber Gerard , Thomas Aurelien , Kutalik Zoltán 
Published: March 2021

AbstractThe number of people affected by Type 2 diabetes mellitus (T2DM) is close to half a billion and is on a sharp rise, representing a major and growing public health burden. Given its mild initial symptoms, T2DM is often diagnosed several years after its onset, leaving half of diabetic individuals undiagnosed. While several classical clinical and genetic biomarkers have been identified, improving early diagnosis by exploring other kinds of omics data remains crucial. In this study, we have combined longitudinal data from two population-based cohorts CoLaus and DESIR (comprising in total 493 incident cases vs. 1360 controls) to identify new or confirm previously implicated metabolomic biomarkers predicting T2DM incidence more than 5 years ahead of clinical diagnosis. Our longitudinal data have shown robust evidence for valine, leucine, carnitine and glutamic acid being predictive of future conversion to T2DM. We confirmed the causality of such association for leucine by 2-sample Mendelian randomisation (MR) based on independent data. Our MR approach further identified new metabolites potentially playing a causal role on T2D, including betaine, lysine and mannose. Interestingly, for valine and leucine a strong reverse causal effect was detected, indicating that the genetic predisposition to T2DM may trigger early changes of these metabolites, which appear well-before any clinical symptoms. In addition, our study revealed a reverse causal effect of metabolites such as glutamic acid and alanine. Collectively, these findings indicate that molecular traits linked to the genetic basis of T2DM may be particularly promising early biomarkers.
Real time observation of the interaction between aluminium salts and sweat under microfluidic conditions
Authors: Sakhawoth Yasine , Dupire Jules , Leonforte Fabien , Chardon Marion , Monti Fabrice , Tabeling Patrick , Cabane Bernard , Botet Robert , Galey Jean-Baptiste 
Published: March 2021

AbstractAluminium salts such as aluminium chlorohydrate (ACH) are the active ingredients of antiperspirant products. Their mechanism of action involves a temporary and superficial plugging of eccrine sweat pores at the skin surface. We developed a microfluidic system that allows the real time observation of the interactions between sweat and ACH in conditions mimicking physiological sweat flow and pore dimensions. Using artificial sweat containing bovine serum albumin as a model protein, we performed experiments under flowing conditions to demonstrate that pore clogging results from the aggregation of proteins by aluminium polycations at specific location in the sweat pore. Combining microfluidic experiments, confocal microscopy and numerical models helps to better understand the physical chemistry and mechanisms involved in pore plugging. The results show that plugging starts from the walls of sweat pores before expanding into the centre of the channel. The simulations aid in explaining the influence of ACH concentration as well as the impact of flow conditions on the localization of the plug. Altogether, these results outline the potential of both microfluidic confocal observations and numerical simulations at the single sweat pore level to understand why aluminium polycations are so efficient for sweat channel plugging.
A dose-escalating toxicology study of the candidate biologic ELP-VEGF
Authors: Waller Jamarius P. , Burke Stephen P. , Engel Jason , Chade Alejandro R. , Bidwell Gene L. 
Published: March 2021

AbstractVascular Endothelial Growth Factor (VEGF), a key mediator of angiogenesis and vascular repair, is reduced in chronic ischemic renal diseases, leading to microvascular rarefaction and deterioration of renal function. We developed a chimeric fusion of human VEGF-A121 with the carrier protein Elastin-like Polypeptide (ELP-VEGF) to induce therapeutic angiogenesis via targeted renal VEGF therapy. We previously showed that ELP-VEGF improves renal vascular density, renal fibrosis, and renal function in swine models of chronic renal diseases. However, VEGF is a potent cytokine that induces angiogenesis and increases vascular permeability, which could cause undesired off-target effects or be deleterious in a patient with a solid tumor. Therefore, the current study aims to define the toxicological profile of ELP-VEGF and assess its risk for exacerbating tumor progression and vascularity using rodent models. A dose escalating toxicology assessment of ELP-VEGF was performed by administering a bolus intravenous injection at doses ranging from 0.1 to 200 mg/kg in Sprague Dawley (SD) rats. Blood pressure, body weight, and glomerular filtration rate (GFR) were quantified longitudinally, and terminal blood sampling and renal vascular density measurements were made 14 days after treatment. Additionally, the effects of a single administration of ELP-VEGF (0.1–10 mg/kg) on tumor growth rate, mass, and vascular density were examined in a mouse model of breast cancer. At doses up to 200 mg/kg, ELP-VEGF had no effect on body weight, caused no changes in plasma or urinary markers of renal injury, and did not induce renal fibrosis or other histopathological findings in SD rats. At the highest doses (100–200 mg/kg), ELP-VEGF caused an acute, transient hypotension (30 min), increased GFR, and reduced renal microvascular density 14 days after injection. In a mouse tumor model, ELP-VEGF did not affect tumor growth rate or tumor mass, but analysis of tumor vascular density by micro-computed tomography (μCT) revealed significant, dose dependent increases in tumor vascularity after ELP-VEGF administration. ELP-VEGF did not induce toxicity in the therapeutic dosing range, and doses one hundred times higher than the expected maximum therapeutic dose were needed to observe any adverse signs in rats. In breast tumor—bearing mice, ELP-VEGF therapy induced a dose-dependent increase in tumor vascularity, demanding caution for potential use in a patient suffering from kidney disease but with known or suspected malignancy.
Radon and thoron levels in the dwellings of Buddonithanda: a village in the environs of proposed uranium mining site, Nalgonda district, Telangana state, India
Authors: Suman G. , Vinay Kumar Reddy K. , Sreenath Reddy M. , Gopal Reddy Ch. , Yadagiri Reddy P. 
Published: March 2021

AbstractElevated levels of radon and thoron in the indoor atmosphere may cause the deleterious effects on the mankind. Mining sites and their environs attract a special interest in radon studies as higher levels are frequently reported in the habitats. In the present study, radon and thoron levels were measured in the dwellings of Buddonithanda, a village in the environs of proposed uranium mining site, with pin-hole (SSNTDs) dosimeters for the period of a year. The measured radon and thoron levels were found to vary widely from 14 to 675 Bq m−3 (geometric mean = 94 Bq m−3) and from 21 to 704 Bq m−3 (geometric mean = 121 Bq m−3), respectively. An attempt was made to understand the large spatial variation of these levels. The seasonal and diurnal variation studies were used in unraveling the behavior of the radioactive isotopes in indoor environment and the same was explained with the help of a simplified mathematical model. Quantification of inhalation dose due to radon and thoron was done with suitable occupancy factors.
Significance of lactate clearance in septic shock patients with high bilirubin levels
Authors: Takahashi Nozomi , Nakada Taka-aki , Walley Keith R. , Russell James A. 
Published: March 2021

AbstractLactate clearance is affected by hepatic function. However, it is unclear whether the association between hepatic dysfunction and lactate clearance can act as a prognostic marker of clinical outcomes in patients with septic shock. We aimed to evaluate the association between lactate clearance and mortality in two cohorts of septic shock patient who had hepatic dysfunction based on their total serum bilirubin levels (TBIL). Lactate clearance at 24 h after the onset of septic shock was analyzed using two cohorts, sub-categorized into two groups based on TBIL: < 2 mg/dL and ≥ 2 mg/dL. In the derivation cohort, lactate clearance was lower in non-survivors than in survivors with TBIL ≥ 2 mg/dL, while there was no significant difference in lactate clearance between non-survivors and survivors with TBIL < 2 mg/dL. Multivariate logistic regression analysis revealed that increased lactate clearance was significantly associated with decreased 28-day mortality in the TBIL ≥ 2 mg/dL group (10% lactate clearance, adjusted odds ratio [OR]: 0.88, 95% confidence interval (CI): 0.80–0.97, P = 0.0075), Creatinine level ≥ 2 mg/dL group (adjusted OR: 0.88, 95% CI: 0.81–0.95, P = 0.00069) and APACHE II score ≥ 35 group (adjusted OR: 0.93, 95% CI: 0.87–0.98, P = 0.013). In the validation cohort, lactate clearance was lower in non-survivors than in survivors with TBIL ≥ 2 mg/dL, while no significant difference in lactate clearance was observed between non-survivors and survivors with TBIL < 2 mg/dL. Increased lactate clearance was significantly associated with decreased 28-day mortality in the TBIL ≥ 2 mg/dL group (10% lactate clearance, adjusted OR: 0.89, 95% CI: 0.83–0.96, P = 0.0038) and the association was just about significant in APACHE II score ≥ 35 group (adjusted OR: 0.86, 95% CI: 0.74–1.00, P = 0.051). In conclusion, increased lactate clearance in septic shock patients with hepatic dysfunction (TBIL ≥ 2 mg/dL) or high severity (APACHE II score ≥ 35) was associated with decreased 28-day mortality.