bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Learning for Characterizing Paleokarst Collapse Features in 3‐D Seismic Images
Authors: Wu Xinming , Yan Shangsheng , Qi Jie , Zeng Hongliu
Published: September 2020

Paleokarst systems are found extensively in carbonate‐prone basins worldwide. They can form large reservoirs and provide efficient pathways for hydrocarbon migration, but they can also create serious engineering geohazards. The full delineation of potentially buried paleokarst systems plays an important role for reservoir characterization, oil and gas production, and other engineering tasks. We propose a supervised convolutional neural network (CNN) to automatically and accurately characterize paleokarst and associated collapse features from 3‐D seismic images. To avoid time‐consuming manual labeling for training the CNN, we propose an efficient workflow to automatically generate numerous 3‐D training image pairs including synthetic seismic images and the corresponding label images of the collapsed paleokarst features simulated in the seismic images. With this workflow, we are able to simulate realistic and diverse geologic structures and collapsed paleokarst features in the training images from which the CNN can effectively learn to recognize the collapsed paleokarst features in real field seismic images. Two field examples from the Fort Worth Basin demonstrate that our CNN‐based method is superior to conventional automatic methods in delineating paleokarst collapse features from seismic images. From the CNN‐based paleokarst characterization, we can further automatically extract 3‐D collapsed paleokarst systems and quantitatively measure their geometric parameters. Our CNN‐based method is highly efficient and takes only seconds to classify collapsed paleokarst features a 3‐D seismic image with 320 × 1, 024 × 1, 024 samples (approximately 268 km2) by using one graphics processing unit.
Seismic Discrimination of Controlled Explosions and Earthquakes Near Mount St. Helens Using P/S Ratios
Authors: Wang Ruijia , Schmandt Brandon , Kiser Eric
Published: September 2020

Explosions and earthquakes are effectively discriminated by P/S amplitude ratios for moderate magnitude events (M ≥ 4) observed at regional to teleseismic distances (≥200 km). It is less clear if P/S ratios are effective explosion discriminants for lower magnitudes observed at shorter distances. We report new tests of P/S discrimination using a dense seismic array in a continental volcanic arc setting near Mount St. Helens, with 23 single‐fired borehole explosions (ML 0.9–2.3) and 406 earthquakes (ML 1–3.3). The array provides up to 95 three‐component broadband seismographs, and most source‐receiver distances are <120 km. Additional insight is provided by ~3,000 vertical component geophone recordings of each explosion. Potential controls on local distance P/S ratios are investigated, including frequency range, distance, magnitude, source depth, number of seismographs, and site effects. A frequency band of about 10–18 Hz performs better than lower or narrower bands because explosion‐induced S wave amplitudes diminish relative to P for higher frequencies. Source depth and magnitude exhibited weak influences on P/S ratios. Site responses for earthquakes and explosions are correlated with each other and with shallow crustal Vp and Vs from traveltime tomography. Overall, the results indicate high potential for local distance P/S explosion discrimination in a continental volcanic arc setting, with ≥98% true positives and ≤6.3% false positives when using the array median from ≥16 stations. Performance is reduced for smaller arrays, especially those with ≤4 stations, thereby emphasizing the importance of array data for discrimination of low magnitude explosions.
Glutamine reliance in cell metabolism
Authors: Yoo Hee Chan , Yu Ya Chun , Sung Yulseung , Han Jung Min
Published: September 2020

As knowledge of cell metabolism has advanced, glutamine has been considered an important amino acid that supplies carbon and nitrogen to fuel biosynthesis. A recent study provided a new perspective on mitochondrial glutamine metabolism, offering mechanistic insights into metabolic adaptation during tumor hypoxia, the emergence of drug resistance, and glutaminolysis-induced metabolic reprogramming and presenting metabolic strategies to target glutamine metabolism in cancer cells. In this review, we introduce the various biosynthetic and bioenergetic roles of glutamine based on the compartmentalization of glutamine metabolism to explain why cells exhibit metabolic reliance on glutamine. Additionally, we examined whether glutamine derivatives contribute to epigenetic regulation associated with tumorigenesis. In addition, in discussing glutamine transporters, we propose a metabolic target for therapeutic intervention in cancer.
The role of lifestyle and non-modifiable risk factors in the development of metabolic disturbances from childhood to adolescence
Authors: Börnhorst Claudia , Russo Paola , Veidebaum Toomas , Tornaritis Michael , Molnár Dénes , Lissner Lauren , Mårild Staffan , De Henauw Stefaan , Moreno Luis A. , Floegel Anna , Ahrens Wolfgang , Wolters Maike
Published: September 2020

Background

The study aimed to identify the effects of lifestyle, C-reactive protein (CRP) and non-modifiable risk factors on metabolic disturbances in the transition from childhood to adolescence.

Methods

In 3889 children of the IDEFICS/I.Family cohort, latent transition analysis was applied to estimate probabilities of metabolic disturbances based on waist circumference, blood pressure, blood glucose, and lipids assessed at baseline and at 2- and 6-year follow-ups. Multivariate mixed-effects models were used to assess the age-dependent associations of lifestyle, non-modifiable risk factors and CRP, with the transformed probabilities of showing abdominal obesity, hypertension, dyslipidemia, or several metabolic disturbances (reference: being metabolically healthy).

Results

Higher maternal body mass index, familial hypertension as well as higher CRP z-score increased the risk for all four metabolic outcomes while low/medium parental education increased the risk of abdominal obesity and of showing several metabolic disturbances. Out of the lifestyle factors, the number of media in the bedroom, membership in a sports club, and well-being were associated with some of the outcomes. For instance, having at least one media in the bedroom increased the risk for showing several metabolic disturbances where the odds ratio (OR) markedly increased with age (1.30 [95% confidence interval 1.18; 1.43] at age 8; 1.18 [1.14; 1.23] for interaction with age; i.e., resulting in an OR of 1.30 × 1.18 = 1.53 at age 9 and so forth). Further, entering puberty at an early age was strongly associated with the risk of abdominal obesity (2.43 [1.60; 3.69] at age 8; 0.75 [0.69; 0.81] for interaction with age) and the risk of showing several metabolic disturbances (2.46 [1.53; 3.96] at age 8; 0.71 [0.65; 0.77] for interaction with age).

Conclusions

Various factors influence the metabolic risk of children revealing the need for multifactorial interventions. Specifically, removing media from children’s bedroom as well as membership in a sports club seem to be promising targets for prevention.
Relationship of leukaemias with long-term ambient air pollution exposures in the adult Danish population
Authors: Puett Robin C. , Poulsen Aslak Harbo , Taj Tahir , Ketzel Matthias , Geels Camilla , Brandt Jørgen , Christensen Jesper H. , Sørensen Mette , Roswall Nina , Hvidtfeldt Ulla , Raaschou-Nielsen Ole
Published: September 2020

Background

Few population-based epidemiological studies of adults have examined the relationship between air pollution and leukaemias.

Methods

Using Danish National Cancer Registry data and Danish DEHM-UBM-AirGIS system-modelled air pollution exposures, we examined whether particulate matter (PM2.5), black carbon (BC), nitrogen dioxide (NO2) and ozone (O3) averaged over 1, 5 or 10 years were associated with adult leukaemia in general or by subtype. In all, 14,986 adult cases diagnosed 1989–2014 and 51,624 age, sex and time-matched controls were included. Separate conditional logistic regression models, adjusted for socio-demographic factors, assessed exposure to each pollutant with leukaemias.

Results

Fully adjusted models showed a higher risk of leukaemia with higher 1-, 5- and 10-year-average exposures to PM2.5 prior to diagnosis (e.g. OR per 10 µg/m3 for 10-year average: 1.17, 95% CI: 1.03, 1.32), and a positive relationship with 1-year average BC. Results were driven by participants 70 years and older (OR per 10 µg/m3 for 10-year average: 1.35, 95% CI: 1.15–1.58). Null findings for younger participants. Higher 1-year average PM2.5 exposures were associated with higher risks for acute myeloid and chronic lymphoblastic leukaemia.

Conclusion

Among older adults, higher risk for leukaemia was associated with higher residential PM2.5 concentrations averaged over 1, 5 and 10 years prior to diagnosis.
Metaplastic breast cancers frequently express immune checkpoint markers FOXP3 and PD-L1
Authors: Kalaw Emarene , Lim Malcolm , Kutasovic Jamie R. , Sokolova Anna , Taege Lucinda , Johnstone Kate , Bennett James , Saunus Jodi M. , Niland Colleen , Ferguson Kaltin , Gresshoff Irma , Bettington Mark , Pathmanathan Nirmala , Tse Gary M. , Papadimos David , Pathmanathan Rajadurai , Harris Gavin , Yamaguchi Rin , Tan Puay Hoon , Fox Stephen , O’Toole Sandra A. , Simpson Peter T. , Lakhani Sunil R. , McCart Reed Amy E.
Published: September 2020

Background

Metaplastic breast carcinoma encompasses a heterogeneous group of tumours with differentiation into squamous and/or spindle, chondroid, osseous or rhabdoid mesenchymal-looking elements. Emerging immunotherapies targeting Programmed Death Ligand 1 (PD-L1) and immune-suppressing T cells (Tregs) may benefit metaplastic breast cancer patients, which are typically chemo-resistant and do not express hormone therapy targets.

Methods

We evaluated the immunohistochemical expression of PD-L1 and FOXP3, and the extent of tumour infiltrating lymphocytes (TILs) in a large cohort of metaplastic breast cancers, with survival data.

Results

Metaplastic breast cancers were significantly enriched for PD-L1 positive tumour cells, compared to triple-negative ductal breast cancers (P < 0.0001), while there was no significant difference in PD-L1 positive TILs. Metaplastic breast cancers were also significantly enriched for TILs expressing FOXP3, with FOXP3 positive intra-tumoural TILs (iTILs) associated with an adverse prognostic outcome (P = 0.0226). Multivariate analysis identified FOXP3 iTILs expression status as an important independent prognostic factor for patient survival.

Conclusions

Our findings indicate the clinical significance and prognostic value of FOXP3, PD-1/PD-L1 checkpoint and TILs in metaplastic breast cancer and confirm that a subset of metaplastics may benefit from immune-based therapies.
BCAT1 binds the RNA-binding protein ZNF423 to activate autophagy via the IRE1-XBP-1-RIDD axis in hypoxic PASMCs
Authors: Xin Wei , Zhang Min , Yu Yang , Li Songlin , Ma Cui , Zhang Junting , Jiang Yuan , Li Yiying , Zheng Xiaodong , Zhang Lixin , Zhao Xijuan , Pei Xuzhong , Zhu Daling
Published: September 2020

Abnormal functional changes in pulmonary artery smooth muscle cells are the main causes of many lung diseases. Among, autophagy plays a crucial role. However, the specific molecular regulatory mechanism of autophagy in PASMCs remains unclear. Here, we first demonstrate that BCAT1 played a key role in the autophagy of hypoxic PASMCs and hypoxic model rats. BCAT1-induced activation and accumulation of the autophagy signaling proteins BECN1 and Atg5 by the endoplasmic reticulum (ER) stress pathway. Interestingly, we discovered that BCAT1 bound IRE1 on the ER to activate expression of its downstream pathway XBP-1-RIDD axis to activate autophagy. More importantly, we identified an RNA-binding protein, zinc finger protein 423, which promoted autophagy by binding adenylate/uridylate (AU)-rich elements in the BCAT1 mRNA 3′-untranslated region. Overall, our results identify BCAT1 as a potential therapeutic target for the clinical treatment of lung diseases and reveal a novel posttranscriptional regulatory mechanism and signaling pathway in hypoxia-induced PASMC autophagy.
Four-octyl itaconate activates Nrf2 cascade to protect osteoblasts from hydrogen peroxide-induced oxidative injury
Authors: Zheng Yuehuan , Chen Zhe , She Chang , Lin Yazhou , Hong Yuan , Shi Liqiang , Zhang Yingzi , Cao Peng , Xu Xiangyang
Published: September 2020

Four-octyl itaconate (4-OI) is the cell-permeable derivative of itaconate that can activate Nrf2 signaling by alkylating Keap1’s cysteine residues. Here, we tested the potential effect of 4-OI on hydrogen peroxide (H2O2)-induced oxidative injury in osteoblasts. In OB-6 cells and primary murine osteoblasts, 4-OI was able to activate Nrf2 signaling cascade and cause Keap1–Nrf2 disassociation, Nrf2 protein stabilization, cytosol accumulation, and nuclear translocation. 4-OI also augmented antioxidant-response element reporter activity and promoted expression of Nrf2-dependent genes (HO1, NQO1, and GCLC). Pretreatment with 4-OI inhibited H2O2-induced reactive oxygen species production, cell death, and apoptosis in osteoblasts. Furthermore, 4-OI inhibited H2O2-induced programmed necrosis by suppressing mitochondrial depolarization, mitochondrial cyclophilin D-ANT1 (adenine nucleotide translocase 1)-p53 association, and cytosol lactate dehydrogenase release in osteoblasts. Ectopic overexpression of immunoresponsive gene 1 (IRG1) increased endogenous itaconate production and activated Nrf2 signaling cascade, thereby inhibiting H2O2-induced oxidative injury and cell death. In OB-6 cells, Nrf2 silencing or CRISPR/Cas9-induced Nrf2 knockout blocked 4-OI-induced osteoblast cytoprotection against H2O2. Conversely, forced Nrf2 activation, by CRISPR/Cas9-induced Keap1 knockout, mimicked 4-OI-induced actions in OB-6 cells. Importantly, 4-OI was ineffective against H2O2 in Keap1-knockout cells. Collectively, 4-OI efficiently activates Nrf2 signaling to inhibit H2O2-induced oxidative injury and death of osteoblasts.
Wnt/β-catenin signaling pathway induces autophagy-mediated temozolomide-resistance in human glioblastoma
Authors: Yun Eun-Jin , Kim Sangwoo , Hsieh Jer-Tsong , Baek Seung Tae
Published: September 2020

Temozolomide (TMZ) is widely used for treating glioblastoma multiforme (GBM), however, the treatment of such brain tumors remains a challenge due to the development of resistance. Increasing studies have found that TMZ treatment could induce autophagy that may link to therapeutic resistance in GBM, but, the precise mechanisms are not fully understood. Understanding the molecular mechanisms underlying the response of GBM to chemotherapy is paramount for developing improved cancer therapeutics. In this study, we demonstrated that the loss of DOC-2/DAB2 interacting protein (DAB2IP) is responsible for TMZ-resistance in GBM through ATG9B. DAB2IP sensitized GBM to TMZ and suppressed TMZ-induced autophagy by negatively regulating ATG9B expression. A higher level of ATG9B expression was associated with GBM compared to low-grade glioma. The knockdown of ATG9B expression in GBM cells suppressed TMZ-induced autophagy as well as TMZ-resistance. Furthermore, we showed that DAB2IP negatively regulated ATG9B expression by blocking the Wnt/β-catenin pathway. To enhance the benefit of TMZ and avoid therapeutic resistance, effective combination strategies were tested using a small molecule inhibitor blocking the Wnt/β-catenin pathway in addition to TMZ. The combination treatment synergistically enhanced the efficacy of TMZ in GBM cells. In conclusion, the present study identified the mechanisms of TMZ-resistance of GBM mediated by DAB2IP and ATG9B which provides insight into a potential strategy to overcome TMZ chemo-resistance.
Macrophage migration inhibitory factor inhibition as a novel therapeutic approach against triple-negative breast cancer
Authors: Charan Manish , Das Subhadip , Mishra Sanjay , Chatterjee Nabanita , Varikuti Sanjay , Kaul Kirti , Misri Swati , Ahirwar Dinesh K. , Satoskar Abhay R. , Ganju Ramesh K.
Published: September 2020

Triple-negative breast cancer (TNBC), defined as loss of estrogen, progesterone, and Her2 receptors, is a subtype of highly aggressive breast cancer with worse prognosis and poor survival rate. Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine aberrantly expressed in many solid tumors and known to promote tumor progression and metastasis. However, its role in TNBC progression and metastasis is unexplored. Here we have shown that in TNBC patients, MIF expression was significantly enriched in the tumor compared to adjacent normal tissue. Using publically available patient datasets, we showed that MIF overexpression correlates with worse survival in TNBC compared to other hormonal status. Orthotopic implantation of TNBC cells into MIF knockout mice showed reduced tumor growth compared to wild-type mice. In addition, we have shown that MIF downregulation inhibits TNBC growth and progression in a syngeneic mouse model. We further showed that CPSI-1306, a small-molecule MIF inhibitor, inhibits the growth of TNBC cells in vitro. Mechanistic studies revealed that CPSI-1306 induces intrinsic apoptosis by alteration in mitochondrial membrane potential, cytochrome c (Cyt c) release, and activation of different caspases. In addition, CPSI-1306 inhibits the activation of cell survival and proliferation-related molecules. CPSI-1306 treatment also reduced the tumor growth and metastasis in orthotopic mouse models of mammary carcinoma. CPSI-1306 treatment of tumor-bearing mice significantly inhibited TNBC growth and pulmonary metastasis in a dose-dependent manner. Histological analysis of xenograft tumors revealed a higher number of apoptotic cells in CPSI-1306-treated tumors compared to vehicle controls. Our studies, for the first time, show that MIF overexpression in TNBC enhances growth and metastasis. Taken together, our results indicate that using small molecular weight MIF inhibitors could be a promising strategy to inhibit TNBC progression and metastasis.
Oxidative stress-mediated mitochondrial dysfunction facilitates mesenchymal stem cell senescence in ankylosing spondylitis
Authors: Ye Guiwen , Xie Zhongyu , Zeng Huiqiong , Wang Peng , Li Jinteng , Zheng Guan , Wang Shan , Cao Qian , Li Ming , Liu Wenjie , Cen Shuizhong , Li Zhaofeng , Wu Yanfeng , Ye Zhizhong , Shen Huiyong
Published: September 2020

Ankylosing spondylitis (AS) is a chronic inflammatory disease possessing a morbid serum microenvironment with enhanced oxidative stress. Long-term exposure to an oxidative environment usually results in cellular senescence alone with cellular dysfunction. Mesenchymal stem cells (MSCs) are a kind of stem cell possessing strong capabilities for immunoregulation, and senescent MSCs may increase inflammation and participate in AS pathogenesis. The objective of this study was to explore whether and how the oxidative serum environment of AS induces MSC senescence. Here, we found that AS serum facilitated senescence of MSCs in vitro, and articular tissues from AS patients exhibited higher expression levels of the cell cycle arrest-related proteins p53, p21 and p16. Importantly, the levels of advanced oxidative protein products (AOPPs), markers of oxidative stress, were increased in AS serum and positively correlated with the extent of MSC senescence induced by AS serum. Furthermore, MSCs cultured with AS serum showed decreased mitochondrial membrane potential and ATP production together with a reduced oxygen consumption rate. Finally, we discovered that AS serum-induced mitochondrial dysfunction resulted in elevated reactive oxygen species (ROS) in MSCs, and ROS inhibition successfully rescued MSCs from senescence. In conclusion, our data demonstrated that the oxidative serum environment of AS facilitated MSC senescence through inducing mitochondrial dysfunction and excessive ROS production. These results may help elucidate the pathogenesis of AS and provide potential targets for AS treatment.
Carbon pricing and planetary boundaries
Authors: Engström Gustav , Gars Johan , Krishnamurthy Chandra , Spiro Daniel , Calel Raphael , Lindahl Therese , Narayanan Badri
Published: September 2020

Human activities are threatening to push the Earth system beyond its planetary boundaries, risking catastrophic and irreversible global environmental change. Action is urgently needed, yet well-intentioned policies designed to reduce pressure on a single boundary can lead, through economic linkages, to aggravation of other pressures. In particular, the potential policy spillovers from an increase in the global carbon price onto other critical Earth system processes has received little attention to date. To this end, we explore the global environmental effects of pricing carbon, beyond its effect on carbon emissions. We find that the case for carbon pricing globally becomes even stronger in a multi-boundary world, since it can ameliorate many other planetary pressures. It does however exacerbate certain planetary pressures, largely by stimulating additional biofuel production. When carbon pricing is allied with a biofuel policy, however, it can alleviate all planetary pressures.
Organic-to-inorganic structural chirality transfer in a 2D hybrid perovskite and impact on Rashba-Dresselhaus spin-orbit coupling
Authors: Jana Manoj K. , Song Ruyi , Liu Haoliang , Khanal Dipak Raj , Janke Svenja M. , Zhao Rundong , Liu Chi , Valy Vardeny Z. , Blum Volker , Mitzi David B.
Published: September 2020

Translation of chirality and asymmetry across structural motifs and length scales plays a fundamental role in nature, enabling unique functionalities in contexts ranging from biological systems to synthetic materials. Here, we introduce a structural chirality transfer across the organic–inorganic interface in two-dimensional hybrid perovskites using appropriate chiral organic cations. The preferred molecular configuration of the chiral spacer cations,R-(+)- orS-(−)-1-(1-naphthyl)ethylammonium and their asymmetric hydrogen-bonding interactions with lead bromide-based layers cause symmetry-breaking helical distortions in the inorganic layers, otherwise absent when employing a racemic mixture of organic spacers. First-principles modeling predicts a substantial bulk Rashba-Dresselhaus spin-splitting in the inorganic-derived conduction band with opposite spin textures betweenR- andS-hybrids due to the broken inversion symmetry and strong spin-orbit coupling. The ability to break symmetry using chirality transfer from one structural unit to another provides a synthetic design paradigm for emergent properties, including Rashba-Dresselhaus spin-polarization for hybrid perovskite spintronics and related applications.
Chromatin remodeling in bovine embryos indicates species-specific regulation of genome activation
Authors: Halstead Michelle M. , Ma Xin , Zhou Chuan , Schultz Richard M. , Ross Pablo J.
Published: September 2020

The shift from maternal to embryonic control is a critical developmental milestone in preimplantation development. Widespread transcriptomic and epigenetic remodeling facilitate this transition from terminally differentiated gametes to totipotent blastomeres, but the identity of transcription factors (TF) and genomic elements regulating embryonic genome activation (EGA) are poorly defined. The timing of EGA is species-specific, e.g., the timing of murine and human EGA differ significantly. To deepen our understanding of mammalian EGA, here we profile changes in open chromatin during bovine preimplantation development. Before EGA, open chromatin is enriched for maternal TF binding, similar to that observed in humans and mice. During EGA, homeobox factor binding becomes more prevalent and requires embryonic transcription. A cross-species comparison of open chromatin during preimplantation development reveals strong similarity in the regulatory circuitry underlying bovine and human EGA compared to mouse. Moreover, TFs associated with murine EGA are not enriched in cattle or humans, indicating that cattle may be a more informative model for human preimplantation development than mice.
Continuous 3D printing from one single droplet
Authors: Zhang Yu , Dong Zhichao , Li Chuxin , Du Huifeng , Fang Nicholas X. , Wu Lei , Song Yanlin
Published: September 2020

3D printing has become one of the most promising methods to construct delicate 3D structures. However, precision and material utilization efficiency are limited. Here, we propose a one-droplet 3D printing strategy to fabricate controllable 3D structures from a single droplet ascribing to the receding property of the three-phase contact line (TCL) of the resin droplet. The well-controlled dewetting force of liquid resin on the cured structure results in the minimization of liquid residue and the high wet and net material utilization efficiency in forming a droplet into a 3D structure. Additionally, extra curing induced protruding or stepped sidewalls under high printing speed, which require high UV intensity, can be prevented. The critical is the free contact surface property of the droplet system with the introduction of the receding TCL, which increased the inner droplet liquid circulation and reduces the adhesion properties among the liquid resin, cured resin, and resin vat.
Array programming with NumPy
Authors: Harris Charles R. , Millman K. Jarrod , van der Walt Stéfan J. , Gommers Ralf , Virtanen Pauli , Cournapeau David , Wieser Eric , Taylor Julian , Berg Sebastian , Smith Nathaniel J. , Kern Robert , Picus Matti , Hoyer Stephan , van Kerkwijk Marten H. , Brett Matthew , Haldane Allan , del Río Jaime Fernández , Wiebe Mark , Peterson Pearu , Gérard-Marchant Pierre , Sheppard Kevin , Reddy Tyler , Weckesser Warren , Abbasi Hameer , Gohlke Christoph , Oliphant Travis E.
Published: September 2020

Array programming provides a powerful, compact and expressive syntax for accessing, manipulating and operating on data in vectors, matrices and higher-dimensional arrays. NumPy is the primary array programming library for the Python language. It has an essential role in research analysis pipelines in fields as diverse as physics, chemistry, astronomy, geoscience, biology, psychology, materials science, engineering, finance and economics. For example, in astronomy, NumPy was an important part of the software stack used in the discovery of gravitational waves1and in the first imaging of a black hole2. Here we review how a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring and analysing scientific data. NumPy is the foundation upon which the scientific Python ecosystem is constructed. It is so pervasive that several projects, targeting audiences with specialized needs, have developed their own NumPy-like interfaces and array objects. Owing to its central position in the ecosystem, NumPy increasingly acts as an interoperability layer between such array computation libraries and, together with its application programming interface (API), provides a flexible framework to support the next decade of scientific and industrial analysis.
Pre-transplant depression decreased overall survival of patients receiving allogeneic hematopoietic stem cell transplantation: a nationwide cohort study
Authors: Wang Sheng-Min , Park Sung-Soo , Park Si-Hyun , Kim Nak-Young , Kang Dong Woo , Na Hae-Ran , Lee Jong Wook , Han Seunghoon , Lim Hyun Kook
Published: September 2020

Studies investigating association of depression with overall survival (OS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) yielded conflicting results. A nationwide cohort study, which included all adult patients [n = 7,170; depression group, 13.3% (N = 956); non-depression group, 86.7% (N = 6,214)] who received allo-HSCT from 2002 to 2018 in South Korea, analyzed risk of pre-transplant depression in OS of allo-HSCT. Subjects were followed from the day they received allo-HSCT, to occurrence of death, or last follow-up day (December 31, 2018). Median age at allo-HSCT for depression and non-depression groups were 50 and 45 (p < 0.0001), respectively. Two groups also differed in rate of females (depression group, 55.8%; non-depression group, 43.8%; p < 0.0001) and leukemia (depression group, 61.4%; non-depression group, 49.7%; p < 0.0001). After a median follow-up of 29.1 months, 5-year OS rate was 63.1%. Cox proportional-hazard regression evaluated an adjusted risk of post-transplant mortality related to depression: OS decreased sequentially from no depression (adjusted hazard ratio [aHR] = 1) to pre-transplant depression only (aHR = 1.167, CI: 1.007–1.352, p = 0.04), and to having both depression and anxiety disorder (aHR = 1.202, CI: 1.038–1.393, p = 0.014) groups. Pre-transplant anxiety (anxiety only) did not have significant influence in OS. Additional medical and psychiatric care might be necessary in patients who experienced depression, especially with anxiety, before allo-HSCT.
Convolutional neural networks versus radiologists in characterization of small hypoattenuating hepatic nodules on CT: a critical diagnostic challenge in staging of colorectal carcinoma
Authors: Khalili Korosh , Lawlor Raymond L. , Pourafkari Marina , Lu Hua , Tyrrell Pascal , Kim Tae Kyoung , Jang Hyun-Jung , Johnson Sarah A. , Martel Anne L.
Published: September 2020

Our objective was to compare the diagnostic performance and diagnostic confidence of convolutional neural networks (CNN) to radiologists in characterizing small hypoattenuating hepatic nodules (SHHN) in colorectal carcinoma (CRC) on CT scans. Retrospective review of CRC CT scans over 6-years yielded 199 patients (550 SHHN) defined as < 1 cm in diameter. The reference standard was established through 1-year stability/MRI for benign or nodule evolution for malignant nodules. Five CNNs underwent supervised training on 150 patients (412 SHHN). The remaining 49 patients (138 SHHN) were used as testing-set to compare performance of 3 radiologists to CNN, measured through ROC AUC analysis of confidence rating assigned to each nodule by the radiologists. Multivariable modeling was used to compensate for radiologist bias from visible findings other than SHHN. In characterizing SHHN as benign or malignant, the radiologists’ mean AUC ROC (0.96) was significantly higher than CNN (0.84, p = 0.0004) but equivalent to CNN adjusted through multivariable modeling for presence of synchronous ≥ 1 cm liver metastases (0.95, p = 0.9). The diagnostic confidence of radiologists and CNN were analyzed. There were significantly lower number of nodules rated with low confidence by CNN (19.6%) and CNN with liver metastatic status (18.1%) than two (38.4%, 44.2%, p < 0.0001) but not a third radiologist (11.1%, p = 0.09). We conclude that in CRC, CNN in combination with liver metastatic status equaled expert radiologists in characterizing SHHN but with better diagnostic confidence.
Transition metals induce control of enhanced NLO properties of functionalized organometallic complexes under laser modulations
Authors: Taboukhat S. , Kichou N. , Fillaut J.-L. , Alévêque O. , Waszkowska K. , Zawadzka A. , El-Ghayoury A. , Migalska-Zalas A. , Sahraoui B.
Published: September 2020

The molecular engineering of organometallic complexes has recently attracted renewed interest on account of their potential technological applications for optoelectronics in general and optical data storage. The transition metal which induces control of enhanced nonlinear optical properties of functionalized organometallic complexes versus not only the intensity but also the polarization of the incident laser beam is original and important for all optical switching. This makes organometallic complexes valuable and suitable candidates for nonlinear optical applications. In the present work, we report the synthesis and full characterization of four organometallic complexes consisting of N, N-dibutylamine and azobenzene fragments but differ by auxiliary alkynyl ligands or metal cations. Thus, a ferrocenyl derivative 1 and three ruthenium complexes 2–4 have been prepared. The nonlinear optical properties of the four new azo-based ruthenium and iron organometallic complexes in the solid state, using polymethylmethacrylate as matrix, have been thoroughly studied. This concept is extended to computing the HOMO and LUMO energy levels of the considered complexes, dipole moment, first and second order hyperpolarizabilities using the 6–31 + G(d,p) + LANL2DZ mixed basis set. The second and third nonlinear optical properties of the resulting polymer composites were obtained by measuring SHG and THG response by means of the Maker fringe technique using a laser generating at 1,064 nm with a 30 ps pulse duration. The values of the second and third order NLO susceptibilities of the four organometallic complexes were found to be higher than the common references used. Theoretical calculation shows that the large first and second order hyperpolarizablities are caused by strong intramolecular charge transfer between the transition metal parts and the ligands though a conjugated transmitter. These results indicate that the present organometallic complexes are valuable candidates for optoelectronic and photonic applications.
Punica granatum L.-derived omega-5 nanoemulsion improves hepatic steatosis in mice fed a high fat diet by increasing fatty acid utilization in hepatocytes
Authors: Zamora-López K. , Noriega L. G. , Estanes-Hernández A. , Escalona-Nández I. , Tobón-Cornejo S. , Tovar A. R. , Barbero-Becerra V. , Pérez-Monter C.
Published: September 2020

Pomegranate seed oil (PSO) is mainly composed of punicic acid (PA), a polyunsaturated fatty acid also known as omega-5 (ω-5), a potent antioxidant associated with a variety of metabolic and cellular beneficial effects. However, the potential benefits of a nanoemulsified version of ω-5 (PSOn) have not been evaluated in a pathological liver condition. Here, we examined whether PSOn had beneficial effects on C57BL/6N mice fed a high-fat diet (HFD), specifically on hepatic steatosis. We observed that PSOn supplementation decreased body weight and body fat mass in control mice, whereas glucose intolerance, insulin resistance, energy expenditure, and hepatic steatosis were improved in both control mice and in mice fed a HFD. Interestingly, PSOn increased fatty acid oxidation in primary hepatocytes and antioxidant gene expression. Altogether, our data indicate that PSOn effectively reduces some of the HFD-derived metabolic syndrome indicators by means of an increase in fatty acid oxidation within hepatocytes.
The landscape of microsatellites in the enset (Ensete ventricosum) genome and web-based marker resource development
Authors: Biswas Manosh Kumar , Darbar Jaypal N. , Borrell James S. , Bagchi Mita , Biswas Dhiman , Nuraga Gizachew Woldesenbet , Demissew Sebsebe , Wilkin Paul , Schwarzacher Trude , Heslop-Harrison J. S.
Published: September 2020

Ensete ventricosum (Musaceae, enset) is an Ethiopian food security crop. To realize the potential of enset for rural livelihoods, further knowledge of enset diversity, genetics and genomics is required to support breeding programs and conservation. This study was conducted to explore the enset genome to develop molecular markers, genomics resources, and characterize enset landraces while giving insight into the organization of the genome. We identified 233 microsatellites (simple sequence repeats, SSRs) per Mbp in the enset genome, representing 0.28% of the genome. Mono- and di-nucleotide repeats motifs were found in a higher proportion than other classes of SSR-motifs. In total, 154,586 non-redundant enset microsatellite markers (EMM) were identified and 40 selected for primer development. Marker validation by PCR and low-cost agarose gel electrophoresis revealed that 92.5% were polymorphic, showing a high PIC (Polymorphism Information Content; 0.87) and expected heterozygosity (He = 0.79–0.82). In silico analysis of genomes of closely related species showed 46.86% of the markers were transferable among enset species and 1.90% were transferable to Musa. The SSRs are robust (with basic PCR methods and agarose gel electrophoresis), informative, and applicable in measuring enset diversity, genotyping, selection and potentially breeding. Enset SSRs are available in a web-based database at https://enset-project.org/EnMom@base.html (or https://enset.aau.edu.et/index.html, downloadable from Figshare).
Effects of different social experiences on emotional state in mice
Authors: Krakenberg Viktoria , Siestrup Sophie , Palme Rupert , Kaiser Sylvia , Sachser Norbert , Richter S. Helene
Published: September 2020

A comprehensive understanding of animals’ emotions can be achieved by combining cognitive, behavioural, and physiological measures. Applying such a multi-method approach, we here examined the emotional state of mice after they had made one of three different social experiences: either a mildly “adverse”, a “beneficial”, or a “neutral” experience. Using a recently established touchscreen paradigm, cognitive judgement bias was assessed twice, once before and once after the respective experience. Anxiety-like behaviour was examined using a standardised battery of behavioural tests and faecal corticosterone metabolite concentrations were measured. Surprisingly, only minor effects of the social experiences on the animals’ cognitive judgement bias and no effects on anxiety-like behaviour and corticosterone metabolite levels were found. It might be speculated that the experiences provided were not strong enough to exert the expected impact on the animals’ emotional state. Alternatively, the intensive training procedure necessary for cognitive judgement bias testing might have had a cognitive enrichment effect, potentially countering external influences. While further investigations are required to ascertain the specific causes underlying our findings, the present study adds essential empirical data to the so far scarce amount of studies combining cognitive, behavioural, and physiological measures of emotional state in mice.
Regional surface chlorophyll trends and uncertainties in the global ocean
Authors: Hammond Matthew L. , Beaulieu Claudie , Henson Stephanie A. , Sahu Sujit K.
Published: September 2020

Changes in marine primary productivity are key to determine how climate change might impact marine ecosystems and fisheries. Satellite ocean color sensors provide coverage of global ocean chlorophyll with a combined record length of ~ 20 years. Coupled physical–biogeochemical models can inform on expected changes and are used here to constrain observational trend estimates and their uncertainty. We produce estimates of ocean surface chlorophyll trends, by using Coupled Model Intercomparison Project (CMIP5) models to form priors as a “first guess”, which are then updated using satellite observations in a Bayesian spatio-temporal model. Regional chlorophyll trends are found to be significantly different from zero in 18/23 regions, in the range ± 1.8% year−1. A global average of these regional trends shows a net positive trend of 0.08 ± 0.35% year−1, highlighting the importance of considering chlorophyll changes at a regional level. We compare these results with estimates obtained with the commonly used “vague” prior, representing no independent knowledge; coupled model priors are shown to slightly reduce trend magnitude and uncertainties in most regions. The statistical model used here provides a robust framework for making best use of all available information and can be applied to improve understanding of global change.
Tape stripping method is useful for the quantification of antimicrobial peptides on the human skin surface including the stratum corneum
Authors: Ono Shigeyuki , Eda Nobuhiko , Mori Takuya , Otsuka Atsuko , Nakamura Nobuhiro , Inai Yuto , Ota Noriyasu , Akama Takao
Published: September 2020

Antimicrobial peptides (AMPs) play an important role in innate immunity in human skin. It is known that AMPs mainly function in the stratum corneum. Therefore, AMP concentrations in the stratum corneum need to be precisely measured to clarify functional and physiological importance of AMPs in cutaneous defence. Tape stripping (TS) is a well-established method by which components in the stratum corneum can be collected. However, the usefulness of the TS method for measuring AMP concentration in human skin remains unclear. Therefore, we compared it with another popular method, skin rinsing, which had been established as a method for measuring AMP concentration in human skin. When investigated on healthy medial forearm using RNase 7, which is one of the typical AMPs, as an index, there was a significant positive correlation between RNase 7 concentrations measured by the TS method at adjacent forearm sites, demonstrating the reproducibility of the TS method. Next, a significant positive correlation was detected in RNase 7 concentrations measured using the TS and the skin rinsing method, indicating that the TS method is comparable to the skin rinsing method. Thus, we speculate that the TS method is useful for measuring AMP concentration in human skin.
Air pollution impairs recovery and tissue remodeling in a murine model of acute lung injury
Authors: de Souza Xavier Costa Natália , Ribeiro Júnior Gabriel , dos Santos Alemany Adair Aparecida , Belotti Luciano , Schalch Alexandre Santos , Cavalcante Marcela Frota , Ribeiro Susan , Veras Mariana Matera , Kallás Esper Georges , Saldiva Paulo Hilário Nascimento , Dolhnikoff Marisa , Ferraz da Silva Luiz Fernando
Published: September 2020

Evidence regarding the impact of air pollution on acute respiratory distress syndrome (ARDS) is limited, and most studies focus on ARDS onset. Our study aimed to evaluate whether exposure to fine particulate matter interferes with lung recovery and remodeling in a murine model of acute lung injury. Forty-eight mice received nebulized LPS or the vehicle (controls). Blood, BALF, lungs and spleen were collected after 5 weeks of exposure to either PM2.5 (PM and LPS + PM group) or filtered air (control and LPS5w groups). Inflammatory cells and cytokines were assessed in the blood, BALF, lungs and spleen. Stereological analyses and remodeling assessments were performed by histology. The LPS + PM group showed increased BALF leukocytes, characterized by increased macrophages, increased IL-1β and IL-6 levels, anemia and thrombocytopenia. Moreover, we also observed septal thickening, decreased alveolar air space total volume and, septa surface density. Finally, regarding tissue remodeling, we observed elastosis of the lung parenchyma, and unlike in the LPS5w group, we did not observe fibrosis in the LPS + PM group. In conclusion, the delayed inflammation resolution due to subchronic exposure to PM2.5 could be influenced by low systemic and local lymphocyte counts, which lead to impaired lung injury recovery and tissue remodeling.
How levelling and scan line corrections ruin roughness measurement and how to prevent it
Authors: Nečas David , Valtr Miroslav , Klapetek Petr
Published: September 2020

Surface roughness plays an important role in various fields of nanoscience and nanotechnology. However, the present practices in roughness measurements, typically based on some Atomic Force Microscopy measurements for nanometric roughness or optical or mechanical profilometry for larger scale roughness significantly bias the results. Such biased values are present in nearly all the papers dealing with surface parameters, in the areas of nanotechnology, thin films or material science. Surface roughness, most typically root mean square value of irregularities Sq is often used parameter that is used to control the technologies or to link the surface properties with other material functionality. The error in estimated values depends on the ratio between scan size and roughness correlation length and on the way how the data are processed and can easily be larger than 10% without us noting anything suspicious. Here we present a survey of how large is the problem, detailed analysis of its nature and suggest methods to predict the error in roughness measurements and possibly to correct them. We also present a guidance for choosing suitable scan area during the measurement.
Optimization of tamoxifen-induced Cre activity and its effect on immune cell populations
Authors: Donocoff Rachel S. , Teteloshvili Nato , Chung Hyunsoo , Shoulson Rivka , Creusot Remi J.
Published: September 2020

Tamoxifen (TAM) inducible Cre recombinase system is an essential tool to study gene function when early ablation or overexpression can cause developmental defects or embryonic lethality. However, there remains a lack of consensus on the optimal route and dosage of TAM administration in vivo. Here, we assessed dosage and delivery of TAM for activation of Cre in immune cell subsets assessed longitudinally and spatially using transgenic mice with ubiquitously expressed Cre/ER and the Cre-inducible fluorescent reporter YFP. After comparing two TAM delivery methods (intraperitoneal versus oral gavage) and different doses, we found that 3 mg of TAM administered orally for five consecutive days provides maximal reporter induction with minimal adverse effects in vivo. Serum levels of TAM peaked 1 week after initiating treatment then slowly decreased, regardless of dosing and delivery methods. TAM concentration in specific tissues (liver, spleen, lymph nodes, and thymus) was also dependent on delivery method and dose. Cre induction was highest in myeloid cells and B cells and substantially lower in T cells, and double-positive thymocytes had a notably higher response to TAM. In addition to establishing optimal dose and administration of TAM, our study reveals a disparate activity of Cre in different cell immune populations when using Cre/ER models.
Evaluation of a new variant in the aggrecan gene potentially associated with chondrodysplastic dwarfism in Miniature horses
Authors: de Andrade Danilo Giorgi Abranches , Basso Roberta Martins , Magro Angelo José , Laufer-Amorim Renée , Borges Alexandre Secorun , de Oliveira-Filho José Paes
Published: September 2020

Chondrodysplastic dwarfism in Miniature horses is an autosomal recessive disorder previously associated with four mutations (D1, D2, D3*, and D4) in the aggrecan (ACAN) gene. The aim of this study was to identify additional variants in the candidate ACAN gene associated with chondrodysplastic dwarfism in Miniature horses. Fifteen dwarf Miniature horses were found to possess only one of the dwarfism-causing variants, and two possessed none of the variants. The ACAN exons (EquCab3.0) of seven dwarf Miniature horses were sequenced. A missense SNP in coding exon 11 (g.95271115A > T, c.6465A > T—RefSeq XM_005602799.2), which resulted in the amino acid substitution p.Leu2155Phe (RefSeq XP_005602856.2), was initially associated with the dwarf phenotype. The variant was tested and found present in 14 dwarf foals as well as one parent of each, and both parents of a dwarf possessing two copies. Genetic testing of 347 phenotypically normal Miniature horses demonstrated that none had more than one of the dwarf alleles or c.6465A > T. However, a study of large breeds revealed the presence of c.6465A > T, which was present in homozygosis in two Mangalarga Marchador horses. We suggest that c.6465A > T as a marker of disequilibrium or complex interactions in the Miniature horse genome could contribute to the associated dwarfism.