bluuebunny/crossref_metadata_2025_split huggingface dataset:
Grain characteristics, electrical conductivity, and hardness of Zn-doped Cu–3Si alloys system
Authors: Nnakwo K. C. , Osakwe F. O. , Ugwuanyi B. C. , Oghenekowho P. A. , Okeke I. U. , Maduka E. A. 
Published: October 2021

AbstractThe grain characteristics, electrical conductivity, hardness, and bulk density of Cu–3Si–(0.1—1 wt%)Zn alloys system fabricated by gravity casting technique were investigated experimentally using optical microscopy (OM), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). The study established the optimal alloy composition and the significance of zinc addition on the tested properties using response surface optimal design (RSOD). The cooled alloy samples underwent normalizing heat treatment at 900 °C for 0.5 h. The average grains size and grains distribution were analyzed using the linear intercept method (ImageJ). The microstructure examination revealed a change in grain characteristics (morphology and size) of the parent alloy by addition of 0.1 wt% zinc. The average grains size of the parent alloy decreased from 12 µm to 7.0 µm after 0.1 wt% zinc addition. This change in grain characteristics led to an increase in the hardness of the parent alloy by 42.2%, after adding 0.1 wt% zinc. The electrical conductivity of the parent alloy decreased from 46.3%IACS to 45.3%IACS, while the density was increased by 8.4% after adding 0.1 wt% zinc. The statistical data confirmed the significance of the change in properties. The result of optimization revealed Cu–3Si–0.233Zn as the optimal alloy composition with optimal properties. The Cu–3Si–xZn alloy demonstrated excellent properties suitable for the fabrication of electrical and automobile components.
The ‘code adjudicator’ model: the Pubs Code, statutory arbitration and the tied lease
Authors: Meers Jed , Hind Liz 
Published: October 2021

AbstractThe ‘code adjudicator’ is a new statutory intervention in business-to-business disputes. They are Janus-faced, combining a statutory arbitration function with a regulatory remit. This paper is a detailed critique of the ‘Pubs Code Adjudicator’, which presides over the Pubs Code Regulations 2016 and intervenes in the contractual relationships between the largest pub-owning companies and their tied tenants. Drawing on a sample of interviews with affected tenants, arbitration data, and legal appeals under the Arbitration Act 1996, we argue that – although these ‘new intermediaries’ show promise – there are a series of limitations with both the function of the Pubs Code Regulations and the ‘code adjudicator’ model itself. In particular, our findings demonstrate the use of delaying tactics, the interaction of code adjudication with the parties’ existing contractual relationships, and issues with the application of arbitration ‘burden of proof’ standards to the exercise of duties under the statutory code.
MONOMIAL AND MONOLITHIC CHARACTERS OF FINITE SOLVABLE GROUPS
Authors: ÇINARCI BURCU 
Published: October 2021

AbstractLet G be a finite solvable group and let p be a prime divisor of
$|G|$
. We prove that if every monomial monolithic character degree of G is divisible by p, then G has a normal p-complement and, if p is relatively prime to every monomial monolithic character degree of G, then G has a normal Sylow p-subgroup. We also classify all finite solvable groups having a unique imprimitive monolithic character.
Tick infestation effects on haemoglobin levels of deer mice (Peromyscus maniculatus)
Authors: Fellin Erica , Schulte-Hostedde Albrecht 
Published: October 2021

AbstractDeer mice (Peromyscus maniculatus) are hosts to ixodid ticks as well as the associated tick-borne pathogens they can spread. As the ranges of black-legged ticks (Ixodes scapularis) and American dog ticks (Dermacentor variabilis) expand northwards, naïve host populations of deer mice are likely to become infested by ticks and experience the physiological effects that ticks can have on them via blood-feeding. The prevalence of these haematophagous ticks can affect the haemoglobin levels of the mice they infest. Haemoglobin levels were compared and analysed in deer mice populations at three different sites with varying tick exposure. These results suggested that without confounding effects, the abundance of black-legged and American dog ticks on individual mice had a significant negative effect on the hosts' haemoglobin levels, but only in an area with high tick infestation. This was seen across the average haemoglobin levels between populations, where there was a significant difference between the source population with the longest established tick populations and the source population where neither black-legged nor American dog ticks were prevalent. As the ticks' ranges expand and they become more abundant, it is important to understand how their prevalence and intensity can alter host physiology, potentially affecting their own range expansion and the spread of the diseases they may carry.
Neuroanatomical markers of familial risk in adolescents with conduct disorder and their unaffected relatives
Authors: Fairchild Graeme , Sully Kate , Passamonti Luca , Staginnus Marlene , Darekar Angela , Sonuga-Barke Edmund J. S. , Toschi Nicola 
Published: October 2021

AbstractBackgroundPrevious studies have reported brain structure abnormalities in conduct disorder (CD), but it is unclear whether these neuroanatomical alterations mediate the effects of familial (genetic and environmental) risk for CD. We investigated brain structure in adolescents with CD and their unaffected relatives (URs) to identify neuroanatomical markers of familial risk for CD.MethodsForty-one adolescents with CD, 24 URs of CD probands, and 38 healthy controls (aged 12–18), underwent structural magnetic resonance imaging. We performed surface-based morphometry analyses, testing for group differences in cortical volume, thickness, surface area, and folding. We also assessed the volume of key subcortical structures.ResultsThe CD and UR groups both displayed structural alterations (lower surface area and folding) in left inferior parietal cortex compared with controls. In contrast, CD participants showed lower insula and pars opercularis volume than controls, and lower surface area and folding in these regions than controls and URs. The URs showed greater folding in rostral anterior cingulate and inferior temporal cortex than controls and greater medial orbitofrontal folding than CD participants. The surface area and volume differences were not significant when controlling for attention-deficit/hyperactivity disorder comorbidity. There were no group differences in subcortical volumes.ConclusionsThese findings suggest that alterations in inferior parietal cortical structure partly mediate the effects of familial risk for CD. These structural changes merit investigation as candidate endophenotypes for CD. Neuroanatomical changes in medial orbitofrontal and anterior cingulate cortex differentiated between URs and the other groups, potentially reflecting neural mechanisms of resilience to CD.
Improved Weather Forecasting Using Neural Network Emulation for Radiation Parameterization
Authors: Song Hwan‐Jin , Roh Soonyoung 
Published: October 2021

AbstractIn this study, a neural network (NN) emulator for radiation parameterization was developed to use in an operational weather forecasting model in the Korea Meteorological Administration. The development of the NN emulator was based on large‐scale training sets and 96 categories (longwave–shortwave, months, land–ocean, and clear–cloud). As the NN emulator replaced the radiation parameterization, a 60‐fold speedup for the radiation process was achieved, with a decrease of 87.26% in the total computation time. The accuracy of the NN emulator was strictly evaluated through comparison with the results obtained from the infrequent use of the original radiation scheme with the same computational cost. The mean errors of the NN emulator for skin temperature and fluxes were significantly reduced by 22%–34% compared with the infrequent method. The combination of using the NN radiation emulator and applying it infrequently provided an additional speedup of up to 36‐fold, corresponding to 2,160 times speedup compared with the control run, without a significant reduction in accuracy. The optimized structure for the radiation emulator designed in this study also showed universal robustness even in the use of limited training sets with incomplete coverage. As a result of the evaluation using surface observations, the use of the NN emulator showed no significant degradation for precipitation and temperature forecasts in comparison with the control run. In conclusion, the NN emulator for radiation parameterization in this study benefits both accuracy and computational cost, making it useful for improving weather forecasting modeling.
Light People: Professor Aydogan Ozcan
Authors: Sun Tingting 
Published: October 2021

EditorialIn 2016, the news that Google’s artificial intelligence (AI) robot AlphaGo, based on the principle of deep learning, won the victory over lee Sedol, the former world Go champion and the famous 9th Dan competitor of Korea, caused a sensation in both fields of AI and Go, which brought epoch-making significance to the development of deep learning. Deep learning is a complex machine learning algorithm that uses multiple layers of artificial neural networks to automatically analyze signals or data. At present, deep learning has penetrated into our daily life, such as the applications of face recognition and speech recognition. Scientists have also made many remarkable achievements based on deep learning. Professor Aydogan Ozcan from the University of California, Los Angeles (UCLA) led his team to research deep learning algorithms, which provided new ideas for the exploring of optical computational imaging and sensing technology, and introduced image generation and reconstruction methods which brought major technological innovations to the development of related fields. Optical designs and devices are moving from being physically driven to being data-driven. We are much honored to have Aydogan Ozcan, Fellow of the National Academy of Inventors and Chancellor’s Professor of UCLA, to unscramble his latest scientific research results and foresight for the future development of related fields, and to share his journey of pursuing Optics, his indissoluble relationship with Light: Science & Applications (LSA), and his experience in talent cultivation.
RING-finger protein 6 promotes colorectal tumorigenesis by transcriptionally activating SF3B2
Authors: Xu Hui , Wong Chi Chun , Li Weilin , Zhou Yunfei , Li Yan , Wang Lifu , Liu Lei , Yu Jun 
Published: October 2021

AbstractRNF6 is a RING finger protein with oncogenic potential. In this study, we established colon-specific RNF6 transgenic (tg) mice, and demonstrated that RNF6 overexpression accelerated colorectal carcinogenesis compared to wild-type littermates in a chemically induced colorectal cancer (CRC) model. To understand whether transcriptional activity of RNF6 underlies its oncogenic effect, we performed integrated chromatin immunoprecipitation (ChIP)-sequencing and RNA-sequencing analysis to identify splicing factor 3b subunit 2 (SF3B2) as a potential downstream target of RNF6. RNF6 binds to the SF3B2 promoter and the overexpression of RNF6 activates SF3B2 expression in CRC cells, primary CRC organoids, and RNF6 tg mice. SF3B2 knockout abrogated the tumor promoting effect of RNF6 overexpression, whereas the reexpression of SF3B2 recused cell growth and migration/invasion in RNF6 knockout cells, indicating that SF3B2 is a functional downstream target of RNF6 in CRC. Targeting of RNF6-SF3B2 axis with SF3B2 inhibitor with pladienolide B suppressed the growth of CRC cells with RNF6 overexpression in vitro and in vivo. Moreover, the combination of 5-fluorouracil (5-FU) plus pladienolide B exerted synergistic effects in CRC with high RNF6 expression, leading to tumor regression in xenograft models. These findings indicate that tumor promoting effect of RNF6 is achieved mainly via transcriptional upregulation of SF3B2, and that RNF6-SF3B2 axis is a promising target for CRC therapy.
IER2-induced senescence drives melanoma invasion through osteopontin
Authors: Kyjacova Lenka , Saup Rafael , Rönsch Kerstin , Wallbaum Sabine , Dukowic-Schulze Stefanie , Foss Amelia , Scherer Sandra D. , Rothley Melanie , Neeb Antje , Grau Nicole , Thiele Wilko , Thaler Sonja , Cremers Natascha , Sticht Carsten , Gretz Norbert , Garvalov Boyan K. , Utikal Jochen , Sleeman Jonathan P. 
Published: October 2021

AbstractExpression of the immediate-early response gene IER2 has been associated with the progression of several types of cancer, but its functional role is poorly understood. We found that increased IER2 expression in human melanoma is associated with shorter overall survival, and subsequently investigated the mechanisms through which IER2 exerts this effect. In experimental melanoma models, sustained expression of IER2 induced senescence in a subset of melanoma cells in a p53/MAPK/AKT-dependent manner. The senescent cells produced a characteristic secretome that included high levels of the extracellular phosphoglycoprotein osteopontin. Nuclear localization of the IER2 protein was critical for both the induction of senescence and osteopontin secretion. Osteopontin secreted by IER2-expressing senescent cells strongly stimulated the migration and invasion of non-senescent melanoma cells. Consistently, we observed coordinate expression of IER2, p53/p21, and osteopontin in primary human melanomas and metastases, highlighting the pathophysiological relevance of IER2-mediated senescence in melanoma progression. Together, our study reveals that sustained IER2 expression drives melanoma invasion and progression through stimulating osteopontin secretion via the stochastic induction of senescence.
Diffuse large B cell lymphoma (DLBCL) in patients older than 65 years: analysis of 3 year Real World data of practice patterns and outcomes in England
Authors: Hounsome L. , Eyre T. A. , Ireland R. , Hodson A. , Walewska R. , Ardeshna K. , Chaganti S. , McKay P. , Davies A. , Fox C. P. , Kalakonda N. , Fields P. A. 
Published: October 2021

Abstract
Background
We wished to examine treatment and outcome patterns in older diffuse large B-cell lymphoma (DLBCL) patients, with a focus on the effect of route-to-diagnosis to outcome.

Methods
Data were extracted from Public Health England’s National Cancer Registration and Analysis Service between 2013 and 2015 included route-to-diagnosis, disease characteristics and survival for 9186 patients ≥65 years. Systemic Anti-Cancer Therapy data identified front-line regimens, cycles and doses.

Results
Route-to-diagnosis were emergency (34%), NHS urgent cancer pathway (rapid haemato-oncologist review <2 weeks), (29%) and standard GP referral (25%). The most common regimen was R-CHOP (n = 4392). 313 patients received R-miniCHOP (7% of R-CHOP). For all patients, 3-year overall survival (OS) for 65–79 years was 57% and for ≥80 years was 32%. Three-year OS for R-CHOP-treated patients diagnosed via emergency presentation was 54% (adjusted hazard ratio (HR) 1.63, p < 0.01) and 75% (adjusted HR 0.81, p < 0.01) on the NHS urgent cancer pathway (reference HR:1.00: GP referrals). 3-year OS was 54% for both R-miniCHOP and R-CHOP in ≥80 years.

Conclusions
Our comprehensive population analysis is the first to show that the NHS urgent cancer pathway is associated with a superior survival after adjusting for multiple confounders. Equivalent survival for R-CHOP and R-mini-CHOP was demonstrated in those ≥80 years.
Autophagy provides a conceptual therapeutic framework for bone metastasis from prostate cancer
Authors: Wang YouZhi , Wu Ning , Jiang Ning 
Published: October 2021

AbstractProstate cancer is a common malignant tumor, which can spread to multiple organs in the body. Metastatic disease is the dominant reason of death for patients with prostate cancer. Prostate cancer usually transfers to bone. Bone metastases are related to pathologic fracture, pain, and reduced survival. There are many known targets for prostate cancer treatment, including androgen receptor (AR) axis, but drug resistance and metastasis eventually develop in advanced disease, suggesting the necessity to better understand the resistance mechanisms and consider multi-target medical treatment. Because of the limitations of approved treatments, further research into other potential targets is necessary. Metastasis is an important marker of cancer development, involving numerous factors, such as AKT, EMT, ECM, tumor angiogenesis, the development of inflammatory tumor microenvironment, and defect in programmed cell death. In tumor metastasis, programmed cell death (autophagy, apoptosis, and necroptosis) plays a key role. Malignant cancer cells have to overcome the different forms of cell death to transfer. The article sums up the recent studies on the mechanism of bone metastasis involving key regulatory factors such as macrophages and AKT and further discusses as to how regulating autophagy is crucial in relieving prostate cancer bone metastasis.
Astrocytic YAP prevents the demyelination through promoting expression of cholesterol synthesis genes in experimental autoimmune encephalomyelitis
Authors: Zhang Jingjing , Xu Xingxing , Liu Huitao , Jin Lingting , Shen Xiya , Xie Changnan , Xiang Weiwei , Yang Danlu , Feng Wenjin , Wang Jiaojiao , Wang Mianxian , Dong Tianyingying , Qiu Haoyu , Wu Lihao , Wang Ying , Zhang Xu , Huang Zhihui 
Published: October 2021

AbstractCholesterols are the main components of myelin, and are mainly synthesized in astrocytes and transported to oligodendrocytes and neurons in the adult brain. It has been reported that Hippo/yes-associated protein (YAP) pathways are involved in cholesterol synthesis in the liver, however, it remains unknown whether YAP signaling can prevent the demyelination through promoting cholesterol synthesis in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of multiple sclerosis characterized by neuroinflammation and demyelination. Here, we found that YAP was upregulated and activated in astrocytes of spinal cords of EAE mice through suppression of the Hippo pathway. YAP deletion in astrocytes aggravated EAE with earlier onset, severer inflammatory infiltration, demyelination, and more loss of neurons. Furthermore, we found that the neuroinflammation was aggravated and the proliferation of astrocytes was decreased in YAPGFAP-CKO EAE mice. Mechanically, RNA-seq revealed that the expression of cholesterol-synthesis pathway genes such as HMGCS1 were decreased in YAP−/− astrocytes. qPCR, western blot, and immunostaining further confirmed the more significant reduction of HMGCS1 in spinal cord astrocytes of YAPGFAP-CKO EAE mice. Interestingly, upregulation of cholesterol-synthesis pathways by diarylpropionitrile (DPN) (an ERβ-ligand, to upregulate the expression of HMGCS1) treatment partially rescued the demyelination deficits in YAPGFAP-CKO EAE mice. Finally, activation of YAP by XMU-MP-1 treatment promoted the expression of HMGCS1 in astrocytes and partially rescued the demyelination and inflammatory infiltration deficits in EAE mice. These findings identify unrecognized functions of astrocytic YAP in the prevention of demyelination through promoting cholesterol synthesis in EAE, and reveal a novel pathway of YAP/HMGCS1 for cholesterol synthesis in EAE pathology.
Circular RNA UBE2Q2 promotes malignant progression of gastric cancer by regulating signal transducer and activator of transcription 3-mediated autophagy and glycolysis
Authors: Yang Jing , Zhang Xing , Cao Jiacheng , Xu Penghui , Chen Zetian , Wang Sen , Li Bowen , Zhang Lu , Xie Li , Fang Lang , Xu Zekuan 
Published: October 2021

AbstractGastric cancer remains the third leading cause of cancer-related mortality worldwide. Emerging evidence has shown that circular RNAs (circRNAs) play a critical regulatory role in the occurrence and development of various cancers through sponging miRNAs or acting as RNA-binding protein (RBP) sponges. We found that circUBE2Q2 was significantly upregulated in GC tissues and cell lines. Knockdown of circUBE2Q2 inhibited proliferation, migration, invasion, and glycolysis, and increased autophagy in vitro. In addition, knockdown of circUBE2Q2 inhibited GC tumorigenicity and metastasis potential in vivo. A series of experiments were performed to confirm that circUBE2Q2 regulates GC progression via the circUBE2Q2-miR-370-3p-STAT3 axis and promotes tumor metastasis through exosomal communication. Further in vivo experiments confirmed that, combination treatment of circUBE2Q2 knocking down and STAT3 inhibitor has synergistic effects on the gastric cancer growth inhibition, which provides a possibility to enhance the sensitivity of targeted drugs to gastric cancer through targeting circUBE2Q2. Our findings revealed that circUBE2Q2 may serve as a new proliferation-promoting factor and prognostic marker in gastric cancer.
Interception of host fatty acid metabolism by mycobacteria under hypoxia to suppress anti-TB immunity
Authors: Yang Hua , Wang Fei , Guo Xinya , Liu Feng , Liu Zhonghua , Wu Xiangyang , Zhao Mengmeng , Ma Mingtong , Liu Haipeng , Qin Lianhua , Wang Lin , Tang Tianqi , Sha Wei , Wang Yang , Chen Jianxia , Huang Xiaochen , Wang Jie , Peng Cheng , Zheng Ruijuan , Tang Fen , Zhang Lu , Wu Chunyan , Oehlers Stefan H. , Song Zhigang , She Jialei , Feng Hua , Xie Xunwei , Ge Baoxue 
Published: October 2021

AbstractPathogenic mycobacteria induce the formation of hypoxic granulomas during latent tuberculosis (TB) infection, in which the immune system contains, but fails to eliminate the mycobacteria. Fatty acid metabolism-related genes are relatively overrepresented in the mycobacterial genome and mycobacteria favor host-derived fatty acids as nutrient sources. However, whether and how mycobacteria modulate host fatty acid metabolism to drive granuloma progression remains unknown. Here, we report that mycobacteria under hypoxia markedly secrete the protein Rv0859/MMAR_4677 (Fatty-acid degradation A, FadA), which is also enriched in tuberculous granulomas. FadA acts as an acetyltransferase that converts host acetyl-CoA to acetoacetyl-CoA. The reduced acetyl-CoA level suppresses H3K9Ac-mediated expression of the host proinflammatory cytokine Il6, thus promoting granuloma progression. Moreover, supplementation of acetate increases the level of acetyl-CoA and inhibits the formation of granulomas. Our findings suggest an unexpected mechanism of a hypoxia-induced mycobacterial protein suppressing host immunity via modulation of host fatty acid metabolism and raise the possibility of a novel therapeutic strategy for TB infection.