bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic modulation reveals differentiation state specificity of oncogene addiction
Authors: Khaliq Mehwish , Manikkam Mohan , Martinez Elisabeth D. , Fallahi-Sichani Mohammad
Published: March 2021

Hyperactivation of the MAPK signaling pathway motivates the clinical use of MAPK inhibitors for BRAF-mutant melanomas. Heterogeneity in differentiation state due to epigenetic plasticity, however, results in cell-to-cell variability in the state of MAPK dependency, diminishing the efficacy of MAPK inhibitors. To identify key regulators of such variability, we screen 276 epigenetic-modifying compounds, individually or combined with MAPK inhibitors, across genetically diverse and isogenic populations of melanoma cells. Following single-cell analysis and multivariate modeling, we identify three classes of epigenetic inhibitors that target distinct epigenetic states associated with either one of the lysine-specific histone demethylases Kdm1a or Kdm4b, or BET bromodomain proteins. While melanocytes remain insensitive, the anti-tumor efficacy of each inhibitor is predicted based on melanoma cells’ differentiation state and MAPK activity. Our systems pharmacology approach highlights a path toward identifying actionable epigenetic factors that extend the BRAF oncogene addiction paradigm on the basis of tumor cell differentiation state.
Cross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2
Authors: Zhao Hanjun , To Kelvin K. W. , Lam Hoiyan , Zhou Xinxin , Chan Jasper Fuk-Woo , Peng Zheng , Lee Andrew C. Y. , Cai Jianpiao , Chan Wan-Mui , Ip Jonathan Daniel , Chan Chris Chung-Sing , Yeung Man Lung , Zhang Anna Jinxia , Chu Allen Wing Ho , Jiang Shibo , Yuen Kwok-Yung
Published: March 2021

Up to date, effective antivirals have not been widely available for treating COVID-19. In this study, we identify a dual-functional cross-linking peptide 8P9R which can inhibit the two entry pathways (endocytic pathway and TMPRSS2-mediated surface pathway) of SARS-CoV-2 in cells. The endosomal acidification inhibitors (8P9R and chloroquine) can synergistically enhance the activity of arbidol, a spike-ACE2 fusion inhibitor, against SARS-CoV-2 and SARS-CoV in cells. In vivo studies indicate that 8P9R or the combination of repurposed drugs (umifenovir also known as arbidol, chloroquine and camostat which is a TMPRSS2 inhibitor), simultaneously interfering with the two entry pathways of coronaviruses, can significantly suppress SARS-CoV-2 replication in hamsters and SARS-CoV in mice. Here, we use drug combination (arbidol, chloroquine, and camostat) and a dual-functional 8P9R to demonstrate that blocking the two entry pathways of coronavirus can be a promising and achievable approach for inhibiting SARS-CoV-2 replication in vivo. Cocktail therapy of these drug combinations should be considered in treatment trials for COVID-19.
Is LRRK2 the missing link between inflammatory bowel disease and Parkinson’s disease?
Authors: Herrick Mary K. , Tansey Malú G.
Published: March 2021

Links that implicate the gastrointestinal system in Parkinson’s disease (PD) pathogenesis and progression have become increasingly common. PD shares several similarities with Crohn’s disease (CD). Intestinal inflammation is common in both PD and CD and is hypothesized to contribute to PD neuropathology. Mutations in leucine-rich repeat kinase 2 (LRRK2) are one of the greatest genetic contributors to PD. Variants in LRRK2 have also been associated with increased incidence of CD. Since its discovery, LRRK2 has been studied intensely in neurons, despite multiple lines of evidence showing that LRRK2 is highly expressed in immune cells. Based on the fact that higher levels of LRRK2 are detectable in inflamed colonic tissue from CD patients and in peripheral immune cells from sporadic PD patients relative to matched controls, we posit that LRRK2 regulates inflammatory processes. Therefore, LRRK2 may sit at a crossroads whereby gut inflammation and higher LRRK2 levels in CD may be a biomarker of increased risk for sporadic PD and/or may represent a tractable therapeutic target in inflammatory diseases that increase risk for PD. Here we will focus on reviewing how PD and CD share overlapping phenotypes, particularly in terms of LRRK2 in the context of the immune system, that could be targeted in future therapies.
Meta-analysis on how manure application changes soil organic carbon storage
Authors: Gross Arthur , Glaser Bruno
Published: March 2021

Manure application to agricultural soils is widely considered as a source of nutrients and a method of maintaining levels of soil organic carbon (SOC) to mitigate climate change. At present, it is still unclear which factors are responsible for the SOC stock dynamics. Therefore, we analyzed the relationship between SOC stock changes and site characteristics, soil properties, experiment characteristics and manure characteristics. Overall, we included 101 studies with a total of 592 treatments. On average, the application of manure on agricultural soils increased SOC stocks by 35.4%, corresponding to 10.7 Mg ha−1. Manure applications in conventional tillage systems led to higher SOC stocks (+ 2.2 Mg ha−1) than applications under reduced tillage. Soil organic carbon increase upon manure application was higher in soils under non-tropical climate conditions (+ 2.7 Mg ha−1) compared to soils under sub-tropical climate. Larger SOC increases after manure application were achieved in intermediate and shallow topsoils (in 0–15 cm by 9.5 Mg ha−1 and in 16–20 cm by 13.6 Mg ha−1), but SOC stocks were also increased in deeper soils (> 20 cm 4.6 Mg ha−1), regardless of the tillage intensity. The highest relative SOC increase (+ 48%) was achieved if the initial SOC was below 1% but the absolute SOC increased with increasing initial SOC. Clay soils showed higher SOC increase rates compared to sandy soils (+ 3.1 Mg ha−1). Acidic soils showed comparable relative effects but a higher stock difference than neutral (+ 5.1 Mg ha−1) and alkaline soils (+ 5.1 Mg ha−1). The application of farmyard-, cattle- and pig manure showed the highest SOC increases (50%, 32% and 41%, respectively), while green manure and straw showed only minor effects. If manure applications were combined with additional mineral fertilizer, the SOC increases were higher (+ 1.7 Mg ha−1) compared to manure alone. Higher applied amounts generally led to higher SOC stocks. However the annually applied amount is only important under conventional tillage, non-tropical climate conditions, and pH-neutral as well as SOC-rich or SOC-depleted soils and if no additional mineral fertilization is applied. Further studies should focus on the SOC dynamics under tropical climate conditions and factors influencing a potential carbon saturation. In both cases, the number of data was too small. For this reason, additional field studies should be conducted primarily in the tropics. On the other hand, long-term field trials should be re-assessed or newly established to specifically investigate potential saturation effects and long-term (> 20 years) fertilizer effects and carbon sequestration.
Optimization of deficit irrigation and nitrogen fertilizer management for peanut production in an arid region
Authors: Rathore Vijay Singh , Nathawat Narayan Singh , Bhardwaj Seema , Yadav Bhagirath Mal , Kumar Mahesh , Santra Priyabrata , Praveen Kumar  , Reager Madan Lal , Yadava Narendra Dev , Yadav Om Parkash
Published: March 2021

Deficit irrigation (DI) has been emerging as an important technique for enhancing crop water productivity (WP). However, advantage of DI under varying nitrogen (N) application rates remains unclear. Field experiments were conducted during 2012–2014 to investigate the impacts of six irrigation levels[FI (full irrigation), DI10, DI20, DI30, DI40 and DI50, with irrigation amount of 100, 90, 80, 70, 60 and 50% of ETc, respectively) and four N application rates (N0, N10, N20 and N30, with 0, 10, 20 and 30 kg N ha−1, respectively) on WP, yield, quality, and net economic return of peanut in hot arid region of India. We used Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) method to obtain the optimal combination of irrigation and N rates. Both irrigation level and nitrogen dose had significant effects on yield and quality parameters examined in the study. Relative to FI, DI40 and DI50 significantly reduced yield (40.2–62.1%), economic benefit (70.8–118.5%), WP (8.2–33.0%), and kernel oil content (7.5–11.9%), but DI20 increased WP by 17.1% with only marginal reduction in economic benefit (2.6%), and yield (3.2%). Compared to N0, the N30 had 1.7, 1.1, and 1.6-folds increased yield, oil content in the kernel, and WP, respectively. Among all treatments, DI0N30 had the greatest yield and net return; DI20N30 had greatest WP and oil content in the kernel. TOPSIS analysis showed that DI20N30 was optimal in balancing of WP, yield, net return, and quality of peanut in northwestern arid India. The results have direct implications for improving irrigation water and N management for irrigated crops in arid regions.
A machine learning aided interpretable model for rupture strength prediction in Fe-based martensitic and austenitic alloys
Authors: Mamun Osman , Wenzlick Madison , Hawk Jeffrey , Devanathan Ram
Published: March 2021

The class of 9–12% Cr ferritic-martensitic alloys (FMA) and austenitic stainless steels have received considerable attention due to their numerous applications in high temperature power generation industries. To design high strength steels with prolonged service life requires a thorough understanding of the long-term properties, e.g., creep rupture strength, rupture life, etc., as a function of the chemical composition and processing parameters that govern the microstructural characteristics. In this article, the creep rupture strength of both 9–12% Cr FMA and austenitic stainless steel has been parameterized using curated experimental datasets with a gradient boosting machine. The trained model has been cross validated against unseen test data and achieved high predictive performance in terms of correlation coefficient ($$R^{2} > 0.98 $$

R
2

>
0.98

for 9–12% Cr FMA and $$R^{2} > 0.95 $$

R
2

>
0.95

for austenitic stainless steel) thus bypassing the need for additional comprehensive tensile test campaigns or physical theoretical calculations. Furthermore, the feature importance has been computed using the Shapley value analysis to understand the complex interplay of different features.
Predictive values, uncertainty, and interpretation of serology tests for the novel coronavirus
Authors: Brownstein Naomi C. , Chen Yian Ann
Published: March 2021

Antibodies testing in the coronavirus era is frequently promoted, but the underlying statistics behind their validation has come under more scrutiny in recent weeks. We provide calculations, interpretations, and plots of positive and negative predictive values under a variety of scenarios. Prevalence, sensitivity, and specificity are estimated within ranges of values from researchers and antibodies manufacturers. Illustrative examples are highlighted, and interactive plots are provided in the Supplementary Information. Implications are discussed for society overall and across diverse locations with different levels of disease burden. Specifically, the proportion of positive serology tests that are false can differ drastically from up to 3%–88% for people from different places with different proportions of infected people in the populations while the false negative rate is typically under 10%.
Impact of tDCS on working memory training is enhanced by strategy instructions in individuals with low working memory capacity
Authors: Assecondi Sara , Hu Rong , Eskes Gail , Pan Xiaoping , Zhou Jin , Shapiro Kim
Published: March 2021

Interventions to improve working memory, e.g. by combining task rehearsal and non-invasive brain stimulation, are gaining popularity. Many factors, however, affect the outcome of these interventions. We hypothesize that working memory capacity at baseline predicts how an individual performs on a working memory task, by setting limits on the benefit derived from tDCS when combined with strategy instructions; specifically, we hypothesize that individuals with low capacity will benefit the most. Eighty-four participants underwent two sessions of an adaptive working memory task (n-back) on two consecutive days. Participants were split into four independent groups (SHAM vs ACTIVE stimulation and STRATEGY vs no STRATEGY instructions). For the purpose of analysis, individuals were divided based on their baseline working memory capacity. Results support our prediction that the combination of tDCS and strategy instructions is particularly beneficial in low capacity individuals. Our findings contribute to a better understanding of factors affecting the outcome of tDCS when used in conjunction with cognitive training to improve working memory. Moreover, our results have implications for training regimens, e.g., by designing interventions predicated on baseline cognitive abilities, or focusing on strategy development for specific attentional skills.
Recurrence in the evolution of air transport networks
Authors: Sugishita Kashin , Masuda Naoki
Published: March 2021

Changes in air transport networks over time may be induced by competition among carriers, changes in regulations on airline industry, and socioeconomic events such as terrorist attacks and epidemic outbreaks. Such network changes may reflect corporate strategies of each carrier. In the present study, we propose a framework for analyzing evolution patterns in temporal networks in discrete time from the viewpoint of recurrence. Recurrence implies that the network structure returns to one relatively close to that in the past. We applied the proposed methods to four major carriers in the US from 1987 to 2019. We found that the carriers were different in terms of the autocorrelation, strength of periodicity, and changes in these quantities across decades. We also found that the network structure of the individual carriers abruptly changes from time to time. Such a network change reflects changes in their operation at their hub airports rather than famous socioeconomic events that look closely related to airline industry. The proposed methods are expected to be useful for revealing, for example, evolution of airline alliances and responses to natural disasters or infectious diseases, as well as characterizing evolution of social, biological, and other networks over time.
Hidden diversity of the most basal tapeworms (Cestoda, Gyrocotylidea), the enigmatic parasites of holocephalans (Chimaeriformes)
Authors: Barčák Daniel , Fan Chia-Kwung , Sonko Pasaikou , Kuchta Roman , Scholz Tomáš , Orosová Martina , Chen Hsuan-Wien , Oros Mikuláš
Published: March 2021

Gyrocotylideans are evolutionary ancient parasitic flatworms, and like their hosts—a relict group of holocephalan fishes (Chimaeriformes)—they are considered to be “living fossils” of a vanished past. However, the species diversity, host associations and biogeography of these most basal tapeworms are poorly known. Herein, we provide evidence of a conspicuous contrast between the genetic and morphological data based on an examination of newly collected and properly processed Gyrocotyle specimens (hologenophores) isolated from holocephalans off Taiwan and Argentina. Our molecular data, inferred from three genes (COI, 28S rRNA, 18S rRNA), showed unexpected genetic interrelationships among isolates of the genus Gyrocotyle, because each of the four genotypes from Taiwan clustered with isolates of distinct gyrocotylideans from the North Atlantic. Three genotypes of Gyrocotyle from Taiwan were morphologically almost indistinguishable from each other but represented distinct genetic lineages; a single specimen of Gyrocotyle sp. genotype 4 exhibited a clear genetic and morphological distinctness, though its formal description as a new species would be premature. Additionally, specimens of Gyrocotyle rugosa Diesing, 1850, from the type host Callorhinchus callorynchus from Argentina, provided the first genetic data on the type species of the genus and enabled us to characterise it, which is necessary for future taxonomic studies. The finding of some specimens of Gyrocotyle sp. genotype 3 in Chimaera phantasma, and another one in C. cf. argiloba, together with the putative conspecificity of an unidentified gyrocotylidean from Callorhinchus milii off Australia and G. rugosa from C. callorynchus off Argentina, represent evidence that one gyrocotylidean species may parasitise more than one holocephalan host species. Existing taxonomic problems and conflicts between morphological and molecular data on species of Gyrocotyle can only be resolved if hologenophores from type hosts and localities of nominal taxa are properly characterised genetically and morphologically.
Amplification of potential thermogenetic mechanisms in cetacean brains compared to artiodactyl brains
Authors: Manger Paul R. , Patzke Nina , Spocter Muhammad A. , Bhagwandin Adhil , Karlsson Karl Æ. , Bertelsen Mads F. , Alagaili Abdulaziz N. , Bennett Nigel C. , Mohammed Osama B. , Herculano-Houzel Suzana , Hof Patrick R. , Fuxe Kjell
Published: March 2021

To elucidate factors underlying the evolution of large brains in cetaceans, we examined 16 brains from 14 cetartiodactyl species, with immunohistochemical techniques, for evidence of non-shivering thermogenesis. We show that, in comparison to the 11 artiodactyl brains studied (from 11 species), the 5 cetacean brains (from 3 species), exhibit an expanded expression of uncoupling protein 1 (UCP1, UCPs being mitochondrial inner membrane proteins that dissipate the proton gradient to generate heat) in cortical neurons, immunolocalization of UCP4 within a substantial proportion of glia throughout the brain, and an increased density of noradrenergic axonal boutons (noradrenaline functioning to control concentrations of and activate UCPs). Thus, cetacean brains studied possess multiple characteristics indicative of intensified thermogenetic functionality that can be related to their current and historical obligatory aquatic niche. These findings necessitate reassessment of our concepts regarding the reasons for large brain evolution and associated functional capacities in cetaceans.
Cyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor
Authors: Chen Chih-Shou , Gao Guan-Lun , Ho Dong-Ru , Lin Chih-Yi , Chou Yu-Ting , Chen Shan-Chun , Huang Min-Cong , Kao Wen-Ya , Su Jyan-Gwo Joseph
Published: March 2021

Prostate cancer is a major cause of death in males. Cyproterone acetate (CPA), the steroidal anti-androgen for part of androgen deprivation therapy, may block the androgen-receptor interaction and then reduce serum testosterone through its weak anti-gonadotropic action. In addition to CPA inducing hepatitis, CPA is known to cause liver tumors in rats also. Aryl hydrocarbon receptor (AhR) is a cytoplasmic receptor and regulates multiple physiological functions. CYP1A1 is an AhR-targeted gene. We found that CPA induced CYP1A1 expression, transcriptional activity of the aryl hydrocarbon response element (AHRE), and the nuclear localization of AhR in mouse Hepa-1c1c7 cells. However, CPA suppressed CYP1A1 mRNA expression and the transcriptional activity of AHRE in human HepG2 and MCF7 cells, and also decreased AhR ligand-induced CYP1A1 protein expression and transcriptional activity of AHRE in HepG2 cells. In summary, CPA is an AhR agonist in mouse cells, but an AhR antagonist in human cells. Accordingly, CPA potentially plays a role as an endocrine disruptor of the AhR. This study helps us to understand why CPA induces acute hepatitis, gene mutation, and many other side effects. In addition, it may trigger further studies investigating the relationships between CPA, glucocorticoid receptor and castration-resistant prostate cancer in the future.
Field-deployable, rapid diagnostic testing of saliva for SARS-CoV-2
Authors: Wei Shan , Suryawanshi Hemant , Djandji Alexandre , Kohl Esther , Morgan Stephanie , Hod Eldad A. , Whittier Susan , Roth Kevin , Yeh Raymond , Alejaldre Juan Carlos , Fleck Elaine , Ferrara Stephen , Hercz Daniel , Andrews David , Lee Lilly , Hendershot Kristopher A. , Goldstein Joshua , Suh Yousin , Mansukhani Mahesh , Williams Zev
Published: March 2021

To safely re-open economies and prevent future outbreaks, rapid, frequent, point-of-need, SARS-CoV-2 diagnostic testing is necessary. However, existing field-deployable COVID-19 testing methods require the use of uncomfortable swabs and trained providers in PPE, while saliva-based methods must be transported to high complexity laboratories for testing. Here, we report the development and clinical validation of High-Performance Loop-mediated isothermal Amplification (HP-LAMP), a rapid, saliva-based, SARS-CoV-2 test with a limit of detection of 1.4 copies of virus per µl of saliva and a sensitivity and specificity with clinical samples of > 96%, on par with traditional RT-PCR based methods using swabs, but can deliver results using only a single fluid transfer step and simple heat block. Testing of 120 patient samples in 40 pools comprised of 5 patient samples each with either all negative or a single positive patient sample was 100% accurate. Thus, HP-LAMP may enable rapid and accurate results in the field using saliva, without need of a high-complexity laboratory.
Hydrological droughts in the southern Andes (40–45°S) from an ensemble experiment using CMIP5 and CMIP6 models
Authors: Aguayo Rodrigo , León-Muñoz Jorge , Garreaud René , Montecinos Aldo
Published: March 2021

The decrease in freshwater input to the coastal system of the Southern Andes (40–45°S) during the last decades has altered the physicochemical characteristics of the coastal water column, causing significant environmental, social and economic consequences. Considering these impacts, the objectives were to analyze historical severe droughts and their climate drivers, and to evaluate the hydrological impacts of climate change in the intermediate future (2040–2070). Hydrological modelling was performed in the Puelo River basin (41°S) using the Water Evaluation and Planning (WEAP) model. The hydrological response and its uncertainty were compared using different combinations of CMIP projects (n = 2), climate models (n = 5), scenarios (n = 3) and univariate statistical downscaling methods (n = 3). The 90 scenarios projected increases in the duration, hydrological deficit and frequency of severe droughts of varying duration (1 to 6 months). The three downscaling methodologies converged to similar results, with no significant differences between them. In contrast, the hydroclimatic projections obtained with the CMIP6 and CMIP5 models found significant climatic (greater trends in summer and autumn) and hydrological (longer droughts) differences. It is recommended that future climate impact assessments adapt the new simulations as more CMIP6 models become available.
Gradual onset of the Maunder Minimum revealed by high-precision carbon-14 analyses
Authors: Miyahara Hiroko , Tokanai Fuyuki , Moriya Toru , Takeyama Mirei , Sakurai Hirohisa , Horiuchi Kazuho , Hotta Hideyuki
Published: March 2021

The Sun exhibits centennial-scale activity variations and sometimes encounters grand solar minimum when solar activity becomes extremely weak and sunspots disappear for several decades. Such an extreme weakening of solar activity could cause severe climate, causing massive reductions in crop yields in some regions. During the past decade, the Sun’s activity has tended to decline, raising concerns that the Sun might be heading for the next grand minimum. However, we still have an underdeveloped understanding of solar dynamo mechanisms and hence precise prediction of near-future solar activity is not attained. Here we show that the 11-year solar cycles were significantly lengthened before the onset of the Maunder Minimum (1645–1715 CE) based on unprecedentedly high-precision data of carbon-14 content in tree rings. It implies that flow speed in the convection zone is an essential parameter to determine long-term solar activity variations. We find that a 16 year-long cycle had occurred three solar cycles before the onset of prolonged sunspot disappearance, suggesting a longer-than-expected preparatory period for the grand minimum. As the Sun has shown a tendency of cycle lengthening since Solar Cycle 23 (1996–2008 CE), the behavior of Solar Cycle 25 can be critically important to the later solar activity.
DropConnect is effective in modeling uncertainty of Bayesian deep networks
Authors: Mobiny Aryan , Yuan Pengyu , Moulik Supratik K. , Garg Naveen , Wu Carol C. , Van Nguyen Hien
Published: March 2021

Deep neural networks (DNNs) have achieved state-of-the-art performance in many important domains, including medical diagnosis, security, and autonomous driving. In domains where safety is highly critical, an erroneous decision can result in serious consequences. While a perfect prediction accuracy is not always achievable, recent work on Bayesian deep networks shows that it is possible to know when DNNs are more likely to make mistakes. Knowing what DNNs do not know is desirable to increase the safety of deep learning technology in sensitive applications; Bayesian neural networks attempt to address this challenge. Traditional approaches are computationally intractable and do not scale well to large, complex neural network architectures. In this paper, we develop a theoretical framework to approximate Bayesian inference for DNNs by imposing a Bernoulli distribution on the model weights. This method called Monte Carlo DropConnect (MC-DropConnect) gives us a tool to represent the model uncertainty with little change in the overall model structure or computational cost. We extensively validate the proposed algorithm on multiple network architectures and datasets for classification and semantic segmentation tasks. We also propose new metrics to quantify uncertainty estimates. This enables an objective comparison between MC-DropConnect and prior approaches. Our empirical results demonstrate that the proposed framework yields significant improvement in both prediction accuracy and uncertainty estimation quality compared to the state of the art.
The less conserved metal-binding site in human CRISP1 remains sensitive to zinc ions to permit protein oligomerization
Authors: Sheng Jie , Gadella Bart M. , Olrichs Nick K. , Kaloyanova Dora V. , Helms J. Bernd
Published: March 2021

Cysteine-rich secretory proteins (CRISPs) are a subgroup of the CRISP, antigen 5 and PR-1 (CAP) superfamily that is characterized by the presence of a conserved CAP domain. Two conserved histidines in the CAP domain are proposed to function as a Zn2+-binding site with unknown function. Human CRISP1 is, however, one of the few family members that lack one of these characteristic histidine residues. The Zn2+-dependent oligomerization properties of human CRISP1 were investigated using a maltose-binding protein (MBP)-tagging approach in combination with low expression levels in XL-1 Blue bacteria. Moderate yields of soluble recombinant MBP-tagged human CRISP1 (MBP-CRISP1) and the MBP-tagged CAP domain of CRISP1 (MBP-CRISP1ΔC) were obtained. Zn2+specifically induced oligomerization of both MBP-CRISP1 and MBP-CRISP1ΔCin vitro. The conserved His142 in the CAP domain was essential for this Zn2+dependent oligomerization process, confirming a role of the CAP metal-binding site in the interaction with Zn2+. Furthermore, MBP-CRISP1 and MBP-CRISP1ΔColigomers dissociated into monomers upon Zn2+removal by EDTA. Condensation of proteins is characteristic for maturing sperm in the epididymis and this process was previously found to be Zn2+-dependent. The Zn2+-induced oligomerization of human recombinant CRISP1 may shed novel insights into the formation of functional protein complexes involved in mammalian fertilization.
Space evaluation in football games via field weighting based on tracking data
Authors: Narizuka Takuma , Yamazaki Yoshihiro , Takizawa Kenta
Published: March 2021

In football game analysis, space evaluation is an important issue because it is directly related to the quality of ball passing or player formations. Previous studies have primarily focused on a field division approach wherein a field is divided into dominant regions in which a certain player can arrive prior to any other players. However, the field division approach is oversimplified because all locations within a region are regarded as uniform herein. The objective of the current study is to propose a fundamental framework for space evaluation based on field weighting. In particular, we employed the motion model and calculated a minimum arrival time $$ \tau $$
τ
for each player to all locations on the football field. Our main contribution is that two variables $$ \tau _{\text{of}} $$

τ
of

and $$ \tau _{\text{df}} $$

τ
df

corresponding to the minimum arrival time for offense and defense teams are considered; using $$ \tau _{\text{of}} $$

τ
of

and $$ \tau _{\text{df}} $$

τ
df

, new orthogonal variables $$ z_{1} $$

z
1

and $$ z_{2} $$

z
2

are defined. In particular, based on real datasets comprising of data from 45 football games of the J1 League in 2018, we provide a detailed characterization of $$ z_{1} $$

z
1

and $$ z_{2} $$

z
2

in terms of ball passing. By using our method, we found that $$ z_{1}(\vec {x}, t) $$

z
1

(

x
→

,
t
)

and $$ z_{2}(\vec {x}, t) $$

z
2

(

x
→

,
t
)

represent the degree of safety for a pass made to $$ \vec {x} $$

x
→

at t and degree of sparsity of $$ \vec {x} $$

x
→

at t, respectively; the success probability of passes could be well-fitted using a sigmoid function. Moreover, a new type of field division approach and evaluation of ball passing just before shots using real game data are discussed.
The relationship between Subfoveal Choroidal Thickness and Hypertensive Retinopathy
Authors: Shao Lei , Zhou Ling Xiao , Xu Liang , Wei Wen Bin
Published: March 2021

The Beijing Eye Study 2011 is a population-based cross-sectional study in Northern China, which enrolled 3468 participants whose age were more than 50 years. A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography with enhanced depth imaging for measurement of SFCT and fundus photography. Blood pressure, fundus photographs and choroidal OCT-images were available for 3237 (93.3%) subjects, with 1953 (56.3 ± 0.8%) of the study population fulfilled the diagnosis of hypertension and 1089 subjects having hypertensive retinopathy. For the hypertensive cases, the SFCT in patients with hypertensive retinopathy (286.48 ± 105.23 µm) was significantly thicker than subjects without hypertensive retinopathy (187.04 ± 78.80 µm, P < 0.001). SFCT was significantly associated with the stage of hypertensive retinopathy (P < 0.001), but not significantly associated with diastolic blood pressure (P = 0.94), history (P = 0.95) and years (P = 0.91) of hypertension. In conclusion, hypertension as systemic disease was not significantly affect the subfoveal choroidal thickness, but as ocular disease, hypertensive retinopathy was significantly related to changes of choroidal thickness. Lesions of choroid during chronic hypertension may play an important role in development of hypertensive retinopathy.
Bumble bee queens activate dopamine production and gene expression in nutritional signaling pathways in the brain
Authors: Sasaki Ken , Yokoi Kakeru , Toga Kouhei
Published: March 2021

To explore the neuroendocrine mechanisms underlying caste-specific behavior and its evolution from primitive to advanced eusocial bees, the monoamine levels and expression of genes involved in monoamine production and signaling in the brain were compared between the castes of Bombus ignitus. Higher levels of dopamine and its related substances were found in the brains of newly emerged queens than in the brains of emerged workers. The degree of caste differences in B. ignitus was smaller than that reported in Apis mellifera, indicating a link to different social stages in the two species. There was no differential expression in genes involved in dopamine biosynthesis between castes, suggesting that the high dopamine production in queens was not largely influenced by the expression of these genes at emergence, rather it might be influenced by tyrosine supply. Genome-wide analyses of gene expression by RNA-sequencing indicated that a greater number of genes involved in nutrition were actively expressed in the brains of newly emerged queens in comparison to the emerged workers. Some of the expression was confirmed by real-time quantitative PCR. The signaling pathways driven by the expression of these genes may be associated with dopamine signaling or the parallel activation of dopamine production.
Effects of administration route on uptake kinetics of 18F-sodium fluoride positron emission tomography in mice
Authors: Gonzalez-Galofre Zaniah N. , Alcaide-Corral Carlos J. , Tavares Adriana A. S.
Published: March 2021

18F-sodium fluoride (18F-NaF) is a positron emission tomography (PET) radiotracer widely used in skeletal imaging and has also been proposed as a biomarker of active calcification in atherosclerosis. Like most PET radiotracers, 18F-NaF is typically administered intravenously. However in small animal research intravenous administrations can be challenging, because partial paravenous injection is common due to the small calibre of the superficial tail veins and repeat administrations via tail veins can lead to tissue injury therefore limiting the total number of longitudinal scanning points. In this paper, the feasibility of using intra-peritoneal route of injection of 8F-NaF to study calcification in mice was studied by looking at the kinetic and uptake profiles of normal soft tissues and bones versus intra-vascular injections. Dynamic PET was performed for 60 min on nineteen isoflurane-anesthetized male Swiss mice after femoral artery (n = 7), femoral vein (n = 6) or intraperitoneal (n = 6) injection of 8F-NaF. PET data were reconstructed and the standardised uptake value (SUV) and standardised uptake value ratio (SUVr) were estimated from the last three frames between 45- and 60-min and 8F-NaF uptake constant (Ki) was derived by Patlak graphical analysis. In soft tissue, the 18F-NaF perfusion phase changes depending on the type on injection route, whereas the uptake phase is similar regardless of the administration route. In bone tissue SUV, SUVr and Ki measures were not significantly different between the three administration routes. Comparison between PET and CT measures showed that bones that had the highest CT density displayed the lowest PET activity and conversely, bones where CT units were low had high 8F-NaF uptake. Intraperitoneal injection is a valid and practical alternative to the intra-vascular injections in small-animal 18F-NaF PET imaging providing equivalent pharmacokinetic data. CT outcome measures report on sites of stablished calcification whereas PET measures sites of higher complexity and active calcification.
Amide proton transfer weighted (APTw) imaging based radiomics allows for the differentiation of gliomas from metastases
Authors: Sartoretti Elisabeth , Sartoretti Thomas , Wyss Michael , Reischauer Carolin , van Smoorenburg Luuk , Binkert Christoph A. , Sartoretti-Schefer Sabine , Mannil Manoj
Published: March 2021

We sought to evaluate the utility of radiomics for Amide Proton Transfer weighted (APTw) imaging by assessing its value in differentiating brain metastases from high- and low grade glial brain tumors. We retrospectively identified 48 treatment-naïve patients (10 WHO grade 2, 1 WHO grade 3, 10 WHO grade 4 primary glial brain tumors and 27 metastases) with either primary glial brain tumors or metastases who had undergone APTw MR imaging. After image analysis with radiomics feature extraction and post-processing, machine learning algorithms (multilayer perceptron machine learning algorithm; random forest classifier) with stratified tenfold cross validation were trained on features and were used to differentiate the brain neoplasms. The multilayer perceptron achieved an AUC of 0.836 (receiver operating characteristic curve) in differentiating primary glial brain tumors from metastases. The random forest classifier achieved an AUC of 0.868 in differentiating WHO grade 4 from WHO grade 2/3 primary glial brain tumors. For the differentiation of WHO grade 4 tumors from grade 2/3 tumors and metastases an average AUC of 0.797 was achieved. Our results indicate that the use of radiomics for APTw imaging is feasible and the differentiation of primary glial brain tumors from metastases is achievable with a high degree of accuracy.
The medicinal plant Tabebuia impetiginosa potently reduces pro-inflammatory cytokine responses in primary human lymphocytes
Authors: Ryan Rachael Y. M. , Fernandez Alejandra , Wong Yide , Miles John J. , Cock Ian E.
Published: March 2021

Bark from theHandroanthus impetiginosus(Mart. ex DC.) Mattos (Bignoniaceae) tree has long been used in traditional South American healing practises to treat inflammation. However, its anti-inflammatory activity has not been closely examined. Here we use chemical extraction, qualitative phytochemical examination, toxicity testing and quantitative examination of anti-inflammatory activity on human cells ex vivo. All extracts were found to be nontoxic. We found different extracts exhibited unique cytokine profiles with some extracts outperforming a positive control used in the clinic. These results verify the immunomodulatory activity ofHandroanthus impetiginosus(Mart. ex DC.) Mattos (Bignoniaceae) tree bark-derived compounds. Collectively, combining a lack of toxicity and potency in human immune cells supports further fractionation and research.
Detection of breeding signatures in wheat using a linkage disequilibrium-corrected mapping approach
Authors: Dadshani Said , Mathew Boby , Ballvora Agim , Mason Annaliese S. , Léon Jens
Published: March 2021

Marker assisted breeding, facilitated by reference genome assemblies, can help to produce cultivars adapted to changing environmental conditions. However, anomalous linkage disequilibrium (LD), where single markers show high LD with markers on other chromosomes but low LD with adjacent markers, is a serious impediment for genetic studies. We used a LD-correction approach to overcome these drawbacks, correcting the physical position of markers derived from 15 and 135 K arrays in a diversity panel of bread wheat representing 50 years of breeding history. We detected putative mismapping of 11.7% markers and improved the physical alignment of 5.4% markers. Population analysis indicated reduced genetic diversity over time as a result of breeding efforts. By analysis of outlier loci and allele frequency change over time we traced back the 2NS/2AS translocation ofAegilops ventricosato one cultivar, “Cardos” (registered in 1998) which was the first among the panel to contain this translocation. A “selective sweep” for this important translocation region on chromosome 2AS was found, putatively linked to plant response to biotic stress factors. Our approach helps in overcoming the drawbacks of incorrectly anchored markers on the wheat reference assembly and facilitates detection of selective sweeps for important agronomic traits.
Using smart speakers to contactlessly monitor heart rhythms
Authors: Wang Anran , Nguyen Dan , Sridhar Arun R. , Gollakota Shyamnath
Published: March 2021

Heart rhythm assessment is indispensable in diagnosis and management of many cardiac conditions and to study heart rate variability in healthy individuals. We present a proof-of-concept system for acquiring individual heart beats using smart speakers in a fully contact-free manner. Our algorithms transform the smart speaker into a short-range active sonar system and measure heart rate and inter-beat intervals (R-R intervals) for both regular and irregular rhythms. The smart speaker emits inaudible 18–22 kHz sound and receives echoes reflected from the human body that encode sub-mm displacements due to heart beats. We conducted a clinical study with both healthy participants and hospitalized cardiac patients with diverse structural and arrhythmic cardiac abnormalities including atrial fibrillation, flutter and congestive heart failure. Compared to electrocardiogram (ECG) data, our system computed R-R intervals for healthy participants with a median error of 28 ms over 12,280 heart beats and a correlation coefficient of 0.929. For hospitalized cardiac patients, the median error was 30 ms over 5639 heart beats with a correlation coefficient of 0.901. The increasing adoption of smart speakers in hospitals and homes may provide a means to realize the potential of our non-contact cardiac rhythm monitoring system for monitoring of contagious or quarantined patients, skin sensitive patients and in telemedicine settings.
Cell-autonomous immune gene expression is repressed in pulmonary neuroendocrine cells and small cell lung cancer
Authors: Cai Ling , Liu Hongyu , Huang Fang , Fujimoto Junya , Girard Luc , Chen Jun , Li Yongwen , Zhang Yu-An , Deb Dhruba , Stastny Victor , Pozo Karine , Kuo Christin S. , Jia Gaoxiang , Yang Chendong , Zou Wei , Alomar Adeeb , Huffman Kenneth , Papari-Zareei Mahboubeh , Yang Lin , Drapkin Benjamin , Akbay Esra A. , Shames David S. , Wistuba Ignacio I. , Wang Tao , Johnson Jane E. , Xiao Guanghua , DeBerardinis Ralph J. , Minna John D. , Xie Yang , Gazdar Adi F.
Published: March 2021

Small cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed “variant” due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings may help guide the design of treatment regimens in SCLC.
Deep oxidization of glucose driven by 4-acetamido-TEMPO for a glucose fuel cell at room temperature
Authors: Li Gangyong , Wang Yuchao , Yu Feng , Lei Yongpeng , Hu Zongqian
Published: March 2021

A novel room temperature glucose/O2 fuel cell equipped with 4-acetamido-TEMPO (ACT) as an anodic electrocatalyst and an air-breathing Pt cathode has been developed.
Promoted crystallization of silicoaluminophosphate zeolites: an efficient way to accelerate crystallization rate and increase solid yield
Authors: Yuan Delin , Wang Qianjin , Shang Yunshan , Liu Hua , Xing Aihua
Published: March 2021

SAPO-34 with 100% yield has been synthesized by an acid-assisted method, which is also applicable to the synthesis of other silicoaluminophosphate zeolites.
A ternary mixture at the border of Soret separation stability
Authors: Prokopev Sergei , Lyubimova Tatyana , Mialdun Aliaksandr , Shevtsova Valentina
Published: March 2021

The metastable state of a ternary liquid mixture observed during Soret separation, when the emerging density profiles of the two components nearly cancel each other out.
Fluoropolymers in biomedical applications: state-of-the-art and future perspectives
Authors: Lv Jia , Cheng Yiyun
Published: March 2021

Biomedical applications of fluoropolymers in gene delivery, protein delivery, drug delivery,19F MRI, PDT, anti-fouling, anti-bacterial, cell culture, and tissue engineering.
Sargassum fusiforme fucoidan modifies gut microbiota and intestinal metabolites during alleviation of hyperglycemia in type 2 diabetic mice
Authors: Wu Qifang , Wu Siya , Cheng Yang , Zhang Zhongshan , Mao Genxiang , Li Shijun , Yang Yue , Zhang Xu , Wu Mingjiang , Tong Haibin
Published: March 2021

Sargassum fusiforme fucoidan (SFF) modifies gut microbiota and intestinal metabolites of HFD/STZ-induced type 2 diabetic mice during alleviation of diabetic symptoms, thus implying the benefits of SFF as an adjuvant agent for T2DM.
Formamide iodide: a new cation additive for inhibiting δ-phase formation of formamidinium lead iodide perovskite
Authors: Raifuku Itaru , Chiang Yu-Hsien , Hou Cheng-Hung , Li Ming-Hsien , Lin Chen-Fu , Lin Pei-Ying , Shyue Jing-Jong , Chen Peter
Published: March 2021

We synthesized formamide iodide (FoAI) and applied as a novel cation additive of perovskite solar cells (PSCs). We found that FoAI additive can improve the performance of FAPbI3 based PSCs by suppressing the formation of non-photoactive phase.
Tetrazine molecules as an efficient electronic diversion channel in 2D organic–inorganic perovskites
Authors: Lédée Ferdinand , Audebert Pierre , Trippé-Allard Gaëlle , Galmiche Laurent , Garrot Damien , Marrot Jérôme , Lauret Jean-Sébastien , Deleporte Emmanuelle , Katan Claudine , Even Jacky , Quarti Claudio
Published: March 2021

Taking advantage of an innovative design concept, we present the synthesis of two novel two-dimensional (2D) hybrid organic–inorganic halide perovskites incorporating for the first time 100% of a photoactive tetrazine derivative as the organic component.
Examination of oestrus-dependent alterations of bovine cervico-vaginal mucus glycosylation for potential as optimum fertilisation indicators
Authors: Le Berre Marie , Gerlach Jared Q. , Loughrey Catherine , Creavin Aileen , Pluta Katarzyna , Gallagher Mary , Carrington Stephen D. , Joshi Lokesh , Kilcoyne Michelle
Published: March 2021

Oestrus is the period in the sexual cycle of female mammals where they become most receptive to mating and are most fertile.
Coupled plasmonic systems: controlling the plasmon dynamics and spectral modulations for molecular detection
Authors: Kitajima Yuto , Sakamoto Hiyori , Ueno Kosei
Published: March 2021

A review on molecular detection using coupled plasmonic systems based on spectral modulations and further near-field enhancements.
Shape tailoring of AgBr microstructures: effect of the cations of different bromide sources and applied surfactants
Authors: Tóth Zsejke-Réka , Pap Zsolt , Kiss János , Baia Lucian , Gyulavári Tamás , Czekes Zsolt , Todea Milica , Magyari Klára , Kovács Gábor , Hernadi Klara
Published: March 2021

Systematic investigation of the effect of different alkali metal cation radii and shape-tailoring agents applied during the synthesis of AgBr-based photocatalysts.
Dendritic fibrous nanosilica-supported dendritic IL/Ru(ii) as photocatalysts for the dicarbofunctionalization of styrenes with carbon dioxide and amines
Authors: Liu Can , Rouhi Jalal
Published: March 2021

The effectual utilization of heterogeneous catalysts from nano sources through chemical moderation for the α-aminomethylcarboxylation of alkenes with carbon dioxide and amines is an attractive area to study.
Inorganic–inorganic nanohybrids for drug delivery, imaging and photo-therapy: recent developments and future scope
Authors: Choi Goeun , Rejinold N. Sanoj , Piao Huiyan , Choy Jin-Ho
Published: March 2021

The present review will be detailing about trending inorganic–inorganic nanohybrids that have been used for various biomedical applications including drug-delivery, bio-imaging and photo therapy.
Enhanced ordering in length-polydisperse carbon nanotube solutions at high concentrations as revealed by small angle X-ray scattering
Authors: Jamali Vida , Mirri Francesca , Biggers Evan G. , Pinnick Robert A. , Liberman Lucy , Cohen Yachin , Talmon Yeshayahu , MacKintosh Fred C. , van der Schoot Paul , Pasquali Matteo
Published: March 2021

Quantitative characterization of the phase behavior of carbon nanotube liquid crystalline solutions at high concentrations using polarized light microscopy and small angle X-ray scattering
3D-printing for forensic chemistry: voltammetric determination of cocaine on additively manufactured graphene–polylactic acid electrodes
Authors: Rocha Raquel G. , Ribeiro Julia S. , Santana Mário H. P. , Richter Eduardo M. , Muñoz Rodrigo A. A.
Published: March 2021

Cocaine is probably one of the most trafficked illicit drugs in the world.