bluuebunny/crossref_metadata_2025 huggingface dataset:
Administrative Records Mask Racially Biased Policing
Authors: KNOX DEAN , LOWE WILL , MUMMOLO JONATHAN
Published: May 2020

Researchers often lack the necessary data to credibly estimate racial discrimination in policing. In particular, police administrative records lack information on civilians police observe but do not investigate. In this article, we show that if police racially discriminate when choosing whom to investigate, analyses using administrative records to estimate racial discrimination in police behavior are statistically biased, and many quantities of interest are unidentified—even among investigated individuals—absent strong and untestable assumptions. Using principal stratification in a causal mediation framework, we derive the exact form of the statistical bias that results from traditional estimation. We develop a bias-correction procedure and nonparametric sharp bounds for race effects, replicate published findings, and show the traditional estimator can severely underestimate levels of racially biased policing or mask discrimination entirely. We conclude by outlining a general and feasible design for future studies that is robust to this inferential snare.
Do COVID-19 Conspiracy Theory Beliefs Form a Monological Belief System?
Authors: Miller Joanne M.
Published: May 2020

Along with criticisms of the U.S. government's response to the COVID-19 pandemic, the disruptions to home, work, and school life resulting from social distancing orders recommended by public health experts, as well as the uncertainty about how long the disruptions will be necessary and when (if ever) we will have a vaccine, have come COVID-19 conspiracy theories (CTs).
Margaret Akiiki Rwaheru v Uganda Revenue Authority
Authors: Solomon Rukundo
Published: May 2020

Value Added Tax (VAT) is a tax on the value added at each stage of the production and distribution process and on the importation of goods. VAT registered importers in Uganda are charged the statutory VAT rate of 18 per cent, however, importers that are not VAT registered are charged both the 18 per cent and an additional 15 per cent, which is designated “Domestic VAT”. The statutory basis of the 15 per cent is unclear. Domestic VAT appears to be a tax created by the Uganda Revenue Authority in a bid to raise revenue from a largely non-compliant base. The legality of the tax was challenged inMargaret Akiiki Rwaheru and 13,945 Others v Uganda Revenue Authority. The court ruled that Domestic VAT was irregular when applied to importers who qualified to register for VAT but had not registered, but was illegal when applied to importers who did not qualify to register for VAT. Despite this ruling, the URA has continued to charge all importers Domestic VAT, regardless of whether they qualify to register for VAT. This article seeks to re-examine the legality of Domestic VAT.
The knowledge that went up in smoke: Reindeer herders’ traditional knowledge of smoked reindeer meat in literature
Authors: Hansen Kia Krarup , Moldenæs Turid , Mathiesen Svein Disch
Published: May 2020

Using a literature review, this paper defines the knowledge status of smoked reindeer meat and investigates to what degree reindeer herders’ traditional knowledge has been included in scientific articles and grey literature. We developed a four-level categorisation of the degree of including traditional knowledge, from “non-participation” to “self-determination,” and three levels of focus. Very few scientific articles on smoked or smoking reindeer meat appeared in the review. Not only did reindeer peoples’ traditional meat smoking knowledge “went up in smoke”—both literally and metaphorically—but also incorrect conclusions were often drawn as a result of that exclusion. We argue that reindeer herders’ traditional knowledges and practices of smoking reindeer meat need examination and inclusion through co-production or self-determination methods across scientific disciplines.
Coronavirus conspiracy beliefs, mistrust, and compliance with government guidelines in England
Authors: Freeman Daniel , Waite Felicity , Rosebrock Laina , Petit Ariane , Causier Chiara , East Anna , Jenner Lucy , Teale Ashley-Louise , Carr Lydia , Mulhall Sophie , Bold Emily , Lambe Sinéad
Published: May 2020

Background

An invisible threat has visibly altered the world. Governments and key institutions have had to implement decisive responses to the danger posed by the coronavirus pandemic. Imposed change will increase the likelihood that alternative explanations take hold. In a proportion of the general population there may be strong scepticism, fear of being misled, and false conspiracy theories. Our objectives were to estimate the prevalence of conspiracy thinking about the pandemic and test associations with reduced adherence to government guidelines.

Methods

A non-probability online survey with 2501 adults in England, quota sampled to match the population for age, gender, income, and region.

Results

Approximately 50% of this population showed little evidence of conspiracy thinking, 25% showed a degree of endorsement, 15% showed a consistent pattern of endorsement, and 10% had very high levels of endorsement. Higher levels of coronavirus conspiracy thinking were associated with less adherence to all government guidelines and less willingness to take diagnostic or antibody tests or to be vaccinated. Such ideas were also associated with paranoia, general vaccination conspiracy beliefs, climate change conspiracy belief, a conspiracy mentality, and distrust in institutions and professions. Holding coronavirus conspiracy beliefs was also associated with being more likely to share opinions.

Conclusions

In England there is appreciable endorsement of conspiracy beliefs about coronavirus. Such ideas do not appear confined to the fringes. The conspiracy beliefs connect to other forms of mistrust and are associated with less compliance with government guidelines and greater unwillingness to take up future tests and treatment.
Objectively Curious Commitments
Authors: Kornbluh Anna
Published: May 2020

In these times of ours, whither art? What is the use of the defamiliarizing and the sublime amidst cataclysmic conflicts over identity and belonging, resources and institutions, climate and extinction? Understandably, many defenders of art have lately come to frame their defenses in terms of messaging: artists make art to convey messages otherwise excluded from official discourse (ideology, policy, history, social science), to testify and self-express, to achieve recognition and elicit identification. Spectators and readers in turn look to art in order to see themselves mirrored, their experience confirmed, their truth avowed.
Changes in dietary patterns when females engage in a weight management programme and their ability to meet Scientific Advisory Committee on Nutrition’s fibre and sugar recommendations
Authors: Strathearn Lauren , Kaçar HK , Avery A
Published: May 2020

Objective:

To investigate how dietary patterns (DP) change following engagement in a weight management programme. Using the DP identified, to study their relationship with weight loss achieved and ability to meet the Scientific Advisory Committee on Nutrition’s 2015 fibre and sugar recommendations.

Design:

Secondary analysis of FFQ data, which collected dietary information at two time points: retrospectively before (T0) and presently during (T1) Slimming World’s programme, was analysed. Principal component analysis derived the DP present.

Setting:

Online FFQ, hosted by Slimming World (SW) in the UK.

Participants:

Female SW members (n 325; 17–68 years old).

Results:

At T0, two DP, ‘plant based’ and ‘processed meat and sugar added by the consumer’ were identified. At T1, three DP were identified, ‘high meat’, ‘high fat salt and sugar (HFSS) products’ and ‘nuts and oils’. Participants with a diet low in ‘HFSS products’ lost significantly more weight (P for trend = 0·001), were more likely to consume breakfast (P = 0·021) and consumed less free sugar compared with high ‘HFSS product’ consumers. Those initially presenting with a low ‘plant based’ diet score lost more weight at T1 (P for trend = 0·046). With engagement, mean fibre intake increased from 24·3 to 32·4 g/d (P < 0·001) and free sugar intake decreased from 12·6 to 8·7 % total dietary energy (P < 0·001).

Conclusions:

An individual’s DP before and with engagement in a weight management programme may indicate their weight loss success. Advising reduced HFSS product intake may aid initial weight loss. SW appears to promote dietary changes towards UK fibre and sugar recommendations.
Association between retinol intake and hyperuricaemia in adults
Authors: Zhang Peipei , Sun Jianping , Guo Yan , Han Minghui , Yang Fan , Sun Yongye
Published: May 2020

Objective:

Current evidences on the association between hyperuricaemia and retinol intake remain inconsistent. Furthermore, no known studies have investigated the relationship between hyperuricaemia and retinol intake from animal food and plant food separately. This study aimed to assess the relationship between different sources of retinol intake and risk of hyperuricaemia among US adults.

Design:

Univariate and multivariate weighted logistic regression models and restricted cubic spline models were used to assess the associations of total, animal-derived and plant-derived retinol intakes with the risk of hyperuricaemia. Dietary retinol was measured through two 24-h dietary recall interviews. Hyperuricaemia was defined as serum uric acid level ≥7·0 and ≥6·0 mg/dl in men and women, respectively.

Setting:

Data from the National Health and Nutrition Examination Survey 2009–2014 were used in this cross-sectional study.

Participants:

Overall, 12 869 participants aged ≥20 years were included.

Results:

Compared with the lowest quintile, the multivariable OR of hyperuricaemia for the highest quintile intake of total, animal-derived and plant-derived retinol were 0·71 (95 % CI 0·52, 0·96), 0·76 (95 % CI 0·59, 0·96) and 0·92 (95 % CI 0·72, 1·17), respectively. The inverse association between dietary intake of total retinol and the risk of hyperuricaemia was observed in men. Dose–response analyses revealed a novel linear trend between the risk of hyperuricaemia and total, animal-derived retinol intake separately.

Conclusions:

Our findings indicated that intakes of total and animal-derived retinol were negatively associated with hyperuricaemia in US adults.
Excessive pricing in the pharmaceutical industry: adding another string to the bow of EU competition law
Authors: Danieli Diletta
Published: May 2020

The paper addresses the issue of excessive price abuse under Article 102(a) of the Treaty on the Functioning of the European Union (TFEU), by drawing inspiration from a recent stream of cases (developed first at the national and then at the EU level) involving pharmaceutical companies marketing off-patent drugs. In particular, the two ‘most advanced’ cases are analysed:Aspenin Italy andPfizer/Flynnin the United Kingdom. This new-found attention towards exploitative practices in the form of excessive and unfair pricing by dominant undertakings that have traditionally been subject to a cautious antitrust scrutiny seems worth exploring for a number of reasons, as illustrated in the paper. Ultimately, it is argued that this further ‘interference’ of competition law into the realms of regulation may be actually justified, albeit subject to precise conditions for enforcement, and may pursue policy objectives in the wider context of EU health law.
The Psychometric Structure of the Spanish Language Version of The Iowa-Netherlands Comparison Orientation Measure in Spain and Chile
Authors: Buunk Abraham , Barelds Dick , Urzúa M. Alfonso , Zurriaga Rosario , González-Navarro Pilar , Dijkstra Pieternel D. , Gibbons Frederick
Published: May 2020

The present study investigated the structure of the Spanish version of the Iowa-Netherlands Comparison Orientation Measure (INCOM-E), an 11-item measure that assesses individual differences in social comparison orientation (SCO), i.e., the extent to which people compare themselves with others. Data came from samples from Spain (n = 1,133) and Chile (n = 2,757). Confirmatory Factor Analyses and Mokken Scale Analyses supported in both samples not the assumed two-factor structure, but a single factor structure, consisting of eight items. The resulting eight-item version of the INCOM-E was reliable in both samples, according the Gutmann’s lambda–2 (.82 in Spain and .83 in Chile), and correlated very strongly with the full-length INCOM-E (.93 in Spain and .97 in Chile). In both samples, there were significant sex differences, ps < .001 with small effect sizes, ƞ2 in both samples = .01,but in the Spanish sample women scored higher, and in the Chilean sample men scored higher in SCO. The relationship with age was negative and significant (ps < .001) in both samples, albeit small (r = .22 in Spain and .13 in Chile) Based on the present research, it is advised to use the shortened eight-item version of the INCOM-E in Spanish speaking countries.
Life Satisfaction and Self-rated Health in Adolescents: The Relationships between them and the Role of Gender and Age
Authors: Atienza-González Francisco L. , Martínez Natalia , Silva Castora
Published: May 2020

The purpose of this study was to analyze the relationships between self-reported life satisfaction, self-rated health, gender, and age in adolescents. 1,141 secondary school students aged between 12 and 17 participated in our study. The data were analyzed using bivariate and nonlinear canonical correlation analyses. The results of the bivariate correlation analysis support the results of previous studies. Life satisfaction was positively correlated with same-day perceived health (r = .37; p < .01) and negatively correlated with anxiety/depression (r = –.37; p < .01). Same-day perceived health was positively correlated with health in the past 12 months (r = .38; p < .01) and negatively correlated with pain/discomfort (r = –.32; p < .01) and with anxiety/depression (r = –.32; p < .01). The nonlinear canonical correlation analysis provided further evidence of the relationship between the variables, suggesting the complementarity of the indicators of self-rated health analyzed. Multiple fit values showed that demographic variables age (.61) and gender (.56) were the variables with the best discriminatory power. Graphically, two groups of related variables were displayed. A non-linear analysis better explains the relationships between the variables analyzed, showing that age and gender have a high level of discriminatory power for life satisfaction and self-rated health, suggesting a role as a moderator in the relationship between health and well-being variables.
Functioning of Cognitive Memory Inhibition Processes in People with Down Syndrome: An Empirical Study
Authors: Palomino Elena , Sotillo María , López-Frutos José María
Published: May 2020

Cognitive inhibition is part of executive functions. When it exercises control over memory processes, it has the function of regulating the accessibility of memories and allows interference to be resolved. The impairment of its functioning has been related to the presence of forgetfulness of relevant information. In this research, we study the functioning of cognitive memory inhibition processes in people with intellectual disabilities in tasks of delayed visual recognition and analyze the influence of age. For this purpose, 36 people with Down syndrome (mean age = 33.44, standard deviation = 7.54, 50% females) and 36 people with neurotypical development (mean age = 33.55, standard deviation = 7.52, 50% females) participated. The results reflected a lower effectiveness in the group of people with Down syndrome,F(1, 68) = 159.09,p< .001,$ {\upeta}_{\mathrm{p}}^2 $= .70. The people in the group with Down syndrome had difficulties in interference resolution, both in the subgroup of young people (p= .014,$ \hat{\updelta\ } $= 0.88) and in the subgroup of older people (p= .022,$ \hat{\updelta\ } $= 0.67). The impairment of cognitive inhibition in people with Down syndrome warrants the need to develop specific intervention programs for this process.
Mass Party Formation: Land, Civil Society, and Party in Postrevolutionary Mexico
Authors: Ackerman Edwin F.
Published: May 2020

What explains mass party formation? Prevailing approaches explain party formation as a process of reflection of preexisting social constituencies, or as the consequence of the rise of the bureaucratic state and in particular the advent of universal suffrage. These approaches fail to explain why Mexico’s Partido Revolucionario Institucional (PRI) emerged as a mass party in some regions but not others despite attempts to do so and similarity in conditions that have been posited as central to party formation. I put forth a novel approach that posits that parties emerge as mass organization through a process of constitution of the very social base they claim to represent, but their constitutive powers are conditioned by fundamental economic structures. Relying on agrarian censuses and archival data, I show that the PRI emerged as a mass party in areas where land privatization had been more intensive. In these areas the party during its process of formation was able to build new, and absorb existing, peasant unions and organizations and carry out strong electoral mobilization. These findings suggest that mass party formation is dependent on the destruction of “pre”-capitalist agrarian structures.
Linking Subsurface to Surface Using Gas Emission and Melt Inclusion Data at Mount Cleveland Volcano, Alaska
Authors: Werner C. , Rasmussen D. J. , Plank T. , Kelly P. J. , Kern C. , Lopez T. , Gliss J. , Power J. A. , Roman D. C. , Izbekov P. , Lyons J.
Published: May 2020

Mount Cleveland is one of Alaska's most active volcanoes, yet little is known about the magmatic system driving persistent and dynamic volcanic activity. Volcanic gas and melt inclusion (MI) data from 2016 were combined to investigate shallow magmatic processes. SO2 emission rates were between 166 and 324 t/day and the H2O/SO2 was 600 ± 53, whereas CO2 and H2S were below detection. Olivine‐, clinopyroxene‐, and plagioclase‐hosted MIs have up to 3.8 wt.% H2O, 514 ppm CO2, and 2,320 ppm S. Equilibration depths, based on MI H2O contents, suggest that a magmatic column extended from 0.5 to 3.0 km (~10–60 MPa). We used MI data to empirically model open‐system H‐C‐S degassing from 0 to 12 km and found that a column of magma between 0.5 and 3 km could produce the measured gas H2O/SO2 ratio. However, additional magma deeper than 3 km is required to sustain emissions over periods greater than days to weeks, if the observed vent dimension is a valid proxy for the conduit. Assuming an initial S content of 2,320 ppm, the total magma supply needed to sustain the annual SO2 flux was 5 to 9.8 Mm3/yr, suggesting a maximum intrusive‐to‐extrusive ratio of 13:1. The model predicts degassing of <50 t/day CO2 for July 2016, which corresponds to a maximum predicted CO2/SO2 of 0.2. Ultimately, frequent recharge from deeper, less degassed magma is required to drive the continuous activity observed over multiple years. During periods of recharge we would expect lower H2O/SO2 and measurable volcanic CO2.
Volatility Dependence of the Aerosol Size Distributions of Nonpolar Organic Compounds: A Case Study in Shanghai
Authors: Lyu Yan , Li Xiang
Published: May 2020

The aerosol size distribution of organic compounds is one of the fundamental characteristics that regulates their atmospheric deposition and environmental fate. In this study, we characterized the organic components (mostly nonpolar organic compounds) in size‐resolved particles, with a focus on polycyclic aromatic hydrocarbons (PAHs), oxygenated PAHs (O‐PAHs), n‐alkanes, and polybrominated diphenyl ethers (PBDEs), in the urban Shanghai atmosphere during a 1‐year sampling period using gas chromatography (GC) coupled to tandem mass spectrometry (GC‐MS/MS) and two‐dimensional GC with a flame ionization detector (GC × GC‐FID). These compounds ranged from volatile organic compounds (VOCs) to extremely low volatility organic compounds (ELVOCs). We related their aerosol size distributions with their volatilities. On average, high positive correlations (p < 0.01) were observed between the size distribution characteristics (e.g., geometric mean diameter [GMD] and mass fraction in coarse particles) and volatility (logarithmic value of the saturation mass concentration, log C*) for the compounds that we examined. A higher ambient temperature tends to increase the slope of the regression line between size distribution and volatility (log C*). Further dry deposition modeling of size‐resolved particles showed a positive correlation (p < 0.01) between the bulk dry deposition velocity and GMD and between the bulk dry deposition velocity and volatility of the target compounds, indicating that low‐volatility organic compounds have a lower dry deposition velocity and are more likely to be transported to remote areas if they do not have a short half‐life in the atmosphere.
Changes of Emission Sources to Nitrate Aerosols in Beijing After the Clean Air Actions: Evidence From Dual Isotope Compositions
Authors: Fan Mei‐Yi , Zhang Yan‐Lin , Lin Yu‐Chi , Cao Fang , Zhao Zhu‐Yu , Sun Yele , Qiu Yanmei , Fu Pingqing , Wang Yuxuan
Published: May 2020

Nitrate (NO3−) is a major contributing species to haze formation in Northern China. So far, formation processes and source apportionments of nitrate aerosols during haze pollution have not yet been well understood. In this study, the PM2.5 samples were collected in Beijing from 13 November to 24 December 2018. In addition to water‐soluble ions, oxygen (δ18O‐NO3−) and nitrogen (δ15N‐NO3−) isotopes in particulate NO3− were also determined, in order to investigate the formation pathways and potential sources of NO3− aerosols. The results showed that NO3− was a dominant species (43%) of secondary inorganic aerosols during the sampling period. The δ18O‐NO3− and δ15N‐NO3− values averaged at 83.8 ± 13.4 and 11.5 ± 5.0‰, respectively. Combining isotope compositions and Bayesian isotope mixing model, we found that heterogeneous reaction and gas phase oxidation contributed equally to nitrate formation during the sampling period. However, the contribution of heterogeneous processes to nitrate increased from 39% during the clean period to 64% during the haze period. On average, coal combustion, biomass burning, vehicle emissions, and soil emission contributed 50%, 26%, 20%, and 4%, respectively, to nitrate aerosols during the sampling period. Compared to the result in 2013, the significant decrease (~21%) of relative contribution of coal combustion to nitrate was due to strict reduction of coal consumption in Beijing. Finally, the relative contribution of traffic emissions to nitrate increased from 18% during the clean period to 30% during the haze period, suggesting that control of traffic emissions would be an important way to decrease nitrate concentrations and improve the air quality in Beijing.
Unified Soil Freezing Characteristic for Variably‐Saturated Saline Soils
Authors: Zhou Jiazuo , Meng Xiangchuan , Wei Changfu , Pei Wansheng
Published: May 2020

Freezing and thawing of soil have a significant impact on the thermal‐hydrological processes in cold regions. Freezing point and unfrozen water content are key variables characterizing the freezing and thawing of soil. The testing results show that unfrozen water content is independent of initial water content in nonsaline silt, based on which a unified model for a soil freezing characteristic curve (SFCC) is presented. The SFCC describes the relationship between unfrozen water content and temperature for variably‐saturated saline soils. It is also demonstrated that the SFCC can describe the variation of soil freezing point with respect to water content and salt concentration. The SFCC model is validated by comparing the experimental data to the calculated result for unfrozen water content and freezing point in a variety of conditions. When the initial water content varies in saline soil, the SFCC changes with constant initial salt concentration, but it remains unchanged with constant gravimetric salt content. The SFCC model can be adopted in the simulation of thermal‐hydrological processes in arid and saline lands and coastal regions. Finally, an example of thermal‐hydrological processes was simulated with the new SFCC model to show the application of the presented model.
NSF Plots a Course for the Next Decade of Earth Sciences Research
Authors: Fritts Rachel
Published: May 2020

Committee members who put together the new report Earth in Time describe this as an “all hands on deck” moment for the field.
Uncertainty Propagation in Hierarchical Paleomagnetic Reconstructions
Authors: Heslop D. , Roberts A. P.
Published: May 2020

Estimation of paleomagnetic directions plays a crucial role in magnetostratigaphy, paleogeographic reconstruction, and constraining past geomagnetic field behavior. While analysis and aggregation of paleomagnetic directional data are performed in a hierarchical fashion, the standard statistical framework employed by paleomagnetists does not consider uncertainty propagation through each level of the hierarchy. With this limitation, inferences drawn from paleomagnetic data will be affected by underestimated uncertainties. We provide here an approximate directional uncertainty propagation scheme that applies to Fisher distributions and, thus, to a number of paleomagnetic data processing tasks. The scheme is a straightforward addition to the existing paleomagnetic statistical framework and is demonstrated using case studies to show how uncertainties can be propagated through different stages of the paleomagnetic data processing chain. Furthermore, we discuss situations, such as the transformation into virtual geomagnetic poles, where this simple form of uncertainty propagation cannot be employed because the data are not Fisher distributed.
Hypoxia-induced GBE1 expression promotes tumor progression through metabolic reprogramming in lung adenocarcinoma
Authors: Li Lifeng , Yang Li , Fan Zhirui , Xue Wenhua , Shen Zhibo , Yuan Yongliang , Sun Xiangdong , Wang Dan , Lian Jingyao , Wang Liping , Zhao Jie , Zhang Yi
Published: May 2020

Hypoxia mediates a metabolic switch from oxidative phosphorylation to glycolysis and increases glycogen synthesis. We previously found that glycogen branching enzyme (GBE1) is downstream of the hypoxia-inducible factor-1 (HIF1) signaling pathway in lung adenocarcinoma (LUAD) cells; however, the molecular mechanism underlying HIF1 regulation of GBE1 expression remains unknown. Herein, the effect of GBE1 on tumor progression via changes in metabolic signaling under hypoxia in vitro and in vivo was evaluated, and GBE1-related genes from human specimens and data sets were analyzed. Hypoxia induced GBE1 upregulation in LUAD cells. GBE1-knockdown A549 cells showed impaired cell proliferation, clone formation, cell migration and invasion, angiogenesis, tumor growth, and metastasis. GBE1 mediated the metabolic reprogramming of LUAD cells. The expression of gluconeogenesis pathway molecules, especially fructose-1,6-bisphosphatase (FBP1), was markedly higher in shGBE1 A549 cells than it was in the control cells. FBP1 inhibited the tumor progression of LUAD. GBE1-mediated FBP1 suppression via promoter methylation enhanced HIF1αlevels through NF-κB signaling. GBE1 may be a negative prognostic biomarker for LUAD patients. Altogether, hypoxia-induced HIF1αmediated GBE1 upregulation, suppressing FBP1 expression by promoter methylation via NF-κB signaling in LUAD cells. FBP1 blockade upregulated HIF1α, triggered the switch to anaerobic glycolysis, and enhanced glucose uptake. Therefore, targeting HIF1α/GBE1/NF-κB/FBP1 signaling may be a potential therapeutic strategy for LUAD.
Identification of low-dose multidrug combinations for sunitinib-naive and pre-treated renal cell carcinoma
Authors: Rausch Magdalena , Weiss Andrea , Achkhanian Joanna , Rotari Andrei , Nowak-Sliwinska Patrycja
Published: May 2020

Background

Combinations of drugs can improve the efficacy of cancer treatment, enable the reduction of side effects and the occurrence of acquired drug resistance.

Methods

We approached this challenge mathematically by using the validated technology called the Therapeutically Guided Multidrug Optimization (TGMO) method. In a set of genetically distinct human renal cell carcinoma (RCC) cell lines, either treated chronically with sunitinib (−ST) or sunitinib-naive, we identified cell line-specific low-dose-optimised drug combinations (ODC).

Results

Six cell-type-specific low-dose drug combinations for three sunitinib-naive as well as three sunitinib pre-treated cells were established. These ODCs effectively inhibited the RCC cell metabolic activity while being ineffective in non-cancerous cells. Based on a single screening test and three searches, starting with ten drugs, we identified highly efficacious drug mixtures containing four drugs. All ODCs contained AZD4547 (FGFR signalling pathway inhibitor) and pictilisib (pan-phosphatidylinositol 3-kinase inhibitor), but varied in the third and fourth drug. ODC treatment significantly decreased cell metabolic activity (up to 70%) and induced apoptosis, independent of the pretreatment with sunitinib. The ODCs outperformed sunitinib, the standard care for RCC. Moreover, short-term starvation potentiated the ODC activity. The translation of the 2D-based results to 3D heterotypic co-culture models revealed significant inhibition of the spheroid growth (up to 95%).

Conclusion

We demonstrate a promising low-dose drug combination development to obtain drug combinations effective in naive as well as resistant tumours. Nevertheless, we emphasise the need for further mechanistic investigation and preclinical development.
Holliday junction recognition protein promotes pancreatic cancer growth and metastasis via modulation of the MDM2/p53 signaling
Authors: Wang Chen-jing , Li Xin , Shi Ping , Ding Hai-yan , Liu Yan-ping , Li Ting , Lin Ping-ping , Wang Yun-shan , Zhang Guo-qing , Cao Yu
Published: May 2020

Holliday junction recognition protein (HJURP) refers to a histone H3 chaperone that has been implicated in different kinds of malignancies. Yet, its character in pancreatic cancer remains unclear. The expression of HJURP was assessed in PDAC tissues by RT-qPCR, immunoblotting, and immunohistochemistry. HJURP-deficient or overexpressed PDAC cell lines were constructed, using shRNA or plasmids with HJURP insert. MTT, sphere formation assay, migration, and invasion assays were performed to evaluate the viability, proliferation, migration, and invasion of PDAC cells. We used xenograft mice models to assess the tumor growth and metastasis in vivo. RNA-seq was applicated in search of the potential downstream target of HJURP in PDAC and subsequent verification were fulfilled via multiple assays, including immunofluorescence. Additionally, chromatin immunoprecipitation and luciferase reporter assay were conducted to explore the potential regulation of MDM2 expression by HJURP through H3K4me2. In this current research, we found that the expression of HJURP in PDAC cells and tissue was significantly higher than those of adjacent normal tissue, and high HJURP expression predicted poor survival. HJURP significantly promoted the viability, sphere formation, migration, and invasion of PDAC cells in vitro, HJURP also facilitated tumor growth and metastasis in vivo. Mechanically, MDM2/p53 axis is critical for HJURP-mediated malignant behaviors in PDAC, and HJURP regulates MDM2 expression through H3K4me2. HJURP could serve as a promising biomarker, and target for PDAC prognosis and treatment.
Integrated near-field thermo-photovoltaics for heat recycling
Authors: Bhatt Gaurang R. , Zhao Bo , Roberts Samantha , Datta Ipshita , Mohanty Aseema , Lin Tong , Hartmann Jean-Michel , St-Gelais Raphael , Fan Shanhui , Lipson Michal
Published: May 2020

Energy transferred via thermal radiation between two surfaces separated by nanometer distances can be much larger than the blackbody limit. However, realizing a scalable platform that utilizes this near-field energy exchange mechanism to generate electricity remains a challenge. Here, we present a fully integrated, reconfigurable and scalable platform operating in the near-field regime that performs controlled heat extraction and energy recycling. Our platform relies on an integrated nano-electromechanical system that enables precise positioning of a thermal emitter within nanometer distances from a room-temperature germanium photodetector to form a thermo-photovoltaic cell. We demonstrate over an order of magnitude enhancement of power generation (Pgen ~ 1.25 μWcm−2) in our thermo-photovoltaic cell by actively tuning the gap between a hot-emitter (TE ~ 880 K) and the cold photodetector (TD ~ 300 K) from ~ 500 nm down to ~ 100 nm. Our nano-electromechanical system consumes negligible tuning power (Pgen/PNEMS ~ 104) and relies on scalable silicon-based process technologies.
Unique hole-accepting carbon-dots promoting selective carbon dioxide reduction nearly 100% to methanol by pure water
Authors: Wang Yiou , Liu Xu , Han Xiaoyu , Godin Robert , Chen Jialu , Zhou Wuzong , Jiang Chaoran , Thompson Jamie F. , Mustafa K. Bayazit , Shevlin Stephen A. , Durrant James R. , Guo Zhengxiao , Tang Junwang
Published: May 2020

Solar-driven CO2 reduction by abundant water to alcohols can supply sustainable liquid fuels and alleviate global warming. However, the sluggish water oxidation reaction has been hardly reported to be efficient and selective in CO2 conversion due to fast charge recombination. Here, using transient absorption spectroscopy, we demonstrate that microwave-synthesised carbon-dots (mCD) possess unique hole-accepting nature, prolonging the electron lifetime (t50%) of carbon nitride (CN) by six folds, favouring a six-electron product. mCD-decorated CN stably produces stoichiometric oxygen and methanol from water and CO2 with nearly 100% selectivity to methanol and internal quantum efficiency of 2.1% in the visible region, further confirmed by isotopic labelling. Such mCD rapidly extracts holes from CN and prevents the surface adsorption of methanol, favourably oxidising water over methanol and enhancing the selective CO2 reduction to alcohols. This work provides a unique strategy for efficient and highly selective CO2 reduction by water to high-value chemicals.
Ultrafast magnetic dynamics in insulating YBa2Cu3O6.1 revealed by time resolved two-magnon Raman scattering
Authors: Yang Jhih-An , Pellatz Nicholas , Wolf Thomas , Nandkishore Rahul , Reznik Dmitry
Published: May 2020

Measurement and control of magnetic order and correlations in real time is a rapidly developing scientific area relevant for magnetic memory and spintronics. In these experiments an ultrashort laser pulse (pump) is first absorbed by excitations carrying electric dipole moment. These then give their energy to the magnetic subsystem monitored by a time-resolved probe. A lot of progress has been made in investigations of ferromagnets but antiferromagnets are more challenging. Here, we introduce time-resolved two-magnon Raman scattering as a real time probe of magnetic correlations especially well-suited for antiferromagnets. Its application to the antiferromagnetic charge transfer insulator YBa2Cu3O6.1 revealed rapid demagnetization within 90 fs of photoexcitation. The relaxation back to thermal equilibrium is characterized by much slower timescales. We interpret these results in terms of slow relaxation of the charge sector and rapid equilibration of the magnetic sector to a prethermal state characterized by parameters that change slowly as the charge sector relaxes.
Strain-induced resonances in the dynamical quadratic magnetoelectric response of multiferroics
Authors: Sayedaghaee S. Omid , Paillard Charles , Prosandeev Sergey , Xu Bin , Bellaiche Laurent
Published: May 2020

For the last few years, the research interest in magnetoelectric (ME) effect, which is the cross-coupling between ferroelectric and magnetic ordering in multiferroic materials, has experienced a significant revival. The extensive recent studies are not only conducted towards the design of sensors, actuators, transducers, and memory devices by taking advantage of the cross-control of polarization (or magnetization) by magnetic (or electric) fields, but also aim to create a clearer picture in understanding the sources of ME responses and the novel effects associated with them. Here we derive analytical models allowing to understand the striking and novel dynamics of ME effects in multiferroics and further confirm it with atomistic simulations. Specifically, the role of strain is revealed to lead to the existence of electroacoustic magnons, a new quasiparticle that mixes acoustic and optical phonons with magnons, which results in resonances and thus a dramatic enhancement of magnetoelectric responses. Moreover, a unique aspect of the dynamical quadratic ME response under a magnetic field with varying frequencies, which is the second harmonic generation (SHG), has not been discussed prior to the present work. These SHGs put emphasis on the fact that nonlinearities should be considered while dealing with such systems.
Frequency-dependent dielectric constant prediction of polymers using machine learning
Authors: Chen Lihua , Kim Chiho , Batra Rohit , Lightstone Jordan P. , Wu Chao , Li Zongze , Deshmukh Ajinkya A. , Wang Yifei , Tran Huan D. , Vashishta Priya , Sotzing Gregory A. , Cao Yang , Ramprasad Rampi
Published: May 2020

The dielectric constant (ϵ) is a critical parameter utilized in the design of polymeric dielectrics for energy storage capacitors, microelectronic devices, and high-voltage insulations. However, agile discovery of polymer dielectrics with desirable ϵ remains a challenge, especially for high-energy, high-temperature applications. To aid accelerated polymer dielectrics discovery, we have developed a machine-learning (ML)-based model to instantly and accurately predict the frequency-dependent ϵ of polymers with the frequency range spanning 15 orders of magnitude. Our model is trained using a dataset of 1210 experimentally measured ϵ values at different frequencies, an advanced polymer fingerprinting scheme and the Gaussian process regression algorithm. The developed ML model is utilized to predict the ϵ of synthesizable 11,000 candidate polymers across the frequency range 60–1015 Hz, with the correct inverse ϵ vs. frequency trend recovered throughout. Furthermore, using ϵ and another previously studied key design property (glass transition temperature, Tg) as screening criteria, we propose five representative polymers with desired ϵ and Tg for capacitors and microelectronic applications. This work demonstrates the use of surrogate ML models to successfully and rapidly discover polymers satisfying single or multiple property requirements for specific applications.
A kinematic and kinetic dataset of 18 above-knee amputees walking at various speeds
Authors: Hood Sarah , Ishmael Marshall K. , Gunnell Andrew , Foreman K. B. , Lenzi Tommaso
Published: May 2020

Motion capture is necessary to quantify gait deviations in individuals with lower-limb amputations. However, access to the patient population and the necessary equipment is limited. Here we present the first open biomechanics dataset for 18 individuals with unilateral above-knee amputations walking at different speeds. Based on their ability to comfortably walk at 0.8 m/s, subjects were divided into two groups, namely K2 and K3. The K2 group walked at [0.4, 0.5, 0.6, 0.7, 0.8] m/s; the K3 group walked at [0.6, 0.8, 1.0, 1.2, 1.4] m/s. Full-body biomechanics was collected using a 10-camera motion capture system and a fully instrumented treadmill. The presented open dataset will enable (i) clinicians to understand the biomechanical demand required to walk with a knee and ankle prosthesis at various speeds, (ii) researchers in biomechanics to gain new insights into the gait deviations of individuals with above-knee amputations, and (iii) engineers to improve prosthesis design and function.
Preservation of hydrogen peroxide-induced oxidative damage in HepG-2 cells by rice protein hydrolysates pretreated with electron beams
Authors: Zhang Xinxia , Wang Li , Lu Hui , Zong Zhaoqin , Chen Zhengxing , Li Yongfu , Luo Xiaohu , Li Yanan
Published: May 2020

In this paper, electron beam irradiated rice protein hydrolysates (ERPHs) were assessed for their ability to prevent hydrogen peroxide-induced oxidative stress in human HepG-2 cells. The related mechanism was also studied by analyzing the structural changes. Cytotoxicity experiments showed that rice protein hydrolysates pretreated with electron beam irradiation (EBI) were not toxic to cells if appropriate concentrations were applied. Cell viability markedly increased when the cells were treated with ERPHs before H2O2 induction. Furthermore, the ERPHs effectively suppressed H2O2-induced ROS production and lipid peroxidation and increased the protein expression levels of the intracellular antioxidant enzymes SOD, GSH-Px and CAT in H2O2-stressed HepG-2 cells. Consequently, the loss of mitochondrial membrane potential and cell apoptosis was alleviated. Circular dichroism analysis showed that pretreatment of rice protein with EBI significantly changed the secondary structure (the conversion of α-helices to random coils), which is beneficial to the improvement of its antioxidative activity. ERPHs exhibited stronger antioxidative effects than those without irradiation, possibly because of the difference in molecular weight distribution and amino acid composition. These findings indicate an efficient way to produce peptides with better antioxidant activity.
Extracellular vesicles produced by human and animal Staphylococcus aureus strains share a highly conserved core proteome
Authors: Tartaglia Natayme Rocha , Nicolas Aurélie , Rodovalho Vinícius de Rezende , Luz Brenda Silva Rosa da , Briard-Bion Valérie , Krupova Zuzana , Thierry Anne , Coste François , Burel Agnes , Martin Patrice , Jardin Julien , Azevedo Vasco , Le Loir Yves , Guédon Eric
Published: May 2020

Staphylococcus aureus is an important opportunistic pathogen of humans and animals. It produces extracellular vesicles (EVs) that are involved in cellular communication and enable inter-kingdom crosstalk, the delivery of virulence factors and modulation of the host immune response. The protein content of EVs determines their biological functions. Clarifying which proteins are selected, and how, is of crucial value to understanding the role of EVs in pathogenesis and the development of molecular delivery systems. Here, we postulated that S. aureus EVs share a common proteome containing components involved in cargo sorting. The EV proteomes of five S. aureus strains originating from human, bovine, and ovine hosts were characterised. The clustering of EV proteomes reflected the diversity of the producing strains. A total of 253 proteins were identified, 119 of which composed a core EV proteome with functions in bacterial survival, pathogenesis, and putatively in EV biology. We also identified features in the sequences of EV proteins and the corresponding genes that could account for their packaging into EVs. Our findings corroborate the hypothesis of a selective sorting of proteins into EVs and offer new perspectives concerning the roles of EVs in S. aureus pathogenesis in specific host niches.
Geometrical Constraints on the Tangling of Bacterial Flagellar Filaments
Authors: Tătulea-Codrean Maria , Lauga Eric
Published: May 2020

Many species of bacteria swim through viscous environments by rotating multiple helical flagella. The filaments gather behind the cell body and form a close helical bundle, which propels the cell forward during a “run”. The filaments inside the bundle cannot be continuously actuated, nor can they easily unbundle, if they are tangled around one another. The fact that bacteria can passively form coherent bundles, i.e. bundles which do not contain tangled pairs of filaments, may appear surprising given that flagella are actuated by uncoordinated motors. In this article, we establish the theoretical conditions under which a pair of rigid helical filaments can form a tangled bundle, and we compare these constraints with experimental data collected from the literature. Our results suggest that bacterial flagella are too straight and too far apart to form tangled bundles based on their intrinsic, undeformed geometry alone. This makes the formation of coherent bundles more robust against the passive nature of the bundling process, where the position of individual filaments cannot be controlled.
Linkages between soil organic carbon fractions and carbon-hydrolyzing enzyme activities across riparian zones in the Three Gorges of China
Authors: Zhang Dandan , Wu Junjun , Yang Fan , Chen Qiong , Feng Jiao , Li Qianxi , Zhang Qian , Wang Weibo , Cheng Xiaoli
Published: May 2020

The effect of flooding on soil enzyme activities and soil organic carbon (SOC) dynamics remains a widely debated topic. Here, we investigated spatial variations in C-hydrolyzing enzyme activities, soil C contents in different fractions [i.e. labile and recalcitrant carbon (LC and RC)] from 6 sites with four different elevations at two soil depths (0–10 cm and 10–30 cm) in riparian zones of the Three Gorges Reservoir, China. At region scales, the SOC, RC contents, and RC/SOC (RIC) generally showed decreasing tendency from the upstream to the downstream. The C-hydrolyzing enzyme activities were higher in the midstream compared to other sites, which did not correspond well with the changing trend of SOC content, but matched with the spatial variation in LC content. At ecosystem scales, the RC and RIC declined with decreased elevations, but the LC showed opposite trend. Whereas, the four C-hydrolyzing enzyme activities and the specific enzyme activities were corresponded well with the changing trend of LC content. Soil C contents and enzyme activities were generally higher in top soil than deep soil across sites and elevation zones. These results reveal that the LC is the tightest factor in regulating C-hydrolyzing enzyme activities, whereas the soil C quality (i.e. RIC) and flooding collectively drive C-hydrolyzing enzyme activities possibly by affecting decomposition rates of SOC in the riparian zones.
Evidence for the Involvement of Vernalization-related Genes in the Regulation of Cold-induced Ripening in ‘D’Anjou’ and ‘Bartlett’ Pear Fruit
Authors: Hewitt Seanna L. , Hendrickson Christopher A. , Dhingra Amit
Published: May 2020

European pear (Pyrus communis L.) cultivars require a genetically pre-determined duration of cold-temperature exposure to induce autocatalytic system 2 ethylene biosynthesis and subsequent fruit ripening. The physiological responses of pear to cold-temperature-induced ripening have been well characterized, but the molecular mechanisms underlying this phenomenon continue to be elucidated. This study employed previously established cold temperature conditioning treatments for ripening of two pear cultivars, ‘D’Anjou’ and ‘Bartlett’. Using a time-course transcriptomics approach, global gene expression responses of each cultivar were assessed at four stages of developmental during the cold conditioning process. Differential expression, functional annotation, and gene ontology enrichment analyses were performed. Interestingly, evidence for the involvement of cold-induced, vernalization-related genes and repressors of endodormancy release was found. These genes have not previously been described to play a role in fruit during the ripening transition. The resulting data provide insight into cultivar-specific mechanisms of cold-induced transcriptional regulation of ripening in European pear, as well as a unique comparative analysis of the two cultivars with very different cold conditioning requirements.