bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasound guidance for Port-A-Cath insertion in children; a comparative study
Authors: Bawazir Osama A. , Bawazir Abdullah
Published: August 2020

Background:

Gaining vascular access in children is challenging. Ultrasound-guided central line insertion in adults became the standard of care; however, its role in children is not clear. Our objective was to evaluate the ultrasound-guided Port-A-Cath or totally implanted long-term venous access device insertion in pediatric patients compared to the traditional approach.

Methods:

This single-institution retrospective cohort study included 169 children who had port-A-catheters between May 2016 and Oct 2019. The patients were divided into two groups; group A included patients who had Port-A-Cath insertion using the landmark method (n = 117), and Group B included patients who had ultrasound-guided Port-A-Cath insertion (n = 52). Preoperative, operative, and postoperative data were collected and compared between the two groups. The study outcomes were operative time and catheter insertion-related complications.

Results:

There was no significant difference in age or gender between both groups (P = .33 and .71, respectively). Eleven cases in group A and two cases in group B were converted to cut down technique because of difficulty in inserting the guidewire. There was no difference in the indication of the need for the port-A-Cath between both groups. The mean operative time for group A was 47 min and for group B was 41.7 min (P < .042). Two patients had intraoperative bleeding and hemothorax and required blood transfusion and chest tube insertion in group A. No statistically significant difference was found in the reported complications between the groups. However, the insertion-related complications were higher in group A (P = .053). No procedure-related mortality was reported.

Conclusions:

Ultrasound-guided insertion of Port-A-Cath is an effective and safe technique with a reduction of failure rate. It should be considered the standard technique for Port-A-Cath insertion in the pediatric population.
The role of probiotics on the roadmap to a healthy microbiota: a symposium report
Authors: Lockyer Stacey , Aguirre Marisol , Durrant Louise , Pot Bruno , Suzuki Kaori
Published: August 2020

The ninth International Yakult Symposium was held in Ghent, Belgium in April 2018. Keynote lectures were from Professor Wijmenga on using biobanks to understand the relationship between the gut microbiota and health; and Professor Hill on phage–probiotic interactions. Session one included talks from Professor Plӧsch on epigenetic programming by nutritional and environmental factors; Professor Wilmes on the use of “omics” methodologies in microbiome research and Professor Rescigno on the gut vascular barrier. Session two explored the evidence behind Lactobacillus casei Shirota with Dr Nanno explaining the plasticity in immunomodulation that enables the strain to balance immune functions; Dr Macnaughtan outlining its potential therapeutic use in cirrhosis and Professor Nishida detailing effects in subjects under stress. The third session saw Professor Marchesi describing that both the host genes and the gut microbiota can play a role in cancer; Professor Bergheim highlighting crosstalk between the gut and the liver and Professor Cani describing the relationship between the gut microbiota and the endocrine system. The final session explored probiotic mechanisms, with Professor Lebeer dissecting the challenges in conducting mechanistic studies; Professor Wehkamp describing the mucosal defence system and Professor Van de Wiele detailing methods for modelling the gut microbiota in vitro.
Future projection of cryospheric and hydrologic regimes in Koshi River basin, Central Himalaya, using coupled glacier dynamics and glacio-hydrological models
Authors: Khadka Mira , Kayastha Rijan Bhakta , Kayastha Rakesh
Published: August 2020

Climate-induced cryospheric changes can have a significant impact on the downstream water availability. In this study, the Open Global Glacier Model (OGGM) and the Glacio-hydrological Degree-day Model (GDM) are integrated to project the response of cryospheric and hydrological systems to climate change until 2100. The study area comprises six sub-basins of glacierized Koshi River basin covering Nepalese and Chinese territories. The output from OGGM is provided as input to GDM along with the spatial and hydro-meteorological data. The average glacier area change in all the sub-basins from 2021 to 2100 is estimated as 65 and 85% decrease and the average glacier volume change is estimated as 76 and 86% decrease for RCP 4.5 and 8.5 scenarios, respectively. The future simulated discharge shows an increasing trend in pre-monsoon and monsoon seasons and a decreasing trend in post-monsoon and winter seasons after 2060 in all the sub-basins, which can lead to wetter wet seasons and drier dry seasons in the far future. A shift in peak flow is observed from August to July in most of the sub-basins. The coupled modelling technique used in this study can largely improve our understanding of glacio-hydrological dynamics in the Himalayan region.
We need to go deeper: measuring electoral violence using convolutional neural networks and social media
Authors: Muchlinski David , Yang Xiao , Birch Sarah , Macdonald Craig , Ounis Iadh
Published: August 2020

Electoral violence is conceived of as violence that occurs contemporaneously with elections, and as violence that would not have occurred in the absence of an election. While measuring the temporal aspect of this phenomenon is straightforward, measuring whether occurrences of violence are truly related to elections is more difficult. Using machine learning, we measure electoral violence across three elections using disaggregated reporting in social media. We demonstrate that our methodology is more than 30 percent more accurate in measuring electoral violence than previously utilized models. Additionally, we show that our measures of electoral violence conform to theoretical expectations of this conflict more so than those that exist in event datasets commonly utilized to measure electoral violence including ACLED, ICEWS, and SCAD. Finally, we demonstrate the validity of our data by developing a qualitative coding ontology.
LLOYD GEORGE AND THE ELECTORAL DECLINE OF THE BRITISH LIBERAL PARTY IN THE 1920s
Authors: BLAXILL LUKE , SALEH TAYM
Published: August 2020

This article reassesses the electoral decline of British Liberalism in the 1920s, especially the catastrophic defeat of 1924. A leading explanation for this disaster is that the Liberals were ‘fighting to lose’ by leaving nearly 250 constituencies uncontested. David Lloyd George is widely seen as deliberately seeking to destroy his party by refusing to finance candidates through his infamous ‘fund’, so he could lead what remained after electoral evisceration. His actions are widely credited with stymieing prospects of a Liberal recovery in the next election, 1929, which confirmed the party's permanent replacement by Labour. Through a wide-ranging statistical reanalysis, supported by a study of grassroots constituency campaigns, this article argues that the lack of candidates was a negligible contributor either to Liberal annihilation in 1924, or to Liberal failure to recover in 1929. The sharply deteriorating health of the party was already felt keenly at the grassroots before, not after, the seemingly freak result of 1924 was known. We thus argue that, contrary to the judgement of historians and contemporaries, the 1924 result represented the truer reflection of the party's fundamental interwar strength, with 1923 the exception. The inaction of Lloyd George in 1924 thus can be interpreted as pragmatic rather than Machiavellian.
A relativistic particle pusher for ultra-strong electromagnetic fields
Authors: Pétri J.
Published: August 2020

Kinetic plasma simulations are nowadays commonly used to study a wealth of nonlinear behaviours and properties in laboratory and space plasmas. In particular, in high-energy physics and astrophysics, the plasma usually evolves in ultra-strong electromagnetic fields produced by intense laser beams for the former or by rotating compact objects such as neutron stars and black holes for the latter. In these ultra-strong electromagnetic fields, the gyro-period is several orders of magnitude smaller than the time scale on which we desire to investigate the plasma evolution. Some approximations are required such as, for instance, artificially decreasing the electromagnetic field strength, which is certainly not satisfactory. The main flaw of this downscaling is that it cannot reproduce particle acceleration to ultra-relativistic speeds with a Lorentz factor above$\gamma \approx 10^3$–$10^4$. In this paper, we design a new algorithm able to catch particle motion and acceleration to a Lorentz factor of up to$10^{15}$or even higher by using Lorentz boosts to special frames where the electric and magnetic field are parallel. Assuming that these fields are locally uniform in space and constant in time, we solve analytically the equation of motion in a tiny region smaller than the length scale of the spatial and temporal gradient of the field. This analytical integration of the orbit severely reduces the constraint on the time step, allowing us to use large time steps, avoiding resolving the ultra-high gyro-frequency. We performed simulations in ultra-strong spatially and time-dependent electromagnetic fields, showing that our particle pusher is able to follow accurately the exact analytical solution for very long times. This property is crucial to properly capture for instance lepton electrodynamics in electromagnetic waves produced by fast rotating neutron stars. We conclude with a simple implementation of our new pusher into a one-dimensional relativistic electromagnetic particle-in-cell code, testing it against plasma oscillations, two-stream instabilities and strongly magnetized relativistic shocks.
Allometric models for sex ratio determination in all stages of ontogeny of Chelonia mydas from Bahía de los Ángeles, México
Authors: Solana-Arellano Elena , Ramírez-Delgado David , Santacruz-López Erika
Published: August 2020

In order to determine the sex of Chelonia mydas individuals found within one of the principal foraging areas of the Gulf of California during any given stage of ontogeny, 529 individuals were sampled in Bahía de los Ángeles from 1995–2012, and their morphometric data were collected. A principal component analysis (PCA) was performed for the morphometric variables, and two principal components were obtained that unambiguously separated sexes and ontogenetic stages. The first component was defined by straight carapace length (SCL), curve carapace length (CCL), plastron length (PL) and carapace depth (CD), while the second factor was represented by total tail length (TTL). Allometric models were fitted with the most important variables determined by the PCA. The model PL = αSCLβ was able to distinguish between adults and immature individuals. For adult organisms, the model that best separated males from females was TTL = αSCLβ. Adult females had SCL values of 66–96.7 cm and TTL values of 16.3–25 cm, while adult males had SCL values of 66.4–12.5 cm and TTL values > 25 cm. As the organisms were considered immature only if SCL < 77.3, we were able to determine the TTL values for immature individuals by using elemental mathematics and solving for SCL in the equation TTL = αSCLβ for each group (i.e. adult females, adult males and immatures). So, considering the mathematical approach and acknowledging the lack of background information, immature individuals may be considered potential females if the TTL value is between 7.04–17.8 cm and potential males if the TTL value > 17.8 cm.
Inconsistency in Ethics
Authors: Hämäläinen Nora
Published: August 2020

Consistency is usually seen as one of the hallmarks and a cardinal virtue of moral theory, as well as of any defensible real-life moral perspective. In everyday life a consistent set of moral beliefs is conductive to moral clarity, communicability, responsibility and responsiveness. But this is just one side of the story. In this paper I argue that inconsistency, properly understood, is a productive and constructive aspect of both moral philosophy and our moral lives. After an introductory glance at Ralf Waldo Emerson and Hannah Arendt, the argument proceeds in three main steps. First, I discuss the philosophical importance of paying heed to inconsistencies in our moral lives, which often are prematurely pruned from moral philosophy. Second, I discuss the positive moral roles of inconsistency in terms of responsiveness to different situations, values, needs and concerns that call upon our attention in everyday life. Third, I argue that moral inconsistencies contribute to the necessary adaptability of our moral understandings to changing conditions. Fourth, in the place of a conclusion, I revisit the issue of consistency, clarity and accountability.
Robust Square-Root Cubature FastSLAM with Genetic Operators
Authors: Havangi Ramazan
Published: August 2020

An improved FastSLAM based on the robust square-root cubature Kalman filter (RSRCKF) with partial genetic resampling is proposed in this paper. In the proposed method, RSRCKF is used to design the proposal distribution of FastSLAM and to estimate environment landmarks. The proposed method does not require a priori knowledge of the noise statistics. In addition, to increase diversity, it uses the genetic operators-based strategy to further improve the particle diversity. In fact, a partial genetic resampling operation is carried out to maintain the diversity of particles. The proposed method is compared with other methods via simulation and experimental data. It can be seen from the results that the proposed method provides significantly more accurate and robust estimation results compared with other methods even with fewer particles and unknown a priori. In addition, the consistency of the proposed method is better than that of other methods.
Vessel Trajectory Prediction Using Historical Automatic Identification System Data
Authors: Alizadeh Danial , Alesheikh Ali Asghar , Sharif Mohammad
Published: August 2020

For maritime safety and security, vessels should be able to predict the trajectories of nearby vessels to avoid collision. This research proposes three novel models based on similarity search of trajectories that predict vessels' trajectories in the short and long term. The first and second prediction models are, respectively, point-based and trajectory-based models that consider constant distances between target and sample trajectories. The third prediction model is a trajectory-based model that exploits a long short-term memory approach to measure the dynamic distance between target and sample trajectories. To evaluate the performance of the proposed models, they are applied to a real automatic identification system (AIS) vessel dataset in the Strait of Georgia, USA. The models' accuracies in terms of Haversine distance between the predicted and actual positions show relative prediction error reductions of 40·85% for the second model compared with the first model and 23% for the third model compared with the second model.
Runtime verification and validation of functional reactive systems
Authors: PEREZ IVAN , NILSSON HENRIK
Published: August 2020

Many types of interactive applications, including reactive systems implemented in hardware, interactive physics simulations and games, raise particular challenges when it comes to testing and debugging. Reasons include de facto lack of reproducibility and difficulties of automatically generating suitable test data. This paper demonstrates that certain variants of functional reactive programming (FRP) implemented in pure functional languages can mitigate such difficulties by offering referential transparency at the level of whole programs. This opens up for a multi-pronged approach for assisting with testing and debugging that works across platforms, including assertions based on temporal logic, recording and replaying of runs (also from deployed code), and automated random testing using QuickCheck. When combined with extensible forms of FRP that allow for constrained side effects, it allows us to not only validate software simulations but to analyse the effect of faults in reactive systems, confirm the efficacy of fault tolerance mechanisms and perform software- and hardware-in-the-loop testing. The approach has been validated on non-trivial systems implemented in several existing FRP implementations, by means of careful debugging using a tool that allows the test or simulation under scrutiny to be controlled, moving along the execution time line, and pin-pointing of violations of assertions on personal computers as well as external devices.
How are words felt in a second language: Norms for 2,628 English words for valence and arousal by L2 speakers
Authors: Imbault Constance , Titone Debra , Warriner Amy Beth , Kuperman Victor
Published: August 2020

The topic of non-native language processing has been of steady interest in past decades. Yet, conclusions about the emotional responses in L2 have been highly variable. We conducted a large-scale rating study to explicitly measure how non-native readers of English respond to the valence and arousal of 2,628 English words. We investigated how the effect of a rater's L2 proficiency, length of time in Canada, and the semantic category of the word affects how L2 readers experience and rate that word. L2 speakers who had lived a longer time in Canada, and reported higher English proficiency, showed emotional responses that were more similar to those of L1 speakers of English. Additionally, valence differences between L1 and L2 raters were greater in words that L2 raters do not typically use in English. These findings highlight the importance of behavioural ecology in language learning, particularly as it applies to emotional word processing.
AI in actuarial science – a review of recent advances – part 2
Authors: Richman Ronald
Published: August 2020

Rapid advances in artificial intelligence (AI) and machine learning are creating products and services with the potential not only to change the environment in which actuaries operate, but also to provide new opportunities within actuarial science. These advances are based on a modern approach to designing, fitting and applying neural networks, generally referred to as “Deep Learning”. This paper investigates how actuarial science may adapt and evolve in the coming years to incorporate these new techniques and methodologies. Part 1 of this paper provides background on machine learning and deep learning, as well as an heuristic for where actuaries might benefit from applying these techniques. Part 2 of the paper then surveys emerging applications of AI in actuarial science, with examples from mortality modelling, claims reserving, non-life pricing and telematics. For some of the examples, code has been provided on GitHub so that the interested reader can experiment with these techniques for themselves. Part 2 concludes with an outlook on the potential for actuaries to integrate deep learning into their activities. Finally, a supplementary appendix discusses further resources providing more in-depth background on machine learning and deep learning.
Forging Foreign Policy: Organizational Identity and Knowledge Production
Authors: Shepherd Hana
Published: August 2020

The ideas and knowledge central to foreign policy are often produced within the context of organizations. How do organizations vet people and ideas for knowledge production? I use original data drawn from archives of the Council on Foreign Relations (CFR), an organization that brought together elites with an interest in foreign policy, to examine the production of post–World War II US foreign policy knowledge. Drawing on literature about how organizations evaluate people and ideas, I assess how the CFR staff selected different foreign policy topics for their Program on Studies from 1955 to 1972. Case studies and multinomial logistic regression provide two forms of evidence: The justifications used by the CFR Program on Studies staff to select ideas and the relationship between recommendations of proposers and idea selection. I compare the effect of positive recommendations from different sources to distinguish between prioritizing quality and prestige and organizational identity on the other. Staff used the identity of the organization as a group of elites with particular expertise as a basis for making everyday decisions regarding which foreign policy knowledge would be codified in the program. In this way, the organization occupied a central position in the production of knowledge. This suggests that scholars of evaluation should attend to organization-level features in addition to individual-level characteristics. I discuss the implications for organizations and intellectual production.
Response of glyphosate-resistant and glyphosate-susceptible biotypes of annual sowthistle (Sonchus oleraceus) to increased carbon dioxide and variable soil moisture
Authors: Mobli Ahmadreza , Florentine Singarayer K , Jha Prashant , Chauhan Bhagirath Singh
Published: August 2020

The growth response of annual sowthistle (Sonchus oleraceusL.) to anticipated future climate conditions is currently unknown, and thus two parallel studies were conducted dealing with glyphosate-resistant (GR) and glyphosate-susceptible (GS) biotypes ofS. oleraceus. The glyphosate efficacy study was conducted using different doses of glyphosate (0 [control], 180, 360, 720 [recommended dose], and 1,440 g ae ha−1) at two different moisture levels (well-watered and water-stressed conditions). In the second study, the growth and seed production of these biotypes were studied under different atmospheric carbon dioxide (CO2) concentrations (450 and 750 ppm) and under well-watered (100% field capacity) and water-stressed (50% field capacity) conditions. Results showed that the GR biotype survived (>68%) at 1,440 g ha−1, but for the GS biotype, no plant survived, and both biotypes were slightly (<10%) affected by moisture regimes. In the elevated CO2condition, the GS biotype plants were >38% taller and produced >44%, >18%, and >21% more leaves, buds, and seeds, respectively, compared with the ambient CO2concentration under both moisture regimes. The biomass also increased by 27% in comparison with the ambient CO2concentration. For the GR biotype, plants at the elevated CO2level, while they also grew 38% taller in comparison with the ambient CO2concentration, the numbers of leaves, buds, and seeds and biomass were not affected by this increase in CO2. Results showed that there were minimal changes in response to glyphosate for GR and GS biotypes ofS. oleraceuswith or without moisture stress. Our study suggests that future climate change with elevated CO2levels can affect the response ofS. oleraceusto glyphosate, and such knowledge will be helpful for weed management in the future.
Examining the Time to Transition From Nonsuicidal Self-Injury to Suicide Attempt
Authors: O'Loughlin Caitlin , Burke Taylor A. , Ammerman Brooke A.
Published: August 2020

Abstract. Background: Nonsuicidal self-injury (NSSI) is a strong predictor of suicide attempts (SA). Characteristics of NSSI have been shown to influence the NSSI–SA relationship; however, the temporal nature of this association is understudied. Aims: This study aimed to elucidate the NSSI-SA relationship by examining the association between NSSI characteristics and time lapsed from NSSI onset to first SA. Method: Participants were 111 individuals with a history of NSSI that preceded their first SA who completed a series of self-report measures. Results: NSSI methods of cutting and burning, and the anti-dissociation function, were associated with a shorter transition time from NSSI to SA. Earlier age of NSSI onset and the interpersonal boundaries function were related to a longer time to transition. Limitations: This sample size was limited, and data were collected cross-sectionally. Conclusion: Findings provide foundational knowledge regarding NSSI characteristics to inform theoretical models of the NSSI–SA association. This information can inform suicide risk assessments among those with a history of NSSI.
Southeastern Pacific Error Leads to Failed El Niño Forecasts
Authors: Hua Lijuan , Su Jingzhi
Published: August 2020

In El Niño‐Southern Oscillation (ENSO) dynamical predictions, the ensemble members may show a large spread, leading to low prediction accuracy. The reasons for unreasonable forecast spreads in dynamical predictions are investigated based on hindcast/forecast results from the North American Multimodel Ensemble system. A category of failed‐forecasting members is defined if a negative Niño34 index in winter is forecasted by one member for the observed El Niño events. Compared with reasonable‐forecasting members, the failed‐forecasting members show significant cold sea surface temperature anomalies (SSTAs) in the southeastern Pacific (SEP). Such cold SSTAs can be traced back to the initial cold error in the SEP region. The initial cold error can be enhanced by positive feedback near the SEP region and further hinder warm SSTAs in equatorial regions, leading to a failed prediction. This result highlights the essential role of the SEP region, providing possible contributions to enhance the ENSO forecast skill.
Linearity of Outgoing Longwave Radiation: From an Atmospheric Column to Global Climate Models
Authors: Zhang Yi , Jeevanjee Nadir , Fueglistaler Stephan
Published: August 2020

The linearity of global‐mean outgoing longwave radiation (OLR) with surface temperature is a basic assumption in climate dynamics. This linearity manifests in global climate models, which robustly produce a global‐mean longwave clear‐sky (LWCS) feedback of 1.9 W/m2/K, consistent with idealized single‐column models (Koll & Cronin, 2018, https//:doi.org/10.1073/pnas.1809868115). However, there is considerable spatial variability in the LWCS feedback, including negative values over tropical oceans (known as the “super‐greenhouse effect”) which are compensated for by larger values in the subtropics/extratropics. Therefore, it is unclear how the idealized single‐column results are relevant for the global‐mean LWCS feedback in comprehensive climate models. Here we show with a simple analytical theory and model output that the compensation of this spatial variability to produce a robust global‐mean feedback can be explained by two facts: (1) When conditioned upon free‐tropospheric column relative humidity (RH), the LWCS feedback is independent of RH, and (2) the global histogram of free‐tropospheric column RH is largely invariant under warming.
Global River Discharge and Floods in the Warmer Climate of the Last Interglacial
Authors: Scussolini Paolo , Eilander Dirk , Sutanudjaja Edwin H. , Ikeuchi Hiroaki , Hoch Jannis M. , Ward Philip J. , Bakker Pepijn , Otto‐Bliesner Bette L. , Guo Chuncheng , Stepanek Christian , Zhang Qiong , Braconnot Pascale , Guarino Maria‐Vittoria , Muis Sanne , Yamazaki Dai , Veldkamp Ted I. E. , Aerts Jeroen C. J. H.
Published: August 2020

We investigate hydrology during a past climate slightly warmer than the present: the last interglacial (LIG). With daily output of preindustrial and LIG simulations from eight new climate models we force hydrological model PCR‐GLOBWB and in turn hydrodynamic model CaMa‐Flood. Compared to preindustrial, annual mean LIG runoff, discharge, and 100‐yr flood volume are considerably larger in the Northern Hemisphere, by 14%, 25%, and 82%, respectively. Anomalies are negative in the Southern Hemisphere. In some boreal regions, LIG runoff and discharge are lower despite higher precipitation, due to the higher temperatures and evaporation. LIG discharge is much higher for the Niger, Congo, Nile, Ganges, Irrawaddy, and Pearl and lower for the Mississippi, Saint Lawrence, Amazon, Paraná, Orange, Zambesi, Danube, and Ob. Discharge is seasonally postponed in tropical rivers affected by monsoon changes. Results agree with published proxies on the sign of discharge anomaly in 15 of 23 sites where comparison is possible.
Global Importance of Hydroxymethanesulfonate in Ambient Particulate Matter: Implications for Air Quality
Authors: Moch Jonathan M. , Dovrou Eleni , Mickley Loretta J. , Keutsch Frank N. , Liu Zirui , Wang Yuesi , Dombek Tracy L. , Kuwata Mikinori , Budisulistiorini Sri Hapsari , Yang Liudongqing , Decesari Stefano , Paglione Marco , Alexander Becky , Shao Jingyuan , Munger J. William , Jacob Daniel J.
Published: August 2020

Sulfur compounds are an important constituent of particulate matter, with impacts on climate and public health. While most sulfur observed in particulate matter has been assumed to be sulfate, laboratory experiments reveal that hydroxymethanesulfonate (HMS), an adduct formed by aqueous phase chemical reaction of dissolved HCHO and SO2, may be easily misinterpreted in measurements as sulfate. Here we present observational and modeling evidence for a ubiquitous global presence of HMS. We find that filter samples collected in Shijiazhuang, China, and examined with ion chromatography within 9 days show as much as 7.6 μg m−3 of HMS, while samples from Singapore examined 9–18 months after collection reveal ~0.6 μg m−3 of HMS. The Shijiazhuang samples show only minor traces of HMS 4 months later, suggesting that HMS had decomposed over time during sample storage. In contrast, the Singapore samples do not clearly show a decline in HMS concentration over 2 months of monitoring. Measurements from over 150 sites, primarily derived from the IMPROVE network across the United States, suggest the ubiquitous presence of HMS in at least trace amounts as much as 60 days after collection. The degree of possible HMS decomposition in the IMPROVE observations is unknown. Using the GEOS‐Chem chemical transport model, we estimate that HMS may account for 10% of global particulate sulfur in continental surface air and over 25% in many polluted regions. Our results suggest that reducing emissions of HCHO and other volatile organic compounds may have a co‐benefit of decreasing particulate sulfur.
The Resilience of Habitable Climates Around Circumbinary Stars
Authors: Wolf Eric T. , Haqq‐Misra Jacob , Kopparapu Ravi , Fauchez Thomas J. , Welsh William F. , Kane Stephen R. , Kostov Veselin , Eggl Siegfried
Published: August 2020

Here we use a 3‐D climate system model to study the habitability of Earth‐like planets orbiting in circumbinary systems. In the most extreme cases, Earth‐like planets in circumbinary systems could experience variations in the incident stellar flux of up to ~50% on ~100‐day timescales. However, we find that Earth‐like planets, having abundant surface liquid water, are generally effective at buffering against these time‐dependent changes in the stellar irradiation due to the high thermal inertia of oceans compared with the relatively short periods of circumbinary‐driven variations in the received stellar flux. Ocean surface temperatures exhibit little to no variation in time; however, land surfaces can experience modest changes in temperature, thus exhibiting an additional mode of climate variability driven by the circumbinary variations. Still, meaningful oscillations in surface temperatures are only found for circumbinary system architectures featuring the largest physically possible amplitudes in the stellar flux variation. In the most extreme cases, an Earth‐like planet could experience circumbinary‐driven variations in the global mean land surface temperature of up to ~5 K, and variations of local daytime maximum temperatures of up to ~12 K on seasonal timescales, while the global mean ocean temperatures vary by less than ~2 K. Such seasonal temperature swings over land areas could potentially pose adaptability challenges for extant life. Still, habitable planets in circumbinary systems appear to be remarkably resilient against circumbinary‐driven climate variations and can avoid any true climate catastrophes.
ASF1B promotes cervical cancer progression through stabilization of CDK9
Authors: Liu Xinjian , Song Jingwei , Zhang Yenan , Wang Huiquan , Sun Hongzhi , Feng Xiaomin , Hou Min , Chen Guo , Tang Qi , Ji Minjun
Published: August 2020

Cervical cancer (CC) is one of the most deadly cancers in women, its current treatments still result in poor outcomes and developing the novel targets and therapeutic strategies are urgently needed. Recent studies have shown that anti-silencing function 1B (ASF1B) might be used as a new proliferation marker for cancer diagnosis and prognosis. However, the expression and function of ASF1B in cervical cancer remain unclear. Here, we induced ASF1B knockdown and overexpression in cervical cancer cell lines and detected the biological behavior changes in vitro. Furthermore, we established two murine models using stable ASF1B-shRNA HeLa cells or normal HeLa cells following AAV-shRNA-ASF1B administration to evaluate how suppression of ASF1B affects tumor growth. We showed that ASF1B functions as an oncogene in cervical cancer cells. Silence of ASF1B suppressed cervical cancer cell growth in vitro and in vivo, while, ASF1B overexpression accelerated cancer cell proliferation. Furthermore, ASF1B deficiency induced cell cycle arrest and apoptosis. Mechanistically, we found that ASF1B formed stable complexes with cyclin-dependent kinase 9 (CDK9), and positively regulated CDK9 stabilization. Taken together, tumorigenic ASF1B could be targeted to suppress cervical cancer tumor growth by inducing apoptotic cell death.
Adipose-derived mesenchymal stromal cells promote corneal wound healing by accelerating the clearance of neutrophils in cornea
Authors: Shang Qianwen , Chu Yunpeng , Li Yanan , Han Yuyi , Yu Daojiang , Liu Rui , Zheng Zhiyuan , Song Lin , Fang Jiankai , Li Xiaolei , Cao Lijuan , Gong Zheng , Zhang Liying , Chen Yongjing , Wang Ying , Shao Changshun , Shi Yufang
Published: August 2020

The dome-shaped cornea is a transparent, non-vascularized, and epithelialized highly organized tissue. Physical and chemical injuries may trigger corneal wound healing (CWH) response and result in neovascularization that impairs the visual function. CWH involves not only migration, proliferation, and differentiation of the cells in different layers of cornea, but also the mobilization of immune cells. We demonstrated here that human adipose-derived mesenchymal stromal cells (ADSCs) could effectively inhibit neovascularization during ethanol-induced injury in mouse cornea. Importantly, we found that while neutrophils are essential for CWH, excessive and prolonged neutrophil retention during the granulation stage contributes to neovascularization. ADSCs were found to promote the clearance of neutrophils in the cornea during the granulation stage, likely via increasing the reverse transendothelial cell migration of CXCR4high neutrophils from cornea to the lung. Our results demonstrate that ADSCs are effective in treating CWH-induced neovascularization and modulation of neutrophil clearance could be novel strategies for better vision recovery after injury.
Tubeimoside I-induced lung cancer cell death and the underlying crosstalk between lysosomes and mitochondria
Authors: Wang Kun , Zhan Yujuan , Chen Bonan , Lu Yuhua , Yin Ting , Zhou Shikun , Zhang Weibin , Liu Xiaodong , Du Biaoyan , Wei Xianli , Xiao Jianyong
Published: August 2020

Cancer cells have developed chemoresistance and have improved their survival through the upregulation of autophagic mechanisms that protect mitochondrial function. Here, we report that the traditional Chinese anticancer agent tubeimoside I (Tub), which is a potent inhibitor of autophagy, can promote mitochondria-associated apoptosis in lung cancer cells. We found that Tub disrupted both mitochondrial and lysosomal pathways. One of its mechanisms was the induction of DRP1-mediated mitochondrial fragmentation. Another mechanism was the blocking of late-stage autophagic flux via impairment of lysosomal acidification through V-ATPase inhibition; this blocks the removal of dysfunctional mitochondria and results in reactive oxygen species (ROS) accumulation. Excessive ROS accumulation causes damage to lysosomal membranes and increases lysosomal membrane permeability, which leads to the leakage of cathepsin B. Finally, cathepsin B upregulates Bax-mediated mitochondrial outer membrane permeability and, subsequently, cytosolic cytochrome C-mediated caspase-dependent apoptosis. Thus, the cancer cell killing effect of Tub is enhanced through the formation of a positive feedback loop. The killing effect of Tub on lung cancer cells was verified in xenografted mice. In summary, Tub exerts a dual anticancer effect that involves the disruption of mitochondrial and lysosomal pathways and their interaction and, thereby, has a specific and enhanced killing effect on lung cancer cells.
A spike-timing-dependent plasticity rule for dendritic spines
Authors: Tazerart Sabrina , Mitchell Diana E. , Miranda-Rottmann Soledad , Araya Roberto
Published: August 2020

The structural organization of excitatory inputs supporting spike-timing-dependent plasticity (STDP) remains unknown. We performed a spine STDP protocol using two-photon (2P) glutamate uncaging (pre) paired with postsynaptic spikes (post) in layer 5 pyramidal neurons from juvenile mice. Here we report that pre-post pairings that trigger timing-dependent LTP (t-LTP) produce shrinkage of the activated spine neck and increase in synaptic strength; and post-pre pairings that trigger timing-dependent LTD (t-LTD) decrease synaptic strength without affecting spine shape. Furthermore, the induction of t-LTP with 2P glutamate uncaging in clustered spines (<5 μm apart) enhances LTP through a NMDA receptor-mediated spine calcium accumulation and actin polymerization-dependent neck shrinkage, whereas t-LTD was dependent on NMDA receptors and disrupted by the activation of clustered spines but recovered when separated by >40 μm. These results indicate that synaptic cooperativity disrupts t-LTD and extends the temporal window for the induction of t-LTP, leading to STDP only encompassing LTP.
Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry
Authors: Guo Wen-Hao , Qi Xiaoli , Yu Xin , Liu Yang , Chung Chan-I , Bai Fang , Lin Xingcheng , Lu Dong , Wang Lingfei , Chen Jianwei , Su Lynn Hsiao , Nomie Krystle J. , Li Feng , Wang Meng C. , Shu Xiaokun , Onuchic José N. , Woyach Jennifer A. , Wang Michael L. , Wang Jin
Published: August 2020

Current efforts in the proteolysis targeting chimera (PROTAC) field mostly focus on choosing an appropriate E3 ligase for the target protein, improving the binding affinities towards the target protein and the E3 ligase, and optimizing the PROTAC linker. However, due to the large molecular weights of PROTACs, their cellular uptake remains an issue. Through comparing how different warhead chemistry, reversible noncovalent (RNC), reversible covalent (RC), and irreversible covalent (IRC) binders, affects the degradation of Bruton’s Tyrosine Kinase (BTK), we serendipitously discover that cyano-acrylamide-based reversible covalent chemistry can significantly enhance the intracellular accumulation and target engagement of PROTACs and develop RC-1 as a reversible covalent BTK PROTAC with a high target occupancy as its corresponding kinase inhibitor and effectiveness as a dual functional inhibitor and degrader, a different mechanism-of-action for PROTACs. Importantly, this reversible covalent strategy is generalizable to improve other PROTACs, opening a path to enhance PROTAC efficacy.
Strange semimetal dynamics in SrIrO3
Authors: Sen K. , Fuchs D. , Heid R. , Kleindienst K. , Wolff K. , Schmalian J. , Le Tacon M.
Published: August 2020

The interplay of electronic correlations, multi-orbital excitations, and spin-orbit coupling is a fertile ground for new states of matter in quantum materials. Here, we report on a polarized Raman scattering study of semimetallic SrIrO3. The momentum-space selectivity of Raman scattering allows to circumvent the challenge to resolve the dynamics of charges with very different mobilities. The Raman responses of both holes and electrons display an electronic continuum extending far beyond the energies allowed in a regular Fermi liquid. Analyzing this response within a memory function formalism, we extract their frequency dependent scattering rate and mass enhancement, from which we determine their DC-mobilities and electrical resistivities that agree well with transport measurement. We demonstrate that its charge dynamics is well described by a marginal Fermi liquid phenomenology, with a scattering rate close to the Planckian limit. This demonstrates the potential of this approach to investigate the charge dynamics in multi-band systems.
On demand shape memory polymer via light regulated topological defects in a dynamic covalent network
Authors: Miao Wusha , Zou Weike , Jin Binjie , Ni Chujun , Zheng Ning , Zhao Qian , Xie Tao
Published: August 2020

The ability to undergo bond exchange in a dynamic covalent polymer network has brought many benefits not offered by classical thermoplastic and thermoset polymers. Despite the bond exchangeability, the overall network topologies for existing dynamic networks typically cannot be altered, limiting their potential expansion into unexplored territories. By harnessing topological defects inherent in any real polymer network, we show herein a general design that allows a dynamic network to undergo rearrangement to distinctive topologies. The use of a light triggered catalyst further allows spatio-temporal regulation of the network topology, leading to an unusual opportunity to program polymer properties. Applying this strategy to functional shape memory networks yields custom designable multi-shape and reversible shape memory characteristics. This molecular principle expands the design versatility for network polymers, with broad implications in many other areas including soft robotics, flexible electronics, and medical devices.
Author Correction: Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: a review and an update
Authors: Lee Andrew G. , Mader Thomas H. , Gibson C. Robert , Tarver William , Rabiei Pejman , Riascos Roy F. , Galdamez Laura A. , Brunstetter Tyson
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Links between central CB1-receptor availability and peripheral endocannabinoids in patients with first episode psychosis
Authors: Dickens Alex M. , Borgan Faith , Laurikainen Heikki , Lamichhane Santosh , Marques Tiago , Rönkkö Tuukka , Veronese Mattia , Lindeman Tuomas , Hyötyläinen Tuulia , Howes Oliver , Hietala Jarmo , Orešič Matej
Published: August 2020

There is an established, link between psychosis and metabolic abnormalities, such as altered glucose metabolism and dyslipidemia, which often precede the initiation of antipsychotic treatment. It is known that obesity-associated metabolic disorders are promoted by activation of specific cannabinoid targets (endocannabinoid system (ECS)). Our recent data suggest that there is a change in the circulating lipidome at the onset of first episode psychosis (FEP). With the aim of characterizing the involvement of the central and peripheral ECSs, and their mutual associations; here, we performed a combined neuroimaging and metabolomic study in patients with FEP and healthy controls (HC). Regional brain cannabinoid receptor type 1 (CB1R) availability was quantified in two, independent samples of patients with FEP (n = 20 and n = 8) and HC (n = 20 and n = 10), by applying three-dimensional positron emission tomography, using two radiotracers, [11C]MePPEP and [18F]FMPEP-d2. Ten endogenous cannabinoids or related metabolites were quantified in serum, drawn from these individuals during the same imaging session. Circulating levels of arachidonic acid and oleoylethanolamide (OEA) were reduced in FEP individuals, but not in those who were predominantly medication free. In HC, there was an inverse association between levels of circulating arachidonoyl glycerol, anandamide, OEA, and palmitoyl ethanolamide, and CB1R availability in the posterior cingulate cortex. This phenomenon was, however, not observed in FEP patients. Our data thus provide evidence of cross talk, and dysregulation between peripheral endocannabinoids and central CB1R availability in FEP.
Recombinant HA-based vaccine outperforms split and subunit vaccines in elicitation of influenza-specific CD4 T cells and CD4 T cell-dependent antibody responses in humans
Authors: Richards K. A. , Moritzky S. , Shannon I. , Fitzgerald T. , Yang H. , Branche A. , Topham D. J. , Treanor J. J. , Nayak J. , Sant Andrea J.
Published: August 2020

Although traditional egg-based inactivated influenza vaccines can protect against infection, there have been significant efforts to develop improved formats to overcome disadvantages of this platform. Here, we have assessed human CD4 T cell responses to a traditional egg-based influenza vaccine with recently available cell-derived vaccines and recombinant baculovirus-derived vaccines. Adults were administered either egg-derived Fluzone®, mammalian cell-derived Flucelvax® or recombinant HA (Flublok®). CD4 T cell responses to each HA protein were assessed by cytokine EliSpot and intracellular staining assays. The specificity and magnitude of antibody responses were quantified by ELISA and HAI assays. By all criteria, Flublok vaccine exhibited superior performance in eliciting both CD4 T cell responses and HA-specific antibody responses, whether measured by mean response magnitude or percent of responders. Although the mechanism(s) underlying this advantage is not yet clear, it is likely that both qualitative and quantitative features of the vaccines impact the response.
Author Correction: The Cannabinoid Content of Legal Cannabis in Washington State Varies Systematically Across Testing Facilities and Popular Consumer Products
Authors: Jikomes Nick , Zoorob Michael
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Nanoscale mechanisms in age-related hip-fractures
Authors: Ma Shaocheng , Goh En Lin , Tay Tabitha , Wiles Crispin C. , Boughton Oliver , Churchwell John H. , Wu Yong , Karunaratne Angelo , Bhattacharya Rajarshi , Terrill Nick , Cobb Justin P. , Hansen Ulrich , Abel Richard L.
Published: August 2020

Nanoscale mineralized collagen fibrils may be important determinants of whole-bone mechanical properties and contribute to the risk of age-related fractures. In a cross-sectional study nano- and tissue-level mechanics were compared across trabecular sections from the proximal femora of three groups (n = 10 each): ageing non-fractured donors (Controls); untreated fracture patients (Fx-Untreated); bisphosphonate-treated fracture patients (Fx-BisTreated). Collagen fibril, mineral and tissue mechanics were measured using synchrotron X-Ray diffraction of bone sections under load. Mechanical data were compared across groups, and tissue-level data were regressed against nano. Compared to controls fracture patients exhibited significantly lower critical tissue strain, max strain and normalized strength, with lower peak fibril and mineral strain. Bisphosphonate-treated exhibited the lowest properties. In all three groups, peak mineral strain coincided with maximum tissue strength (i.e. ultimate stress), whilst peak fibril strain occurred afterwards (i.e. higher tissue strain). Tissue strain and strength were positively and strongly correlated with peak fibril and mineral strains. Age-related fractures were associated with lower peak fibril and mineral strain irrespective of treatment. Indicating earlier mineral disengagement and the subsequent onset of fibril sliding is one of the key mechanisms leading to fracture. Treatments for fragility should target collagen-mineral interactions to restore nano-scale strain to that of healthy bone.