bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment status of extremely premature infants with gestational age < 28 weeks in a Chinese perinatal center from 2010 to 2019
Authors: Zhang Wen-Wen , Yu Yong-Hui , Dong Xiao-Yu , Reddy Simmy
Published: November 2021

Background

There is a paucity of studies conducted in China on the outcomes of all live-birth extremely premature infants (EPIs) and there is no unified recommendation on the active treatment of the minimum gestational age in the field of perinatal medicine in China. We aimed to investigate the current treatment situation of EPIs and to provide evidence for formulating reasonable treatment recommendations.

Methods

We established a real-world ambispective cohort study of all live births in delivery rooms with gestational age (GA) between 24+0 and 27+6 weeks from 2010 to 2019.

Results

Of the 1163 EPIs included in our study, 241 (20.7%) survived, while 849 (73.0%) died in the delivery room and 73 (6.3%) died in the neonatal intensive care unit. Among all included EPIs, 862 (74.1%) died from withholding or withdrawal of care. Regardless of stratification according to GA or birth weight, the proportion of total mortality attributable to withdrawal of care is high. For infants with the GA of 24 weeks, active treatment did not extend their survival time (P = 0.224). The survival time without severe morbidity of the active treatment was significantly longer than that of withdrawing care for infants older than 25 weeks (P < 0.001). Over time, the survival rate improved, and the withdrawal of care caused by socioeconomic factors and primary nonintervention were reduced significantly (P < 0.001).

Conclusions

The mortality rate of EPIs is still high. Withdrawal of care is common for EPIs with smaller GA, especially in the delivery room. It is necessary to use a multi-center, large sample of real-world data to find the survival limit of active treatment based on our treatment capabilities.
Molecular control to salt tolerance mechanisms of woody plants: recent achievements and perspectives
Authors: Llanes Analia , Palchetti María Virginia , Vilo Claudia , Ibañez Cristian
Published: November 2021

Key message

Woody plants have salt-tolerant mechanisms similar to those developed by non-woody plants. Among others, compartmentalization of ions, production of compatible solutes, synthesis of specific proteins and metabolites, and induction of transcriptional factors are the most relevant. Woody plant-associated microbial interactions as well as naturally stress-adapted trees are resources that deserve to be deepened to fully understand the tolerance mechanisms.

Context

The high variability of salinity responses found in woody plants implies a high potentiality for germplasm selection and breeding. Salt tolerance mechanisms of plants are regulated by numerous genes, which control ion homeostasis, production of compatible solutes and specific proteins, and activation or repression of specific transcription factors. Despite the fact that numerous studies have been done on herbaceous model plants, knowledge about salt tolerance mechanisms in woody plants is still scarce.

Aims

The present review critically evaluates molecular control of salt tolerance mechanisms of woody plants, focusing on the regulation and compartmentalization of ions, production of compatible solutes, activation of transcription factors, and differential expression of stress response-related proteins, including omics-based approaches and the role of plant-microbial interactions. The potential identification of genes from naturally stress-adapted woody plants and the integration of the massive omics data are also discussed.

Conclusion

In woody plants, salt tolerance mechanisms seem not to diverge to those identified in non-woody plants. More comparative studies between woody and non-woody salt tolerance plants will be relevant to identify potential molecular mechanisms specifically developed for wood plants. In this sense, the activation of metabolic pathways and molecular networks by novel genetic engineering techniques is key to establish strategies to improve the salt tolerance in woody plant species and to contribute to more sustainable agricultural and forestry systems.
Microstructure and mechanical properties of melt-grown alumina-mullite/glass composites fabricated by directed laser deposition
Authors: Zhao Dake , Wu Dongjiang , Shi Jing , Niu Fangyong , Ma Guangyi
Published: November 2021

Melt-grown alumina-based composites are receiving increasing attention due to their potential for aerospace applications; however, the rapid preparation of high-performance components remains a challenge. Herein, a novel route for 3D printing dense (< 99.4%) high-performance melt-grown alumina-mullite/glass composites using directed laser deposition (DLD) is proposed. Key issues on the composites, including phase composition, microstructure formation/evolution, densification, and mechanical properties, are systematically investigated. The toughening and strengthening mechanisms are analyzed using classical fracture mechanics, Griffith strength theory, and solid/glass interface infiltration theory. It is demonstrated that the composites are composed of corundum, mullite, and glass, or corundum and glass. With the increase of alumina content in the initial powder, corundum grains gradually evolve from near-equiaxed dendrite to columnar dendrite and cellular structures due to the weakening of constitutional undercooling and small nucleation undercooling. The microhardness and fracture toughness are the highest at 92.5 mol% alumina, with 18.39±0.38 GPa and 3.07±0.13 MPa·m1/2, respectively. The maximum strength is 310.1±36.5 MPa at 95 mol% alumina. Strength enhancement is attributed to the improved densification due to the trace silica doping and the relief of residual stresses. The method unravels the potential of preparing dense high-performance melt-grown alumina-based composites by the DLD technology.
Characterization of ultrafine-grained copper joints acquired by rotary friction welding
Authors: Ciemiorek M. , Morawiński Ł. , Jasiński C. , Orłowska M. , Chmielewski T. , Olejnik L. , Lewandowska M.
Published: November 2021

Copper rods with ultrafine-grained microstructure, obtained by multi-turn ECAP processing, were subjected to Direct Drive Rotary Friction Welding using various processing parameters, such as rotational speed and pressure, which resulted in different energy and heat input. Even though friction welding is a high energy process, by a proper selection of processing parameters it was possible to maintain grain size at around 0.7 µm in the weld zone and preserve the UFG microstructure. These microstructural features translated into mechanical properties: the YS for those specimens was around 330 MPa. Processing parameters that resulted in a larger heat input caused an increase in grain size to around 2 µm; this, however, increased ductility and led to a uniform elongation exceeding 5%. Corrosion resistance in the stir zone increased, as was evident in the higher open circuit potential and higher corrosion potential in comparison with base material; the observed differences were about 50 mV. These changes can be explained by the higher fraction of HAGBs in the SZ.
A regenerative 3D scaffold for inguinal hernia repair. MR imaging and histological cross evidence. Qualitative study
Authors: Amato Giuseppe , Agrusa Antonino , Puleio Roberto , Micci Giuseppe , Cassata Giovanni , Cicero Luca , Di Buono Giuseppe , Calò Pietro Giorgio , Galia Massimo , Romano Giorgio
Published: November 2021

Abstract

Background

Inguinal hernia is a degenerative disease occurring in a high motile surround. Stopping degeneration and promoting tissue regeneration should be the treatment goal. Groin hernias are conventionally managed with static flat meshes, mostly fixated to the delicate inguinal environment. Far from a regenerative effect, the biologic response of conventional hernia meshes is characterized by a foreign body reaction leading to a stiff/shrunken scar plate, which is often the source of unpleasant complications. Recently, a newly engineered 3D device for inguinal hernia repair – ProFlor-has been developed to produce a regenerative biological response. Unlike conventional hernia meshes, this regenerative 3D hernia scaffold seems to demonstrate suitable features for a pathogenetical and physiological coherent treatment of the disease. The aim of this manuscript is to cross evidence these features through magnetic resonance imaging (MRI) and histology.

Study design

The biological response of ProFlor at three defined post-implantation stages has been evaluated through MRI signal intensity and compared to neighbouring muscles and fat. As additional proof, histology of tissue specimens excised at the same post-implantation periods from porcine models during an experimental attempt were also evaluated.

Results

MRI of newly ingrown tissue in ProFlor demonstrated similar signal intensity of muscles while fat tissue showed remarkably higher values. These data matched with the histology of ProFlor biopsies excised from pigs.

Conclusions

The motile compliance to groin movements of ProFlor appears to induce a probiotic biologic response comparable to a regenerative scaffold, allowing to physiologically resolve the degenerative source of inguinal hernia disease.

Highlights
Policing for Peace
Authors: Nanes Matthew
Published: November 2021

In communities plagued by conflict along ethnic, racial, and religious lines, how does the representation of previously-marginalized groups in the police affect crime and security? Drawing on new evidence from policing in Iraq and Israel, Policing for Peace shows that an inclusive police force provides better services and reduces conflict, but not in the ways we might assume. Including members of marginalized groups in the police improves civilians' expectations of how the police and government will treat them, both now and in the future. These expectations are enhanced when officers are organized into mixed rather than homogeneous patrols. Iraqis indicate feeling most secure when policed by mixed officers, even more secure than they feel when policed by members of their own group. In Israel, increases in police officer diversity are associated with lower crime victimization for both Arab and Jewish citizens. In many cases, inclusive policing benefits all citizens, not just those from marginalized groups.
Monetizing Legal Assets: Social and Economic Benefits of Third-Party Dispute Finance in Asia
Authors: Khong Cheng-Yee
Published: November 2021

This article explains third-party dispute finance, including practical issues relating to the funding process and how to choose a funder. It examines some of the social benefits of funding and its importance in an economic downturn, and looks at some of the risks of dispute finance. It also considers the regulation of dispute finance in various Asian jurisdictions, as well as recent industry trends, including the use of dispute funding by well-resourced corporates and dispute-finance products for companies. It explains funding for insolvency-related claims and funding for the enforcement of awards and judgments. Finally, it provides two case-studies in which funding provided access to justice and enabled the funded party to recover a non-performing loan in multiple jurisdictions.
The K-property for some unique equilibrium states in flows and homeomorphisms
Authors: CALL BENJAMIN
Published: November 2021

We set out some general criteria to prove the K-property, refining the assumptions used in an earlier paper for the flow case, and introducing the analogous discrete-time result. We also introduce one-sided
$\lambda $
-decompositions, as well as multiple techniques for checking the pressure gap required to show the K-property. We apply our results to the family of Mañé diffeomorphisms and the Katok map. Our argument builds on the orbit decomposition theory of Climenhaga and Thompson.
CHINESE CAPITAL GOES GLOBAL: THE BELT AND ROAD INITIATIVE AND BEYOND
Authors: Shi Weiyi , Ye Min
Published: November 2021

The Belt and Road Initiative (BRI), and China's state-led model for economic globalization more generally, have attracted controversy: Are state-led overseas investment and lending driven by strategic motives or market rationale? How have the recipient economies reacted to the influx of Chinese capital? This special issue sheds light on these questions by first outlining the fragmented state system driving the BRI, a system featuring both Beijing's strategic logic at the top and market considerations in policy implementation. The role of the state is unpacked further in China's globalizing coal industry and in the growth of Chinese industry export to BRI countries. Finally, the issue explores the mechanisms behind public backlash and political pushback facing China in Zambia and Australia. As the COVID-19 pandemic continues to shift China's relationship with the world, this special issue contributes to a more nuanced understanding of themodus operandiof Chinese capital going global.
PEDDLING OR PERSUADING: CHINA'S ECONOMIC STATECRAFT IN AUSTRALIA
Authors: Wong Audrye
Published: November 2021

With the globalization of Chinese capital, economic statecraft has become an increasingly prominent component of China's foreign policy. In this article, I examine China's use of economic inducements in developed democracies, a topic of growing concern for policymakers, focusing on the case of Australia. I show how Beijing's attempts to coopt public voices and influence Australia's foreign policy using non-transparent political donations and academic funding generated a strong backlash. At the same time, economic interdependence has provided a buffering effect, with key domestic actors in Australia advocating for cooperative relations, although this effect can in turn be limited by Beijing's coercive economic tactics. My findings underline the reputational costs of certain approaches to economic statecraft, the value of building supportive coalitions, and the challenges faced by China's authoritarian state capitalist model. They also highlight the impacts of globalized Chinese capital in developed democracies, including the resilience and vulnerabilities inherent in democratic political processes.
Dimensions of temperament and character as predictors of antidepressant discontinuation, response and adverse reactions during treatment with nortriptyline and escitalopram
Authors: Köhler-Forsberg Ole , Keers Robert , Uher Rudolf , Hauser Joanna , Maier Wolfgang , Rietschel Marcella , McGuffin Peter , Farmer Anne E. , Aitchison Katherine J. , Mors Ole
Published: November 2021

Background

Personality traits may predict antidepressant discontinuation and response. However, previous studies were rather small, only explored a few personality traits and did not include adverse drug effects nor the interdependency between antidepressant discontinuation patterns and response.

Methods

GENDEP included 589 patients with unipolar moderate-severe depression treated with escitalopram or nortriptyline for 12 weeks. Seven personality dimensions were measured using the self-reported 240-item Temperament and Character Inventory-Revised (TCI-R). We applied Cox proportional models to study discontinuation patterns, logistic and linear regression to investigate response and remission after 8 and 12 weeks, and mixed-effects linear models regarding time-varying treatment response and adverse drug reactions.

Results

Low harm avoidance, low cooperativeness, high self-transcendence and high novelty seeking were associated with higher risks for antidepressant discontinuation, independent of depressed mood, adverse drug reactions, drug, sex and age. Regression analyses showed that higher novelty seeking and cooperativeness scores were associated with a greater likelihood of response and remission after 8 and 12 weeks, respectively, but we found no correlations with response in the mixed-effects models. Only high harm avoidance was associated with more self-reported adverse effects.

Conclusions

This study, representing the largest investigation between several personality traits and response to two different antidepressants, suggests that correlations between personality traits and antidepressant treatment response may be confounded by differential rates of discontinuation. Future trials on personality in the treatment of depression need to consider this interdependency and study whether interventions aiming at improving compliance for some personality types may improve response to antidepressants.
The long-term course of cognition in bipolar disorder: a systematic review and meta-analysis of patient-control differences in test-score changes
Authors: Samamé Cecilia , Cattaneo Brenda Lucía , Richaud María Cristina , Strejilevich Sergio , Aprahamian Ivan
Published: November 2021

Neuropsychological impairment represents a key aspect of bipolar disorder (BD) that is evident even in early-course patients and is a strong predictor of functional outcomes among those affected. Previous meta-analyses of longitudinal studies suggest that BD-related cognitive deficits may not progress along the course of the disorder. However, short test-retest periods were used in most primary studies and comparisons with healthy controls were limited. The aim of this review was to synthesize the findings of research reports comparing long-term neurocognitive trajectories between BD patients and healthy individuals. PubMed, PsycINFO, and Scopus databases were searched from inception through July 2021. Publications were considered for inclusion if they reported cognitive test scores of BD patients and healthy controls at two different time points, with a minimum test-retest interval of 5 years. Fifteen studies compared the long-term course of cognition in BD patients with that of healthy controls. Ten of these were included in the quantitative analysis and involved 540 BD patients and 644 healthy individuals (mean follow-up period: 8.9 years). Patient-control effect sizes (standardized mean differences) were calculated for test-score changes in 24 neuropsychological variables and combined by means of meta-analytic procedures. No significant differences were found between patients and controls regarding long-term cognitive outcomes. These findings are consistent with previous shorter-term longitudinal meta-analyses and do not provide evidence for progressive cognitive deterioration in most bipolar individuals. Future studies should address the longitudinal course of cognition in different subgroups of BD patients and its prognostic and therapeutic value.
The language of suppression: Muslims, migrant workers, and India's response to COVID-19
Authors: Nagar Ila
Published: November 2021

When a society faces a moment of crisis, its language can mirror, expose, and reinforce societal chaos and fault lines. As India came to terms with COVID-19, the coronavirus’ impacts on different populations exposed and widened India's deep social, economic, and religious divides. This article studies the language of India's response to COVID-19 surrounding three major events that occurred in the early months of the pandemic: the janta curfew, the Tablighi Jamaat incident, and the migrant worker crisis. Through an analysis of media reports, speeches made by Prime Minister Narendra Modi, and representations on social media, we see how forms of linguistic trickery—silence, presuppositions, accommodations, othering, dog whistling, and povertyism—were used to suppress, harm, and marginalize two minority groups: Muslims and migrant workers. This article demonstrates how those in power use language to reflect, shape, and reinforce meaning, social hierarchies, and marginalization in a time of crisis. (Linguistic trickery, othering, silence, presupposition, accommodation, dog whistling, povertyism)
Mothers’ emotional expressivity in urban and rural societies: Salience and links with young adolescents’ emotional wellbeing and expressivity
Authors: Ding Ruyi , Bi Shuang , Luo Yuhan , Liu Tuo , Wang Pusheng , He Wei , Ni Shiguang
Published: November 2021

This research aims to investigate the salience of mothers’ emotional expressivity and its links with adolescents’ emotional wellbeing and expressivity in an urban society endorsing more individualism and a rural society ascribing to more collectivism. By comparing Chinese urban (N = 283, Mage = 14.13) and rural (N = 247, Mage = 14.09) adolescents, this research found that urban mothers’ expression of positive-dominant and positive-submissive emotions (PD and PS) were more common while expression of negative-dominant (ND) emotions was less common than rural mothers’. PD and PS had significant links with urban and rural adolescents’ increased emotional expressivity and self-esteem, however, only significantly related to urban adolescents’ decreased depression but not with rural adolescents’. ND had significant links with both urban and rural adolescents’ expression of negative emotions, however, only significantly correlated with urban adolescents’ less level of self-esteem and rural adolescents’ more expression of positive emotions. No significant difference was found in the salience of urban and rural mothers’ expression of negative-submissive (NS) emotions, which positively related to both urban and rural adolescents’ depression and emotional expressivity. Moreover, we found that adolescents’ emotional wellbeing (i.e., self-esteem and depression) mediated the relationship between mothers’ emotional expressivity and adolescents’ expressivity in both societies. Overall, the study findings document that the salience of mothers’ emotional expressivity and its relations with adolescents’ emotional adjustment differ between urban and rural societies.
Sectoral labor mobility and optimal monetary policy
Authors: Cantelmo Alessandro , Melina Giovanni
Published: November 2021

How should central banks optimally aggregate sectoral inflation rates in the presence of imperfect labor mobility across sectors? We study this issue in a two-sector New-Keynesian model and show that a lower degree of sectoral labor mobility, ceteris paribus, increases the optimal weight on inflation in a sector that would otherwise receive a lower weight. We analytically and numerically find that, with limited labor mobility, adjustment to asymmetric shocks cannot fully occur through the reallocation of labor, thus putting more pressure on wages, causing inefficient movements in relative prices, and creating scope for central bank’ s intervention. These findings challenge standard central banks’ practice of computing sectoral inflation weights based solely on sector size and unveil a significant role for the degree of sectoral labor mobility to play in the optimal computation. In an extended estimated model of the US economy, featuring customary frictions and shocks, the estimated inflation weights imply a decrease in welfare up to 10% relative to the case of optimal weights.
Revisiting Insularity and Expansion: A Theory Note
Authors: Schuessler John M. , Shifrinson Joshua , Blagden David
Published: November 2021

What is the relationship between insularity—a state’s separation from other states via large bodies of water—and expansion? The received wisdom, prominent in (though not exclusive to) realist theories, holds that insularity constrains expansion by making conquest difficult. We contend, by contrast, that this received wisdom faces important limits. Focusing on U.S. expansion via means short of conquest, we interrogate the underlying theoretical logics to demonstrate that insular powers enjoy two distinct advantages when it comes to expansion. First, insularity translates into a “freedom to roam”: because insular powers are less threatened at home, they can project more power and influence abroad. Second, insularity “sterilizes” power, which explains why insular powers are seen as attractive security providers and why we do not see more counterbalancing against them. On net, existing scholarship is correct to argue that insularity impedes conquest between great powers. Still, it has missed the ways that insularity abets expansion via spheres of influence abroad. One consequence is an under-appreciation for the role of geography writ large and insularity in particular in shaping contemporary great power behavior.
Predicting Playa Inundation Using a Long Short‐Term Memory Neural Network
Authors: Solvik Kylen , Bartuszevige Anne M. , Bogaerts Meghan , Joseph Maxwell B.
Published: November 2021

In the Great Plains, playas are critical wetland habitats for migratory birds and a source of recharge for the agriculturally important High Plains aquifer. The temporary wetlands exhibit complex hydrology, filling rapidly via local rain storms and then drying through evaporation and groundwater infiltration. Using a long short‐term memory (LSTM) neural network to account for these complex processes, we modeled the probability of playa inundation for 71,842 playas in the Great Plains from 1984 to 2018. At the level of individual playas, the model achieved an F1‐score of 0.522 on a withheld test set, displaying the ability to predict complex inundation patterns. When simulating playa inundation over the entire region, the model is able to very closely track inundation trends, even during periods of drought. Our results demonstrate potential for using LSTMs to model complex hydrological dynamics. Our modeling approach could be used to model playa inundation into the future under different climate scenarios to better understand how wetland habitats and groundwater will be impacted by changing climate.
On the Detection of COVID‐Driven Changes in Atmospheric Carbon Dioxide
Authors: Lovenduski Nicole S. , Chatterjee Abhishek , Swart Neil C. , Fyfe John C. , Keeling Ralph F. , Schimel David
Published: November 2021

We assess the detectability of COVID‐like emissions reductions in global atmospheric CO2 concentrations using a suite of large ensembles conducted with an Earth system model. We find a unique fingerprint of COVID in the simulated growth rate of CO2 sampled at the locations of surface measurement sites. Negative anomalies in growth rates persist from January 2020 through December 2021, reaching a maximum in February 2021. However, this fingerprint is not formally detectable unless we force the model with unrealistically large emissions reductions (2 or 4 times the observed reductions). Internal variability and carbon‐concentration feedbacks obscure the detectability of short‐term emission reductions in atmospheric CO2. COVID‐driven changes in the simulated, column‐averaged dry air mole fractions of CO2 are eclipsed by large internal variability. Carbon‐concentration feedbacks begin to operate almost immediately after the emissions reduction; these feedbacks reduce the emissions‐driven signal in the atmosphere carbon reservoir and further confound signal detection.
“Time Variable Earth Gravity Field Models From the First Spaceborne Laser Ranging Interferometer"
Authors: Pie N. , Bettadpur S. V. , Tamisiea M. , Krichman B. , Save H. , Poole S. , Nagel P. , Kang Z. , Jacob G. , Ellmer M. , Fahnestock E. , Landerer F. W. , McCullough C. , Yuan D.‐N. , Wiese D. N.
Published: November 2021

The Gravity Recovery and Climate Experiment Follow‐On (GRACE‐FO), launched May 22, 2018 and collecting science data since June 2018, is extending the 15‐year data record of Earth mass change established by its predecessor GRACE mission (2002–2017). The GRACE‐FO satellites carry onboard a novel technology demonstration instrument for intersatellite ranging, the Laser Ranging Interferometer (LRI), in addition to the microwave interferometer (MWI) carried on GRACE. The LRI has out‐performed its in‐orbit performance requirements both in terms of accuracy as well as the duration of tracking. Here, we compare and validate LRI‐based gravity solutions for January 2019 to September 2020 against the MWI solutions. The comparison between the two sets of gravity solutions shows great similarities in general and nearly perfect consistency at a large hydrologic basin spatial scale (100,000 km2 and above), commonly viewed as the spatial resolution established by GRACE. The comparison in the spectral domain shows differences at the higher degrees of the spectrum, with lower error in the zonal and near zonal terms for the LRI solutions. We conclude that the LRI observations can be used to recover time‐varying gravity signals to at least the level of accuracy established by the MWI‐based solutions. This is a promising finding, especially when considering the benefits of using the LRI over the MWI, such as the great stability of the instrument and the low occurrence of instrument reboot events.
Improved Flood Forecasting in Basins With No Precipitation Stations: Constrained Runoff Correction Using Multiple Satellite Precipitation Products
Authors: Dou Yanhong , Ye Lei , Gupta Hoshin V. , Zhang Hairong , Behrangi Ali , Zhou Huicheng
Published: November 2021

Satellite‐based precipitation products (SPPs) with short latencies provide a new opportunity for flood forecasting in basins with no precipitation stations. However, the larger uncertainties associated with these near‐real‐time SPPs can influence the accuracy of flood forecasts. Here, we propose a real‐time updating method, referred to as “Constrained Runoff Correction using Multiple SPPs” (CRC‐M). The method is based on the hypothesis that the range of runoff volumes computed using different near‐real‐time SPPs provides an indication of the approximate range in which the true runoff volume lies. Accordingly, a constrained runoff correction is performed using the discharge observed at the basin outlet within this range. Evaluation using real data indicates that the new method performs well with Nash–Sutcliffe (NS) values of 0.85 and 0.87 during calibration and validation, respectively. The necessity of imposing constraints using multiple SPPs is demonstrated by comparing CRC‐M with 2 controls, referred to as “Unconstrained Runoff Correction using Single SPP” (URC‐S) and “Constrained Runoff Correction using Single SPP with perturbations” (CRC‐S). Experiments indicate that the key factors that result in good performance are (a) relatively reliable SPPs and (b) wider constraint ranges. Overall, the CRC‐M method can result in accurate and stable flood forecasts in basins with no precipitation stations, without the shortening of leading time and the need for increased model complexity (i.e., the numbers of model parameters).
Free Alternate Bars in Rivers: Key Physical Mechanisms and Simple Formation Criterion
Authors: Redolfi Marco
Published: November 2021

Free alternate bars are large‐scale, downstream‐migrating bedforms characterized by an alternating sequence of three‐dimensional depositional fronts and scour holes that frequently develop in rivers as the result of an intrinsic instability of the erodible bed. Theoretical models based on two‐dimensional shallow water and Exner equations have been successfully employed to capture the bar instability phenomenon, and to estimate bar properties such as height, wavelength and migration rate. However, the mathematical complexity of the problem hampered the understanding of the key physical mechanisms that sustain bar formation. To fill this gap, we considered a simplified version of the equations, based on neglecting the deformation of the free surface, which allows us to: (a) provide the first complete explanation of the bar formation mechanism as the result of a simple bond between variations of the water weight and flow acceleration; (b) derive a simplified, physically based formula for predicting bar formation in a river reach, depending on channel width‐to‐depth ratio, Shields number and relative submergence. Comparison with an unprecedented large set of laboratory experiments reveals that our simplified formula appropriately predicts alternate bar formation in a wide range of conditions. Noteworthy, the hypothesis of negligible free surface effect also implies that bar formation is fully independent of the Froude number. We show that this intriguing property is intimately related to the three‐dimensional nature of river bars, which allows for a gentle lateral deviation of the flow without significant deformation of the water surface.
Disrupted mitochondrial homeostasis coupled with mitotic arrest generates antineoplastic oxidative stress
Authors: Hao Xiaohe , Bu Wenqing , Lv Guosheng , Xu Limei , Hou Dong , Wang Jing , Liu Xiaojie , Yang Tingting , Zhang Xiyu , Liu Qiao , Gong Yaoqin , Shao Changshun
Published: November 2021

Reactive oxygen species (ROS) serve as critical signals in various cellular processes. Excessive ROS cause cell death or senescence and mediates the therapeutic effect of many cancer drugs. Recent studies showed that ROS increasingly accumulate during G2/M arrest, the underlying mechanism, however, has not been fully elucidated. Here, we show that in cancer cells treated with anticancer agent TH287 or paclitaxel that causes M arrest, mitochondria accumulate robustly and produce excessive mitochondrial superoxide, which causes oxidative DNA damage and undermines cell survival and proliferation. While mitochondrial mass is greatly increased in cells arrested at M phase, the mitochondrial function is compromised, as reflected by reduced mitochondrial membrane potential, increased SUMOylation and acetylation of mitochondrial proteins, as well as an increased metabolic reliance on glycolysis. CHK1 functional disruption decelerates cell cycle, spares the M arrest and attenuates mitochondrial oxidative stress. Induction of mitophagy and blockade of mitochondrial biogenesis, measures that reduce mitochondrial accumulation, also decelerate cell cycle and abrogate M arrest-coupled mitochondrial oxidative stress. These results suggest that cell cycle progression and mitochondrial homeostasis are interdependent and coordinated, and that impairment of mitochondrial homeostasis and the associated redox signaling may mediate the antineoplastic effect of the M arrest-inducing chemotherapeutics. Our findings provide insights into the fate of cells arrested at M phase and have implications in cancer therapy.
The brain targeted delivery of programmed cell death 4 specific siRNA protects mice from CRS-induced depressive behavior
Authors: Jia Yufeng , Zhuang Xiao , Zhang Yi , Zhao Ming , Chen Nuo , Li Wen , Zhu Faliang , Guo Chun , Li Yan , Wang Qun , Li Yuan , Zhang Lining
Published: November 2021

Depression is one of the most common psychiatric disorders. Recently, studies demonstrate that antidepressants generating BDNF not only maintain synaptic signal transmission but also repress neuroinflammatory cytokines such as IL-6 and IL-1β. Therefore, promoting BDNF expression provides a strategy for the treatment of depression. Our recent research has indicated that programmed cell death 4 (Pdcd4) is a new target for antidepressant treatment by facilitating BDNF. Herein, we modified Pdcd4 specific small interfering RNA (siPdcd4) with the rabies virus glycoprotein peptide (RVG/siPdcd4) which enables it cross the blood-brain barrier (BBB). We found that RVG/siPdcd4 complex was selectively delivered to neurons and microglia and silenced the expression of Pdcd4, thereby up-regulating the level of BDNF and down-regulating IL-6 and IL-1β expression. More importantly, RVG/siPdcd4 injection attenuated synaptic plasticity impairment and protected mice from CRS-induced depressive behavior. These findings suggest that RVG/siPdcd4 complex is a potential therapeutic medicine for depression.
MRPS31 loss is a key driver of mitochondrial deregulation and hepatocellular carcinoma aggressiveness
Authors: Min Seongki , Lee Young-Kyoung , Hong Jiwon , Park Tae Jun , Woo Hyun Goo , Kwon So Mee , Yoon Gyesoon
Published: November 2021

Deregulated mitochondrial energetics is a metabolic hallmark of cancer cells. However, the causative mechanism of the bioenergetic deregulation is not clear. In this study, we show that somatic copy number alteration (SCNA) of mitoribosomal protein (MRP) genes is a key mechanism of bioenergetic deregulation in hepatocellular carcinoma (HCC). Association analysis between the genomic and transcriptomic profiles of 82 MRPs using The Cancer Genome Atlas-Liver HCC database identified eight key SCNA-dependent MRPs: MRPS31, MRPL10, MRPL21, MRPL15, MRPL13, MRPL55, and DAP3. MRPS31 was the only downregulated MRP harboring a DNA copy number (DCN) loss. MRPS31 loss was associated specifically with the DCN losses of many genes on chromosome 13q. Survival analysis revealed a unique dependency of HCC on the MRPS31 deficiency, showing poor clinical outcome. Subclass prediction analysis using several public classifiers indicated that MRPS31 loss is linked to aggressive HCC phenotypes. By employing hepatoma cell lines with SCNA-dependent MRPS31 expression (JHH5, HepG2, Hep3B, and SNU449), we demonstrated that MRPS31 deficiency is the key mechanism, disturbing the whole mitoribosome assembly. MRPS31 suppression enhanced hepatoma cell invasiveness by augmenting MMP7 and COL1A1 expression. Unlike the action of MMP7 on extracellular matrix destruction, COL1A1 modulated invasiveness via the ZEB1-mediated epithelial-to-mesenchymal transition. Finally, MRPS31 expression further stratified the high COL1A1/DDR1-expressing HCC groups into high and low overall survival, indicating that MRPS31 loss is a promising prognostic marker.

Significance

Our results provide new mechanistic insight for mitochondrial deregulation in HCC and present MRPS31 as a novel biomarker of HCC malignancy.
Regio- and enantioselective umpolung gem-difluoroallylation of hydrazones via palladium catalysis enabled by N-heterocyclic carbene ligand
Authors: Huang Shuai , Tong Fei-Fei , Bai Da-Chang , Zhang Gao-Peng , Jiang Yang-Jie , Zhang Bo , Leng Xuebing , Guo Ying-Long , Wan Xiao-Long , Zhang Xingang , Ding Chang-Hua , Hou Xue-Long
Published: November 2021

The enantioselective construction of C–CF2R (R: alkyl or fluoroalkyl) bonds has attracted the attention of synthetic chemists because of the importance of chiral fluorinated compounds in life and materials sciences. Catalytic asymmetric fluoroalkylation has mainly been realized under organocatalysis and Lewis acid catalysis, with substrates limited to carbonyl compounds. Few examples using transition-metal catalysis exist, owing to side reactions including decomposition and isomerization of fluoroalkylating reagents. Herein we report umpolung asymmetric difluoroallylation of hydrazones with 3-bromo-3,3-difluoropropene (BDFP) under palladium catalysis. Difluoroallylation products having quaternary chiral carbon centers are afforded in good yields with high α/γ- and enantioselectivities. The usefulness of the reaction products is demonstrated and an inner-sphere mechanism of the reaction is proposed. The use of chiral N-heterocyclic carbene as ligand is the key for the selectivities as well as the productivity of the reaction.
Entropy-based metrics for predicting choice behavior based on local response to reward
Authors: Trepka Ethan , Spitmaan Mehran , Bari Bilal A. , Costa Vincent D. , Cohen Jeremiah Y. , Soltani Alireza
Published: November 2021

For decades, behavioral scientists have used the matching law to quantify how animals distribute their choices between multiple options in response to reinforcement they receive. More recently, many reinforcement learning (RL) models have been developed to explain choice by integrating reward feedback over time. Despite reasonable success of RL models in capturing choice on a trial-by-trial basis, these models cannot capture variability in matching behavior. To address this, we developed metrics based on information theory and applied them to choice data from dynamic learning tasks in mice and monkeys. We found that a single entropy-based metric can explain 50% and 41% of variance in matching in mice and monkeys, respectively. We then used limitations of existing RL models in capturing entropy-based metrics to construct more accurate models of choice. Together, our entropy-based metrics provide a model-free tool to predict adaptive choice behavior and reveal underlying neural mechanisms.
WRN helicase safeguards deprotected replication forks in BRCA2-mutated cancer cells
Authors: Datta Arindam , Biswas Kajal , Sommers Joshua A. , Thompson Haley , Awate Sanket , Nicolae Claudia M. , Thakar Tanay , Moldovan George-Lucian , Shoemaker Robert H. , Sharan Shyam K. , Brosh Robert M.
Published: November 2021

The tumor suppressor BRCA2 protects stalled forks from degradation to maintain genome stability. However, the molecular mechanism(s) whereby unprotected forks are stabilized remains to be fully characterized. Here, we demonstrate that WRN helicase ensures efficient restart and limits excessive degradation of stalled forks in BRCA2-deficient cancer cells. In vitro, WRN ATPase/helicase catalyzes fork restoration and curtails MRE11 nuclease activity on regressed forks. We show that WRN helicase inhibitor traps WRN on chromatin leading to rapid fork stalling and nucleolytic degradation of unprotected forks by MRE11, resulting in MUS81-dependent double-strand breaks, elevated non-homologous end-joining and chromosomal instability. WRN helicase inhibition reduces viability of BRCA2-deficient cells and potentiates cytotoxicity of a poly (ADP)ribose polymerase (PARP) inhibitor. Furthermore, BRCA2-deficient xenograft tumors in mice exhibited increased DNA damage and growth inhibition when treated with WRN helicase inhibitor. This work provides mechanistic insight into stalled fork stabilization by WRN helicase when BRCA2 is deficient.
Transition metal-doped Ni-rich layered cathode materials for durable Li-ion batteries
Authors: Sun H. Hohyun , Kim Un-Hyuck , Park Jeong-Hyeon , Park Sang-Wook , Seo Dong-Hwa , Heller Adam , Mullins C. Buddie , Yoon Chong S. , Sun Yang-Kook
Published: November 2021

Doping is a well-known strategy to enhance the electrochemical energy storage performance of layered cathode materials. Many studies on various dopants have been reported; however, a general relationship between the dopants and their effect on the stability of the positive electrode upon prolonged cell cycling has yet to be established. Here, we explore the impact of the oxidation states of various dopants (i.e., Mg2+, Al3+, Ti4+, Ta5+, and Mo6+) on the electrochemical, morphological, and structural properties of a Ni-rich cathode material (i.e., Li[Ni0.91Co0.09]O2). Galvanostatic cycling measurements in pouch-type Li-ion full cells show that cathodes featuring dopants with high oxidation states significantly outperform their undoped counterparts and the dopants with low oxidation states. In particular, Li-ion pouch cells with Ta5+- and Mo6+-doped Li[Ni0.91Co0.09]O2 cathodes retain about 81.5% of their initial specific capacity after 3000 cycles at 200 mA g−1. Furthermore, physicochemical measurements and analyses suggest substantial differences in the grain geometries and crystal lattice structures of the various cathode materials, which contribute to their widely different battery performances and correlate with the oxidation states of their dopants.
Local DNA shape is a general principle of transcription factor binding specificity in Arabidopsis thaliana
Authors: Sielemann Janik , Wulf Donat , Schmidt Romy , Bräutigam Andrea
Published: November 2021

Understanding gene expression will require understanding where regulatory factors bind genomic DNA. The frequently used sequence-based motifs of protein-DNA binding are not predictive, since a genome contains many more binding sites than are actually bound and transcription factors of the same family share similar DNA-binding motifs. Traditionally, these motifs only depict sequence but neglect DNA shape. Since shape may contribute non-linearly and combinational to binding, machine learning approaches ought to be able to better predict transcription factor binding. Here we show that a random forest machine learning approach, which incorporates the 3D-shape of DNA, enhances binding prediction for all 216 tested Arabidopsis thaliana transcription factors and improves the resolution of differential binding by transcription factor family members which share the same binding motif. We observed that DNA shape features were individually weighted for each transcription factor, even if they shared the same binding sequence.
Health impacts of wildfire-related air pollution in Brazil: a nationwide study of more than 2 million hospital admissions between 2008 and 2018
Authors: Requia Weeberb J. , Amini Heresh , Mukherjee Rajarshi , Gold Diane R. , Schwartz Joel D.
Published: November 2021

We quantified the impacts of wildfire-related PM2.5 on 2 million hospital admissions records due to cardiorespiratory diseases in Brazil between 2008 and 2018. The national analysis shows that wildfire waves are associated with an increase of 23% (95%CI: 12%–33%) in respiratory hospital admissions and an increase of 21% (95%CI: 8%–35%) in circulatory hospital admissions. In the North (where most of the Amazon region is located), we estimate an increase of 38% (95%CI: 30%–47%) in respiratory hospital admissions and 27% (95%CI: 15%–39%) in circulatory hospital admissions. Here we report epidemiological evidence that air pollution emitted by wildfires is significantly associated with a higher risk of cardiorespiratory hospital admissions.
The RNA-binding protein HuR is required for maintenance of the germinal centre response
Authors: Osma-Garcia Ines C. , Capitan-Sobrino Dunja , Mouysset Mailys , Bell Sarah E. , Lebeurrier Manuel , Turner Martin , Diaz-Muñoz Manuel D.
Published: November 2021

The germinal centre (GC) is required for the generation of high affinity antibodies and immunological memory. Here we show that the RNA binding protein HuR has an essential function in GC B cells to sustain the GC response. In its absence, the GC reaction and production of high-affinity antibody is severely impaired. Mechanistically, HuR affects the transcriptome qualitatively and quantitatively. The expression and splicing patterns of hundreds of genes are altered in the absence of HuR. Among these genes, HuR is required for the expression of Myc and a Myc-dependent transcriptional program that controls GC B cell proliferation and Ig somatic hypermutation. Additionally, HuR regulates the splicing and abundance of mRNAs required for entry into and transition through the S phase of the cell cycle, and it modulates a gene signature associated with DNA deamination protecting GC B cells from DNA damage and cell death.
Computational redesign of Fab CC12.3 with substantially better predicted binding affinity to SARS-CoV-2 than human ACE2 receptor
Authors: Treewattanawong Wantanee , Sitthiyotha Thassanai , Chunsrivirot Surasak
Published: November 2021

SARS-CoV-2 is responsible for COVID-19 pandemic, causing large numbers of cases and deaths. It initiates entry into human cells by binding to the peptidase domain of angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain of S1 subunit of spike protein (SARS-CoV-2-RBD). Employing neutralizing antibodies to prevent binding between SARS-CoV-2-RBD and ACE2 is an effective COVID-19 therapeutic solution. Previous studies found that CC12.3 is a highly potent neutralizing antibody that was isolated from a SARS-CoV-2 infected patient, and its Fab fragment (Fab CC12.3) bound to SARS-CoV-2-RBD with comparable binding affinity to ACE2. To enhance its binding affinity, we employed computational protein design to redesign all CDRs of Fab CC12.3 and molecular dynamics (MD) to validate their predicted binding affinities by the MM-GBSA method. MD results show that the predicted binding affinities of the three best designed Fabs CC12.3 (CC12.3-D02, CC12.3-D05, and CC12.3-D08) are better than those of Fab CC12.3 and ACE2. Additionally, our results suggest that enhanced binding affinities of CC12.3-D02, CC12.3-D05, and CC12.3-D08 are caused by increased SARS-CoV-2-RBD binding interactions of CDRs L1 and L3. This study redesigned neutralizing antibodies with better predicted binding affinities to SARS-CoV-2-RBD than Fab CC12.3 and ACE2. They are promising candidates as neutralizing antibodies against SARS-CoV-2.