bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuous Quantity and Quality Modeling for Assessing the Effect of SUDS: Application on a Conceptual Urban Drainage Basin
Authors: Ferrans Pascual , Temprano Javier
Published: November 2022

The development of computational tools based on urban drainage models is fundamental for the correct selection of SUDS. The present study proposes a systematic approach based on continuous modeling on USEPA SWMM. The objective was to select the most suitable Sustainable Urban Drainage Systems (SUDS) by evaluating several aspects related to their design and configuration. The proposed methodology was applied to a conceptual watershed with meteorological information from Santander, Spain. The analysis of SUDS design parameters showed that only the surface variables showed a sensitivity of ≈20% for berm height and vegetation volume. The optimal configuration for the case study was a SUDS train consisting of green roofs, permeable pavements, vegetated swales and rain gardens, with 1% of the total subcatchment area cover, one structure, and a semi-aggregated spatial distribution. The methodology proved efficient but also highly dependent on the case study parameters and the meteorological conditions. The SUDS proved to have different efficiencies (30%—90%) in reducing the total runoff volume, the peak flow, and the pollutant loads depending on the region where the conceptual watershed was modeled. The methodology proved to be efficient for studying the combinations and interconnection of seven different typologies, as well as the effect of SUDS configuration, design and distribution on their performance.
KM-408, a novel phenoxyalkyl derivative as a potential anticonvulsant and analgesic compound for the treatment of neuropathic pain
Authors: Waszkielewicz Anna , Marona Henryk , Pańczyk-Straszak Katarzyna , Filipek Barbara , Rapacz Anna , Sałat Kinga , Kubacka Monika , Cios Agnieszka , Fedak Filip , Walczak Maria , Hubicka Urszula , Kwiecień Anna , Żuromska-Witek Barbara , Szafrański Przemysław W. , Koczurkiewicz-Adamczyk Paulina , Pękala Elżbieta , Przejczowska-Pomierny Katarzyna , Pociecha Krzysztof , Wyska Elżbieta
Published: November 2022

Background

Epilepsy frequently coexists with neuropathic pain. Our approach is based on the search for active compounds with multitarget profiles beneficial in terms of potential side effects and on the implementation of screening for potential multidirectional central activity.

Methods

Compounds were synthesized by means of chemical synthesis. After antiseizure and neurotoxicity screening in vivo,KM-408and its enantiomers were chosen for analgesic activity evaluations. Further safety studies included acute toxicity in mice, the effect on normal electrocardiogram and on blood pressure in rats, whole body plethysmography in rats, and in vitro and biochemical assays. Pharmacokinetics has been studied in rats afterivandpoadministration. Metabolism has been studied in vivo in rat serum and urine. Radioligand binding studies were performed as part of the mechanism of action investigation.

Results

Selected results forKM-408: Kisigma = 7.2*10–8; Ki5-HT1A = 8.0*10–7; ED50MES (mice,ip) = 13.3 mg/kg; formalin test (I phase, mice,ip)—active at 30 mg/kg; SNL (rats,ip)—active at 6 mg/kg; STZ-induced pain (mice,ip)—active at 1 mg/kg (von Frey) and 10 mg/kg (hot plate); hot plate test (mice,ip)—active at 30 mg/kg; ED50capsaicin test (mice,ip) = 18.99 mg/kg; tail immersion test (mice)—active at 0.5%; corneal anesthesia (guinea pigs)—active at 0.125%; infiltration anesthesia (guinea pigs)—active at 0.125%.

Conclusions

Within the presented study a novel compound,R,S-2-((2-(2-chloro-6-methylphenoxy)ethyl)amino)butan-1-ol hydrochloride (KM-408) with dual antiseizure and analgesic activity has been developed for potential use in neuropathic pain treatment.

Graphical abstract
Theoretical and experimental analysis of guided wave propagation in plate-like structures with sinusoidal thickness variations
Authors: Zima Beata , Moll Jochen
Published: November 2022

Guided waves have attracted significant attention for non-destructive testing (NDT) and structural health monitoring (SHM) due to their ability to travel relatively long distances without significant energy loss combined with their sensitivity to even small defects. Therefore, they are commonly used in damage detection and localization applications. The main idea of incorporating guided waves in NDT and SHM is based on processing the received signals and appropriate interpretation of their characteristics. A great amount of research devoted to diagnostics of plate-like structures considers specimens with constant thickness, which significantly facilities the diagnostic process. In such a case the velocity is also assumed to be constant. However, the developed diagnostic methods should be applicable, especially for the structures exposed to an aggressive environment, excessive load, or unfavorable weather conditions, etc., when the probability of damage occurring is much higher. In such cases, the assumption about the uniform thickness alongside the propagation path cannot be applied in every case. Thus, the present study is focused on wave propagation in metallic plates with variable thickness. The results of theoretical, numerical and experimental investigations of antisymmetric Lamb mode propagation in aluminum plates with a sine-shaped surface are presented. In the first step, the influence of non-uniform thickness distribution on wave velocity has been described. Next, the inverse problem aimed at shape reconstruction based on time of flight (ToF) analysis and spatially varying wave velocity was solved and compared with the standard dispersion curve-fitting method.
Effectiveness of Different Feeding Techniques for Post-stroke Dysphagia: An Updated Systematic Review and Meta-analysis
Authors: Wang Shaowei , Zeng Xi , Zhang Qiongshuai , Li Heping
Published: November 2022

Purpose

With the improvement of people’s life expectancy, the incidence of stroke is high in the world. Post-stroke Dysphagia seriously affects people’s quality of life, among which malnutrition and pulmonary infection are the most common complications of post-stroke Dysphagia. At this point, it is very important to choose the right enteral and parenteral feeding mode. Current nutrition methods commonly used in patients with dysphagia after stroke include Intermittent oral to esophageal tube feeding (IOE), Nasogastric tube (NG), Nasal Jejunal feeding tubes (NJ), Percutaneous endoscopic gastrostomy (PEG).The purpose of this meta-analysis was to study the prognosis of patients with dysphagia after stroke who chose different nutritional methods.

Methods

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTS) to examine the effects of different nutritional modalities on outcomes in patients with post-stroke dysphagia. We searched the Cochrane Library, PubMed, Medline, China National Knowledge Infrastructure (CNKI), Wanfang, and the VIP database. The search period is from the library's establishment to December 31, 2021.At least 2 reviewers independently assessed eligibility criteria, extracted data, and assessed the risk of bias. Standardized mean difference (SMD), relative risk (RR), and odds ratio (OR) were calculated using a random-effects model.

Results

Fourteen studies were identified across six databases that met the inclusion criteria, The results of meta-analysis showed that Intermittent oral to esophageal tube feeding (IOE) could improve the nutritional levels of patients better than nasogastric tube (NG) (MD 1.95, 95%CI 1.22–2.67, P < 0.00001, I2 = 0%), and reduced the incidence of aspiration pneumonia (RR 0.39, 95%CI 0.23–0.66, P = 0.0004, I2 = 0%), improved swallowing function (OR 3.92, 95%CI 2.15–7.14, P < 0.00001, I2 = 0%). Although Percutaneous endoscopic gastrostomy (PEG) can improve the nutrition of patients in the short term, the long-term prognosis remains to be discussed. In addition, the Nasal Jejunal feeding tubes (NJ) significantly reduced the incidence of post-stroke pneumonia compared with NG (RR 0.51, 95%CI 0.29–0.92, P = 0.03, I2 = 0%).

Conclusions

According to the results of meta-analysis, IOE can better improve the nutritional level of patients and reduce the incidence of complications. However, due to the lack of popularity and small target clients, patients who do not accept IOE enteral feeding for various reasons and choose nasal feeding can consider using NJ as a long-term enteral feeding method, and guard against adverse events when performing supplementary nutrition.
EU Private Law
Authors: Basedow Jürgen
Published: November 2022

The book deals with the impact of EU law on private relations. While EU law has principally developed through vertical relations of the Union and its Member States with private persons, its foundations, principles and enforcement mechanisms are increasingly affecting the growing body of EU law governing horizontal relations between individuals and undertakings. The results are sometimes unexpected and sometimes inappropriate.
China and the Barbarians
Authors: Schulte Nordholt Henk
Published: November 2022

Since times immemorial China regarded its culture, philosophy and statecraft as superior to all other nations, hence the saying Hua Yi Zhi Bian - China and the barbarians are different. In the so-called 'Age of Humiliation' (1839-1949), Western and Japanese imperialists reduced the old empire to a semi-colony. China has now regained its economic and military strength, but what drives its domestic and foreign policy? President Xi Jinping has declared that 'Socialism with Chinese Characteristics for a New Era' is at hand, but China can better be described as a country in search of a new identity. The philosopher Tu Weiming sees China as a battlefield of Socialism, Liberalism and Confucianism. The outcome of this struggle will have profound repercussions. Continuation of the present policy will only lead to increased tensions with its neighbours, because the Communist Party claims that only she can restore China’s rightful position under heaven. Beijing's land reclamation in the South China Sea and the 'One Belt, One Road' initiative are foremost driven by a yearning to restore the days of China's imperial grandeur. If China choses the 'third way' of blending the Confucian meritocratic tradition with a western style representative government, a clash with its neighbours and the United States can be avoided. China and the barbarians offers a fascinating insight into the thinking of China’s philosophers and powerbrokers of the past and present. Interviews with eight prominent Chinese intellectuals add an authentic ring to this book.
Inferring Advective Timescales and Overturning Pathways of the Deep Western Boundary Current in the North Atlantic Through Labrador Sea Water Advection
Authors: Chomiak Leah N. , Yashayaev Igor , Volkov Denis L. , Schmid Claudia , Hooper James A.
Published: November 2022

The Subpolar North Atlantic plays a critical role in the formation of the deep water masses which drive Atlantic Meridional Overturning Circulation (AMOC). Labrador Sea Water (LSW) is formed in the Labrador Sea and exported predominantly via the Deep Western Boundary Current (DWBC). The DWBC is an essential component of the AMOC advecting deep waters southward, flowing at depth along the continental slope of the western Atlantic. By combining sustained hydrographic observations from the Labrador Sea to 26.5°N, we investigate the signal propagation and advective timescales of LSW via the DWBC from its source region to the Tropical Atlantic through various approaches using robust neutral density classifications. Two individually defined LSW classes are observed to advect on timescales that support a new plausible hydrographically observed advective pathway. We find each LSW class to advect on independent timescales, and validate a hypothesized alternative‐interior advection pathway branching from the DWBC by observing the arrival of LSW outside of the DWBC in the Bermuda basin on timescales similar to arriving at 26.5°N, 10–15 yr after leaving the source region. Advective timescales estimated herein indicate that this interior pathway is likely the main advective pathway; it remains uncertain whether a direct pathway plays a significant advective role. Using LSW convective signals as advective tracers along the DWBC permits the estimation of advective timescales from the subpolar to tropical latitudes, illuminating deep water advection pathways across the North Atlantic and the lower‐limb of AMOC as a whole.
On Constructing a Realistic Truth Model Using Ionosonde Data for Observation System Simulation Experiments
Authors: Hughes Joseph , Forsythe Victoriya , Blay Ryan , Azeem Irfan , Crowley Geoff , Wilson Walter “Junk” , Dao Eugene , Colman Jonah , Parris Richard
Published: November 2022

The ionosphere contains many small‐scale electron density variations that are under represented in smooth physics‐based or climatological models. This can negatively impact the results of Observation System Simulation Experiments, which use a truth model to simulate data. This paper addresses this problem by using ionosonde data to study ionospheric variability and build a new truth model with empirically driven variations. The variations are studied for their amplitude, horizontal and vertical size, and temporal extent. Results are presented for different local times, seasons, and at solar minimum and solar maximum. We find that these departures from a smooth background are often as large as 25% and are most prevalent near 250 km in altitude. They have horizontal spatial extents that vary from a few hundred to a few thousand kilometers, and typically have the largest horizontal extent at high altitudes. Their vertical extents follow the same pattern of being larger at high altitudes, but they only vary from 10s of km up to 200 km in vertical size. Temporally, these variations can last for a few hours. A procedure for using these spatial and temporal distributions to add empirically driven variance to a smooth truth model is outlined. This process is used to make a truth model with representative variations, which is compared to ionosonde data as well as Global Positioning System Total Electron Content data that was not used to inform the model. The new model resembles the data much better than the smooth models traditionally used.
Dual‐Band Huygens Source Antennas With Partially Reflective Surfaces
Authors: Kawdungta S. , Torrungrueng D. , Boonpoonga A. , Chou H.‐T.
Published: November 2022

This paper presents an antenna architecture from Huygens sources placed in a middle cavity formed by a metal reflector and a partially reflective surface (PRS) of dielectric superstrates. The proposed antenna is excited by a pair of cross‐feedings to produce two frequency resonances in reflection coefficients and radiate unidirectional patterns. In contrast to conventional designs, the proposed PRS‐supported Huygens source antenna may effectively broaden the bandwidth and increase radiation gains with a low profile, including low cost. Simulation results show broadband radiation characteristics at 2.45 and 5 GHz bands, where the impedance bandwidths are in the ranges of 2.4–2.5 GHz and 4.8–5.8 GHz, respectively. In addition, the measurement results of the antenna prototype validate the simulation results in terms of reflection coefficients and radiation patterns. It is found that the gains are 5.0 dBi (2.45 GHz) and 3.0 dBi (5 GHz), where simulation and measurement results are agreed well for practical applications of wireless communications.
Managing Waldenström’s macroglobulinemia with BTK inhibitors
Authors: Buske Christian , Jurczak Wojciech , Salem Joe-Elie , Dimopoulos Meletios A.
Published: November 2022

Bruton’s tyrosine kinase (BTK) inhibition is one of the treatment standards for patients with relapsed/refractory Waldenström’s macroglobulinemia (WM) and for patients with WM who are unsuitable for immunochemotherapy (ICT). It offers deep and durable responses with a manageable safety profile that is generally favorable compared with ICT regimens. However, the limitations of the first approved BTK inhibitor (BTKi), ibrutinib, include reduced efficacy in patients lacking the characteristic WM mutation (MYD88L265P) and toxicities related to off-target activity. The risk of atrial fibrillation (AF) and other cardiovascular side effects are a notable feature of ibrutinib therapy. Several next-generation covalent BTKis with greater selectivity for BTK are at various stages of development. In November 2021, zanubrutinib became the first of these agents to be approved by the European Medicines Agency for the treatment of WM. Head-to-head trial data indicate that it has comparable efficacy to ibrutinib for patients with WM overall, although it may be more effective in patients with CXCR4 mutations or wild-type MYD88. In the clinical trial setting, its greater selectivity translates into a reduced risk of cardiovascular side effects, including AF. Acalabrutinib, which is pre-approval in WM, appears to offer similar advantages over ibrutinib in terms of its safety profile. Beyond the next-generation covalent BTKis, non-covalent BTKis are an emerging class with the potential to provide a therapeutic option for patients who relapse on covalent BTKis. In the future, BTKis may be increasingly utilized within combination regimens. Several ongoing trials in WM are investigating the potential for BTKi use in combination with established and novel targeted agents.
Genetic investigation of the contribution of body composition to anorexia nervosa in an electronic health record setting
Authors: Mack Taralynn , Sanchez-Roige Sandra , Davis Lea K.
Published: November 2022

Anorexia nervosa (AN) is a psychiatric disorder defined by anthropometric symptoms, such as low body weight, and cognitive-behavioral symptoms, such as restricted eating, fear of weight gain, and distorted body image. Recent studies have identified a genetic association between AN and metabolic/anthropometric factors, including body mass index (BMI). Although the reported associations may be under pleiotropic genetic influences, they may represent independent risk factors for AN. Here we examined the independent contributions of genetic predisposition to low body weight and polygenic risk (PRS) for AN in a clinical population (Vanderbilt University Medical Center biobank, BioVU). We fitted logistic and linear regression models in a retrospective case-control design (123 AN patients, 615 age-matched controls). We replicated the genetic correlations between PRSBMIand AN (p = 1.12 × 10−3, OR = 0.96), but this correlation disappeared when controlling for lowest BMI (p = 0.84, OR = 1.00). Additionally, we performed a phenome-wide association analysis of the PRSANand found that the associations with metabolic phenotypes were attenuated when controlling for PRSBMI. These findings suggest that the genetic association between BMI and AN may be a consequence of the weight-related diagnostic criteria for AN and that genetically regulated anthropometric traits (like BMI) may be independent of AN psychopathology. If so, individuals with cognitive-behavioral symptomatology suggestive of AN, but with a higher PRSBMI, may be under-diagnosed given current diagnostic criteria. Furthermore, PRSBMImay serve as an independent risk factor for weight loss and weight gain during recovery.
Cell-cell contact-driven EphB1 cis- and trans- signalings regulate cancer stem cells enrichment after chemotherapy
Authors: Wang Lujuan , Peng Qiu , Xie Yaohuan , Yin Na , Xu Jiaqi , Chen Anqi , Yi Junqi , Shi Wenhua , Tang Jingqun , Xiang Juanjuan
Published: November 2022

Reactivation of chemotherapy-induced dormant cancer cells is the main cause of relapse and metastasis. The molecular mechanisms underlying remain to be elucidated. In this study, we introduced a cellular model that mimics the process of cisplatin responsiveness in NSCLC patients. We found that during the process of dormancy and reactivation induced by cisplatin, NSCLC cells underwent sequential EMT-MET with enrichment of cancer stem cells. The ATAC-seq combined with motif analysis revealed that OCT4-SOX2-TCF-NANOG motifs were associated with the enrichment of cancer stem cells induced by chemotherapy. Gene expression profiling suggested a dynamic regulatory mechanism during the process of enrichment of cancer stem cells, where Nanog showed upregulation in the dormant state and SOX2 showed upregulation in the reactivated state. Further, we showed that EphB1 and p-EphB1 showed dynamic expression in the process of cancer cell dormancy and reactivation, where the expression profiles of EphB1 and p-EphB1 showed negatively correlated. In the dormant EMT cells which showed disrupted cell-cell contacts, ligand-independent EphB1 promoted entry of lung cancer cells into dormancy through activating p-p38 and downregulating E-cadherin. On the contrary, in the state of MET, in which cell-cell adhesion was recovered, interactions of EphB1 and ligand EphrinB2 in trans promoted the stemness of cancer cells through upregulating Nanog and Sox2. In conclusion, lung cancer stem cells were enriched during the process of cellular response to chemotherapy. EphB1 cis- and trans- signalings function in the dormant and reactivated state of lung cancer cells respectively. It may provide a therapeutic strategy that target the evolution process of cancer cells induced by chemotherapy.
PRDM15 interacts with DNA-PK-Ku complex to promote radioresistance in rectal cancer by facilitating DNA damage repair
Authors: Yu Yue , Liu Tingting , Yu Guanyu , Wang Hang , Du Zhipeng , Chen Yuanyuan , Yang Nan , Cao Kun , Liu Chunlei , Wan Zhijie , Shen Hui , Gao Fu , Yang Yanyong , Zhang Wei
Published: November 2022

Neoadjuvant radiotherapy is a standard treatment for locally advanced rectal cancer, however, resistance to chemoradiotherapy is one of the main obstacles to improving treatment outcomes. The goal of this study was to explore the role of PRDM15 involved in the radioresistance of colorectal cancer and to clarify the underlying mechanism. In present study, we demonstrated that, after DNA damage, PRDM15 was upregulated and localized to DNA damage sites, co-localizing with γ-H2AX. Knockdown of PRDM15 inhibited DNA damage repair and increased radiosensitivity in colorectal cancer cells. Mechanistically, PRDM15 promoted DNA repair by interacting with DNA-PKcs and Ku70/Ku80 complex. In preclinical models of rectal cancer, knockdown of PRDM15 sensitized cell derived xenograft and patient derived xenograft to radiotherapy. In 80 rectal cancer patients treated with neoadjuvant chemoradiotherapy, higher PRDM15 expression was observed associated with weaker tumor regression and poorer prognosis. Our findings revealed that inhibiting PRDM15 was potent to overcome radioresistance through abrogating DNA repair in colorectal cancer cells. Additionally, the expression level of PRDM15 could be applied to predict radiotherapy responsiveness and the outcome of neoadjuvant radiotherapy in rectal cancer patients.
BNIP3-dependent mitophagy safeguards ESC genomic integrity via preventing oxidative stress-induced DNA damage and protecting homologous recombination
Authors: Zhao Qian , Liu Kun , Zhang Lin , Li Zheng , Wang Liang , Cao Jiani , Xu Youqing , Zheng Aihua , Chen Quan , Zhao Tongbiao
Published: November 2022

Embryonic stem cells (ESCs) have a significantly lower mutation load compared to somatic cells, but the mechanisms that guard genomic integrity in ESCs remain largely unknown. Here we show that BNIP3-dependent mitophagy protects genomic integrity in mouse ESCs. Deletion of Bnip3 increases cellular reactive oxygen species (ROS) and decreases ATP generation. Increased ROS in Bnip3−/− ESCs compromised self-renewal and were partially rescued by either NAC treatment or p53 depletion. The decreased cellular ATP in Bnip3−/− ESCs induced AMPK activation and deteriorated homologous recombination, leading to elevated mutation load during long-term propagation. Whereas activation of AMPK in X-ray-treated Bnip3+/+ ESCs dramatically ascended mutation rates, inactivation of AMPK in Bnip3−/− ESCs under X-ray stress remarkably decreased the mutation load. In addition, enhancement of BNIP3-dependent mitophagy during reprogramming markedly decreased mutation accumulation in established iPSCs. In conclusion, we demonstrated a novel pathway in which BNIP3-dependent mitophagy safeguards ESC genomic stability, and that could potentially be targeted to improve pluripotent stem cell genomic integrity for regenerative medicine.
Antigenic sin of wild-type SARS-CoV-2 vaccine shapes poor cross-neutralization of BA.4/5/2.75 subvariants in BA.2 breakthrough infections
Authors: Ju Bin , Fan Qing , Wang Miao , Liao Xuejiao , Guo Huimin , Wang Haiyan , Ge Xiangyang , Liu Lei , Zhang Zheng
Published: November 2022

With declining SARS-CoV-2-specific antibody titers and increasing numbers of spike mutations, the ongoing emergence of Omicron subvariants causes serious challenges to current vaccination strategies. BA.2 breakthrough infections have occurred in people who have received the wild-type vaccines, including mRNA, inactivated, or recombinant protein vaccines. Here, we evaluate the antibody evasion of recently emerged subvariants BA.4/5 and BA.2.75 in two inactivated vaccine-immunized cohorts with BA.2 breakthrough infections. Compared with the neutralizing antibody titers against BA.2, marked reductions are observed against BA.2.75 in both 2-dose and 3-dose vaccine groups. In addition, although BA.2 breakthrough infections induce a certain cross-neutralization capacity against later Omicron subvariants, the original antigenic sin phenomenon largely limits the improvement of variant-specific antibody response. These findings suggest that BA.2 breakthrough infections seem unable to provide sufficient antibody protection against later subvariants such as BA.2.75 in the current immunization background with wild-type vaccines.
Electricity consumption variation versus economic structure during COVID-19 on metropolitan statistical areas in the US
Authors: Wang Jinning , Li Fangxing , Cui Hantao , Shi Qingxin , Mingee Trey
Published: November 2022

The outbreak of novel coronavirus disease (COVID-19) has resulted in changes in productivity and daily life patterns, and as a result electricity consumption (EC) has also shifted. In this paper, we construct estimates of EC changes at the metropolitan level across the continental U.S., including total EC and residential EC during the initial two months of the pandemic. The total and residential data on the state level were broken down into the county level, and then metropolitan level EC estimates were aggregated from the counties included in each metropolitan statistical area (MSA). This work shows that the reduction in total EC is related to the shares of certain industries in an MSA, whereas regardless of the incidence level or economic structure, the residential sector shows a trend of increasing EC across the continental U.S. Since the MSAs account for 86% of the total population and 87% of the total EC of the continental U.S., the analytical result in this paper can provide important guidelines for future social-economic crises.
How people wake up is associated with previous night’s sleep together with physical activity and food intake
Authors: Vallat Raphael , Berry Sarah E. , Tsereteli Neli , Capdevila Joan , Khatib Haya Al , Valdes Ana M. , Delahanty Linda M. , Drew David A. , Chan Andrew T. , Wolf Jonathan , Franks Paul W. , Spector Tim D. , Walker Matthew P.
Published: November 2022

How people wake up and regain alertness in the hours after sleep is related to how they are sleeping, eating, and exercising. Here, in a prospective longitudinal study of 833 twins and genetically unrelated adults, we demonstrate that how effectively an individual awakens in the hours following sleep is not associated with their genetics, but instead, four independent factors: sleep quantity/quality the night before, physical activity the day prior, a breakfast rich in carbohydrate, and a lower blood glucose response following breakfast. Furthermore, an individual’s set-point of daily alertness is related to the quality of their sleep, their positive emotional state, and their age. Together, these findings reveal a set of non-genetic (i.e., not fixed) factors associated with daily alertness that are modifiable.
Charge-separation driven mechanism via acylium ion intermediate migration during catalytic carbonylation in mordenite zeolite
Authors: Chen Wei , Tarach Karolina A. , Yi Xianfeng , Liu Zhiqiang , Tang Xiaomin , Góra-Marek Kinga , Zheng Anmin
Published: November 2022

By employing ab initio molecular dynamic simulations, solid-state NMR spectroscopy, and two-dimensional correlation analysis of rapid scan Fourier transform infrared spectroscopy data, a new pathway is proposed for the formation of methyl acetate (MA) via the acylium ion (i.e.,CH3 − C ≡ O+) in 12-membered ring (MR) channel of mordenite by an integrated reaction/diffusion kinetics model, and this route is kinetically and thermodynamically more favorable than the traditional viewpoint in 8MR channel. From perspective of the complete catalytic cycle, the separation of these two reaction zones, i.e., the C-C bond coupling in 8MR channel and MA formation in 12MR channel, effectively avoids aggregation of highly active acetyl species or ketene, thereby reducing undesired carbon deposit production. The synergistic effect of different channels appears to account for the high carbonylation activity in mordenite that has thus far not been fully explained, and this paradigm may rationalize the observed catalytic activity of other reactions.
How Carvedilol activates β2-adrenoceptors
Authors: Benkel Tobias , Zimmermann Mirjam , Zeiner Julian , Bravo Sergi , Merten Nicole , Lim Victor Jun Yu , Matthees Edda Sofie Fabienne , Drube Julia , Miess-Tanneberg Elke , Malan Daniela , Szpakowska Martyna , Monteleone Stefania , Grimes Jak , Koszegi Zsombor , Lanoiselée Yann , O’Brien Shannon , Pavlaki Nikoleta , Dobberstein Nadine , Inoue Asuka , Nikolaev Viacheslav , Calebiro Davide , Chevigné Andy , Sasse Philipp , Schulz Stefan , Hoffmann Carsten , Kolb Peter , Waldhoer Maria , Simon Katharina , Gomeza Jesus , Kostenis Evi
Published: November 2022

Carvedilol is among the most effective β-blockers for improving survival after myocardial infarction. Yet the mechanisms by which carvedilol achieves this superior clinical profile are still unclear. Beyond blockade of β1-adrenoceptors, arrestin-biased signalling via β2-adrenoceptors is a molecular mechanism proposed to explain the survival benefits. Here, we offer an alternative mechanism to rationalize carvedilol’s cellular signalling. Using primary and immortalized cells genome-edited by CRISPR/Cas9 to lack either G proteins or arrestins; and combining biological, biochemical, and signalling assays with molecular dynamics simulations, we demonstrate that G proteins drive all detectable carvedilol signalling through β2ARs. Because a clear understanding of how drugs act is imperative to data interpretation in basic and clinical research, to the stratification of clinical trials or to the monitoring of drug effects on the target pathway, the mechanistic insight gained here provides a foundation for the rational development of signalling prototypes that target the β-adrenoceptor system.
Drivers of recent decline in dust activity over East Asia
Authors: Wu Chenglai , Lin Zhaohui , Shao Yaping , Liu Xiaohong , Li Ying
Published: November 2022

It is essential to understand the factors driving the recent decline of dust activity in East Asia for future dust projections. Using a physically-based dust emission model, here we show that the weakening of surface wind and the increasing of vegetation cover and soil moisture have all contributed to the decline in dust activity during 2001 to 2017. The relative contributions of these three factors to the dust emission reduction during 2010–2017 relative to 2001 are 46%, 30%, and 24%, respectively. Much (78%) of the dust emission reduction is from barren lands, and a small fraction (4.6%) of the reduction is attributed to grassland vegetation increase that is partly ascribed to the ecological restoration. This suggests that the ecological restoration plays a minor role in the decline of dust activity. Rather, the decline is mainly driven by climatic factors, with the weakening of surface wind playing the dominant role.
Consistent diel activity patterns of forest mammals among tropical regions
Authors: Vallejo-Vargas Andrea F. , Sheil Douglas , Semper-Pascual Asunción , Beaudrot Lydia , Ahumada Jorge A. , Akampurira Emmanuel , Bitariho Robert , Espinosa Santiago , Estienne Vittoria , Jansen Patrick A. , Kayijamahe Charles , Martin Emanuel H. , Lima Marcela Guimarães Moreira , Mugerwa Badru , Rovero Francesco , Salvador Julia , Santos Fernanda , Spironello Wilson Roberto , Uzabaho Eustrate , Bischof Richard
Published: November 2022

An animal’s daily use of time (their “diel activity”) reflects their adaptations, requirements, and interactions, yet we know little about the underlying processes governing diel activity within and among communities. Here we examine whether community-level activity patterns differ among biogeographic regions, and explore the roles of top-down versus bottom-up processes and thermoregulatory constraints. Using data from systematic camera-trap networks in 16 protected forests across the tropics, we examine the relationships of mammals’ diel activity to body mass and trophic guild. Also, we assess the activity relationships within and among guilds. Apart from Neotropical insectivores, guilds exhibited consistent cross-regional activity in relation to body mass. Results indicate that thermoregulation constrains herbivore and insectivore activity (e.g., larger Afrotropical herbivores are ~7 times more likely to be nocturnal than smaller herbivores), while bottom-up processes constrain the activity of carnivores in relation to herbivores, and top-down processes constrain the activity of small omnivores and insectivores in relation to large carnivores’ activity. Overall, diel activity of tropical mammal communities appears shaped by similar processes and constraints among regions reflecting body mass and trophic guilds.
Integrating transcription factor occupancy with transcriptome-wide association analysis identifies susceptibility genes in human cancers
Authors: He Jingni , Wen Wanqing , Beeghly Alicia , Chen Zhishan , Cao Chen , Shu Xiao-Ou , Zheng Wei , Long Quan , Guo Xingyi
Published: November 2022

Transcriptome-wide association studies (TWAS) have successfully discovered many putative disease susceptibility genes. However, TWAS may suffer from inaccuracy of gene expression predictions due to inclusion of non-regulatory variants. By integrating prior knowledge of susceptible transcription factor occupied elements, we develop sTF-TWAS and demonstrate that it outperforms existing TWAS approaches in both simulation and real data analyses. Under the sTF-TWAS framework, we build genetic models to predict alternative splicing and gene expression in normal breast, prostate and lung tissues from the Genotype-Tissue Expression project and apply these models to data from large genome-wide association studies (GWAS) conducted among European-ancestry populations. At Bonferroni-correctedP < 0.05, we identify 354 putative susceptibility genes for these cancers, including 189 previously unreported in GWAS loci and 45 in loci unreported by GWAS. These findings provide additional insight into the genetic susceptibility of human cancers. Additionally, we show the generalizability of the sTF-TWAS on non-cancer diseases.
The non-catalytic role of DNA polymerase epsilon in replication initiation in human cells
Authors: Vipat Sameera , Gupta Dipika , Jonchhe Sagun , Anderspuk Hele , Rothenberg Eli , Moiseeva Tatiana N.
Published: November 2022

DNA polymerase epsilon (PolE) in an enzyme essential for DNA replication. Deficiencies and mutations in PolE cause severe developmental abnormalities and cancers. Paradoxically, the catalytic domain of yeast PolE catalytic subunit is dispensable for survival, and its non-catalytic essential function is linked with replicative helicase (CMG) assembly. Less is known about the PolE role in replication initiation in human cells. Here we use an auxin-inducible degron system to study the effect of POLE1 depletion on replication initiation in U2OS cells. POLE1-depleted cells were able to assemble CMG helicase and initiate DNA synthesis that failed shortly after. Expression of POLE1 non-catalytic domain rescued this defect resulting in slow, but continuous DNA synthesis. We propose a model where in human U2OS cells POLE1/POLE2 are dispensable for CMG assembly, but essential during later steps of replication initiation. Our study provides some insights into the role of PolE in replication initiation in human cells.
Imperceptible, designable, and scalable braided electronic cord
Authors: Chen Min , Ouyang Jingyu , Jian Aijia , Liu Jia , Li Pan , Hao Yixue , Gong Yuchen , Hu Jiayu , Zhou Jing , Wang Rui , Wang Jiaxi , Hu Long , Wang Yuwei , Ouyang Ju , Zhang Jing , Hou Chong , Wei Lei , Zhou Huamin , Zhang Dingyu , Tao Guangming
Published: November 2022

Flexible sensors, friendly interfaces, and intelligent recognition are important in the research of novel human-computer interaction and the development of smart devices. However, major challenges are still encountered in designing user-centered smart devices with natural, convenient, and efficient interfaces. Inspired by the characteristics of textile-based flexible electronic sensors, in this article, we report a braided electronic cord with a low-cost, and automated fabrication to realize imperceptible, designable, and scalable user interfaces. The braided electronic cord is in a miniaturized form, which is suitable for being integrated with various occasions in life. To achieve high-precision interaction, a multi-feature fusion algorithm is designed to recognize gestures of different positions, different contact areas, and different movements performed on a single braided electronic cord. The recognized action results are fed back to varieties of interactive terminals, which show the diversity of cord forms and applications. Our braided electronic cord with the features of user friendliness, excellent durability and rich interaction mode will greatly promote the development of human-machine integration in the future.
Structural and functional asymmetry of RING trimerization controls priming and extension events in TRIM5α autoubiquitylation
Authors: Herkules Frank , Yu Corey H. , Taylor Alexander B. , Dougherty Vi , Weintraub Susan T. , Ivanov Dmitri N.
Published: November 2022

TRIM5α is an E3 ubiquitin ligase of the TRIM family that binds to the capsids of primate immunodeficiency viruses and blocks viral replication after cell entry. Here we investigate how synthesis of K63-linked polyubiquitin is upregulated by transient proximity of three RING domains in honeycomb-like assemblies formed by TRIM5α on the surface of the retroviral capsid. Proximity of three RINGs creates an asymmetric arrangement, in which two RINGs form a catalytic dimer that activates E2-ubiquitin conjugates and the disordered N-terminus of the third RING acts as the substrate for N-terminal autoubiquitylation. RING dimerization is required for activation of the E2s that contribute to the antiviral function of TRIM5α, UBE2W and heterodimeric UBE2N/V2, whereas the proximity of the third RING enhances the rate of each of the two distinct steps in the autoubiquitylation process: the initial N-terminal monoubiquitylation (priming) of TRIM5α by UBE2W and the subsequent extension of the K63-linked polyubiquitin chain by UBE2N/V2. The mechanism we describe explains how recognition of infection-associated epitope patterns by TRIM proteins initiates polyubiquitin-mediated downstream events in innate immunity.
Physics-informed deep learning approach for modeling crustal deformation
Authors: Okazaki Tomohisa , Ito Takeo , Hirahara Kazuro , Ueda Naonori
Published: November 2022

The movement and deformation of the Earth’s crust and upper mantle provide critical insights into the evolution of earthquake processes and future earthquake potentials. Crustal deformation can be modeled by dislocation models that represent earthquake faults in the crust as defects in a continuum medium. In this study, we propose a physics-informed deep learning approach to model crustal deformation due to earthquakes. Neural networks can represent continuous displacement fields in arbitrary geometrical structures and mechanical properties of rocks by incorporating governing equations and boundary conditions into a loss function. The polar coordinate system is introduced to accurately model the displacement discontinuity on a fault as a boundary condition. We illustrate the validity and usefulness of this approach through example problems with strike-slip faults. This approach has a potential advantage over conventional approaches in that it could be straightforwardly extended to high dimensional, anelastic, nonlinear, and inverse problems.
In situ monitoring of Lentilactobacillus parabuchneri biofilm formation via real-time infrared spectroscopy
Authors: Bajrami Diellza , Fischer Stephan , Barth Holger , Sarquis María A. , Ladero Victor M. , Fernández María , Sportelli Maria. C. , Cioffi Nicola , Kranz Christine , Mizaikoff Boris
Published: November 2022

Foodborne pathogenic microorganisms form biofilms at abiotic surfaces, which is a particular challenge in food processing industries. The complexity of biofilm formation requires a fundamental understanding on the involved molecular mechanisms, which may then lead to efficient prevention strategies. In the present study, biogenic amine producing bacteria, i.e., Lentilactobacillus parabuchneri DSM 5987 strain isolated from cheese were studied in respect with biofilm formation, which is of substantial relevance given their contribution to the presence of histamine in dairy products. While scanning electron microscopy was used to investigate biofilm adhesion at stainless steel surfaces, in situ infrared attenuated total reflection spectroscopy (IR-ATR) using a custom flow-through assembly was used for real-time and non-destructive observations of biofilm formation during a period of several days. The spectral window of 1700–600 cm−1 provides access to vibrational signatures characteristic for identifying and tracking L. parabuchneri biofilm formation and maturation. Especially, the amide I and II bands, lactic acid produced as the biofilm matures, and a pronounced increase of bands characteristic for extracellular polymeric substances (EPS) provide molecular insight into biofilm formation, maturation, and changes in biofilm architecture. Finally, multivariate data evaluation strategies were applied facilitating the unambiguous classification of the observed biofilm changes via IR spectroscopic data.
Long-time simulations for fixed input states on quantum hardware
Authors: Gibbs Joe , Gili Kaitlin , Holmes Zoë , Commeau Benjamin , Arrasmith Andrew , Cincio Lukasz , Coles Patrick J. , Sornborger Andrew
Published: November 2022

Publicly accessible quantum computers open the exciting possibility of experimental dynamical quantum simulations. While rapidly improving, current devices have short coherence times, restricting the viable circuit depth. Despite these limitations, we demonstrate long-time, high fidelity simulations on current hardware. Specifically, we simulate an XY-model spin chain on Rigetti and IBM quantum computers, maintaining a fidelity over 0.9 for 150 times longer than is possible using the iterated Trotter method. Our simulations use an algorithm we call fixed state Variational Fast Forwarding (fsVFF). Recent work has shown an approximate diagonalization of a short time evolution unitary allows a fixed-depth simulation. fsVFF substantially reduces the required resources by only diagonalizing the energy subspace spanned by the initial state, rather than over the total Hilbert space. We further demonstrate the viability of fsVFF through large numerical simulations, and provide an analysis of the noise resilience and scaling of simulation errors.
Hnf1b renal expression directed by a distal enhancer responsive to Pax8
Authors: Goea L. , Buisson I. , Bello V. , Eschstruth A. , Paces-Fessy M. , Le Bouffant R. , Chesneau A. , Cereghini S. , Riou J. F. , Umbhauer M.
Published: November 2022

Xenopusprovides a simple and efficient model system to study nephrogenesis and explore the mechanisms causing renal developmental defects in human.Hnf1b(hepatocyte nuclear factor 1 homeobox b), a gene whose mutations are the most commonly identified genetic cause of developmental kidney disease, is required for the acquisition of a proximo-intermediate nephron segment inXenopusas well as in mouse. Genetic networks involved inHnf1bexpression during kidney development remain poorly understood. We decided to explore the transcriptional regulation ofHnf1bin the developingXenopuspronephros and mammalian renal cells. Using phylogenetic footprinting, we identified an evolutionary conserved sequence (CNS1) located several kilobases (kb) upstream theHnf1btranscription start and harboring epigenomic marks characteristics of a distal enhancer in embryonic and adult renal cells in mammals. By means of functional expression assays inXenopusand mammalian renal cell lines we showed that CNS1 displays enhancer activity in renal tissue. Using CRISPR/cas9 editing inXenopus tropicalis, we demonstrated the in vivo functional relevance of CNS1 in drivinghnf1bexpression in the pronephros. We further showed the importance of Pax8-CNS1 interaction for CNS1 enhancer activity allowing us to conclude thatHnf1bis a direct target of Pax8. Our work identified for the first time aHnf1brenal specific enhancer and may open important perspectives into the diagnosis for congenital kidney anomalies in human, as well as modelingHNF1B-related diseases.