bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atomic-Resolution Prediction of
Degrader-mediated Ternary Complex Structures
by Combining Molecular Simulations with
Hydrogen Deuterium Exchange
Authors: Dixon Tom , MacPherson Derek , Mostofian Barmak , Dauzhenka Taras , Lotz Samuel , McGee Dwight , Shechter Sharon , Shrestha Utsab , Wiewiora Rafal , McDargh Zachary , Pei Fen , Pal Rajat , Ribeiro Joao Vieira , Wilkerson Tanner , Sachdeva Vipin , Gao Ning , Jain Shourya , Sparks Samuel , Li Yunxing , Vinitsky Alexander , Zhang Xin , Razavi Asghar , Kolossváry István , Imbriglio Jason , Evdokimov Artem , Bergeron Louise , Dickson Alex , Xu Huafeng , Sherman Woody , Izaguirre Jesus 
Published: February 2022

Abstract
Targeted protein degradation (TPD) has emerged as a powerful approach for removing (rather than inhibiting) proteins implicated in diseases. A key step in TPD is the formation of an induced proximity complex where a degrader molecule recruits an E3 ligase to the protein of interest (POI), facilitating the transfer of ubiquitin to the POI and initiating the proteasomal degradation process. Here, we address three critical aspects of the TPD process using atomistic simulations: 1) formation of the ternary complex induced by a degrader molecule, 2) conformational heterogeneity of the ternary complex, and 3) degradation efficiency via the full Cullin Ring Ligase (CRL) macromolecular assembly. The novel approach described here combines experimental biophysical data with molecular dynamics (MD) simulations to accurately predict ternary complex structures at atomic resolution. We integrate hydrogen-deuterium exchange mass spectrometry (HDX-MS, which measures the solvent exposure of protein residues) with MD to improve the efficiency and accuracy of the ternary structure predictions of the bromodomain of the cancer target SMARCA2 with the E3 ligase VHL, as mediated by three different degrader molecules. The simulations accurately reproduce X-ray crystal structures -- including a new structure that we determined in this work (PDB ID: 7S4E) -- with root mean square deviations (RMSD) of 1.1 to 1.6 A. The simulations also reveal a structural ensemble of low-energy conformations of the ternary complex. Snapshots from these simulations are used as seeds for additional simulations, where we perform 7.1 milliseconds of aggregate simulation time using Folding@home. The detailed free energy surface captures the crystal structure conformation within a low-energy basin and is consistent with solution-phase experimental data (HDX-MS and SAXS). Finally, we graft a structural ensemble of the ternary complexes onto the full CRL and perform enhanced sampling simulations, which suggest that differences in degradation efficiency may be related to the proximity distribution of lysine residues on the POI relative to the E2-loaded ubiquitin.
Sleep patterns and screen time in US school children during the first 6 months of the COVID-19 pandemic
Authors: Hassinger Amanda B , Monegro Alberto , Perez Geovanny 
Published: February 2022

Abstract
Background: This study compared sleep duration, screen exposure and sleep quality in school-aged children before COVID-19 to that during school closures and again when schools re-opened in fall 2020.Methods: Cross-sectional anonymous, online survey of parents of children 5-13 years old. Questions elicited information about sleep timing and quality, screen time, and schooling at three distinct periods: before the pandemic, when schools first closed and then re-opened in the fall.Results: Respondents described 101 children who were an average of 8.5 years old and 51% male. In lockdown, children slept 25 minutes more (95%CI 00:13-00:38) due to later wake times (75 minutes, 95% CI 0:57-1:34) with later bedtimes (29 minutes, 95%CI 0:00-0:58). When schools re-opened, sleep duration returned to pre-pandemic levels, but sleep onset and offset times remained later. Despite more sleep, sleep quality and habits (e.g. bedtime refusal) worsened during lockdown and did not normalize in fall 2020. During lockdown, screen time increased in 65% of all children, and 96% of those in private schools. When schools reopened, 78% of children in hybrid/virtual learning had more than 4 hours of screen exposure daily. Less screen time was associated with 2-fold higher odds of better sleep (OR 2.66, 95%CI 1.15-6.14). Conclusions: Although school-aged children had more total sleep when schools were closed, sleep quality and habits worsened. Upon return to school, sleep times and quality did not normalize and were linked to screen time.
Sex Differences In The Mortality Of Hospitalized Patients With COVID-19 And Non-ICU Policies In The Netherlands
Authors: Freytag Astrid , Hoogerwerf Jacobien , Dofferhoff Anton S.M. , Janssen Nico , Blaauw Marc , Hassing Robert-Jan , Apeldoorn Marjan van , Kerckhoffs Angèle , Veerman Karin , de Maat Josephine van , Oertelt-Prigione Sabine 
Published: February 2022

Abstract
Introduction: Several international studies have reported sex differences in COVID-19 mortality. The Dutch healthcare system is characterized by as strong focus on primary care and active patient participation in medical choices, such as invasive therapies. This study aims at identifying potential sex-specific predictors of in-hospital mortality and non-ICU policy in patients with COVID-19. Methods: In this observational cohort study, we included participants hospitalized with COVID-19 during the first wave (March-May 2020) of the pandemic in six regional hospitals in the Netherlands. We computed descriptive statistics and logistic regression models using sex-disaggregated data to identify predictors of in-hospital mortality. Followingly, we analyzed the clinical features of female and male COVID-19 patients who had a non-ICU policy.Results: We included 1262 patients (63.7% men) in this study. Higher age, higher LDH level, lower diastolic blood pressure, and lower peripheral oxygen saturation were associated with in-hospital mortality in female and male patients. Shorter symptom duration before admission and more comorbidities associated with in-hospital mortality only in female patients. 33.8% of the female and 30.6% of the male patients had a non-ICU policy. We identified a significant rise in this policy in female patients over the course of the first wave compared to males, which could not be explained solely by age and clinical differences. Discussion: Potential sex differences in symptom development and the sex-specific impact of immune dysfunction on COVID-19 prognosis need further evaluation. Sex differences in ICU care preferences of these patients should be examined to identify underlying gender-related patterns.
Impacts of Illegal Urbanization on Fire Crash Hazards: A Case Study of Dhaka, Bangladesh
Authors: Islam Md Saiful , ŞAHİN Ali 
Published: February 2022

Abstract
The study discusses the illegal urbanization and unfortunate fire crash hazards in different parts of Dhaka city. The security and safety of the city’s people and their entire economy’s wheel will inevitably come to a halt, even when the crisis remains the same in a particular phase. Thus, Dhaka city’s infrastructure, as well as the country’s economy, will be threatened. The quantitative method was adopted, and data was collected via an online questionnaire survey and existing published sources, official records, and survey reports. The Ordinal Logistic Regression (OLR) analysis revealed fire crash hazards in Dhaka due to illegal urbanization. Some disappointing factors of urbanization have been identified that are responsible for fire crash hazards in Dhaka city. The study results also detect that fire crash hazards have a high economic effect. For this reason, policymakers, city planners, and politicians need to search for solutions to these fire crash hazards. Requiring sustainable directions and urban progress of Dhaka city, the study outcomes come up with several relatable strategy policies and initiatives embedded at the end of the research.
SQLE inhibition suppresses the development of pancreatic ductal adenocarcinoma and enhances its sensitivity to chemotherapeutic agents in vitro
Authors: Zhao Fengyun , Huang Yanni , Zhang Yinheng , Li Xun , Chen Caizhao , Long Yihao , Li Fugui , Ma Xiaodong 
Published: February 2022

Abstract
PurposeIn this study, we sought to explore the function of seven important enzymes(MSMO1, EBP, HMGCS1, IDI2, DHCR7, FDFT1, and SQLE) involved in cholesterol biosynthesis especially SQLE in PDAC therapy. Methods and results The TCGA and Oncomine dataset were used to explore the expression of the seven enzymes in normal and cancerous pancreatic individual, and their anti-proliferation efficiency against PDAC cells was measured by cell viability assay. Expression level and prognostic values of SQLE were evaluated by western blot and Kaplan-Meier analysis. The influence of SQLE knockdown by shRNA in PDAC cells was assessed by Transwell, colony formation and cell cycle analysis. RNA-seq and GSEA were utilized to investigate the potential mechanisms. The synergistic effect of SQLE inhibitor, terbinafine, combined with six chemotherapeutic drugs in PDAC cells was tested by CCK-8 method. We demonstrated that downregulation of those enzymes especially SQLE significantly suppressed PDAC cells survival. SQLE was upregulated in PDAC cell lines, and the elevated level of SQLE is correlated with poor prognosis in pancreatic cancer samples. SQLE knockdown could significantly inhibit the proliferation and migration of PDAC cells. Cell cycle was blocked in S phase after SQLE silencing. Mechanistically, GSEA analysis with RNA-seq data revealed that SQLE silencing negatively mediated mTORC1 and TNFα/NF-κB signaling pathways. Besides, SQLE inhibitor terbinafine enhanced chemotherapeutic sensitivity of the six compounds. Conclusions﻿This study demonstrated that SQLE is a novel target for PDAC therapy. The synergism role of SQLE inhibition and chemotherapy may be potential therapeutic strategies for pancreatic cancer treatment.
Prediction Of The Influence Of Cutting Conditions On Surface Morphology After Its Thermal Spraying With Stellite 6 Alloy
Authors: Řehoř Jan , Gombár Miroslav , Harničárová Marta , Kušnerová Milena , Houdková-Šimůnková Šárka , Valíček Jan , Fulemová Jaroslava , Vagaská Alena 
Published: February 2022

Abstract
The presented paper is devoted to the basic influences of the cutting conditions on the basic parameters of the roughness of the surface machined by longitudinal turning; the investigated surface was before the machining modified by the technology of thermal spraying. High-speed Oxy-Fuel (HVOF) thermal sprays, in particular, Stellite 6 sprays based on Cobalt and Chromium alloy, are widely used in the industry thanks to their excellent mechanical properties, wear resistance, corrosion resistance and good temperature stability in comparison with steel for example. From experimental results in the specified range of cutting speeds, feeds and cutting depths, new predictive models of roughness parameters were compiled using mathematical and statistical methods, followed by application of neural networks in order to confirm the obtained conclusions. Research results have proved that feed turning technology is a suitable technology for machining coatings generated by Stellite 6 alloy thermal sprays in such user cases where additional surface treatment is required for specific reasons.
Calculation method of static carrying curve for double-row different-diameter ball slewing bearing
Authors: Li Yunfeng , Wang Rundong , Li Jincheng 
Published: February 2022

Abstract
The calculation method of the static carrying curve of the double-row different-diameter ball slewing bearing was proposed. The relationship between the internal maximum rolling element load of each row and the external load combination of the slewing bearing was established by using the deformation compatibility conditions and the force equilibrium conditions. Using the rolling element load distribution range parameter of the main raceway and the auxiliary raceway of the double-row different-diameter ball slewing bearing respectively as input invariable, the corresponding external load combinations of axial load and tilting moment load of the slewing bearing were obtained. These external load combinations were plotted in the coordinate system to obtain the static carrying curve of the slewing bearing. The obtained static carrying curve was compared with that calculated by the finite element method for the verification purpose. Finally, influence laws of the detailed design parameters, such as raceway groove radius coefficient, raceway contact angle and rolling element diameter on the carrying capacity of the double-row different-diameter ball slewing bearing were analyzed by using the carrying curves. The results show that decreasing of raceway groove radius coefficient, increasing of rolling element diameter or increasing of raceway contact angle appropriately is advantageous for enhancing the carrying capacity of the double-row different-diameter ball slewing bearing.
Modeling Streamflow and Sediment Yield with Determination of Soil Erosion Prone Areas by Using the SWAT Model
Authors: KARAKOYUN ERKAN , Kaya Nihat 
Published: February 2022

Abstract
In this study, the Soil and Water Assessment Tool (SWAT) was used to estimate the streamflow, sediment yield, and the identification of soil erosion prone areas at the sub-watershed scale to enrich the water management practices. The upper part of the Euphrates-Tigris basin called as Murat River basin was selected as a study area. Nash-Sutcliffe Efficiency (NSE), coefficient of determination (R2), and percent bias (PBIAS) were used for the assessment of the model performance with the observed data at two gage stations located on the watershed, E21A074, and E21A077. The Modified Universal Soil Loss Equation was used in the SWAT model in order to predict sediment yield and soil erosion. Sediment Delivery Ratio was also computed to identify its relationship with sediment yield at the sub-watershed scale. NSE, R2, and PBIAS for monthly streamflow prediction were calculated as 0.71, 0.72, and -11.6 in the calibration period, as 0.77, 0.79, and -9.1 in the validation period, at the station E21A077, respectively. Daily simulation the results of NSE, R2, and PBIAS were calculated as 0.56, 0.57, and -15 in the calibration period, while 0.55, 0.56, and 1.2, respectively, in the validation period at the station E21A074. The statistical results for monthly sediment yield calibration and validation were calculated as follows: 0.75 and 0.80 for NSE, 0.76 and 0.84 for R2, -0.9 and 12.2 for PBIAS from the station E21A074. 32% area of the total watershed is under severe and very severe soil erosion conditions. Most of the soil erosion occurred at the barren land use and in the sub-watersheds with a slope greater than 25%. Overall, the SWAT model satisfactorily simulated the streamflow and sediment yield at the Murat River basin which may help the researchers in water resource management.
A diagnostic strategy for adjusting Covid-19 vaccination to individual immune state
Authors: Kuechler Anna Sabrina , Weinhold Sandra , Boege Fritz , Adams Ortwin , Müller Lisa , Babor Florian , Bennstein Sabrina , Pham Thi Xuan Uyen , Hejazi Maryam , Reusing Sarah , Hermsen Derik , Uhrberg Markus , Schulze-Bosse Karin 
Published: February 2022

Abstract
Purpose: We describe a diagnostic procedure suitable for scheduling (re-)vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) according to individual state of humoral immunization. Methods: To clarify the relation between antibody measurements and immune protection, we monitored 124 individuals before, during and six months after vaccination with Spikevax (Moderna). Antibodies against SARS-CoV-2 spike (S1) protein receptor binding domain (S1-AB) and against nucleocapsid antigen were measured by chemiluminescent immunoassay (Roche). Virus-neutralizing activities were determined by surrogate assays (NeutraLISA, Euroimmune; cPass, GenScript). Neutralization of SARS-CoV-2 in cell culture (full virus NT) served as ex-vivo correlate for humoral immunity. Results: Vaccination responses varied considerably. Six months after 2nd vaccination, participants still positive for full virus NT were safely discriminated by S1-AB levels ≥1000 U/ml. The full virus NT-positive fraction of participants with S1-AB levels <1000 U/ml was discriminated by virus-neutralizing activities >70 % as determined by surrogate assays (NeutraLISA or cPas). Participants that were full virus NT-negative and therefore presumably insufficiently immune protected could be identified by the above procedure with a sensitivity of >83 % and a specificity of >95 %. Conclusion: In summary, the described diagnostic tool strategy enables individualized (re-)vaccination schedules based on simple and rapid measurement of serum-based SARS-CoV-2 antibody levels. Our data apply only to WUHAN-type SARS-CoV-2 virus and the current version of mRNA vaccine from Moderna. Adaptation to other vaccines and more recent SARS-CoV-2 strains will require modification of cut-offs and re-evaluation of sensitivity/specificity.Study numbers: 2021-1455 and 2020-1259_1, Ethics Committee Med. Fac. HHU.
Autonomous Self-Drilling Seed Carriers for Aerial Seeding with Superior Success Rates
Authors: Yao Lining , Luo Danli , Maheshwari Aditi , Danielescu Andreea , Li Jiaji , Yang Yue , Tao Ye , Sun Lingyun , Wang Guanyun , Yang Shu , Zhang Teng 
Published: February 2022

Abstract
Aerial seeding can quickly cover large and physically inaccessible areas to improve soil quality and scavenge residual nitrogen in agriculture, for postfire reforestation3–6 and wildland restoration. However, it suffers from low germination rates due to the direct exposure of unburied seeds to harsh sunlight, wind, granivorous birds, and undesirable air humidity and temperature1. Inspired by Erodium seeds, we design and fabricate self-drilling seed carriers, turning wood veneer into highly stiff (7.2 GPa when dry, and 1.2 GPa when wet) and hygromorphic bending or coiling actuators with an extremely large bending curvature (1854 m-1), 45 times larger than the literature values. Our three-tailed carrier has an 80% drilling success rate on flat land after two triggering cycles due to the beneficial resting angle (25° - 30°) of its tail anchoring, whereas the natural Erodium seed’s success rate is 0%. Our carriers can carry payloads of different sizes and contents including biofertilizers and plant seeds as large as those of whitebark pine, which are 11 mm in length. We compare experiments with numerical simulation to elucidate the curvature transformation and actuation mechanisms to guide the design and optimization of the seed carriers. Our system will significantly improve the effectiveness of aerial seeding to relieve agricultural and environmental stresses, and has potential applications in energy harvesting, soft robotics and sustainable buildings.
Irisin Ameliorates Neuroinflammation and Neuronal Apoptosis Through Integrin αVβ5/AMPK Signaling Pathway After Intracerebral Hemorrhage in Mice
Authors: Wang Yao , Tian Mi , Tan Jiaying , Pei Xu , Lu Chaocheng , Xin Yuewen , Deng Shuixiang , Zhao Feng , Gao Yanqin , Gong Ye 
Published: February 2022

Abstract
Background: Neuroinflammation is a crucial factor in the development of secondary brain injury after intracerebral hemorrhage (ICH). Irisin is a newly identified myokine confers strong neuroprotective effects in experimental ischemic stroke. However, whether this myokine can exert neuroprotection effects after ICH remains unknown. This study aimed to investigate the impact of irisin treatment on neuroinflammation and neuronal apoptosis and the underlying mechanism involving integrin αVβ5/AMPK pathway after ICH.Methods: Two hundred eighty-five adult (8-week-old) maleC57BL/6 mice were randomly assigned to sham and ICHsurgery groups. ICH was induced via intrastriatal injection of autologous blood. Irisin was administered intranasally at 30 min after ICH. To elucidate the underlying mechanism, cilengitide (a selective integrin αVβ5 inhibitor) and dorsomorphin (a selective phosphorylatedAMPK inhibitor) were administered prior to irisin treatment. The short- and long-termneurobehavior tests, brain edema, quantitative-PCR, western blotting,Fluoro-Jade C, TUNEL, and immunofluorescence staining were performed to assess the neurofunctional outcome at the level of molecular, cell, histology and function.Results: Endogenous irisin and its receptor, integrin αVβ5, were increased, peaked at 24 h after ICH. irisin post-treatment improved both short- and long-term neurological functions, reduced brain edema after ICH. Interestingly, integrin αVβ5 was mainly located in the microglia after ICH, and irisin post-treatment inhibited microglia/macrophage pro-inflammatory polarization and promoted anti-inflammatory polarization. Moreover, irisin treatment inhibited neutrophil infiltration, andsuppressed neuronal apoptotic cell death in perihematomal areas after ICH. Mechanismly, irisin post-treatment significantly increased the expression of integrin αVβ5, p-AMPK and Bcl-2, and decreased the expression of IL-1β, TNF-α, MPO, and Bax following ICH.The neuroprotective effects of irisin were abolished by both integrin αVβ5 inhibitor cilengitide and AMPK inhibitor dorsomorphin.Conclusions:This study demonstrated that irisin post-treatment ameliorated neurological deficits, reduced brain edema, and ameliorated neuroinflammation and neuronal apoptosis, at least in part, through the integrin αVβ5/AMPKsignaling pathway after ICH. Thus, irisin post-treatment may provide a promising therapeutic approach for the early management of ICH.
Synthesis, characterization and biological activities of Co(II), Cu(II), Zn(II), and Cd(II) metal complexes of 1,10 phenanthroline based Schiff base
Authors: Sumathi S. , MAHADEVI PICHANDI 
Published: February 2022

Abstract
A Schiff base ligand prepared from amino acid (L-Histidine) and salicylaldehyde (L1), 1,10 phenanthroline (L2) and its transition metal complexes of general formula [ML1L2] (where M = Co(II), Cu(II), Zn(II), and Cd(II)) has been synthesized and tested for in vitro antimicrobial study against harmful bacterial strains Escherichia coli (gram negative bacteria), Bacillus subtilis, Staphylococcus aureus (gram positive bacteria), and fungal organisms Aspergillus flavus, Rhizophus stolonifer and Mucor ellipsoideus respectively via agar-well diffusion technique. The larvicidal activity of the complexes was tested against Culex quinquefasciatus mosquito. The synthesized complexes exhibited excellent antioxidant properties both by DPPH and Hydrogen peroxide assays. Analytical and spectroscopic techniques such as UV-Visible, FTIR, SEM, NMR, and HRMS were used to characterize the produced Schiff base metal complexes. TGA-DTA analysis was used to investigate the thermal stability of the complexes. The redox characteristics of the complexes were examined using cyclic voltammetry. Cd(II) complex shows the maximum zone of inhibition values 20 mm and 21 mm for S. aureus, and M. ellipsoideus, respectively. Among the synthesized complexes, Cd(II) complex showed highest antimicrobial, larvicidal activity and very good antioxidant property.