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The polygon effect seriously affects the running stability and safety of the vehicle. In order to suppress the wheel polygon, a dynamic model is established that can calculate the force on the resilient wheel's rim and core. With straight lines, curves, and vertical curves as input excitation, combined with wheel–rail force and acceleration, the suppression effect of the resilient wheel on the polygon is analyzed from the perspective of the time domain, frequency domain, and polygon order. The results show that the resilient wheel can effectively reduce the vertical wheel–rail force and restrain the wheel polygon. After 30 Hz, with the increase in frequency, the suppression effect of the resilient wheel on the polygon becomes increasingly significant. The resilient wheel can sufficiently suppress the polygons generated by 50–150 Hz carriage vibration without affecting the dominant frequency of carriage vibration. This study can provide a new idea for the suppression of wheel polygon.

Background Hip fractures are devastating injuries, with high health and social care costs. Despite national standards and guidelines, substantial variation persists in hospital delivery of hip fracture care and patient outcomes. This qualitative study aimed to identify organisational processes that can be targeted to reduce variation in service provision and improve patient care. Methods Interviews were conducted with 40 staff delivering hip fracture care in four UK hospitals. Twenty-three anonymised British Orthopaedic Association reports addressing under-performing hip fracture services were analysed. Following Thematic Analysis of both data sources, themes were transposed onto domains both along and across the hip fracture care pathway. Results Effective pre-operative care required early alert of patient admission and the availability of staff in emergency departments to undertake assessments, investigations and administer analgesia. Coordinated decision-making between medical and surgical teams regarding surgery was key, with strategies to ensure flexible but efficient trauma lists. Orthogeriatric services were central to effective service delivery, with collaborative working and supervision of junior doctors, specialist nurses and therapists. Information sharing via multidisciplinary meetings was facilitated by joined up information and technology systems. Service provision was improved by embedding hip fracture pathway documents in induction and training and ensuring their consistent use by the whole team. Hospital executive leadership was important in prioritising hip fracture care and advocating service improvement. Nominated specialty leads, who jointly owned the pathway and met regularly, actively steered services and regularly monitored performance, investigating lapses and consistently feeding back to the multidisciplinary team. Conclusion Findings highlight the importance of representation from all teams and departments involved in the multidisciplinary care pathway, to deliver integrated hip fracture care. Complex, potentially modifiable, barriers and facilitators to care delivery were identified, informing recommendations to improve effective hip fracture care delivery, and assist hospital services when re-designing and implementing service improvements.

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The equivalent in-plane elastic modulus [Formula: see text] of a honeycomb sandwich in the direction of cell vertical wall can be assessed by the law of mixture from the modulus of face sheet [Formula: see text] and the equivalent modulus of honeycomb core [Formula: see text]. However, significant errors as large as 40% can be made depending on material and geometry parameters, when the used [Formula: see text] is obtained from a cellular model of core alone without considering the skin effect of face sheet. The main reason of the error is that the rigidity to deformation of y-direction is different greatly between the vertical cell wall of core and inclined cell wall of core. In the present paper, an analytical model is proposed to assess [Formula: see text] of honeycomb sandwich with considering the interference effect of the core with the face sheet. In the proposed model, the influence of the face sheet rigidity on [Formula: see text] is taken into account. The results demonstrate that the contribution of the core to [Formula: see text] is also dependent on the face sheet rigidity significantly. The validity of presented model is verified by comparing the results with numerical results of FEA.

Sepsis is a common critical illness in the Intensive care unit(ICU) and its management and treatment has always been a major challenge in critical care medicine. The dysregulated host response to infection, causing systemic multi-organ and multi-system damage is the main pathogenesis. Notably, intense stress during sepsis can lead to metabolic disturbances of ions, lipids and energy in the organism. Ferroptosis is an iron-dependent, non-apoptotic cell death distinguished by a disruption of iron metabolism and iron-dependent accumulation of lipid peroxides. Mounting researches have established that ferroptosis has an essential part in anti-inflammatory and sepsis, and drugs targeting ferroptosis-related molecules, such as ferroptosis inhibitors, are gradually proving their effectiveness in sepsis. This paper summarizes and reviews the pathogenesis of ferroptosis, its regulatory network, and its vital involvement in the initiation of sepsis and related organ damage, and finally discusses the possible target drugs provided by the above mechanisms, describes the dilemmas as well as the outlook, in the hope of finding more links between ferroptosis and sepsis and providing new perspectives for the future treatment of sepsis.

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Carbon fiber/polyimide composites were prepared by high temperature molding process with carbon fiber, 450 °C resistant polyimide resin and related additives as raw materials. Effects of prepreg resin content, porosity and post-treatment temperature on properties of composites were studied, and fracture shape was analyzed. Results show that high temperature shear properties of carbon fiber can be improved by more than 50% after removing sizing agent, and mechanical properties of composites are the best when the resin content of prepreg is (30 to 40)%. Retention rate of mechanical properties of composites is more than 90% when porosity is less than 1.5%. And mechanical properties decline sharply when porosity is greater than 2%. Carbon fiber/polyimide composites have good high temperature resistance below 450°C, and mechanical properties of composites can be improved to a certain extent after treatment at room temperature to 300°C. Fracture morphology analysis shows that high temperature mechanical properties of composites depend on heat resistance of resin and matching between resin and fiber.

In order to improve the risk early-warning performance of highway bridges caused by typhoon disasters, a fast and intelligent risk assessment model for highway bridges is proposed in this paper. A three-level accident possibility index system is established in which the top-level index is the possibility of bridge accident, the second-level indices comprise the accident causing factor, the surrounding environment factor, and the accident bearing body, and the third-level indices are selected from the disaster conditions and the bridge’s own technical conditions. With the rapid risk assessment model of highway bridges under typhoon disasters, the intelligent risk assessment software platform is developed. In the case analysis, the automatic and intelligent risk assessment of highway bridges in Ningbo under Typhoon “Lekima” on August 10, 2019, was realized.

In order to improve the bearing and wear resistance of the sector composite wear plate, a new sector composite wear plate is designed based on the finite element method. By establishing the finite element calculation models of integral, segmented small circle inlaid and new fan-shaped combined anti-wear plate ball bearings, the pressure bearing and wear resistance of three types of wear plates are analyzed, calculated and compared. The results show that the three types of wear plates can meet the pressure bearing capacity. The pressure bearing capacity of the new fan-shaped composite wear-resistant plate is similar to that of the integral type, which is superior to that of the segmented small circle inlaid type. Because of the advantages in structure, processing and installation of the new fan-shaped composite wear-resistant plate, it is particularly worth popularizing and applying in the super spherical bearing.

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The largemouth bass Micropterus salmoides is an important freshwater aquaculture fish in China. Recently, largemouth bass at a fish farm in Guangdong province experienced an outbreak of a serious ulcer disease. As part of the investigations conducted to identify the aetiology and identify potentially effective control measures, we isolated a pathogenic bacterium (NK-1 strain) from the diseased fish. It was identified as Nocardia seriolae through morphological observation, physiological and biochemical analysis, and molecular identification, and its pathogenicity was verified by experimental infection. Pathological changes in the diseased fish included granulomatous lesions in the liver and spleen, destruction of renal tubules, necrosis of intestinal epithelial cells, infiltration of inflammatory cells in the brain, vacuolation of cells, and swelling and cracking of the mitochondria and endoplasmic reticulum. Bacterial detection using qPCR showed that the spleen and intestine were the main organs targeted by N. seriolae. The mortality of largemouth bass experimentally infected with N. seriolae at 21°C was significantly lower than that in fish infected at higher temperatures between 24 and 33°C; there were no significant differences in the levels of mortality at these higher temperatures. The level of mortality of largemouth bass infected with N. seriolae was lowest at a neutral water pH of 7 but increased significantly at higher and lower pH. Of the tested Chinese herbal medicines, Chinese sumac Galla chinensis and Chinese skullcap Scutellaria baicalensis exhibited the best antibacterial effects. This study lays a foundation for the clinical diagnosis and scientific control of ulcer disease in largemouth bass.

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Introduction: Young individuals with colorectal cancer (CRC) tend to be diagnosed at advanced stages and are not routinely included in screening programmes. This study describes the incidence, disease pattern and factors affecting overall survival in young- onset CRC. Methods: A retrospective study of young-onset CRC patients diagnosed between 2010 and 2017 in a tertiary hospital was conducted. Results: There were 99 patients, 69.7% had left-sided while 30.3% had right-sided CRC. The mean age was 43.3 years (43.3±5.0) and 62 patients (62.6%) were male. The incidence of young-onset CRC has been on the rise since 2014. Out of 99 patients, 65 (65.7%) underwent elective surgery, 30 (30.3%) underwent emergency surgery and the remainder 5 (4.0%) were palliated. The most common presenting complaints for patients who underwent elective surgery were abdominal pain, per-rectal bleeding and altered bowel habits. For patients who required emergency surgery, 20 (66.6%) presented with intestinal obstruction and 10 (33.3%) had intestinal perforation. There were 42 (42.4%) stage III CRC and 20 (20.2%) stage IV CRC. The most frequent metastatic site was the liver (20/20, 100%). Five patients had signet ring cells (5.1%) in their histology while 15 (15.2%) had mucinous features. The overall 5-year survival of young-onset CRC was 82.0%. Advanced overall stage (hazard ratio (HR) 6.1, CI 1.03–3.62) and signet ring histology (HR 34.2, CI 2.24–5.23) were associated with poor prognosis. Conclusion: Young-onset CRC tend to be left-sided with advanced presentations. However, their 5-year survival remains favourable as compared to the general population. Keywords: Colorectal screening in the young, early-onset colorectal cancer, signet ring cell colorectal cancer

Glycerol is used as a bovine semen osmotic cryoprotectant that greatly improves the quality of frozen and thawed bovine sperm. However, high glycerol concentrations can have a toxic effect on frozen and thawed bovine sperm. Therefore, this experiment investigated the effect of replacing a portion of the glycerol in a cryoprotectant solution with crocin on the sperm apoptosis, protamine deficiency and membrane lipid oxidation of frozen and thawed Yanbian yellow cattle sperm. The experiment included a control group (6% glycerol) and four treatment groups: I (3% glycerol), II (3% glycerol +0.5 mM crocin), III (3% glycerol + 1 mM crocin) and IV (3% glycerol + 2 mM crocin). Computer assisted semen analysis was used to detect sperm motility, Hoechst 33,342, propidium iodide, and JC-1 staining were used to analyse sperm viability and mitochondrial membrane potential, chromomycin A3 staining was used to detect protamine deficiency and DNA damage, flow cytometry was used for sperm membrane lipid disorder detection and analysis, and real-time quantitative RT-qPCR was used to detect the mRNA expression levels of protamine-related genes (PRM2, PRM3), sperm acrosome-associated genes (SPACA3), oxidative stress-related genes (ROMO1) and apoptosis-related genes (BCL2, BAX). Compared to the control group, replacing a portion of glycerol with 1 mM crocin significantly improved sperm motility, plasma membrane integrity, membrane lipid disorders (p < .05) and viability, mitochondrial membrane potential, protamine deficiency (p < .01). The expression level of PRM2, PRM3, SPACA3 and BCL2 significantly increased (p < .05), while the expression levels of ROMO1 and BAX significantly decreased (p < .05). Accordingly, the BCL2/BAX ratio significantly increased (p < .05). In summary, the substitution of a portion of glycerol with crocin in cryoprotective solution improved the quality of Yanbian yellow cattle sperm after freezing and thawing.

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It is widely believed that liver transplantation is the only way to cure hepatic cirrhosis. However, due to limited funds and liver donors, liver transplantation is seldom performed in Asia, especially in China. For patients who have experienced oesophageal and gastric varices bleeding and waiting for a liver transplant, transjugular intrahepatic portosystemic shunt (TIPS) has proven to be an ideal treatment procedure. However, TIPS may lead to severe complications. At present, TIPS infections remain a rare complication, and the definition remains controversial. Specific pathogenesis has not been elucidated. In the literature, no pathogenic bacterium has been confirmed as a major pathogen of TIPS infection, and no infections have been attributed to the placement of TIPS. Whether or not such infections are all associated with stent implantation of TIPS remains a question that needs to be answered. We report a case involving successful treatment of this patient that potentially can be used as a reference in clinics

Simple Summary The utility of a diagnostic algorithm for the detection of HPV-driven oral cavity (OCC), oropharyngeal (OPC), and laryngeal (LC) carcinomas using HPV-DNA testing followed by p16(INK4a) immunohistochemistry, taking E6*I mRNA detection as the reference standard, was assessed in HPV-DNA-positive formalin-fixed paraffin-embedded samples from 29 countries. The concordance of p16(INK4a) and E6*I mRNA among 78, 257, and 51 HPV-DNA-positive OCC, OPC, and LC, respectively, was moderate to substantial in OCC and OPC but only fair in LC. A different p16(INK4a) expression pattern was observed in those cases HPV-DNA-positive for types other than HPV16, as compared to HPV16-positive cases. We concluded that the diagnostic algorithm of HPV-DNA testing followed by p16(INK4a) immunohistochemistry might be helpful in the diagnosis of HPV-driven OCC and OPC, but not LC. Our study provides new insights into the use HPV-DNA, p16(INK4a), and HPV-E6*I mRNA for diagnosing an HPV-driven head and neck carcinoma. Background: Tests or test algorithms for diagnosing HPV-driven oral cavity and laryngeal head and neck carcinomas (HNC) have not been yet validated, and the differences among oral cavity and laryngeal sites have not been comprehensively evaluated. We aimed to assess the utility of a diagnostic algorithm for the detection of HPV-driven oral cavity (OCC), oropharyngeal (OPC) and laryngeal (LC) carcinomas using HPV-DNA testing followed by p16(INK4a) immunohistochemistry, taking E6*I mRNA detection as the reference standard. Methods: Formalin-fixed paraffin-embedded OCC, OPC, and LC carcinomas were collected from pathology archives in 29 countries. All samples were subjected to histopathological evaluation, DNA quality control, and HPV-DNA detection. All HPV-DNA-positive samples (including 78 OCC, 257 OPC, and 51 LC out of 3680 HNC with valid HPV-DNA results) were also tested for p16(INK4a) immunohistochemistry and E6*I mRNA. Three different cutoffs of nuclear and cytoplasmic staining were evaluated for p16(INK4a): (a) >25%, (b) >50%, and (c) >= 70%. The concordance of p16(INK4a) and E6*I mRNA among HPV-DNA-positive OCC, OPC, and LC cases was assessed. Results: A total of 78 OCC, 257 OPC, and 51 LC were HPV-DNA-positive and further tested for p16(INK4a) and E6*I mRNA. The percentage of concordance between p16(INK4a) (cutoff >= 70%) and E6*I mRNA among HPV-DNA-positive OCC, OPC, and LC cases was 79.5% (95% CI 69.9-89.1%), 82.1% (95% CI 77.2-87.0%), and 56.9% (95% CI 42.3-71.4%), respectively. A p16(INK4a) cutoff of >50% improved the concordance although the improvement was not statistically significant. For most anatomical locations and p16(INK4a) cutoffs, the percentage of discordant cases was higher for HPV16- than HPV-non16-positive cases. Conclusions: The diagnostic algorithm of HPV-DNA testing followed by p16(INK4a) immunohistochemistry might be helpful in the diagnosis of HPV-driven OCC and OPC, but not LC. A different p16(INK4a) expression pattern was observed in those cases HPV-DNA-positive for types other than HPV16, as compared to HPV16-positive cases. Our study provides new insights into the use HPV-DNA, p16(INK4a), and HPV-E6*I mRNA for diagnosing an HPV-driven HNC, including the optimal HPV test or p16(INK4a) cutoffs to be used. More studies are warranted to clarify the role of p16(INK4a) and HPV status in both OPC and non-OPC HNC.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

The western U.S. has been experiencing a mega-scale drought since 2000. By killing trees and drying out forests, the drought triggers widespread wildfire activities. In the 2020 California fire season alone, more than 10.3 million acres of land were burned and over 10000 structures were damaged. The estimated cost is over $12 billion. Drought also devastates agriculture and drains the social and emotional well-being of impacted communities. This work aims at predicting the occurrence and severity of drought, and thus helping mitigate drought related adversaries. A machine learning based framework was developed, including time series data collection, model training, forecast and visualization. The data source is from the National Drought Monitor center with FIPS (Federal Information Processing Standards) geographic identification codes. For model training and forecasting, a Bayesian structural time series (BSTS) based statistical model was employed for a time-series forecasting of drought spatially and temporally. In the model, a time-series component captures the general trend and seasonal patterns in the data; a regression component captures the impact of the drought in measurements such as severity of drought, temperature, etc. The statistical measure, Mean Absolute Percentage Error, was used as the model accuracy metric. The last 10 years of drought data up to 2020-09-01 was used for model training and validation. Back-testing was implemented to validate the model . Afterwards, the drought forecast was generated for the upcoming 3 weeks of the United States based on the unit of county level. 2-D heat maps were also integrated for visual reference.

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To analyze the vibrational modes of water and methane in structure I gas hydrates, we constructed a 178-atom supercell with two small cages of type 512 and six large cages of type 51262. We applied the density functional theory method to simulate the vibrational spectrum and normal modes of methane hydrates. In accord with our previous studies, we confirmed that two groups of hydrogen bond (H-bond) peaks (at around 291 and 210 cm−1) in the translational bands come from two kinds of intermolecular H-bond vibrational modes. This is the first investigation of H-bond vibrations in methane hydrates. The partial modes of CH4 were extracted. We found that the CH4 phonons in the translational region are below 180 cm−1 so that the influence of methane on the H-bond is insignificant. We proposed a new method to decompose gas hydrates via direct application of terahertz radiation to the H-bonds. Herein, we confirmed that CH4 molecules do not absorb this energy.

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Background The pharmacokinetics (PK) of antibiotics change during sepsis and continuous renal replacement therapies in critically ill patients. Limited evidence exists on the use of the oXiris® high-adsorbent membrane. Objectives To develop a PK/pharmacodynamic (PD) model for meropenem in critically ill sepsis patients undergoing continuous venovenous haemodiafiltration (CVVHDF) with the oXiris® membrane, and to design an optimal dosing regimen assessed according to the PTA. Methods A prospective, open-label, observational PK trial was performed (EUDRACT 2011-005902-30). We conducted PK studies (plasma and ultrafiltrate) for at least 24 h after concomitant administration of CVVHDF and meropenem 1 g q8h. We constructed a PK model using the non-linear mixed-effects approach (NONMEM 7.3). We evaluated the suitability of different dosage regimens using Monte Carlo simulations and calculated the PTA as the percentage of subjects achieving a given percentage of time above the MIC (fT>MIC). Results The PK of meropenem was best captured by a two-open-compartment model with zero-order input kinetics and first-order elimination. Extracorporeal CL was 7.78 L/h [relative standard error (RSE) 16.45 L/h] and central compartment V (Vc) was 24.9 L (RSE 13.73 L). Simulations showed that, for susceptible Pseudomonas aeruginosa isolates (EUCAST MIC ≤2 mg/L) and attainment of 100%fT>MIC, 500 mg q8h given as extended (EI) or continuous infusion (CI) would be sufficient. For a target of 100%fT>4×MIC, CI of 3000 mg q24h or 2000 mg q8h administered as EI or CI would be required. Conclusions We have constructed a PK model of meropenem in sepsis patients undergoing CVVHDF using the oXiris® membrane. This tool will support physicians when calculating the optimal initial dose.

In this paper, direct numerical simulation (DNS) of spatially evolving flat plate hypersonic turbulent boundary layer with free-stream Mach number 8 is used to study the effects of wall temperature on compressibility and Reynolds stress contribution. The DNS contains two cases with different wall temperatures, T-w/T-infinity=10.03 and 1.9. The results show that lower wall temperature enhances both the compressibility and injection-and-sweeping motions near the wall.

Empowering lay screeners, such as pre-school teachers, on vision screening is a cost-effective way to ensure larger populations of children can be screened. Although the validity of lay screeners in conducting vision screening were reported in several studies, none showed data concerning improvement of the level of knowledge among lay screeners after completing vision screening training, which could indicate the effectiveness of the training program. This study aimed to determine the level of knowledge of pre-school teachers before and after attending a training program. Sixty pre-school teachers from Tabika and Taska KEMAS were randomly selected. The Study Group (n = 30) was given theory and practical training on vision screening, whereas the Control Group (n = 30) was only given brief verbal instructions on how to conduct the screening. A theory test containing 15 questions related to the training modules were administered to both groups, before and after their training/briefing respectively. The findings showed that the level of knowledge among preschool teachers in the Study Group (73.24 ± 11.73%) was significantly higher than the Control Group (56.22 ± 13.11%) (p < 0.01). There was also a significant improvement in the level of knowledge among pre-school teachers in the Study Group after the training (p

As cardiovascular implantable electronic devices (CIEDs) are increasingly indicated in older patients, and the burden of cancer is rising with the aging population, the management of patients with CIEDs who require radiotherapy (RT) is a timely concern. The objective of the study was to evaluate the management of, and malfunctions in, patients with CIEDs undergoing RT. A retrospective study of patients with CIEDs receiving RT at Kingston Health Sciences Center from March 2007–April 2018 was conducted. Data on demographics, RT, devices, and management were compared for the primary outcome of device malfunction. Of the 189 patients with CIEDs receiving a total of 297 courses of RT, 4 patients (2.1%) experienced device malfunctions. Higher beam energy was associated with a malfunction (p

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The establishment of a possible connection between neutrino emission and gravitational-wave (GW) bursts is important to our understanding of the physical processes that occur when black holes or neutron stars merge. In the Daya Bay experiment, using the data collected from December 2011 to August 2017, a search was performed for electron-Antineutrino signals that coincided with detected GW events, including GW150914, GW151012, GW151226, GW170104, GW170608, GW170814, and GW170817. We used three time windows of 10, 500, and 1000 s relative to the occurrence of the GW events and a neutrino energy range of 1.8 to 100 MeV to search for correlated neutrino candidates. The detected electron-Antineutrino candidates were consistent with the expected background rates for all the three time windows. Assuming monochromatic spectra, we found upper limits (90% confidence level) of the electron-Antineutrino fluence of (1.13-2.44)×1011 cm-2 at 5 MeV to 8.0×107 cm-2 at 100 MeV for the three time windows. Under the assumption of a Fermi-Dirac spectrum, the upper limits were found to be (5.4-7.0)×109 cm-2 for the three time windows.

Recent publications have argued that there are potentially serious consequences for researchers in recognising distinct genera in the terminal fusarioid clade of the family Nectriaceae. Thus, an alternate hypothesis, namely a very broad concept of the genus Fusarium was proposed. In doing so, however, a significant body of data that supports distinct genera in Nectriaceae based on morphology, biology, and phylogeny is disregarded. A DNA phylogeny based on 19 orthologous protein-coding genes was presented to support a very broad concept of Fusarium at the F1 node in Nectriaceae. Here, we demonstrate that re-analyses of this dataset show that all 19 genes support the F3 node that represents Fusarium sensu stricto as defined by F.sambucinum (sexual morph synonym Gibberella pulicaris). The backbone of the phylogeny is resolved by the concatenated alignment, but only six of the 19 genes fully support the F1 node, representing the broad circumscription of Fusarium. Furthermore, a re-analysis of the concatenated dataset revealed alternate topologies in different phylogenetic algorithms, highlighting the deep divergence and unresolved placement of various Nectriaceae lineages proposed as members of Fusarium. Species of Fusarium s. str. are characterised by Gibberella sexual morphs, asexual morphs with thin- or thick-walled macroconidia that have variously shaped apical and basal cells, and trichothecene mycotoxin production, which separates them from other fusarioid genera. Here we show that the Wollenweber concept of Fusarium presently accounts for 20 segregate genera with clear-cut synapomorphic traits, and that fusarioid macroconidia represent a character that has been gained or lost multiple times throughout Nectriaceae. Thus, the very broad circumscription of Fusarium is blurry and without apparent synapomorphies, and does not include all genera with fusarium-like macroconidia, which are spread throughout Nectriaceae (e.g., Cosmosporella, Macroconia, Microcera). In this study four new genera are introduced, along with 18 new species and 16 new combinations. These names convey information about relationships, morphology, and ecological preference that would otherwise be lost in a broader definition of Fusarium. To assist users to correctly identify fusarioid genera and species, we introduce a new online identification database, Fusarioid-ID, accessible at www.fusarium.org. The database comprises partial sequences from multiple genes commonly used to identify fusarioid taxa (act1, CaM, his3, rpb1, rpb2, tef1, tub2, ITS, and LSU). In this paper, we also present a nomenclator of names that have been introduced in Fusarium up to January 2021 as well as their current status, types, and diagnostic DNA barcode data. In this study, researchers from 46 countries, representing taxonomists, plant pathologists, medical mycologists, quarantine officials, regulatory agencies, and students, strongly support the application and use of a more precisely delimited Fusarium (= Gibberella) concept to accommodate taxa from the robust monophyletic node F3 on the basis of a well-defined and unique combination of morphological and biochemical features. This F3 node includes, among others, species of the F.fujikuroi, F. incarnatum-equiseti, F. oxysporum, and F.sambucinum species complexes, but not species of Bisifusarium [F.dimerum species complex (SC)], Cyanonectria (F.buxicola SC), Geejayessia (F.staphyleae SC), Neocosmospora (F.solani SC) or Rectifusarium (F.ventricosum SC). The present study represents the first step to generating a new online monograph of Fusarium and allied fusarioid genera (www.fusarium.org).

The interplay between topological electronic structure and superconductivity has attracted tremendous research interests recently as they could induce topological superconductivity (TSCs) which may be used to realize topological qubits for quantum computation. Among various TSC candidates, superconducting BaSn3 (Tc∼4.4K) has been predicted to be a topological Dirac semimetal (TDS) hosting two pairs of Dirac points along the Γ-A direction. Here, by combining the use of angle-resolved photoemission spectroscopy and ab initio calculations, we identified the predicted topological Dirac fermions and confirmed the TDS nature of the compound. In addition, we observed surface states connecting the Dirac points. Our observations demonstrate BaSn3 as a superconductor with nontrivial topological electronic structures.

SUMMARYEvidence has long suggested that epidermal growth factor receptor (EGFR) may play a prominent role in triple-negative breast cancer (TNBC) pathogenesis, but clinical trials of EGFR inhibitors have yielded disappointing results. Using a candidate drug screen, we discovered that inhibition of CDK12 dramatically sensitizes diverse models of TNBC to EGFR blockade. Instead of functioning through CDK12’s well-established roles proximal to transcription, this combination therapy drives cell death through the 4E-BP1-dependent suppression of the translation and consequent stability of driver oncoproteins, including MYC. A genome-wide CRISPR/Cas9 screen identified the CCR4-NOT complex as a major determinant of sensitivity to the combination therapy whose loss renders 4E-BP1 unresponsive to drug-induced dephosphorylation, rescuing MYC translational suppression and stability. The central roles of CCR4-NOT and 4E-BP1 in response to the combination therapy were further underscored by the observation of CNOT1 loss and rescue of 4E-BP1 phosphorylation in TNBC cells that naturally evolved therapy resistance. Thus, pharmacological inhibition of CDK12 reveals a long proposed EGFR dependence in TNBC that functions through the cooperative regulation of translation-coupled oncoprotein stability.