bluuebunny/crossref_metadata_2025_split huggingface dataset:
A method for automated digital image‐based tracking of delamination fronts in translucent glass fibre‐laminated composite materials
Authors: Bak Brian Lau Verndal , Lindgaard Esben 
Published: April 2020

AbstractA new automated digital image‐based method for tracking both the position and shape of the crack front of delaminations in translucent glass fibre‐laminated test specimens is proposed. The method is applicable to both fracture toughness tests and fatigue tests. The digital image‐based algorithm identifies the newly formed crack area by the change in reflected light and then extracts both the crack front shape and the position. The method is used in a standard double cantilevered beam specimen test setup with the addition of light sources and a camera. The method does not rely on subjective test operator interpretations or calibrations. A reference pattern on the specimen is used to correctly map between the camera coordinate system and the specimen coordinate system, which makes the method insensitive to the camera position and camera or specimen movement during the test. Experimental test examples are provided, which shows that the whole crack front can be tracked with significantly higher accuracy than possible with existing methods.
Arabidopsis Raf‐like kinases act as positive regulators of subclass III SnRK2 in osmostress signaling
Authors: Katsuta Shohei , Masuda Goro , Bak Hyeokjin , Shinozawa Akihisa , Kamiyama Yoshiaki , Umezawa Taishi , Takezawa Daisuke , Yotsui Izumi , Taji Teruaki , Sakata Yoichi 
Published: April 2020

SUMMARYGiven their sessile nature, land plants must use various mechanisms to manage dehydration under water‐deficit conditions. Osmostress‐induced activation of the SNF1‐related protein kinase 2 (SnRK2) family elicits physiological responses such as stomatal closure to protect plants during drought conditions. With the plant hormone ABA receptors [PYR (pyrabactin resistance)/PYL (pyrabactin resistance‐like)/RCAR (regulatory component of ABA receptors) proteins] and group A protein phosphatases, subclass III SnRK2 also constitutes a core signaling module for ABA, and osmostress triggers ABA accumulation. How SnRK2 is activated through ABA has been clarified, although its activation through osmostress remains unclear. Here, we show that Arabidopsis ABA and abiotic stress‐responsive Raf‐like kinases (AtARKs) of the B3 clade of the mitogen‐activated kinase kinase kinase (MAPKKK) family are crucial in SnRK2‐mediated osmostress responses. Disruption of AtARKs in Arabidopsis results in increased water loss from detached leaves because of impaired stomatal closure in response to osmostress. Our findings obtained in vitro and in planta have shown that AtARKs interact physically with SRK2E, a core factor for stomatal closure in response to drought. Furthermore, we show that AtARK phosphorylates S171 and S175 in the activation loop of SRK2E in vitro and that Atark mutants have defects in osmostress‐induced subclass III SnRK2 activity. Our findings identify a specific type of B3‐MAPKKKs as upstream kinases of subclass III SnRK2 in Arabidopsis. Taken together with earlier reports that ARK is an upstream kinase of SnRK2 in moss, an existing member of a basal land plant lineage, we propose that ARK/SnRK2 module is evolutionarily conserved across 400 million years of land plant evolution for conferring protection against drought.
A plant’s diet, surviving in a variable nutrient environment
Authors: Oldroyd Giles E. D. , Leyser Ottoline 
Published: April 2020

Root growth regulation by requirement
Plant productivity depends on the elemental nutrients nitrogen and phosphorus, which are drawn from the soil. Oldroyd and Leyser review how root growth patterns adjust according to the physiological needs of the above-ground plant. Systemic signals, including small peptide signals, mediate communication between the shoot's needs and the root's supply.

Science
, this issue p.
eaba0196
Monomeric NADH-Oxidizing Methylenetetrahydrofolate Reductases fromMycobacterium smegmatisLack Flavin Coenzyme
Authors: Sah Shivjee , Lahry Kuldeep , Talwar Chandana , Singh Sudhir , Varshney Umesh 
Published: April 2020

ABSTRACT5,10-Methylenetetrahydrofolate reductase (MetF/MTHFR) is an essential enzyme in one-carbon metabolism forde novobiosynthesis of methionine. Ourin vivoandin vitroanalyses of MSMEG_6664/MSMEI_6484, annotated as putative MTHFR inMycobacterium smegmatis, failed to reveal their function as MTHFRs. However, we identified two hypothetical proteins, MSMEG_6596 and MSMEG_6649, as noncanonical MTHFRs in the bacterium. MTHFRs are known to be oligomeric flavoproteins. Both MSMEG_6596 and MSMEG_6649 are monomeric proteins and lack flavin coenzymes.In vitro, the catalytic efficiency (kcat/Km) of MSMEG_6596 (MTHFR1) for 5,10-CH2-THF and NADH was ∼13.5- and 15.3-fold higher than that of MSMEG_6649 (MTHFR2). Thus, MSMEG_6596 is the major MTHFR. This interpretation was further supported by better rescue of theE. coliΔmthfrstrain by MTHFR1 than by MTHFR2. As identified by liquid chromatography-tandem mass spectrometry, the product of MTHFR1- or MTHFR2-catalyzed reactions was 5-CH3-THF. TheM. smegmatisΔmsmeg_6596strain was partially auxotrophic for methionine and grew only poorly without methionine or without being complemented with a functional copy of MTHFR1 or MTHFR2. Furthermore, the Δmsmeg_6596strain was more sensitive to folate pathway inhibitors (sulfachloropyridazine,p-aminosalicylic acid, sulfamethoxazole, and trimethoprim). The studies reveal that MTHFR1 and MTHFR2 are two noncanonical MTHFR proteins that are monomeric and lack flavin coenzyme. Both MTHFR1 and MTHFR2 are involved inde novomethionine biosynthesis and required for antifolate resistance in mycobacteria.IMPORTANCEMTHFR/MetF is an essential enzyme in a one-carbon metabolic pathway forde novobiosynthesis of methionine. MTHFRs are known to be oligomeric flavoproteins. Ourin vivoandin vitroanalyses ofMycobacterium smegmatisMSMEG_6664/MSMEI_6484, annotated as putative MTHFR, failed to reveal their function as MTHFRs. However, we identified two of the hypothetical proteins, MSMEG_6596 and MSMEG_6649, as MTHFR1 and MTHFR2, respectively. Interestingly, both MTHFRs are monomeric and lack flavin coenzymes.M. smegmatisdeleted for the majormthfr(mthfr1) was partially auxotroph for methionine and more sensitive to folate pathway inhibitors (sulfachloropyridazine,para-aminosalicylic acid, sulfamethoxazole, and trimethoprim). The studies reveal that MTHFR1 and MTHFR2 are novel MTHFRs involved inde novomethionine biosynthesis and required for antifolate resistance in mycobacteria.
The role of eolian-fluvial interactions and dune dams in landscape change, late Pleistocene–Holocene, Mojave Desert, USA
Authors: Sweeney Mark R. , McDonald Eric V. , Chabela Lucas P. , Hanson Paul R. 
Published: April 2020

AbstractThe formation of the Kelso Dunes in the eastern Mojave Desert, California, was a landscape-changing event triggered by an increase in sediment supply that followed the incision of Afton Canyon by the Mojave River ca. 25 ka. Eastward migration of sand dunes occurred along a well-defined eolian transport corridor. Dunes temporarily blocked washes resulting in substantial aggradation of eolian and fluvial sediments. Stratigraphic exposures reveal numerous fining-up sequences with interbedded eolian sands that provide evidence of dune dams and subsequent aggradation. Luminescence ages reveal that dune blocking and aggradation correspond to a regional pulse of alluvial fan sedimentation that occurred ca. 14–9 ka. Meanwhile, relative landscape stability occurred downstream of dune dams, resulting in the formation of a moderately developed soil on abandoned fluvial deposits. The next pulse of alluvial fan activity ca. 6–3 ka likely resulted in the breaching of the dune dams, followed by incision. Eolian system sediment state theory suggests that eolian activity in the Mojave Desert is closely tied to enhanced sediment supply, primarily related to the Mojave River–Lake Mojave system. Our data suggests that Intermittent Lake Mojave I, ca. 26–22 ka, triggered a large dune-building event that impounded massive amounts of sediment derived from alluvial fans deposited during the Pleistocene-Holocene transition. Breaching of dune dams and sediment recycling may have also increased sediment supply that contributed to late Holocene eolian activity. This profound impact on the regional geomorphology highlights the critical importance of eolian-fluvial interactions in desert environments.
Geophysical analysis of the 30 July 1972 Sitka, Alaska, earthquake sequence
Authors: Ochoa Chavez Juan A. , Doser Diane I. 
Published: April 2020

AbstractThe 1972 Mw 7.6 Sitka earthquake is the largest historical event along the southeastern Alaska portion of the strike-slip Queen Charlotte fault, the transform boundary between the Pacific and North American plates. The fault is one of the fastest moving transform boundaries in the world, having accumulated enough slip since 1972 to produce an event of comparable size in the near future. Thus, understanding the controls on the rupture process of the 1972 mainshock is important for seismic hazard assessment in Alaska. Following the mainshock, the U.S. Geological Survey installed a network of portable seismographs that recorded over 200 aftershocks. These locations were never published, and the original seismograms and digital phase data were misplaced. However, we were able to scan paper copies of the phase data, convert the data to digital form, and successfully relocate 87 aftershocks. The relocations show two clusters of aftershocks along the Queen Charlotte fault, one ∼40 km north of the mainshock epicenter and the other just south of the mainshock, both regions adjacent to portions of the fault that experienced maximum moment release in 1972. Many of the northern aftershocks locate east of the Queen Charlotte fault. This pattern is similar to aftershocks observed in the 2013 Mw = 7.5 Craig, Alaska earthquake. Recent and pre-1971 (1925–1970) seismicity indicates that the regions where aftershocks clustered remained active through time. Gravity, magnetic, and bathymetric anomalies suggest that the structural variations in both the Pacific and North American plates (e.g., age, density, rock type, and thickness) play roles in rupture nucleation and termination along the northern Queen Charlotte fault.
Outcome measures evaluating physical functioning and their measurement properties in adolescent idiopathic scoliosis: a protocol for a systematic review
Authors: Alamrani Samia , Rushton Alison , Gardner Adrian , Falla Deborah , Heneghan Nicola R 
Published: April 2020

IntroductionPhysical functioning (PF) is the ability to carry out the physical activity of daily living. It is an important outcome that provides a meaningful evaluation of individuals’ life. PF can be assessed using patient-reported outcome measures, performance-based outcome measures or body structure and function measure. Measures need to be valid, reliable and responsive to change to evaluate the effects of an intervention. Adolescent idiopathic scoliosis (AIS) is the most common deformity among the paediatric population and impacts on individuals’ lives. This systematic review will appraise evidence on the measurement properties of PF tools in individuals with AIS.Methods/analysisA protocol for systematic review and meta-analysis informed by Cochrane guidelines is reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analysis-P. MEDLINE, PsycINFO, EMBASE, CINAHL, SPORTdiscus, Web of Science and PubMed will be searched in two stages, from inception until December 2019. Search 1 will inventory all studies that assessed PF in participants with AIS, without any limitations. The search terms will be scoliosis, adolescent and PF-related terms. Search 2 will include studies which investigated instrument measurement properties in the same population for measures identified in search one. Two reviewers will independently perform study selection, data extraction, risk of bias and overall quality assessment. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) risk of bias and a modified Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines will be used. A meta-analysis will be conducted if possible, or the evidence will be synthesised and summarised per measurement property per outcome measure per measurement type.Ethics and disseminationThis review will provide recommendations for practice and future research, considering psychometric properties of outcome measures of PF in AIS. The results of this study will be disseminated through a peer-reviewed publication and conference presentation.PROSPERO registration numberCRD42019142335.
Sick leave and return to work after surgery for type II SLAP lesions of the shoulder: a secondary analysis of a randomised sham-controlled study
Authors: Brox Jens Ivar , Skare Øystein , Mowinckel Petter , Brox Jostein Skranes , Reikerås Olav , Schrøder Cecilie Piene 
Published: April 2020

ObjectivesTo compare days on sick leave and assess predictors of return to work following shoulder surgery.DesignA secondary analysis of a randomised controlled trial.SettingOrthopaedic department.Participants114 patients with type II superior labral tear from anterior to posterior of the shoulder.InterventionsLabral repair, biceps tenodesis or sham surgery.Outcome measuresSick leave was obtained from national registers for the last year before and 2 years following surgery. Total and shoulder related number of days on sick leave were obtained, using international diagnostic codes. We applied the difference-in-difference approach to compare the differences in the change in mean work days on sick leave between groups over time, backwards logistic regression and lasso regression to evaluate predictors.ResultsMean total number of work days on sick leave during the 2 years after surgery was 148 (range 0–460) days. More than 80% of the sick leave days were taken by 22% of the patients. Days on sick leave classified as shoulder-related constituted 80% of the total. In all three treatment groups, the mean total number of days on sick leave doubled the year after surgery. Sham surgery and labral repair had fewer postoperative sickness absence days compared with biceps tenodesis but differences were not significant when adjusted for days of sick leave the year before surgery. Predictors of return to work at 2 years analysed by logistic regression were no sick leave (OR 8.0, 95% CI 2.4 to 26.0) and moderate symptoms of anxiety or depression (OR 0.16, 95% CI 0.05 to 0.5) at inclusion. Similar results were obtained by lasso regression but manual work was an additional predictor.ConclusionsChange in mean work days on sick leave comparing sham surgery, labral repair and biceps tenodesis, was not significantly different. Sick leave, symptoms of anxiety and depression, and manual work at inclusion predicted work status 2 years after surgery.Trial registration numberNCT00586742.
Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection
Authors: Lin Lu , Jiang Xiayang , Zhang Zhenling , Huang Siwen , Zhang Zhenyi , Fang Zhaoxiong , Gu Zhiqiang , Gao Liangqing , Shi Honggang , Mai Lei , Liu Yuan , Lin Xianqi , Lai Renxu , Yan Zhixiang , Li Xiaofeng , Shan Hong 
Published: April 2020

ObjectiveTo study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients.DesignWe analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues.ResultsAmong the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients.ConclusionsGI tract may be a potential transmission route and target organ of SARS-CoV-2.
Occupational exposure to soft paper dust and mortality
Authors: Torén Kjell , Neitzel Richard , Sallsten Gerd , Andersson Eva 
Published: April 2020

ObjectivesOccupational exposure to soft paper dust is associated with impaired lung function. Whether there is an increased risk for asthma or chronic obstructive pulmonary disease (COPD) is unclear.MethodsWe studied 7870 workers from three Swedish soft paper mills, and defined high-exposed workers, as having been exposed to soft paper dust exceeding 5 mg/m3 for at least 5 years. The remaining workers were classified as ‘low exposed’. Person-years at risk were calculated and stratified according to gender, age and calendar-year. The follow-up time was from 1960 to 2013. The expected numbers of deaths were calculated using the Swedish population as reference and standardised mortality ratios (SMRs) with 95% CIs were assessed.ResultsThere was an increased mortality due to obstructive lung disease (asthma and COPD), among high-exposed workers, SMR 1.89, 95% CI 1.20 to 2.83, based on 23 observed cases. High-exposed workers had an increased mortality from asthma, SMR 4.13, 95% CI 1.78 to 8.14, based on eight observed cases. The increased asthma mortality was also observed among high-exposed men, SMR 4.38, 95% CI 1.42 to 10.2, based on five observed cases. The asthma mortality among low-exposed workers, both men and women, was not increased. The COPD mortality was not clearly increased among high-exposed workers (SMR 1.52, 95% CI 0.85 to 2.50).ConclusionHigh occupational exposure to soft paper dust increases the mortality due to asthma, and the results suggest that soft paper dust levels in workplaces should be below 5 mg/m3.
Resolving the low mass puzzle of $$\Lambda _c(2940)^+$$
Authors: Luo Si-Qiang , Chen Bing , Liu Zhan-Wei , Liu Xiang 
Published: April 2020

AbstractFor the long standing low mass puzzle of $$\Lambda _c(2940)^+$$Λc(2940)+, we propose an unquenched picture. Our calculation explicitly shows that the mass of the $$\Lambda _c(2P,3/2^-)$$Λc(2P,3/2-) state can be lowered down to be consistent with the experimental data of $$\Lambda _c(2940)^+$$Λc(2940)+ by introducing the $$D^*N$$D∗N channel contribution. It means that the low mass puzzle of $$\Lambda _c(2940)^+$$Λc(2940)+ can be solved. What is more important is that we predict a mass inversion relation for the 2P$$\Lambda _{c}^+$$Λc+ states, i.e., the $$\Lambda _c(2P,1/2^-)$$Λc(2P,1/2-) state is higher than the $$\Lambda _c(2P,3/2^-)$$Λc(2P,3/2-), which is totally different from the result of conventional quenched quark model. It provides a criterion to test such an unquenched scenario for $$\Lambda _c(2940)^+$$Λc(2940)+. We expect the future experimental progress from the LHCb and Belle II.
Rapid Expansion of Highly Functional Antigen-Specific T Cells from Patients with Melanoma by Nanoscale Artificial Antigen-Presenting Cells
Authors: Ichikawa Junya , Yoshida Tatsuya , Isser Ariel , Laino Andressa S. , Vassallo Melinda , Woods David , Kim Sojung , Oelke Mathias , Jones Kristi , Schneck Jonathan P. , Weber Jeffrey S. 
Published: April 2020

AbstractPurpose:Generation of antigen-specific T cells from patients with cancer employs large numbers of peripheral blood cells and/or tumor-infiltrating cells to generate antigen-presenting and effector cells commonly requiring multiple rounds of restimulation ex vivo. We used a novel paramagnetic, nanoparticle-based artificial antigen-presenting cell (nano-aAPC) that combines anti-CD28 costimulatory and human MHC class I molecules that are loaded with antigenic peptides to rapidly expand tumor antigen–specific T cells from patients with melanoma.Experimental Design:Nano-aAPC–expressing HLA-A*0201 molecules and costimulatory anti-CD28 antibody and HLA-A*0201 molecules loaded with MART-1 or gp100 class I–restricted peptides were used to stimulate CD8 T cells purified from the peripheral blood of treatment-naïve or PD-1 antibody–treated patients with stage IV melanoma. Expanded cells were restimulated with fresh peptide-pulsed nano-aAPC at day 7. Phenotype analysis and functional assays including cytokine release, cytolysis, and measurement of avidity were conducted.Results:MART-1–specific CD8 T cells rapidly expanded up to 1,000-fold by day 14 after exposure to peptide-pulsed nano-aAPC. Expanded T cells had a predominantly stem cell memory CD45RA+/CD62L+/CD95+ phenotype; expressed ICOS, PD-1, Tim3, and LAG3; and lacked CD28. Cells from patients with melanoma were polyfunctional; highly avid; expressed IL2, IFNγ, and TNFα; and exhibited cytolytic activity against tumor cell lines. They expanded 2- to 3-fold after exposure to PD-1 antibody in vivo, and expressed a highly diverse T-cell receptor V beta repertoire.Conclusions:Peptide-pulsed nano-aAPC rapidly expanded polyfunctional antigen-specific CD8 T cells with high avidity, potent lytic function, and a stem cell memory phenotype from patients with melanoma.
Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor Models
Authors: Kulukian Anita , Lee Patrice , Taylor Janelle , Rosler Robert , de Vries Peter , Watson Daniel , Forero-Torres Andres , Peterson Scott 
Published: April 2020

AbstractHER2 is a transmembrane tyrosine kinase receptor that mediates cell growth, differentiation, and survival. HER2 is overexpressed in approximately 20% of breast cancers and in subsets of gastric, colorectal, and esophageal cancers. Both antibody and small-molecule drugs that target HER2 and block its tyrosine kinase activity are effective in treating HER2-driven cancers. In this article, we describe the preclinical properties of tucatinib, an orally available, reversible HER2-targeted small-molecule tyrosine kinase inhibitor. In both biochemical and cell signaling experiments, tucatinib inhibits HER2 kinase activity with single-digit nanomolar potency and provides exceptional selectivity for HER2 compared with the related receptor tyrosine kinase EGFR, with a &gt;1,000-fold enhancement in potency for HER2 in cell signaling assays. Tucatinib potently inhibits signal transduction downstream of HER2 and HER3 through the MAPK and PI3K/AKT pathways and is selectively cytotoxic in HER2-amplified breast cancer cell lines in vitro. In vivo, tucatinib is active in multiple HER2+ tumor models as a single agent and shows enhanced antitumor activity in combination with trastuzumab or docetaxel, resulting in improved rates of partial and complete tumor regression. These preclinical data, taken together with the phase-I tucatinib clinical trial results demonstrating preliminary safety and activity, establish the unique pharmacologic properties of tucatinib and underscore the rationale for investigating its utility in HER2+ cancers.