bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase 1, open-label, drug–drug interaction study of rucaparib with rosuvastatin and oral contraceptives in patients with advanced solid tumors
Authors: Liao Mingxiang , Jeziorski Krzysztof G. , Tomaszewska-Kiecana Monika , Láng István , Jasiówka Marek , Skarbová Viera , Centkowski Piotr , Ramlau Rodryg , Górnaś Maria , Lee John , Edwards Sarah , Habeck Jenn , Nash Eileen , Grechko Nikolay , Xiao Jim J.
Published: August 2021

Purpose

This study aimed at evaluating the effect of rucaparib on the pharmacokinetics of rosuvastatin and oral contraceptives in patients with advanced solid tumors and the safety of rucaparib with and without coadministration of rosuvastatin or oral contraceptives.

Methods

Patients received single doses of oral rosuvastatin 20 mg (Arm A) or oral contraceptives ethinylestradiol 30 µg + levonorgestrel 150 µg (Arm B) on days 1 and 19 and continuous doses of rucaparib 600 mg BID from day 5 to 23. Serial blood samples were collected with and without rucaparib for pharmacokinetic analysis.

Results

Thirty-six patients (n = 18 each arm) were enrolled and received at least 1 dose of study drug. In the drug–drug interaction analysis (n = 15 each arm), the geometric mean ratio (GMR) of maximum concentration (Cmax) with and without rucaparib was 1.29 for rosuvastatin, 1.09 for ethinylestradiol, and 1.19 for levonorgestrel. GMR of area under the concentration–time curve from time zero to last quantifiable measurement (AUC0–last) was 1.34 for rosuvastatin, 1.43 for ethinylestradiol, and 1.56 for levonorgestrel. There was no increase in frequency of treatment-emergent adverse events (TEAEs) when rucaparib was given with either of the probe drugs. In both arms, most TEAEs were mild in severity and considered unrelated to study treatment.

Conclusion

Rucaparib 600 mg BID weakly increased the plasma exposure to rosuvastatin or oral contraceptives. Rucaparib safety profile when coadministered with rosuvastatin or oral contraceptives was consistent with that of rucaparib monotherapy. Dose adjustments of rosuvastatin and oral contraceptives are not necessary when coadministered with rucaparib.

ClinicalTrials.gov NCT03954366; Date of registration May 17, 2019.
The understudied links of the retromer complex to age-related pathways
Authors: Wilson Kenneth A.
Published: August 2021

Neuronal aging is associated with numerous diseases resulting in memory impairment and functional decline. A common hallmark of these disorders is the accumulation of intracellular and extracellular protein aggregates. The retromer complex plays a central role in sorting proteins by marking them for reuse rather than degradation. Retromer dysfunction has been shown to induce protein aggregates and neurodegeneration, suggesting that it may be important for age-related neuronal decline and disease progression. Despite this, little is known about how aging influences retromer stability and the proteins with which it interacts. Detailed insights into age-dependent changes in retromer structure and function could provide valuable information towards treating and preventing many age-related neurodegenerative disorders. Here, we visit age-related pathways which interact with retromer function that ought to be further explored to determine its role in age-related neurodegeneration.
Process–Structure–Property Relationship in FeCoNiAlxMnx Complex Concentrated Alloys Processed by Additive Manufacturing
Authors: Poulia A. , Azar A. S. , Schrade M. , Graff J. S. , Bazioti C. , Gunnæs A. E. , Carvalho P. A. , Diplas S.
Published: August 2021

Fourteen alloys of the FeCoNiAlxMnx system were processed by laser metal deposition (LMD). The feedstock was a weighted and proportional blend of the containing elemental powders, targeting the nominal alloy compositions. Prior to processing, the composition and particle characteristics of the feedstock were assessed. The microstructural features and crystal structures of all LMD processed materials were characterized with scanning electron microscopy/energy dispersive spectroscopy and x-ray diffraction, in both as-received and heat-treated conditions. Selected samples were investigated via scanning transmission electron microscopy and electron backscattered diffraction for further structural understanding. Hardness tests, under various indentation loads and dwelling times, were performed to assess the mechanical properties of the processed samples. The results showed a rise in hardness as Al and Mn contents increase. The variation of hardness with composition follows a reverse sigma-type curve, reflecting the microstructural evolution and grain size variations in the alloys. Based on the hardness data, we suggest a trained and validated predictive model, which can be used in alloy design for future developments.
Logging evaluation on mechanical-damage characteristics of the vicinity of the wellbore in tight reservoirs
Authors: Ma Tianshou , Gui Junchuan , Chen Ping
Published: August 2021

The rock mechanical behavior and damage characteristic is of great importance for in situ stress evaluation, wellbore stability analysis and hydraulic fracturing design. The velocities of elastic waves are usually reduced in the presence of rock damage, it may be used for determining the progressive damage of the rock. Therefore, this paper aims to investigate the damage characteristics of transversely isotropic tight sand formation, the rock mechanical and damage parameters in the vicinity of the wellbore were calculated using acoustic logging data. The results indicated that the Poisson's ratio and damage parameters decrease with increasing in radial distance, while the elastic modulus and Thomsen’s coefficients increase. At the same radial position, the vertical elastic modulus is smaller than that of the horizontal, the degree of anisotropy for P-wave is greater than that of S-wave, and the horizontal damage parameter is greater than that of the vertical, which indicated that the micro-cracks near the wellbore mainly occur in the horizontal direction. The changes in mechanical parameters, Thomsen’s coefficients and damage parameters rapidly changed in the range of 1.0–1.8 times of borehole radius. The variations of Thomsen’s coefficients and damage parameters in mudstone are obviously greater than that of sandstone, which may be due to the induced damage between rocks and drilling fluid of mudstone is much higher than sandstone.
Electron beam welding of rectangular copper wires applied in electrical drives
Authors: Tóth Tamás , Hensel Jonas , Thiemer Sven , Sieber Philipp , Dilger Klaus
Published: August 2021

The so-called hairpin winding technology, which is specially tailored to electrical traction components, deploys rectangular plug-in copper wires in the stator. The fusion welding of the adjacent wire ends is associated with challenges due to the high thermal conductivity as well as the porosity formation of the copper. During this study, the electron beam (EB) welding of electrolytic tough pitch (ETP) and oxygen-free electronic grade (OFE) copper connectors was investigated. Subsequently, the specimens underwent X-ray computed tomography (CT) and metallographic examinations to characterize the joints. It was discovered that the residual oxygen content of the base material is responsible for the pore formation. With only a very low level of oxygen content in the copper, a porosity- and spatter-free welding can be reproducibly realized using the robust EB welding technology, especially for copper materials. By optimizing the parameters accordingly, joints exhibiting a low level of porosity were achieved even in the case of the alloy containing a high amount of residual oxygen. Beyond this, detailed analyses in terms of pore distribution were carried out and a good correlation between technological parameters and welding results was determined.
Asymptotic properties of distance-weighted discrimination and its bias correction for high-dimension, low-sample-size data
Authors: Egashira Kento , Yata Kazuyoshi , Aoshima Makoto
Published: August 2021

While distance-weighted discrimination (DWD) was proposed to improve the support vector machine in high-dimensional settings, it is known that the DWD is quite sensitive to the imbalanced ratio of sample sizes. In this paper, we study asymptotic properties of the DWD in high-dimension, low-sample-size (HDLSS) settings. We show that the DWD includes a huge bias caused by a heterogeneity of covariance matrices as well as sample imbalance. We propose a bias-corrected DWD (BC-DWD) and show that the BC-DWD can enjoy consistency properties about misclassification rates. We also consider the weighted DWD (WDWD) and propose an optimal choice of weights in the WDWD. Finally, we discuss performances of the BC-DWD and the WDWD with the optimal weights in numerical simulations and actual data analyses.
Repeated and Systematic Intimate Partner Violence in Rural Areas in Sweden
Authors: Strand Susanne J. M. , Selenius Heidi , Petersson Joakim , Storey Jennifer E.
Published: August 2021

Violence against women lacks geographical boundaries, although research demonstrates higher rates of such violence in rural areas compared to urban areas. The repeated and systematic intimate partner violence (IPV) is especially problematic in isolated areas. This study aims to investigate how repeated and systematic IPV, was handled by the criminal justice system in rural areas in Sweden and how risk and victim vulnerability factors were related to recidivism in this longitudinal prospective study. The sample consisted of alleged perpetrators of repeated and systematic IPV who had been either reported, charged, or convicted of repeated and systematic IPV defined according to the Swedish Law Gross Violation of a Woman’s Integrity targeting such violence, in two rural Swedish police districts during 2011–2014 (N = 258). Results demonstrated that 30% of IPV perpetrators were charged with the Gross violation offense and 5% were charged for other IPV-related offenses. The conviction for the Gross violation offense was 11% and 24% for other IPV-related offenses. 56% were not charged or convicted of any IPV-related offenses. Perpetrators convicted of the Gross Violation offense were more likely to receive longer prison sentences than perpetrators convicted of other IPV-related offenses. Victim cooperation in the police investigation increased the likelihood for prosecution with 7.3 times and for a conviction with 6.1 times. In terms of recidivism 24% engaged in IPV towards the same victim and another 27% recidivated into general criminality. Recidivists had higher summary risk ratings and more individual risk factors than non-recidivists, such as general criminality, employment problems and mental health problems, and victim vulnerability factors including personal problems. To reduce re-victimization, risk and vulnerability factors and supporting victims to cooperate in the police investigation should be considered when forming risk management strategies to protect victims of repeated and systematic IPV in such rural areas.
Aircraft descent performance based on flight data
Authors: Hall C.A. , Burnell S.R. , Deshpande A.P.
Published: August 2021

There are significant variations in the fuel consumption of aircraft during the descent phase of a flight. This paper uses aircraft flight data measurements to develop an improved understanding of these variations. A model of the aircraft engines is developed that is matched to flight data and shown to reproduce the time history of engine parameters. This model is used to determine the overall engine efficiency at each point during a descent. This enables an energy breakdown to be completed, in terms of mechanical energy from fuel, gravitational potential energy and kinetic energy. During descent, the aircraft engines operate at low overall pressure ratios corresponding to low fuel flow rates and low overall efficiencies. On average, the engine overall efficiency during descent is one-third of cruise efficiency. The airframe aerodynamic performance is deteriorated during descent with an average lift-to-drag ratio that is 87% of the average value at cruise. There are also large variations in air-track efficiency, and for the flights analysed the great circle descent distance was found to be 85% of the average descent air distance. To minimise fuel burn, flights should cruise as far as possible before starting descent and follow a trajectory with the shortest possible air distance. The descent air speed should be set to maximise the aircraft lift-to-drag ratio. Such descents could save up to 0.5% of the total aircraft mass in fuel.
Educating for diversity, equity, and inclusion: A review of commonly used educational approaches
Authors: Corsino Leonor , Fuller Anthony T.
Published: August 2021

Diversity, equity, and inclusion (DEI) are fundamentally important concepts for advancing clinical and translational science (CTS) education. CTS education spans a wide range of disciplines from cell biology to clinical and community/population research. This large scope both in terms of intellectual areas and target groups requires an understanding of existing educational approaches for DEI as we translate DEI from mere concepts into equitable actions within CTS education. In this  review, we provide the readers with the most common DEI educational approaches, including cultural humility, bias training, and improving mentoring to diversify the workforce. DEI educational materials can achieve maximal success and long-term impact when implemented as institutional-wide interventions, and the materials are not seen as an isolated or independent curriculum. Approaches, strategies, and programs to achieve this are many. However, many questions remain unanswered about what the best approach, strategies, and programs are to be implemented in institutional-wide education that will be embedded in CTS education.
Davidson on Pure Intending: A Non-Reductionist Judgement-Dependent Account
Authors: Hossein Khani Ali
Published: August 2021

I will argue that Davidson's account of pure intending can be construed as a first-person-based judgement-dependent account of intention. For Davidson, pure intending to do φ is to make an all-out judgement that φing is desirable. On this anti-reductionist account, intention is treated as an irreducible state of the subject. I will draw a comparison between this account and Wright's and I will show that Davidson's account can be viewed as a non-reductionist judgement-dependent account along the lines suggested by Wright. I then explain how this account can help deal with various perplexities in Davidson's later view of meaning and mental content.
Immune cell arrival kinetics to peritoneum and role during murine-experimental trichomoniasis
Authors: Rangel-Mata F. J. , Ávila-Muro E. E. , Reyes-Martínez J. E. , Olmos-Ortiz L. M. , Brunck M. E. , Arriaga-Pizano L. A. , Cuéllar-Mata P.
Published: August 2021

Trichomonas vaginaliscauses trichomoniasis, an inflammatory process related to an increased rate of HIV transmission. In order to studyT. vaginalisinfection response in a microorganism-free environment, an infection model was established providing a host–parasite interaction system useful to study the interplay between immune cells and the parasite. Infected mice peritoneal cells were immunophenotyped at different times after infection using flow cytometry. Neutrophils and macrophages showed the most relevant increase from third to 12th day post-infection. A high number of B lymphocytes were present on 15th day post-infection, and an increase in memory T cells was observed on sixth day post-infection. The levels of NO increased at day 10 post-infection; no significant influence was observed onT. vaginalisclearance. Increased viability ofT. vaginaliswas observed when the NETs inhibitors, metformin and Cl−amidine, were administrated, highlighting the importance of this mechanism to control parasite infection (43 and 86%, respectively). This report presents a comprehensive cell count of the immune cells participating against trichomoniasis in anin vivointeraction system. These data highlight the relevance of innate mechanisms such as specific population changes of innate immune cells and their impact on theT. vaginalisviability.
Molecular and morphological characterisation of Diplostomum phoxini (Faust, 1918) with a revised classification and an updated nomenclature of the species-level lineages of Diplostomum (Digenea: Diplostomidae) sequenced worldwide
Authors: Schwelm Jessica , Georgieva Simona , Grabner Daniel , Kostadinova Aneta , Sures Bernd
Published: August 2021

We characterised morphologically and molecularly Diplostomum phoxini (Faust, 1918) based on cercarial isolates from the snail Ampullaceana balthica (L.) (Gastropoda: Lymnaeidae) and metacercariae from the Eurasian minnow, Phoxinus phoxinus (L.) (Cypriniformes: Leuciscidae), and provided molecular evidence for the identification of the snail intermediate host. Phylogenetic analyses based on the cytochrome c oxidase subunit 1 (cox1) gene depicted 44 molecularly characterised species and genetically distinct lineages of Diplostomum, and resulted in: (i) a re-identification/re-classification of 98 isolates plus D. baeri sampled in North America; (ii) re-definition of the composition of the D. baeri species complex which now includes nine molecularly characterised species/lineages; (iii) re-definition of the composition of the D. mergi species complex which now includes seven molecularly characterised species/lineages; and (iv) an updated nomenclature for the molecularly characterised species-level lineages of Diplostomum.
In situevidence of the role ofCrangon crangonin infection of codGadus morhuawith nematode parasiteHysterothylacium aduncumin the Baltic Sea
Authors: Pawlak Joanna
Published: August 2021

Cod was one of the most important fish species in the Baltic Sea, but its condition is deteriorating for several reasons, including an increasing parasite burden. The aim of this study was to determine the source of infection of Baltic cod with parasites by examination of invertebrates foundin situin the cod stomach. A total of 1681 cod were sampled during four research cruises in the southern Baltic Sea in 2012, 2013 and 2014 and the composition of their diet was analysed. Each prey item from cod stomach was identified to the lowest possible taxonomic level and a parasitological analysis of all invertebrates collected was performed.Crangon crangon,Saduria entomonandMysis mixtawere the most commonly represented invertebrates among food items.Hysterothylacium aduncumwas found only inC. crangon. This host–parasite system is reported here for the first timein situin the stomach of cod from the Baltic Sea, confirming the role ofC. crangonin cod infection withH. aduncum.
The social meaning of a merger: The evaluation of an Andalusian Spanish consonant merger (ceceo)
Authors: Regan Brendan
Published: August 2021

This study analyzes the social evaluations of the Andalusian Spanishceceomerger and its split,distinción. A matched-guise experiment was created by digitally manipulating spontaneous speech from twelve Western Andalusian speakers, varying only in syllable-initial [s̪] and [θ] for
 and , creatingceceoanddistinciónguises. Based on 221 listeners from Huelva and Lepe, Spain, mixed effects linear regression models found that speakers withdistinciónguises were evaluated as being of higher social status, more urban, and more formal than speakers withceceoguises. Additionally, listeners' comments referred not only to the sounds and graphemes, but also to the merger itself and its social connotations. The implications are two-fold: (i) consonant mergers may be subject to more overt social evaluation than vocalic mergers; and (ii) a merger can acquire social meaning, and this meaning in turn, may promote its split. (Mergers, splits, sociolinguistic perception, language attitudes, Andalusian Spanish, sociophonetics, dialect levelling,ceceo,distinción)*
‘Chasing every mark’. High stakes assessment and curriculum narrowing: the case of disciplinary literacy in the Irish secondary music classroom
Authors: Hennessy Jennifer , Corr Sinéad
Published: August 2021

The critical role of disciplinary literacy in enhancing understanding and engagement within arts-based subjects has drawn increased recognition amongst researchers and practitioners alike in recent years. The successful integration of disciplinary literacy into the classroom however has been challenged in equal measures by a prevailing sense of confusion and misunderstanding surrounding the concept of disciplinary literacy and by the concurrent, deep-rooted pressures of performativity experienced by teachers and pupils operating within regimes of examination intensification. The result of these tensions has been a documented increase in reductionist classroom-based approaches to the development of disciplinary literacy. Given the frequently cited importance of engaged disciplinary literacy encounters in the music classroom, a review of the dominant pedagogical practices in this field is germane. This paper reports on the findings of a study exploring the integration of disciplinary literacy in the Irish secondary school music classroom. The findings of this research demonstrate a dominance of listening and performing strategies in classroom-based literacy development initiatives and an aligned relegation of student verbalisation in the music classroom. Recommendations for more disciplinary engaged, student-centred approaches in the development of music literacy within the secondary classroom are outlined.
Barriers and enablers to undergraduate music students undertaking a Postgraduate Certificate in Education (PGCE) secondary music programme
Authors: Breeze Thomas , Beauchamp Gary
Published: August 2021

In the context of falling recruitment to Initial Teacher Education programmes in the UK, this article focuses on motivators and demotivators affecting undergraduate students’ attitudes towards training as a teacher and considers these under the broad headings of altruistic (such as wanting to share a love of the subject and working with young people) and pragmatic (stable career, regular salary, good holidays). A review of the literature suggests that there are differences between the US and the UK in terms of the extent to which students can develop an identity as a teacher during their formative undergraduate years. An online survey was distributed to undergraduates in UK higher education institutions, the results were related to the issues identified in the literature and the differences between genders examined. The results suggested that there was no single significant barrier to undergraduate students deciding to train as secondary music teachers, but that there are opportunities to increase the number of students developing an identity as a music teacher while studying for their undergraduate degrees, and some gender-specific issues which could be addressed.
Indexing that something is sufficient: Interactional functions of ingressive particles in Finnish and Danish
Authors: Steensig Jakob , Hakulinen Auli , Larsen Tine
Published: August 2021

Sounds spoken on the inbreath have been shown to be common in the world’s languages, and in the Nordic languages ingressive speech seems to be especially frequent. The present study focuses on Finnish and Danish response particles spoken on the inbreath, by examining their uses in everyday talk-in-interaction in corpora of recorded interactions. The particles we examine and their non-ingressive counterparts can perform confirming and acknowledging actions. We analyze the particles as receipts to answers to questions, as responses to questions, as responses to assessments, and as responses to affiliation-seeking utterances. In these positions, the ingressive particles turn out to index that the content of the previous turn was already sufficiently established and, consequently, that there is nothing to add. In cases where an engaged response is called for, the particles are shown to have a disaffiliative potential.
On a reaction–diffusion system modelling infectious diseases without lifetime immunity
Authors: YIN HONG-MING
Published: August 2021

In this paper, we study a mathematical model for an infectious disease caused by a virus such as Cholera without lifetime immunity. Due to the different mobility for susceptible, infected human and recovered human hosts, the diffusion coefficients are assumed to be different. The resulting system is governed by a strongly coupled reaction–diffusion system with different diffusion coefficients. Global existence and uniqueness are established under certain assumptions on known data. Moreover, global asymptotic behaviour of the solution is obtained when some parameters satisfy certain conditions. These results extend the existing results in the literature. The main tool used in this paper comes from the delicate theory of elliptic and parabolic equations. Moreover, the energy method and Sobolev embedding are used in derivinga prioriestimates. The analysis developed in this paper can be employed to study other epidemic models in biological, ecological and health sciences.
Post-operative kinetics of C-reactive protein to distinguish between bacterial infection and systemic inflammation in infants after cardiopulmonary bypass surgery: the early and the late period
Authors: Renk Hanna , Grosse David , Schober Sarah , Schlensak Christian , Hofbeck Michael , Neunhoeffer Felix
Published: August 2021

Objectives:

Differentiation between post-operative inflammation and bacterial infection remains an important issue in infants following congenital heart surgery. We primarily assessed kinetics and predictive value of C-reactive protein for bacterial infection in the early (days 0–4) and late (days 5–28) period after cardiopulmonary bypass surgery. Secondary objectives were frequency, type, and timing of post-operative infection related to the risk adjustment for congenital heart surgery score.

Methods:

This 3-year single-centre retrospective cohort study in a paediatric cardiac ICU analysed 191 infants accounting for 235 episodes of CPBP surgery. Primary outcome was kinetics of CRP in the first 28 days after CPBP surgery in infected and non-infected patients.

Results:

We observed 22 infectious episodes in the early and 34 in the late post-operative period. CRP kinetics in the early post-operative period did not accurately differentiate between infected and non-infected patients. In the late post-operative period, infected infants displayed significantly higher CRP values with a median of 7.91 (1.64–22.02) and 6.92 mg/dl (1.92–19.65) on days 2 and 3 compared to 4.02 (1.99–15.9) and 3.72 mg/dl (1.08–9.72) in the non-infection group. Combining CRP on days 2 and 3 after suspicion of infection revealed a cut-off of 9.47 mg/L with an acceptable predictive accuracy of 76%.

Conclusions:

In neonates and infants, CRP kinetics is not useful to predict infection in the first 72 hours after CPBP surgery due to the inflammatory response. However, in the late post-operative period, CRP is a valuable adjunctive diagnostic test in conjunction with clinical presentation and microbiological diagnostics.
Comparison of myocardial T1 mapping during breath-holding and free-breathing
Authors: Oka Hideharu , Nakau Kouichi , Nakagawa Sadahiro , Kobayashi Yuki , Imanishi Rina , Iwata Kunihiro , Azuma Hiroshi
Published: August 2021

Background:

T1 mapping is a recently developed imaging analysis method that allows quantitative assessment of myocardial T1 values obtained using MRI. In children, MRI is performed under free-breathing. Thus, it is important to know the changes in T1 values between free-breathing and breath-holding. This study aimed to compare the myocardial T1 mapping during breath-holding and free-breathing.

Methods:

Thirteen patients and eight healthy volunteers underwent cardiac MRI, and T1 values obtained during breath-holding and free-breathing were examined and compared. Statistical differences were determined using the paired t-test.

Results:

The mean T1 values during breath-holding were 1211.1 ± 39.0 ms, 1209.7 ± 37.4 ms, and 1228.9 ± 52.5 ms in the basal, mid, and apical regions, respectively, while the mean T1 values during free-breathing were 1165.1 ± 69.0 ms, 1103.7 ± 55.8 ms, and 1112.0 ± 81.5 ms in the basal, mid, and apical regions, respectively. The T1 values were lower during free-breathing than during breath-holding in almost all segments (basal: p = 0.008, mid: p < 0.001, apical: p < 0.001). The mean T1 values in each cross section were 3.1, 7.8, and 7.7% lower during free-breathing than during breath-holding in the basal, mid, and apical regions, respectively.

Conclusions:

We found that myocardial T1 values during free-breathing were about 3–8% lower in all cross sections than those during breath-holding. In free-breathing, it may be difficult to assess myocardial T1 values, except in the basal region, because of underestimation; thus, the findings should be interpreted with caution, especially in children.
Asylum in the EU: One of the Many Faces of Rule of Law Backsliding?
Authors: Tsourdi Evangelia (Lilian)
Published: August 2021

EU values – Rule of law backsliding – Rule of law and fundamental rights interrelation – Refugee protection – Common European Asylum System – Implementation gap in asylum – Lack of fair responsibility sharing in asylum – Structural deficiencies in national asylum systems – Defiance of asylum obligations and the duty of sincere cooperation – Systemic fundamental rights violations – Upholding the rule of law – European Asylum System redesign – Systemic infringement actions – Rule of law monitoring
The Dependence of Ecosystem Water Use Partitioning on Vegetation Productivity at the Inter‐Annual Time Scale
Authors: Jing Zhaoxia , Cheng Lei , Zhang Lu , Wang Ying‐Ping , Liu Pan , Zhang Xiang , Wang Qilin
Published: August 2021

The dependence of inter‐annual ecosystem evapotranspiration (ET) partitioning on vegetation dynamics is crucial for understanding the long term coupling relationship between the water and carbon cycles. The objective of this study was to determine the spatial variation of ET partitioning (T/ET) and the inter‐annual dependencies of T/ET on vegetation gross primary productivity (GPP). The investigation was conducted at the global scale based on seven global datasets and at the point scale at 37 flux sites. The spatial variations of T/ET were divided into three phases, that is, the rapidly increasing phase (P1), slowly increasing phase (P2), and decreasing phase (P3), which were located in arid and cold regions, temperate regions, and tropical rainforest regions, respectively. The three‐phase spatial variations were primarily driven by the different spatial variations of the two water use pathways (i.e., transpiration, T and evaporation, E) in ecosystems with different productivity levels. In P1 and P2 ecosystems, the inter‐annual dependencies of T/ET on GPP were mostly positive, and in P3 ecosystems, it was mostly negative. This revealed a significantly decreased dependence as GPP increased, which was attributed to the different dependencies of T and E on GPP. Based on the effects of GPP on ET under climate variations (represented by precipitation, P), ET had the smallest inter‐annual variations in most of global vegetated grid cells due to the joint regulation of T and E by GPP and P. This study highlights the significant role of vegetation productivity in regulating inter‐annual ET partitioning, and improves understandings on the coupled water‐carbon cycles.
Stress‐Driven Failure of Cylindrical Volcanic Conduits
Authors: Mullet B. G. , Segall P.
Published: August 2021

Many explosive volcanic eruption sequences are characterized by exceedingly unsteady behavior, often punctuated by multiple explosive phases, separated by hours to days. What causes this unsteady behavior is not fully understood. Here, we explore one possible mechanism: stress‐driven failure of the volcanic conduit wall rock. We present a multiphase conduit flow model that predicts the shear and normal tractions exerted on the conduit wall, and couple (one way) these tractions with a numerical model of host rock failure. While analytical estimations of host rock stress serve as useful guides, analytical approximations which ignore shear tractions are insufficient to adequately predict conduit instability. Failure generally initiates near the fragmentation depth, where shear tractions are highest and magma pressure is low relative to the lithostatic stress. Shear tractions on the conduit wall, caused by viscous drag, promote strain localization and failure. The in situ stress state not only determines the range of conduit pressures which promotes failure, but also influences the style of failure. The mechanism that is most likely to lead to the disruption of flow, where wall rock moves radially into the conduit along normal faults, occurs in extensional stress regimes when large shear tractions at the fragmentation depth enhance normal fault formation. The results of this study indicate that conduit stability strongly depends on the ambient stress field and the nature of conduit flow at the fragmentation depth.
Predicting Dominance of Sand Transport by Waves, Tides, and Their Interactions on Sandy Continental Shelves
Authors: King E. V. , Conley D. C. , Masselink G. , Leonardi N.
Published: August 2021

Waves and tidal currents resuspend and transport shelf sediments, influencing sediment distributions and bedform morphology with implications for various disciplines including benthic habitats, marine operations, and marine spatial planning. Shelf‐scale assessments of wave‐tide‐dominance of sand transport tend not to fully include wave‐tide interactions, which nonlinearly enhance bed shear stress and apparent roughness, change the current profile, modulate wave forcing, and can dominate net sand transport. Assessment of the contribution of wave‐tide interactions to net sand transport requires computationally/labor intensive coupled numerical modeling, making comparison between regions or climate conditions challenging. Using the Northwest European Shelf, we show the dominant forcing mode and potential magnitude of net sand transport is predictable from readily available, uncoupled wave, tide, and morphological data in a computationally efficient manner using a k‐Nearest Neighbor algorithm. Shelf areas exhibit different dominant forcing modes for similar wave exceedance conditions, related to differences in depth, grain size, tide range, and wave exposure. Wave‐tide interactions dominate across most areas in energetic combined conditions. Meso‐macrotidal areas exhibit tide‐dominance while shallow, fine‐grained, microtidal regions show wave‐dominance over a statistically representative year, with wave‐tide interactions dominating extensively >30 m depth. Sediment transport mode strongly affects seabed morphology. Sand wave geometry varies significantly between predicted dominance classes with increased wave length and asymmetry, and decreased height, for increasing wave‐dominance. This approach efficiently indicates where simple noninteractive wave and tide processes may be sufficient for modeling sediment transport, and enables efficient interregional comparisons and sensitivity testing to changing climate conditions with applications globally.
FANCI plays an essential role in spermatogenesis and regulates meiotic histone methylation
Authors: Xu Lan , Xu Weiwei , Li Duan , Yu Xiaoxia , Gao Fei , Qin Yingying , Yang Yajuan , Zhao Shidou
Published: August 2021

FANCI is an essential component of Fanconi anemia pathway, which is responsible for the repair of DNA interstrand cross-links (ICLs). As an evolutionarily related partner of FANCD2, FANCI functions together with FANCD2 downstream of FA core complex. Currently, growing evidences showed that the essential role of FA pathway in male fertility. However, the underlying mechanisms for FANCI in regulating spermatogenesis remain unclear. In the present study, we found that the male Fanci−/− mice were sterile and exhibited abnormal spermatogenesis, including massive germ cell apoptosis in seminiferous tubules and dramatically decreased number of sperms in epididymis. Besides, FANCI deletion impaired maintenance of undifferentiated spermatogonia. Further investigation indicated that FANCI was essential for FANCD2 foci formation and regulated H3K4 and H3K9 methylation on meiotic sex chromosomes. These findings elucidate the role and mechanism of FANCI during spermatogenesis in mice and provide new insights into the etiology and molecular basis of nonobstructive azoospermia.
TRIM28 SUMOylates and stabilizes NLRP3 to facilitate inflammasome activation
Authors: Qin Ying , Li Qi , Liang Wenbo , Yan Rongzhen , Tong Li , Jia Mutian , Zhao Chunyuan , Zhao Wei
Published: August 2021

The cellular NLRP3 protein level is crucial for assembly and activation of the NLRP3 inflammasome. Various posttranslational modifications (PTMs), including phosphorylation and ubiquitination, control NLRP3 protein degradation and inflammasome activation; however, the function of small ubiquitin-like modifier (SUMO) modification (called SUMOylation) in controlling NLRP3 stability and subsequent inflammasome activation is unclear. Here, we show that the E3 SUMO ligase tripartite motif-containing protein 28 (TRIM28) is an enhancer of NLRP3 inflammasome activation by facilitating NLRP3 expression. TRIM28 binds NLRP3, promotes SUMO1, SUMO2 and SUMO3 modification of NLRP3, and thereby inhibits NLRP3 ubiquitination and proteasomal degradation. Concordantly, Trim28 deficiency attenuates NLRP3 inflammasome activation both in vitro and in vivo. These data identify a mechanism by which SUMOylation controls the cellular NLRP3 level and inflammasome activation, and reveal correlations and interactions of NLRP3 SUMOylation and ubiquitination during inflammasome activation.
High thermoelectric performance enabled by convergence of nested conduction bands in Pb7Bi4Se13 with low thermal conductivity
Authors: Hu Lei , Fang Yue-Wen , Qin Feiyu , Cao Xun , Zhao Xiaoxu , Luo Yubo , Repaka Durga Venkata Maheswar , Luo Wenbo , Suwardi Ady , Soldi Thomas , Aydemir Umut , Huang Yizhong , Liu Zheng , Hippalgaonkar Kedar , Snyder G. Jeffrey , Xu Jianwei , Yan Qingyu
Published: August 2021

Thermoelectrics enable waste heat recovery, holding promises in relieving energy and environmental crisis. Lillianite materials have been long-term ignored due to low thermoelectric efficiency. Herein we report the discovery of superior thermoelectric performance in Pb7Bi4Se13 based lillianites, with a peak figure of merit, zT of 1.35 at 800 K and a high average zT of 0.92 (450–800 K). A unique quality factor is established to predict and evaluate thermoelectric performances. It considers both band nonparabolicity and band gaps, commonly negligible in conventional quality factors. Such appealing performance is attributed to the convergence of effectively nested conduction bands, providing a high number of valley degeneracy, and a low thermal conductivity, stemming from large lattice anharmonicity, low-frequency localized Einstein modes and the coexistence of high-density moiré fringes and nanoscale defects. This work rekindles the vision that Pb7Bi4Se13 based lillianites are promising candidates for highly efficient thermoelectric energy conversion.
Identification of potent human neutralizing antibodies against SARS-CoV-2 implications for development of therapeutics and prophylactics
Authors: Zhao Shaojuan , Zhang Huajun , Yang Xinglou , Zhang Haiwei , Chen Ying , Zhan Yancheng , Zhang Xiaoqing , Jiang Rendi , Liu Meiqin , Liu Lan , Chen Li , Tang Wei , Peng Cheng , Gao Xiaoxiao , Zhang Zhe , Shi Zhengli , Gong Rui
Published: August 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that is spreading rapidly, which seriously impacts global public health and economy. Thus, developing effective drugs remains urgent. We identify two potent antibodies, nCoVmab1 and nCoVmab2, targeting the SARS-CoV-2 spike protein receptor-binding domain (RBD) with high affinities from a naïve human phage-displayed Fab library. nCoVmab1 and nCoVmab2 neutralize authentic SARS-CoV-2 with picomolar and nanomolar IC50 values, respectively. No detectable defects of nCoVmab1 and nCoVmab2 are found during the preliminary druggability evaluation. nCoVmab1 could reduce viral titer and lung injury when administered prophylactically and therapeutically in human angiotensin-converting enzyme II (hACE2)-transgenic mice. Therefore, phage display platform could be efficiently used for rapid development of neutralizing monoclonal antibodies (nmabs) with clinical potential against emerging infectious diseases. In addition, we determinate epitopes in RBD of these antibodies to elucidate the neutralizing mechanism. We also convert nCoVmab1 and nCoVmab2 to their germline formats for further analysis, which reveals the contribution of somatic hypermutation (SHM) during nCoVmab1 and nCoVmab2 maturation. Our findings not only provide two highly potent nmabs against SARS-CoV-2 as prophylactic and therapeutic candidates, but also give some clues for development of anti-SARS-CoV-2 agents (e.g., drugs and vaccines) targeting the RBD.
Detection and characterization of the SARS-CoV-2 lineage B.1.526 in New York
Authors: West Anthony P. , Wertheim Joel O. , Wang Jade C. , Vasylyeva Tetyana I. , Havens Jennifer L. , Chowdhury Moinuddin A. , Gonzalez Edimarlyn , Fang Courtney E. , Di Lonardo Steve S. , Hughes Scott , Rakeman Jennifer L. , Lee Henry H. , Barnes Christopher O. , Gnanapragasam Priyanthi N. P. , Yang Zhi , Gaebler Christian , Caskey Marina , Nussenzweig Michel C. , Keeffe Jennifer R. , Bjorkman Pamela J.
Published: August 2021

Wide-scale SARS-CoV-2 genome sequencing is critical to tracking viral evolution during the ongoing pandemic. We develop the software tool, Variant Database (VDB), for quickly examining the changing landscape of spike mutations. Using VDB, we detect an emerging lineage of SARS-CoV-2 in the New York region that shares mutations with previously reported variants. The most common sets of spike mutations in this lineage (now designated as B.1.526) are L5F, T95I, D253G, E484K or S477N, D614G, and A701V. This lineage was first sequenced in late November 2020. Phylodynamic inference confirmed the rapid growth of the B.1.526 lineage. In concert with other variants, like B.1.1.7, the rise of B.1.526 appears to have extended the duration of the second wave of COVID-19 cases in NYC in early 2021. Pseudovirus neutralization experiments demonstrated that B.1.526 spike mutations adversely affect the neutralization titer of convalescent and vaccinee plasma, supporting the public health relevance of this lineage.
Data analytics approach to predict high-temperature cyclic oxidation kinetics of NiCr-based Alloys
Authors: Peng Jian , Pillai Rishi , Romedenne Marie , Pint Bruce A. , Muralidharan Govindarajan , Allen Haynes J. , Shin Dongwon
Published: August 2021

Although of practical importance, there is no established modeling framework to accurately predict high-temperature cyclic oxidation kinetics of multi-component alloys due to the inherent complexity. We present a data analytics approach to predict the oxidation rate constant of NiCr-based alloys as a function of composition and temperature with a highly consistent and well-curated experimental dataset. Two characteristic oxidation models, i.e., a simple parabolic law and a statistical cyclic oxidation model, have been chosen to numerically represent the high-temperature oxidation kinetics of commercial and model NiCr-based alloys. We have successfully trained machine learning (ML) models using highly ranked key input features identified by correlation analysis to accurately predict experimental parabolic rate constants (kp). This study demonstrates the potential of ML approaches to predict oxidation kinetics of alloys over wide composition and temperature ranges. This approach can also serve as a basis for introducing more physically meaningful ML input features to predict the comprehensive cyclic oxidation behavior of multi-component high-temperature alloys with proper constraints based on the known underlying mechanisms.
Quantum-enhanced analysis of discrete stochastic processes
Authors: Blank Carsten , Park Daniel K. , Petruccione Francesco
Published: August 2021

Discrete stochastic processes (DSP) are instrumental for modeling the dynamics of probabilistic systems and have a wide spectrum of applications in science and engineering. DSPs are usually analyzed via Monte-Carlo methods since the number of realizations increases exponentially with the number of time steps, and importance sampling is often required to reduce the variance. We propose a quantum algorithm for calculating the characteristic function of a DSP, which completely defines its probability distribution, using the number of quantum circuit elements that grows only linearly with the number of time steps. The quantum algorithm reduces the Monte-Carlo sampling to a Bernoulli trial while taking all stochastic trajectories into account. This approach guarantees the optimal variance without the need for importance sampling. The algorithm can be further furnished with the quantum amplitude estimation algorithm to provide quadratic speed-up in sampling. The Fourier approximation can be used to estimate an expectation value of any integrable function of the random variable. Applications in finance and correlated random walks are presented. Proof-of-principle experiments are performed using the IBM quantum cloud platform.
CcrZ is a pneumococcal spatiotemporal cell cycle regulator that interacts with FtsZ and controls DNA replication by modulating the activity of DnaA
Authors: Gallay Clement , Sanselicio Stefano , Anderson Mary E. , Soh Young Min , Liu Xue , Stamsås Gro A. , Pelliciari Simone , van Raaphorst Renske , Dénéréaz Julien , Kjos Morten , Murray Heath , Gruber Stephan , Grossman Alan D. , Veening Jan-Willem
Published: August 2021

Most bacteria replicate and segregate their DNA concomitantly while growing, before cell division takes place. How bacteria synchronize these different cell cycle events to ensure faithful chromosome inheritance by daughter cells is poorly understood. Here, we identify Cell Cycle Regulator protein interacting with FtsZ (CcrZ) as a conserved and essential protein in pneumococci and related Firmicutes such as Bacillus subtilis and Staphylococcus aureus. CcrZ couples cell division with DNA replication by controlling the activity of the master initiator of DNA replication, DnaA. The absence of CcrZ causes mis-timed and reduced initiation of DNA replication, which subsequently results in aberrant cell division. We show that CcrZ from Streptococcus pneumoniae interacts directly with the cytoskeleton protein FtsZ, which places CcrZ in the middle of the newborn cell where the DnaA-bound origin is positioned. This work uncovers a mechanism for control of the bacterial cell cycle in which CcrZ controls DnaA activity to ensure that the chromosome is replicated at the right time during the cell cycle.