bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex Structure in the Nootka Fault Zone Revealed by Double‐Difference Tomography and a New Earthquake Catalog
Authors: Merrill Reid J. , Bostock Michael G. , Peacock Simon M. , Schaeffer Andrew J. , Roecker Steven W.
Published: February 2022

We employ an automatic earthquake detection algorithm to seismic waveforms recorded between the years 2000 and 2020 in southwest British Columbia. 32,121 events which possess at least three paired P‐ and S‐wave arrival times are located, compared to 21,538 seismic events in the existing Geologic Survey of Canada catalog. This augmented catalog is employed for double‐difference seismic tomography across Vancouver Island, with particular focus on the Nootka Fault zone (NFZ). The NFZ is a transform boundary that separates the Juan de Fuca and Explorer plates in a zone of distributed left‐lateral strike‐slip faulting. Tomographic results indicate that a double seismic zone exists within the NFZ that parallels Vp/Vs structure typically observed in subduction zones. Specifically, a dipping high Vp/Vs layer is underlain by reduced Vp/Vs material. Structural complexities are revealed by three Mw > 6 events and their aftershocks. The 2004 Mw 6.3 and 2011 Mw 6.4 events are interpreted to reside southeast of the NFZ within the Juan de Fuca plate at depths as shallow as 20 km, and the 2014 Mw 6.6 event is interpreted to reside within oceanic lithosphere of the NFZ at depths >35 km. Vp/Vs structure further indicates that underthrust oceanic lithosphere of the Explorer plate extends to 20 km depth beneath Brooks Peninsula. Our results support the hypothesis that the NFZ represents a structurally independent slice of oceanic lithosphere that exhibits (a) a more northerly trajectory than typically depicted, and (b) increased plate curvature when compared to either the Juan de Fuca or Explorer plates.
Silicate Volcanism on Europa's Seafloor and Implications for Habitability
Authors: Bland M. T. , Elder C. M.
Published: February 2022

Habitable ocean environments on Europa require an influx of reactants to maintain chemical disequilibrium. One possible source of reactants is seafloor volcanism. Modeling has shown that dissipation of tidal energy in Europa's asthenosphere can generate melt, but melt formation cannot be equated with volcanism. Melt must also be transported through Europa's cold lithosphere to erupt at the seafloor. Here, we use two models of dike propagation to show that dikes can only traverse the lithosphere if either the fracture toughness of the lithosphere or the flux into the dike is large (>500 MPa m1/2 or ∼1 m2 s−1, respectively). We conclude that cyclic volcanic episodes might provide reactants to Europa's ocean if magma accumulates at the base of the lithosphere for several thousand years. However, if dikes form too frequently, or are too numerous, the magma flux into each will be insufficient, and volcanism cannot support a habitable ocean environment.
Melatonergic agents influence the sleep-wake and circadian rhythms in healthy and psychiatric participants: a systematic review and meta-analysis of randomized controlled trials
Authors: Moon Eunsoo , Partonen Timo , Beaulieu Serge , Linnaranta Outi
Published: February 2022

Exogenous melatonergic agents are widely used to treat insomnia and sleep disturbance. Several studies have shown that they might also modulate circadian rhythms. The purpose of this systematic review and meta-analysis was to summarize current knowledge about the effects of melatonin supplements and melatonin agonists on the sleep-wake cycle as well as on the circadian rhythm of melatonin in healthy participants and in patients with psychiatric disorders. The following electronic databases were searched: EMBASE, PubMed, Web of Science, CINAHL, and Cochrane Library. Of the 12,719 articles, we finally selected 30 studies including 1294 healthy participants and 8 studies including 687 patients with psychiatric disorders. Cochrane risk of bias tool was used to assess the risk of bias. Using meta-ANOVA, studies on healthy participants showed advancing effects of melatonergic supplements and agonists on sleep-wake cycle according to dosing time and dosage, despite the fact that the original individual melatonin rhythm was within a normal range (fixed effect model standardized mean difference[95% Confidence Interval]= −0.639[−0.968 to −0.310]). In a limited number of randomized controlled trials with psychiatric patients, the findings seemed similar to those with healthy participants, despite the psychiatric disorders and treatment related factors affecting circadian rhythms. Given the unmet clinical need for evidence-based treatments to correct circadian rhythms in psychiatric disorders, efficacy of melatonergic agents seen in healthy participants, and similarity of findings among psychiatric patients, large scale, well-designed randomized controlled trials are needed to test efficacy on circadian parameters in psychiatric disorders.
Ferredoxin reductase and p53 are necessary for lipid homeostasis and tumor suppression through the ABCA1–SREBP pathway
Authors: Zhang Yanhong , Mohibi Shakur , Vasilatis Demitria M. , Chen Mingyi , Zhang Jin , Chen Xinbin
Published: February 2022

p53 is known to modulate metabolism and FDXR is required for steroidogenesis. Given that FDXR is a target/regulator of p53, the FDXR–p53 axis may play a unique role in lipid metabolism. Here, we found that expression of ABCA1, a cholesterol-efflux pump, was suppressed by loss of FDXR and/or p53, leading to activation of master lipogenic regulators SREBP1/2. Accordingly, lipid droplets, cholesterol, and triglycerides were increased by loss of FDXR or p53, which were further increased by loss of both FDXR and p53. To explore the biological significance of the FDXR–p53 axis, we generated a cohort of mice deficient in Fdxr and/or Trp53. We found that Fdxr+/−, Trp53+/−, and Fdxr+/−;Trp53+/− mice had a short life span and were prone to spontaneous tumors and liver steatosis. Moreover, the levels of serum cholesterol and triglycerides were significantly increased in Fdxr+/− and Trp53+/− mice, which were further increased in Fdxr+/−;Trp53+/− mice. Interestingly, loss of Fdxr but not p53 led to accumulation of serum low-density lipoprotein. Together, our findings reveal that the FDXR–p53 axis plays a critical role in lipid homeostasis and tumor suppression.
Chronic pediatric diseases and risk for reading difficulties: a narrative review with recommendations
Authors: Perazzo Donna , Moore Ryan , Kasparian Nadine A. , Rodts Megan , Horowitz-Kraus Tzipi , Crosby Lori , Turpin Brian , Beck Andrew F. , Hutton John
Published: February 2022

Literacy is a major social determinant of health, rooted in skills that develop during early childhood. Children arriving at kindergarten unprepared to learn to read are more likely to have low reading proficiency thereafter. General and health literacy are highly correlated, affecting understanding of health conditions, treatment adherence, and transition to self-care and adult healthcare services. The American Academy of Pediatrics (AAP) recommends literacy and school readiness promotion during well-visits and neurodevelopmental surveillance is emphasized across primary and subspecialty care. While genetic and environmental risk factors for reading difficulties are well-established, risks related to complex and chronic medical conditions are less appreciated and under-researched. This review applies an eco-bio-developmental framework to explore literacy across five complex chronic conditions affecting millions of children worldwide: asthma, cancer, congenital heart disease, epilepsy, and sickle cell disease. In each, integration of an efficient reading brain network may be impacted by direct factors, such as ischemia, anesthesia, and/or medications, and also indirect factors, such as altered parent–child routines, hospital stays, and missed school. By integrating literacy into care management plans for affected children, pediatric primary care and specialty providers are poised to identify risks early, target guidance and interventions, and improve academic and health outcomes.

Impact

While genetic and environmental risk factors for reading difficulties are well-established, risks related to complex and/or chronic medical conditions such as asthma, cancer, congenital heart disease, epilepsy, and sickle cell disease are substantial, less appreciated, and under-researched.

General and health literacy are highly correlated, with implications for the understanding one’s health condition, treatment adherence, and transitioning to self-care, which is especially important for children with complex and/or chronic illness.

Pediatric primary care and specialty providers are poised to integrate reading and literacy into care management plans for children with complex and/or chronic illness, including early screening, guidance, support, and interventions.
Interplay between soluble CD74 and macrophage-migration inhibitory factor drives tumor growth and influences patient survival in melanoma
Authors: Fukuda Yasunari , Bustos Matias A. , Cho Sung-Nam , Roszik Jason , Ryu Suyeon , Lopez Victor M. , Burks Jared K. , Lee Jeffrey E. , Grimm Elizabeth A. , Hoon Dave S. B. , Ekmekcioglu Suhendan
Published: February 2022

Soluble forms of receptors play distinctive roles in modulating signal-transduction pathways. Soluble CD74 (sCD74) has been identified in sera of inflammatory diseases and implicated in their pathophysiology; however, few relevant data are available in the context of cancer. Here we assessed the composition and production mechanisms, as well as the clinical significance and biological properties, of sCD74 in melanoma. Serum sCD74 levels were significantly elevated in advanced melanoma patients compared with normal healthy donors, and the high ratio of sCD74 to macrophage-migration inhibitory factor (MIF) conferred significant predictive value for prolonged survival in these patients (p = 0.0035). Secretion of sCD74 was observed primarily in melanoma cell lines as well as a THP-1 line of macrophages from monocytes and primary macrophages, especially in response to interferon-γ (IFN-γ). A predominant form that showed clinical relevance was the 25-KDa sCD74, which originated from the 33-KDa isoform of CD74. The release of this sCD74 was regulated by either a disintegrin and metalloproteinase-mediated cell-surface cleavage or cysteine-protease-mediated lysosomal cleavage, depending on cell types. Both recombinant and THP-1 macrophage-released endogenous sCD74 suppressed melanoma cell growth and induced apoptosis under IFN-γ stimulatory conditions via inhibiting the MIF/CD74/AKT-survival pathway. Our findings demonstrate that the interplay between sCD74 and MIF regulates tumor progression and determines patient outcomes in advanced melanoma.
Systems-based approaches to study immunometabolism
Authors: Purohit Vinee , Wagner Allon , Yosef Nir , Kuchroo Vijay K.
Published: February 2022

Technical advances at the interface of biology and computation, such as single-cell RNA-sequencing (scRNA-seq), reveal new layers of complexity in cellular systems. An emerging area of investigation using the systems biology approach is the study of the metabolism of immune cells. The diverse spectra of immune cell phenotypes, sparsity of immune cell numbers in vivo, limitations in the number of metabolites identified, dynamic nature of cellular metabolism and metabolic fluxes, tissue specificity, and high dependence on the local milieu make investigations in immunometabolism challenging, especially at the single-cell level. In this review, we define the systemic nature of immunometabolism, summarize cell- and system-based approaches, and introduce mathematical modeling approaches for systems interrogation of metabolic changes in immune cells. We close the review by discussing the applications and shortcomings of metabolic modeling techniques. With systems-oriented studies of metabolism expected to become a mainstay of immunological research, an understanding of current approaches toward systems immunometabolism will help investigators make the best use of current resources and push the boundaries of the discipline.
Control of the conversion between circularly polarized photons and spin by introducing chiral orbit in organic complexes
Authors: Hu Renjie , Qin Wei
Published: February 2022

Spin tunability by circularly polarized photons occurs in an unconnected method, providing more spaces to design memory devices. Here, by involving an artificially fabricated organic chiral structure, we let circularly polarized photons interact with the electron spins of organic materials. The spiral potential field of the chiral structure can endow electrons with additional orbital angular momentum to realize coupling between circularly polarized photons and electron spins. Switching the incident light from linearly to circularly polarized light, while keeping the intensity constant, results in the magnetic field-decreased photoluminescence changing to magnetic field-enhanced photoluminescence. Because the interaction between right-handed circularly polarized photons and chiral lattices is stronger in the fabricated chiral complexes, tuning photoluminescence by a magnetic field is more pronounced under the stimulus of right-handed circularly polarized light. In addition, applying an external bias and changing the temperature of organic chiral complexes are tested to further study the conversion between circularly polarized photons and spins. It is expected that this study could help us to further understand the coupling between spins and circularly polarized photons in organic chiral materials.
Highly selective synthesis of all-carbon tetrasubstituted alkenes by deoxygenative alkenylation of carboxylic acids
Authors: Li Yantao , Shao Qianzhen , He Hengchi , Zhu Chengjian , Xue Xiao-Song , Xie Jin
Published: February 2022

The synthesis of all-carbon tetrasubstituted olefins under mild reaction conditions is challenging because of the inevitable issues including significant steric hindrance and the uncontrolled Z/E stereoselectivity. In this paper, we report the synthesis of all-carbon tetrasubstituted alkenes from readily available carboxylic acids and alkenyl triflates with the synergistic catalysis of cyclo-octa-1,5-diene(tetramethyl-1,4-benzoquinone)nickel and visible light under an air atmosphere, thus avoiding the need for a glovebox or a Schlenk line. A wide range of aromatic carboxylic acids and cyclic and acyclic alkenyl triflates undergo the C-C coupling process smoothly, forming structurally diverse alkenes stereospecifically in moderate to good yields. The practicality of the method is further illustrated by the late-stage modification of complex molecules, the one pot synthesis and gram-scale applications. This is an important step towards the valuable utilization of carboxylic acids, and it also simplifies the experimental operation of metallophotoredox catalysis with moisture sensitive nickel(0) catalysis.
Femtometer-amplitude imaging of coherent super high frequency vibrations in micromechanical resonators
Authors: Shao Lei , Gokhale Vikrant J. , Peng Bo , Song Penghui , Cheng Jingjie , Kuo Justin , Lal Amit , Zhang Wen-Ming , Gorman Jason J.
Published: February 2022

Dynamic measurement of femtometer-displacement vibrations in mechanical resonators at microwave frequencies is critical for a number of emerging high-impact technologies including 5G wireless communications and quantum state generation, storage, and transfer. However, the resolution of continuous-wave laser interferometry, the method most commonly used for imaging vibration wavefields, has been limited to vibration amplitudes just below a picometer at several gigahertz. This is insufficient for these technologies since vibration amplitudes precipitously decrease for increasing frequency. Here we present a stroboscopic optical sampling approach for the transduction of coherent super high frequency vibrations. Phase-sensitive absolute displacement detection with a noise floor of 55 fm/√Hz for frequencies up to 12 GHz is demonstrated, achieving higher bandwidth and significantly lower noise floor simultaneously compared to previous work. An acoustic microresonator with resonances above 10 GHz and displacements smaller than 70 fm is measured using the presented method to reveal complex mode superposition, dispersion, and anisotropic propagation.
Catastrophic slab loss in southwestern Pangea preserved in the mantle and igneous record
Authors: Gianni Guido M. , Navarrete César R.
Published: February 2022

The Choiyoi Magmatic Province represents a major episode of silicic magmatism in southwestern Pangea in the mid-Permian-Triassic, the origin of which remains intensely debated. Here, we integrate plate-kinematic reconstructions and the lower mantle slab record beneath southwestern Pangea that provide clues on late Paleozoic-Mesozoic subducting slab configurations. Also, we compile geochronological information and analyze geochemical data using tectono-magmatic discrimination diagrams. We demonstrate that this magmatic event resulted from a large-scale slab loss. This is supported by a paleogeographic coincidence between a reconstructed 2,800-3,000-km-wide slab gap and the Choiyoi Magmatic Province and geochemical data indicating a slab break-off fingerprint in the latter. The slab break-off event is compatible with Permian paleogeographic modifications in southwestern Pangea. These findings render the Choiyoi Magmatic Province the oldest example of a geophysically constrained slab loss event and open new avenues to assess the geodynamic setting of silicic large igneous provinces back to the late Paleozoic.
Bacterial filamentation as a mechanism for cell-to-cell spread within an animal host
Authors: Tran Tuan D. , Ali Munira Aman , Lee Davin , Félix Marie-Anne , Luallen Robert J.
Published: February 2022

Intracellular pathogens are challenged with limited space and resources while replicating in a single host cell. Mechanisms for direct invasion of neighboring host cells have been discovered in cell culture, but we lack an understanding of how bacteria directly spread between host cells in vivo. Here, we describe the discovery of intracellular bacteria that use filamentation for spreading between the intestinal epithelial cells of a natural host, the rhabditid nematode Oscheius tipulae. The bacteria, which belong to the new species Bordetella atropi, can infect the nematodes following a fecal-oral route, and reduce host life span and fecundity. Filamentation requires UDP-glucose biosynthesis and sensing, a highly conserved pathway that is used by other bacteria to detect rich conditions and inhibit cell division. Our results indicate that B. atropi uses a pathway that normally regulates bacterial cell size to trigger filamentation inside host cells, thus facilitating cell-to-cell dissemination.
A neomorphic variant in SP7 alters sequence specificity and causes a high-turnover bone disorder
Authors: Lui Julian C. , Raimann Adalbert , Hojo Hironori , Dong Lijin , Roschger Paul , Kikani Bijal , Wintergerst Uwe , Fratzl-Zelman Nadja , Jee Youn Hee , Haeusler Gabriele , Baron Jeffrey
Published: February 2022

SP7/Osterix is a transcription factor critical for osteoblast maturation and bone formation. Homozygous loss-of-function mutations in SP7 cause osteogenesis imperfecta type XII, but neomorphic (gain-of-new-function) mutations of SP7 have not been reported in humans. Here we describe a de novo dominant neomorphic missense variant (c.926 C > G:p.S309W) in SP7 in a patient with craniosynostosis, cranial hyperostosis, and long bone fragility. Histomorphometry shows increased osteoblasts but decreased bone mineralization. Mice with the corresponding variant also show a complex skeletal phenotype distinct from that of Sp7-null mice. The mutation alters the binding specificity of SP7 from AT-rich motifs to a GC-consensus sequence (typical of other SP family members) and produces an aberrant gene expression profile, including increased expression of Col1a1 and endogenous Sp7, but decreased expression of genes involved in matrix mineralization. Our study identifies a pathogenic mechanism in which a mutation in a transcription factor shifts DNA binding specificity and provides important in vivo evidence that the affinity of SP7 for AT-rich motifs, unique among SP proteins, is critical for normal osteoblast differentiation.
Leveraging deep phenotyping from health check-up cohort with 10,000 Korean individuals for phenome-wide association study of 136 traits
Authors: Choe Eun Kyung , Shivakumar Manu , Verma Anurag , Verma Shefali Setia , Choi Seung Ho , Kim Joo Sung , Kim Dokyoon
Published: February 2022

The expanding use of the phenome-wide association study (PheWAS) faces challenges in the context of using International Classification of Diseases billing codes for phenotype definition, imbalanced study population ethnicity, and constrained application of the results in research. We performed a PheWAS utilizing 136 deep phenotypes corroborated by comprehensive health check-ups in a Korean population, along with trans-ethnic comparisons through using the UK Biobank and Biobank Japan Project. Meta-analysis with Korean and Japanese population was done. The PheWAS associated 65 phenotypes with 14,101 significant variants (P < 4.92 × 10–10). Network analysis, visualization of cross-phenotype mapping, and causal inference mapping with Mendelian randomization were conducted. Among phenotype pairs from the genotype-driven cross-phenotype associations, we evaluated penetrance in correlation analysis using a clinical database. We focused on the application of PheWAS in order to make it robust and to aid the derivation of biological meaning post-PheWAS. This comprehensive analysis of PheWAS results based on a health check-up database will provide researchers and clinicians with a panoramic overview of the networks among multiple phenotypes and genetic variants, laying groundwork for the practical application of precision medicine.
Magnetization–structure–composition phase diagram mapping in Co-Fe-Ni alloys using diffusion multiples and scanning Hall probe microscopy
Authors: Shamsutdinov Girfan , Zhao Peng , Bhattiprolu Sreenivas , Zhao Ji-Cheng , Nadgorny Boris
Published: February 2022

Transition metal alloys are essential for magnetic recording, memory, and new materials-by-design applications. Saturation magnetization in these alloys have previously been measured by conventional techniques, for a limited number of samples with discrete compositions, a laborious and time-consuming effort. Here, we propose a method to construct complete saturation magnetization diagrams for Co–Fe–Ni alloys using scanning Hall probe microscopy (SHPM). A composition gradient was created by the diffusion multiple technique, generating a full combinatorial materials library with an identical thermal history. The composition and crystallographic phases of the alloys were identified by integrated energy dispersive X-ray spectroscopy and electron backscatter diffraction. “Pixel-by-pixel” perpendicular components of the magnetic field were converted into maps of saturation magnetization using the inversion matrix technique. The saturation magnetization dependence for the binary alloys was consistent with the Slater-Pauling behavior. By using a significantly denser data point distribution than previously available, the maximum of the Slater-Pauling curve for the Co–Fe alloys was identified at ~ 32 at% of Co. By mapping the entire ternary diagram of Co–Fe–Ni alloys recorded in a single experiment, we have demonstrated that SHPM—in concert with the combinatorial approach—is a powerful high-throughput characterization tool, providing an effective metrology platform to advance the search for new magnetic materials.
A problem of proportions: estimates of metabolic associated fatty liver disease and liver fibrosis in Australian adults in the nationwide 2012 AusDiab Study
Authors: Farrell Ann M. , Magliano Dianna J. , Shaw Jonathan E. , Thompson Alexander J. , Croagh Catherine , Ryan Marno C. , Howell Jessica
Published: February 2022

Metabolic Associated Fatty Liver Disease (MAFLD) is the most common cause of liver disease in Australia, but prevalence data are limited. We aimed to describe the frequency of alanine aminotransferase (ALT) elevation, and MAFLD within a large prospective Australian cohort. Cross-sectional analysis of the 2012 survey of the Australian Diabetes, Obesity and Lifestyle (AusDiab) study which included 4747 Australian adults (aged 34–97 yrs) was performed. Frequency of ALT elevation (men ≥ 40 IU/L, women ≥ 30 IU/L) and MAFLD (Fatty Liver Index (FLI) > 60 alongside metabolic risk factors) was determined and risk of advanced fibrosis stratified using the BARD score. Elevated ALT was found in 13% of the cohort, including 22% of people with diabetes, 18% with obesity, and 17% with the metabolic syndrome. 37% of the cohort had MAFLD, and those with MAFLD were more likely to be older (OR 1.01 per 1 year (95% CI 1.00–1.02)), male (OR 1.37 (95% CI 1.17–1.59)), have ALT elevation (OR 3.21 (95% CI 2.59–3.99)), diabetes (OR 3.39 (95% CI 2.61–4.39)), lower HDL-C (OR 0.15 per 1 mmol/L (95% CI 0.12–0.19)), higher diastolic blood pressure (OR 1.05 per 10 mmHg (95% CI 1.05–1.06)), a sedentary lifestyle (OR 1.99 (95% CI 1.59–2.50)) and less likely to have tertiary education (OR 0.81 (95% CI 0.7–0.94) compared to those without MAFLD. Of those with MAFLD, 61% had a BARD score suggesting risk of advanced fibrosis and 22% had an elevated ALT. Over 10% of this Australian cohort had elevated ALT, and 37% had MAFLD, with many at risk for advanced fibrosis.
Temporal motifs in patent opposition and collaboration networks
Authors: Liu Penghang , Masuda Naoki , Kito Tomomi , Sarıyüce Ahmet Erdem
Published: February 2022

Patents are intellectual properties that reflect innovative activities of companies and organizations. The literature is rich with the studies that analyze the citations among the patents and the collaboration relations among companies that own the patents. However, the adversarial relations between the patent owners are not as well investigated. One proxy to model such relations is the patent opposition, which is a legal activity in which a company challenges the validity of a patent. Characterizing the patent oppositions, collaborations, and the interplay between them can help better understand the companies’ business strategies. Temporality matters in this context as the order and frequency of oppositions and collaborations characterize their interplay. In this study, we construct a two-layer temporal network to model the patent oppositions and collaborations among the companies. We utilize temporal motifs to analyze the oppositions and collaborations from structural and temporal perspectives. We first characterize the frequent motifs in patent oppositions and investigate how often the companies of different sizes attack other companies. We show that large companies tend to engage in opposition with multiple companies. Then we analyze the temporal interplay between collaborations and oppositions. We find that two adversarial companies are more likely to collaborate in the future than two collaborating companies oppose each other in the future.
One-way flow over uniformly heated U-shaped bodies driven by thermal edge effects
Authors: Taguchi Satoshi , Tsuji Tetsuro
Published: February 2022

The thermal edge flow is a gas flow typically induced near a sharp edge (or a tip) of a uniformly heated (or cooled) flat plate. This flow has potential applicability as a nonmechanical pump or flow controller in microelectromechanical systems (MEMS). However, it has a shortcoming: the thermal edge flows from each edge cancel out, resulting in no net flow. In this study, to circumvent this difficulty, the use of a U-shaped body is proposed and is examined numerically. More specifically, a rarefied gas flow over an array of U-shaped bodies, periodically arranged in a straight channel, is investigated using the direct simulation Monte-Carlo (DSMC) method. The U-shaped bodies are kept at a uniform temperature different from that of the channel wall. Two types of U-shaped bodies are considered, namely, a square-U shape and a round-U shape. It is demonstrated that a steady one-way flow is induced in the channel for both types. The mass flow rate is obtained for a wide range of the Knudsen numbers, i.e., the ratio of the molecular mean free path to the characteristic size of the U-shape body. For the square-U type, the direction of the overall mass flow is in the same direction for the entire range of the Knudsen numbers investigated. For the round-U type, the direction of the total mass flux is reversed when the Knudsen number is moderate or larger. This reversal of the mass flow rate is attributed to a kind of thermal edge flow induced over the curved part of the round-U-shaped body, which overwhelms the thermal edge flow induced near the tip. The force acting on each of the bodies is also investigated.
Refined characterization of circulating tumor DNA through biological feature integration
Authors: Markus Havell , Chandrananda Dineika , Moore Elizabeth , Mouliere Florent , Morris James , Brenton James D. , Smith Christopher G. , Rosenfeld Nitzan
Published: February 2022

Circulating tumor DNA (ctDNA) in blood plasma is present at very low concentrations compared to cell-free DNA (cfDNA) of non-tumor origin. To enhance ctDNA detection, recent studies have been focused on understanding the non-random fragmentation pattern of cfDNA. These studies have investigated fragment sizes, genomic position of fragment end points, and fragment end motifs. Although these features have been described and shown to be aberrant in cancer patients, there is a lack of understanding of how the individual and integrated analysis of these features enrich ctDNA fraction and enhance ctDNA detection. Using whole genome sequencing and copy number analysis of plasma samples from 5 high grade serious ovarian cancer patients, we observed that (1) ctDNA is enriched not only in fragments shorter than mono-nucleosomes (~ 167 bp), but also in those shorter than di-nucleosomes (~ 240–330 bp) (28–159% enrichment). (2) fragments that start and end at the border or within the nucleosome core are enriched in ctDNA (5–46% enrichment). (3) certain DNA motifs conserved in regions 10 bp up- and down- stream of fragment ends (i.e. cleavage sites) could be used to detect tumor-derived fragments (10–44% enrichment). We further show that the integrated analysis of these three features resulted in a higher enrichment of ctDNA when compared to using fragment size alone (additional 7–25% enrichment after fragment size selection). We believe these genome wide features, which are independent of genetic mutational changes, could allow new ways to analyze and interpret cfDNA data, as significant aberrations of these features from a healthy state could improve its utility as a diagnostic biomarker.
Genetic studies of fall armyworm indicate a new introduction into Africa and identify limits to its migratory behavior
Authors: Nagoshi Rodney N. , Goergen Georg , Koffi Djima , Agboka Komi , Adjevi Anani Kossi Mawuko , Du Plessis Hannalene , Van den Berg Johnnie , Tepa-Yotto Ghislain T. , Winsou Jeannette K. , Meagher Robert L. , Brévault Thierry
Published: February 2022

The fall armyworm, Spodoptera frugiperda (J.E. Smith) is native to the Americas and a major pest of corn and several other crops of economic importance. The species has characteristics that make it of particular concern as an invasive pest, including broad host range, long-distance migration behavior, and a propensity for field-evolved pesticide resistance. The discovery of fall armyworm in western Africa in 2016 was followed by what was apparently a remarkably rapid spread throughout sub-Saharan Africa by 2018, causing economic damage estimated in the tens of billions USD and threatening the food security of the continent. Understanding the history of the fall armyworm invasion of Africa and the genetic composition of the African populations is critical to assessing the risk posed to different crop types, the development of effective mitigation strategies, and to make Africa less vulnerable to future invasions of migratory moth pests. This paper tested and expanded on previous studies by combining data from 22 sub-Saharan nations during the period from 2016 to 2019. The results support initial descriptions of the fall armyworm invasion, including the near absence of the strain that prefers rice, millet, and pasture grasses, while providing additional evidence that the magnitude and extent of FAW natural migration on the continent is more limited than expected. The results also show that a second entry of fall armyworm likely occurred in western Africa from a source different than that of the original introduction. These findings indicate that western Africa continues to be at high risk of future introductions of FAW, which could complicate mitigation efforts.
A functionalized graphene oxide with improved cytocompatibility for stimuli-responsive co-delivery of curcumin and doxorubicin in cancer treatment
Authors: Yaghoubi Fatemeh , Motlagh Najmeh Sadat Hosseini , Naghib Seyed Morteza , Haghiralsadat Fateme , Jaliani Hossein Zarei , Moradi Ali
Published: February 2022

Nowadays, the usage of nanoparticles in various fields such as drug delivery, attracts the attention of many researchers in the treatment of cancers. Graphene oxide (GO) is one of the novel drug delivery systems which is used broadly owing to its unique features. In this survey, doxorubicin (DOX) was accompanied by natural medicine, curcumin (CUR), to diminish its side effects and enhance its efficiency. Cytotoxicity assay in human gastric cancer (AGS), prostate cancer (PC3), and ovarian cancer (A2780), was evaluated. Also, the uptake of DOX and CUR into cells, was assessed using a fluorescence microscope. Moreover, real-time PCR was applied for the evaluation of the expression of RB1 and CDK2 genes, which were involved in the cell cycle. In both separate and simultaneous forms, DOX and CUR were loaded with high efficiency and the release behavior of both drugs was pH-sensitive. The higher release rate was attained at pH 5.5 and 42 °C for DOX (80.23%) and CUR (13.06), respectively. The intensity of fluorescence in the free form of the drugs, was higher than the loaded form. In the same concentration, the free form of CUR and DOX were more toxic than the loaded form in all cell lines. Also, free drugs showed more impact on the expression of RB1 and CDK2 genes. Co-delivery of CUR and DOX into the mentioned cell lines, was more effective than the free form of CUR and DOX due to its lower toxicity to normal cells.
Identification and validation of an autophagy-related gene signature for predicting prognosis in patients with esophageal squamous cell carcinoma
Authors: Shi Xiaobo , Li You , Pan Shupei , Liu Xiaoxiao , Ke Yue , Guo Wei , Wang Yuchen , Ruan Qinli , Zhang Xiaozhi , Ma Hongbing
Published: February 2022

Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Since autophagy-related genes (ARGs) play a key role in the pathogenesis of many tumors, including ESCC, the purpose of this study is to establish an autophagy-related prognostic risk signature based on ARGs expression profile, and to provide a new method for improving prediction of clinical outcomes. We obtained the expression profiles of ESCC from public data (GSE53625) and extracted the portion of ARGs. Differential expression analysis and enrichment analysis were performed to confirm abnormal autophagy-related biological functions. Univariate and multivariate Cox regression analyses were performed on RNA microarray data (GSE53625) to construct a prognostic risk signature associated with autophagy. The performance of the model was evaluated by receiver operating characteristic (ROC) analysis, survival analysis and Brier score. The model was subjected to bootstrap internal validation. The potential molecular mechanism of gene signature was explored by gene set enrichment analysis (GSEA). Spearman correlation coefficient examined the correlation between risk score and immune status and ferroptosis. The expression levels of genes and proteins were validated by qRT-PCR and immunohistochemistry in ESCC cell lines and ESCC tissues. We constructed and validated an autophagy-related prognostic risk signature in 179 patients with ESCC. The long-term survival of patients in high-risk group was lower than that in low-risk group (log-rank, P value < 0.001). ROC analysis and Brier score confirmed the reliability of the signature. GSEA results showed significant enrichment of cancer- and autophagy-related signaling pathways in the high-risk ESCC patients and immunoregulatory signaling pathways in the low-risk ESCC patients. Correlation analysis showed that the risk signature can effectively predict the effect of immunotherapy. About 33.97% (71/209) ferroptosis-related genes were significantly correlated with risk scores. Finally, the results of qRT-PCR and immunohistochemistry experiments were consistent with bioinformatics analysis. In brief, we constructed a novel autophagy-related gene signature (VIM, UFM1, TSC2, SRC, MEFV, CTTN, CFTR and CDKN1A), which could improve the prediction of clinical outcomes in patients with ESCC.
NPY1R exerts inhibitory action on estradiol-stimulated growth and predicts endocrine sensitivity and better survival in ER-positive breast cancer
Authors: Bhat Raksha , Thangavel Hariprasad , Abdulkareem Noor Mazin , Vasaikar Suhas , De Angelis Carmine , Bae Leon , Cataldo Maria Letizia , Nanda Sarmistha , Fu Xiaoyong , Zhang Bing , Schiff Rachel , Trivedi Meghana V.
Published: February 2022

G Protein-Coupled Receptors (GPCRs) represent the largest superfamily of cell-surface proteins. However, the expression and function of majority of GPCRs remain unexplored in breast cancer (BC). We interrogated the expression and phosphorylation status of 398 non-sensory GPCRs using the landmark BC proteogenomics and phosphoproteomic dataset from The Cancer Genome Atlas. Neuropeptide Y Receptor Y1 (NPY1R) gene and protein expression were significantly higher in Luminal A tumors versus other BC subtypes. The trend of NPY1R gene, protein, and phosphosite (NPY1R-S368s) expression was decreasing in the order of Luminal A, Luminal B, Basal, and human epidermal growth factor receptor 2 (HER2) subtypes. NPY1R gene expression increased in response to estrogen and reduced with endocrine therapy in estrogen receptor-positive (ER+) BC cells and xenograft models. Conversely, NPY1R expression decreased in ER+ BC cells resistant to endocrine therapies (estrogen deprivation, tamoxifen, and fulvestrant) in vitro and in vivo. NPY treatment reduced estradiol-stimulated cell growth, which was reversed by NPY1R antagonist (BIBP-3226) in ER+ BC cells. Higher NPY1R gene expression predicted better relapse-free survival and overall survival in ER+ BC. Our study demonstrates that NPY1R mediates the inhibitory action of NPY on estradiol-stimulated growth of ER+ BC cells, and its expression serves as a biomarker to predict endocrine sensitivity and survival in ER+ BC patients.
Effects of white matter hyperintensities distribution and clustering on late-life cognitive impairment
Authors: Jiménez-Balado Joan , Corlier Fabian , Habeck Christian , Stern Yaakov , Eich Teal
Published: February 2022

White matter hyperintensities (WMH) are a key hallmark of subclinical cerebrovascular disease and are known to impair cognition. Here, we parcellated WMH using a novel system that segments WMH based on both lobar regions and distance from the ventricles, dividing the brain into a coordinate system composed of 36 distinct parcels (‘bullseye’ parcellation), and then investigated the effect of distribution on cognition using two different analytic approaches. Data from a well characterized sample of healthy older adults (58 to 84 years) who were free of dementia were included. Cognition was evaluated using 12 computerized tasks, factored onto 4 indices representing episodic memory, speed of processing, fluid reasoning and vocabulary. We first assessed the distribution of WMH according to the bullseye parcellation and tested the relationship between WMH parcellations and performance across the four cognitive domains. Then, we used a data-driven approach to derive latent variables within the WMH distribution, and tested the relation between these latent components and cognitive function. We observed that different, well-defined cognitive constructs mapped to specific WMH distributions. Speed of processing was correlated with WMH in the frontal lobe, while in the case of episodic memory, the relationship was more ubiquitous, involving most of the parcellations. A principal components analysis revealed that the 36 bullseye regions factored onto 3 latent components representing the natural aggrupation of WMH: fronto-parietal periventricular (WMH principally in the frontal and parietal lobes and basal ganglia, especially in the periventricular region); occipital; and temporal and juxtacortical WMH (involving WMH in the temporal lobe, and at the juxtacortical region from frontal and parietal lobes). We found that fronto-parietal periventricular and temporal & juxtacortical WMH were independently associated with speed of processing and episodic memory, respectively. These results indicate that different cognitive impairment phenotypes might present with specific WMH distributions. Additionally, our study encourages future research to consider WMH classifications using parcellations systems other than periventricular and deep localizations.
Impaired neutrophil extracellular trap formation in β-thalassaemia/HbE
Authors: Thubthed Rattanawan , Siriworadetkun Sirikwan , Paiboonsukwong Kittiphong , Fucharoen Suthat , Pattanapanyasat Kovit , Vadolas Jim , Svasti Saovaros , Chaichompoo Pornthip
Published: February 2022

Neutrophil dysfunction contributes to a high susceptibility to severe bacterial infection which is a leading cause of morbidity and mortality in β-thalassaemia/HbE, especially in splenectomised patients. This study demonstrated another abnormality of neutrophil function, namely neutrophil extracellular trap (NET) formation in splenectomised and non-splenectomised β-thalassaemia/HbE patients who had iron overload. A classification system of morphological NET formation using confocal microscopy was developed, and samples were categorized into early and late phases which were subdivided into web-like and non-web structures. At baseline, neutrophils from non-splenectomised patients (58 ± 4%) and splenectomised patients (65 ± 3%) had higher early phase NETs than those from normal subjects (33 ± 1%). As a mimic of iron overload and infection, haemin/PMA/LPS treatment led to a significant reduction of early NETs and an increase of late NETs in neutrophils from normal and non-splenectomised patients. Interestingly, neutrophils from splenectomised patients had impaired development of late NETs. This suggests that during infection bacteria might not be trapped and may spread from the site of infection resulting in higher susceptibility to severe bacterial infection in splenectomised patients.
Enantioselective synthesis of cis-hexahydro-γ-carboline derivatives via Ir-catalyzed asymmetric hydrogenation
Authors: Zheng Long-Sheng , Yin Congcong , Wang Fangyuan , Chen Gen-Qiang , Zhang Xumu
Published: February 2022

A novel synthetic protocol was developed for the construction of chiral cis-hexahydro-γ-carboline derivatives through Ir/ZhaoPhos-catalyzed asymmetric hydrogenation with up to 99% yield, up to > 99 : 1 dr, and up to 99% ee.
Enhancing cellular sulfane sulfur through β-glycosidase-activated persulfide donors: mechanistic insights and oxidative stress mitigation
Authors: Bora Prerona , Sathian Manjima B. , Chakrapani Harinath
Published: February 2022

A new cell-permeable persulfide and hydrogen sulfide donor that protects cells from oxidative stress is reported.
Dynamic signatures of electronically nonadiabatic coupling in sodium hydride: a rigorous test for the symmetric quasi-classical model applied to realistic, ab initio electronic states in the adiabatic representation
Authors: Talbot Justin J. , Head-Gordon Martin , Miller William H. , Cotton Stephen J.
Published: February 2022

Wave packet dynamics and the symmetric quasi-classical approach are employed to study the nonadiabatic dynamics of gas phase sodium hydride.
Understanding the effect of mechanical strains on the catalytic activity of transition metals
Authors: Martínez-Alonso Carmen , Guevara-Vela José Manuel , LLorca Javier
Published: February 2022

The effect of mechanical strains on the volcano plot for the HER and for the ORR was determined from first principles calculations for thirteen transition metals. The lines stand for the variation in the catalytic activity of each metal as a function of the applied elastic strain.
Solving the structure of “single-atom” catalysts using machine learning – assisted XANES analysis
Authors: Xiang Shuting , Huang Peipei , Li Junying , Liu Yang , Marcella Nicholas , Routh Prahlad K. , Li Gonghu , Frenkel Anatoly I.
Published: February 2022

Quantitative structural information of the single-atom catalyst was obtained by machine learning-assisted XANES data analysis.
Can a molecular switch exist in both superalkali electride and superalkalide forms?
Authors: Yi Xiu-Guang , Wang Yin-Feng , Zhang Hua-Rong , Cai Jin-Hua , Liu Xue-Xia , Li Jia , Wang Zhi-Jun , Bai Fu-Quan , Li Zhi-Ru
Published: February 2022

The superalkali electride e−⋯Li3+–PHY and superalkalide Liδ−–Li2(1–δ)−–PHY−show a good switchable effect.
Strain-induced bandgap engineering in CsGeX3 (X = I, Br or Cl) perovskites: insights from first-principles calculations
Authors: Xiang Guangbiao , Wu Yanwen , Zhang Man , Leng Jiancai , Cheng Chen , Ma Hong
Published: February 2022

The electronic structures, DOSs, carrier transport properties, and optical properties of CsGeX3 (X = I, Br or Cl) perovskites under triaxial strains of −4% to 4% were investigated based on density functional theory.
Surface ligands enhance the catalytic activity of supported Au nanoparticles for the aerobic α-oxidation of amines to amides
Authors: Chatterjee Puranjan , Wang Hsin , Manzano J. Sebastián , Kanbur Uddhav , Sadow Aaron D. , Slowing Igor I.
Published: February 2022

Surface ligands control the electronic properties of supported Au nanoparticles and thereby regulate their catalytic activity for the selective aerobic oxidation of amines to amides.
Application of 3D mullite fiber matrix as a lithiophilic interlayer in lithium metal anodes
Authors: Fan Jinxin , Tian Yuan , Wang Cheng
Published: February 2022

The lithiophilic 3D mullite fiber sheet can guide and accommodate the lithium deposition inside the porous structure avoiding the accumulation of dead Li, thus promoting cell lifetime and stabilizing the cycling behavior.
Spatial distribution and biogeochemistry of redox active species in arctic sedimentary porewaters and seeps
Authors: Hudson Jeffrey M. , Michaud Alexander B. , Emerson David , Chin Yu-Ping
Published: February 2022

Schematic showing how voltammetric microelectrodes were used to profile arctic lake sediments, where different locations contained different distributions of redox-active species.
Thermo-responsive polymer–black phosphorus nanocomposites for NIR-triggered bacterial capture and elimination
Authors: Deng Shuo , Wang Dongsheng , Xiong Zhiqiang , Zhang Siyu , Li Dengyu , Zeng Jin , Zhang Xuejiao , Zhao Qing
Published: February 2022

BP–PNIPAM can capture and eliminate bacteria under NIR light irradiation through hydrophilic-to-hydrophobic phase transition and hyperthermia.
In vitro dynamic digestion and anti-fatigue effects of wheat embryo albumin
Authors: Li Xiao-Xiao , Liao Ai-Mei , Dong Yu-Qi , Hou Yinchen , Pan Long , Li Chen , Zheng Shuai-Nan , Yuan Yong-Jian , Zhang Jie , Huang Ji-Hong
Published: February 2022

Wheat embryo albumin demonstrates attractive anti-fatigue and health benefits in mice.