bluuebunny/crossref_metadata_2025 huggingface dataset:
An $$L^2$$ approach to viscous flow in the half space with free elastic surface
Authors: Farwig Reinhard , Schmidt Andreas
Published: September 2021

We consider a linearized fluid-structure interaction problem, namely the flow of an incompressible viscous fluid in the half space $${\mathbb {R}}^n_+$$

R

+
n

such that on the lower boundary a function h satisfying an undamped Kirchhoff-type plate equation is coupled to the flow field. Originally, h describes the height of an underlying nonlinear free surface problem. Since the plate equation contains no damping term, this article uses $$L^2$$

L
2

-theory yielding the existence of strong solutions on finite time intervals in the framework of homogeneous Bessel potential spaces. The proof is based on $$L^2$$

L
2

-Fourier analysis and also deals with inhomogeneous boundary data of the velocity field on the “free boundary” $$x_n=0$$

x
n

=
0

.
Can e-commerce mitigate the negative impact of COVID-19 on international trade?
Authors: Hayakawa Kazunobu , Mukunoki Hiroshi , Urata Shujiro
Published: September 2021

This study aims to empirically investigate the role of E-commerce (EC) on the trade impacts of COVID-19. To this end, we estimate gravity equations for bilateral trade among 34 reporting countries and their 145 partner countries during January–August in 2019 and 2020. Our major findings can be summarized as follows. A larger number of confirmed cases or deaths in both importing and exporting countries significantly decrease international trade. However, we found that EC development in importing countries contributes to mitigating this negative effect of COVID-19 on trade while that in exporting countries does not. These results are robust for our use of multiple measures of EC development.
Detection of Fraud in a Clinical Trial Using Unsupervised Statistical Monitoring
Authors: de Viron Sylviane , Trotta Laura , Schumacher Helmut , Lomp Hans-Juergen , Höppner Sebastiaan , Young Steve , Buyse Marc
Published: September 2021

Background

A central statistical assessment of the quality of data collected in clinical trials can improve the quality and efficiency of sponsor oversight of clinical investigations.

Material and Methods

The database of a large randomized clinical trial with known fraud was reanalyzed with a view to identifying, using only statistical monitoring techniques, the center where fraud had been confirmed. The analysis was conducted with an unsupervised statistical monitoring software using mixed-effects statistical models. The statistical analyst was unaware of the location, nature, and extent of the fraud.

Results

Five centers were detected as atypical, including the center with known fraud (which was ranked 2). An incremental analysis showed that the center with known fraud could have been detected after only 25% of its data had been reported.

Conclusion

An unsupervised approach to central monitoring, using mixed-effects statistical models, is effective at detecting centers with fraud or other data anomalies in clinical trials.
Understanding Coronavirus
Authors: Rabadan Raul
Published: September 2021

Since the identification of the first cases of the coronavirus in December 2019, there has been a significant amount of confusion regarding the origin and spread of the so-called 'coronavirus', SARS-CoV-2, and the cause of the disease COVID-19. Conflicting messages from the media and officials across different countries and organizations, the abundance of disparate sources of information, unfounded conspiracy theories on the origins of the virus, unproven therapies, and inconsistent public health measures, have all served to increase anxiety in the population. Where did the virus come from? How is it transmitted? How does it cause disease? Is it like flu? What is a pandemic? In this concise and accessible introduction, a leading expert provides answers to these commonly asked questions. This revised and updated edition now also covers how the virus mutates, how important these mutations are, how vaccines work, and what we can expect in the near and long-term future.
Virtual Paleontology
Authors: Bauer Jennifer E. , Rahman Imran A.
Published: September 2021

Imaging and visualizing fossils in three dimensions with tomography is a powerful approach in paleontology. Here, the authors introduce select destructive and non-destructive tomographic techniques that are routinely applied to fossils and review how this work has improved our understanding of the anatomy, function, taphonomy, and phylogeny of fossil echinoderms. Building on this, this Element discusses how new imaging and computational methods have great promise for addressing long-standing paleobiological questions. Future efforts to improve the accessibility of the data underlying this work will be key for realizing the potential of this virtual world of paleontology.
MicroRNAs regulating SOX2 in cancer progression and therapy response
Authors: Mirzaei Sepideh , Saebfar Hamidreza , Gholami Mohammad Hossein , Hashemi Farid , Zarrabi Ali , Zabolian Amirhossein , Entezari Maliheh , Hushmandi Kiavash , Samarghandian Saeed , Aref Amir Reza , Ashrafizadeh Milad , Khan Haroon
Published: September 2021

The proliferation, metastasis and therapy response of tumour cells are tightly regulated by interaction among various signalling networks. The microRNAs (miRNAs) can bind to 3′-UTR of mRNA and down-regulate expression of target gene. The miRNAs target various molecular pathways in regulating biological events such as apoptosis, differentiation, angiogenesis and migration. The aberrant expression of miRNAs occurs in cancers and they have both tumour-suppressor and tumour-promoting functions. On the contrary, SOX proteins are capable of binding to DNA and regulating gene expression. SOX2 is a well-known member of SOX family that its overexpression in different cancers to ensure progression and stemness. The present review focuses on modulatory impact of miRNAs on SOX2 in affecting growth, migration and therapy response of cancers. The lncRNAs and circRNAs can function as upstream mediators of miRNA/SOX2 axis in cancers. In addition, NF-κB, TNF-α and SOX17 are among other molecular pathways regulating miRNA/SOX2 axis in cancer. Noteworthy, anti-cancer compounds including bufalin and ovatodiolide are suggested to regulate miRNA/SOX2 axis in cancers. The translation of current findings to clinical course can pave the way to effective treatment of cancer patients and improve their prognosis.
Direct numerical simulation of convective heat transfer of supercritical pressure in a vertical tube with buoyancy and thermal acceleration effects
Authors: Cao Y.L. , Xu R.N. , Yan J.J. , He S. , Jiang P.X.
Published: September 2021

Supercritical pressure fluids are widely used in heat transfer and energy systems. The benefit of high heat transfer performance and the successful avoidance of phase change from the use of supercritical pressure fluids are well-known, but the complex behaviours of such fluids owing to dramatic thermal property variations pose strong challenges to the design of heat transfer applications. In this paper, the turbulent flow and heat transfer of supercritical pressure

$\textrm {CO}_2$

in a small vertical tube influenced by coupled effects of buoyancy and thermal acceleration are numerically investigated using direct numerical simulation. Both upward and downward flows with an inlet Reynolds number of 3540 and pressure of 7.75 MPa have been simulated and the results are compared with corresponding experimental data. The flow and heat transfer results reveal that under buoyancy and thermal acceleration, the turbulent flow and heat transfer exhibit four developing periods in which buoyancy and thermal acceleration alternately dominate. The results suggest a way to distinguish the dominant factor of heat transfer in different periods and a criterion for heat transfer degradation under the complex coupling of buoyancy and thermal acceleration. An analysis of the orthogonal decomposition and the generative mechanism of turbulent structures indicates that the flow acceleration induces a stretch-to-disrupt mechanism of coherent turbulent structures. The significant flow acceleration can destroy the three-dimensional flow structure and stretch the vortices resulting in dissipation.
Stability of expanding accretion shocks for an arbitrary equation of state
Authors: Huete César , Velikovich Alexander L. , Martínez-Ruiz Daniel , Calvo-Rivera Andrés
Published: September 2021

We present a theoretical stability analysis for an expanding accretion shock that does not involve a rarefaction wave behind it. The dispersion equation that determines the eigenvalues of the problem and the explicit formulae for the corresponding eigenfunction profiles are presented for an arbitrary equation of state and finite-strength shocks. For spherically and cylindrically expanding steady shock waves, we demonstrate the possibility of instability in a literal sense, a power-law growth of shock-front perturbations with time, in the range of$h_c< h<1+2 {\mathcal {M}}_2$, where$h$is the D'yakov-Kontorovich parameter,$h_c$is its critical value corresponding to the onset of the instability and${\mathcal {M}}_2$is the downstream Mach number. Shock divergence is a stabilizing factor and, therefore, instability is found for high angular mode numbers. As the parameter$h$increases from$h_c$to$1+2 {\mathcal {M}}_2$, the instability power index grows from zero to infinity. This result contrasts with the classic theory applicable to planar isolated shocks, which predicts spontaneous acoustic emission associated with constant-amplitude oscillations of the perturbed shock in the range$h_c< h<1+2 {\mathcal {M}}_2$. Examples are given for three different equations of state: ideal gas, van der Waals gas and three-terms constitutive equation for simple metals.
Progressive brain structural abnormality in depression assessed with MR imaging by using causal network analysis
Authors: Han Shaoqiang , Zheng Ruiping , Li Shuying , Liu Liang , Wang Caihong , Jiang Yu , Wen Mengmeng , Zhou Bingqian , Wei Yarui , Pang Jianyue , Li Hengfen , Zhang Yong , Chen Yuan , Cheng Jingliang
Published: September 2021

Background

As a neuroprogressive illness, depression is accompanied by brain structural abnormality that extends to many brain regions. However, the progressive structural alteration pattern remains unknown.

Methods

To elaborate the progressive structural alteration of depression according to illness duration, we recruited 195 never-treated first-episode patients with depression and 130 healthy controls (HCs) undergoing T1-weighted MRI scans. Voxel-based morphometry method was adopted to measure gray matter volume (GMV) for each participant. Patients were first divided into three stages according to the length of illness duration, then we explored stage-specific GMV alterations and the causal effect relationship between them using causal structural covariance network (CaSCN) analysis.

Results

Overall, patients with depression presented stage-specific GMV alterations compared with HCs. Regions including the hippocampus, the thalamus and the ventral medial prefrontal cortex (vmPFC) presented GMV alteration at onset of illness. Then as the illness advanced, others regions began to present GMV alterations. These results suggested that GMV alteration originated from the hippocampus, the thalamus and vmPFC then expanded to other brain regions. The results of CaSCN analysis revealed that the hippocampus and the vmPFC corporately exerted causal effect on regions such as nucleus accumbens, the precuneus and the cerebellum. In addition, GMV alteration in the hippocampus was also potentially causally related to that in the dorsolateral frontal gyrus.

Conclusions

Consistent with the neuroprogressive hypothesis, our results reveal progressive morphological alteration originating from the vmPFC and the hippocampus and further elucidate possible details about disease progression of depression.
Taxonomic scale dependency of Bergmann’s patterns: a cross-scale comparison of hawkmoths and birds along a tropical elevational gradient
Authors: Mungee Mansi , Pandit Rohan , Athreya Ramana
Published: September 2021

Bergmann’s rule predicts a larger body size for endothermic organisms in colder environments. The contrasting results from previous studies may be due to the differences in taxonomic (intraspecific, interspecific and community) and spatial (latitudinal vs elevational) scales. We compared Bergmann’s patterns for endotherms (Aves) and ectotherms (Lepidoptera: Sphingidae) along the same 2.6 km elevational transect in the eastern Himalayas. Using a large data spanning 3,302 hawkmoths (76 morpho-species) and 15,746 birds (245 species), we compared the patterns at the intraspecific (hawkmoths only), interspecific and community scales. Hawkmoths exhibited a positive Bergmann’s pattern at the intraspecific and abundance-weighted community scale. Contrary to this, birds exhibited a strong converse Bergmann’s pattern at interspecific and community scales, both with and without abundance. Overall, our results indicate that incorporation of information on intraspecific variation and/or species relative abundances influences the results to a large extent. The multiplicity of patterns at a single location provides the opportunity to disentangle the relative contribution of individual- and species-level processes by integrating data across multiple nested taxonomic scales for the same taxa. We suggest that future studies of Bergmann’s patterns should explicitly address taxonomic and spatial scale dependency, with species relative abundance and intraspecific trait variation as essential ingredients especially at short elevational scales.
L2 GRIT
Authors: Elahi Shirvan Majid , Taherian Tahereh , Yazdanmehr Elham
Published: September 2021

Given the longitudinal nature of L2 grit, the use of conventional research methodologies with cross-sectional data to examine the validity of L2 grit scale seems inadequate. The present research was an attempt to extend the domain-specific phase of research on L2 grit, with the pursuit of long-term goals at its core, into a dynamic one. Thus, we adopted a longitudinal confirmatory factor analysis-curve of factors model (LCFA-CFM) approach to trace changes in L2 learners’ grit at different points of time in an EFL course. LCFA-CFM ensures measurement invariance over time, deals with second-order latent variables, takes into account measurement errors, and is capable of assessing interindividual differences. With this in mind, we, first, employed LCFA to test the factor invariance of L2 grit based on a bifactor CFA model over time and, second, used CFM to measure change of L2 grit during an L2 course. To do so, we collected data from 437 adult EFL learners in Iran in four time phases using the L2 grit scale and analyzed them using Mplus 7.4. The model fit was accepted and invariance of the latent factor of L2 grit was confirmed over time. Also, the negative covariance between initial level of L2 grit and its rate of change over time (second-order latent variables) suggested a steeper increase in the construct over time for learners with lower initial scores of the construct. That is, L2 learners who started at a higher level of L2 grit experienced less change in L2 grit over time. The LCFA-CFM ensured that the factor structure of L2 grit is invariant over time and provided insights into how L2 grit changes over an L2 course.
Modelling Mandarin speakers’ phonotactic knowledge
Authors: Gong Shuxiao , Zhang Jie
Published: September 2021

This paper investigates the nature of native Mandarin Chinese speakers’ phonotactic knowledge via an experimental study and formal modelling of the experimental results. Results from a phonological well-formedness judgement experiment suggest that Mandarin speakers’ phonotactic knowledge is sensitive not only to lexical statistics, but also to grammatical principles such as systematic and accidental phonotactic constraints, allophonic restrictions and segment–tone co-occurrence restrictions. We employ the UCLA Phonotactic Learner to model Mandarin speakers’ phonotactic knowledge, and compare the model's well-formedness predictions with speakers’ judgements. The disparity between the model's predictions and the well-formedness ratings from the experiment indicates that grammatical principles and the lexicon are still not sufficient to explain all of the variations in the speakers’ judgements. We argue that multiple biases, such as naturalness bias, allophony bias and suprasegmental bias, are effective during phonotactic learning.
Challenges on the effect of cell phone radiation on mammalian embryos and fetuses: a review of the literature
Authors: Mahaldashtian Maryam , Khalili Mohammad Ali , Anbari Fatemeh , Seify Mohammad , Belli Manuel
Published: September 2021

Cell phones operate with a wide range of frequency bands and emit radiofrequency-electromagnetic radiation (RF-EMR). Concern on the possible health hazards of RF-EMR has been growing in many countries because these RF-EMR pulses may be absorbed into the body cells, directly affecting them. There are some in vitro and in vivo animal studies related to the consequences of RF-EMR exposure from cell phones on embryo development and offspring. In addition, some studies have revealed that RF-EMR from cellular phone may lead to decrease in the rates of fertilization and embryo development, as well as the risk of the developmental anomalies, other studies have reported that it does not interfere with in vitro fertilization or intracytoplasmic sperm injection success rates, or the chromosomal aberration rate. Of course, it is unethical to study the effect of waves generated from cell phones on the forming human embryos. Conversely, other mammals have many similarities to humans in terms of anatomy, physiology and genetics. Therefore, in this review we focused on the existing literature evaluating the potential effects of RF-EMR on mammalian embryonic and fetal development.
These Newcomes: William Makepeace Thackeray and Novelistic Particularity
Authors: Gao Timothy
Published: September 2021

Through a sustained close reading of William Makepeace Thackeray's 1855 novel The Newcomes, this essay examines three analogous types of particularity in the novel: the particularity of loved ones in the social network, of fictional persons in the literary work, and of the individual text. Drawing on recent sociological and network readings of Victorian narrative, I argue that Thackeray's plot about relationships in the marriage market is reflected (on the level of form) by the structural relation between characters and text, and (on the level of the reading experience) by the affective engagement of the reader to the novel. As characters encounter problems in replacing old relations (former lovers, deceased spouses, estranged relatives) with new ones, the novel raises analogous questions about the replaceability of characters as textual constructs or fictional persons, and of the novel itself as one experience among multitudes on offer in the nineteenth-century market. A tension between the continual or particular experience of an individual novel and the felt historical pressure of novels en masse registers in the text itself as a formal and narrative problem, one that leads us suggestively toward recent methodological debates about intimate and distant reading.
Seltene Befunde bei der Abklärung von Bauchschmerzen
Authors: Siegrist Véronique , Fontana Enzo , Miftaroski Almir , Precup Mihaela , Egger Bernard
Published: September 2021

Zusammenfassung. Unspezifische Symptome, wie z.B. (Ober-)Bauchschmerzen, sind bei Personen mit chronischen Erkrankungen, insbesondere Adipositas, Typ-2-Diabetes, Hypertonie oder ischämischer Herzerkrankung, manchmal schwierig zu beurteilen. Hier beschreiben wir zwei Fälle von grossen Nebennierentumoren, die erst mehrere Jahre nach dem Auftreten unspezifischer Symptome entdeckt wurden.
CME/Antworten: Traumatisierte Geflüchtete in der Hausarztpraxis – ein Kurzleitfaden
Authors: Schick Matthis
Published: September 2021

Zusammenfassung. Traumatische Erfahrungen, Flucht und das Leben im Exil stellen per se keine Krankheit dar, gehen jedoch mit einem erhöhten psychischen Erkrankungsrisiko einher. Die Hausarztpraxis bleibt angesichts des Mangels an spezialisierten Therapieplätzen oft die einzige Behandlungsstelle für traumatisierte Geflüchtete. Besonders herausfordernd ist die Kombination von komplexen Beschwerdebildern, mehrdimensionalen psychosozialen Belastungssituationen und erschwerten Behandlungsbedingungen, welche im dichten Praxisalltag betriebswirtschaftlichen und organisatorischen Grenzen gegenüberstehen. Im Artikel werden Empfehlungen für den Umgang mit dieser heterogenen Patientengruppe diskutiert.
Interventional Reperfusion Strategies for Acute Pulmonary Embolism
Authors: Draxler Dominik F. , Stortecky Stefan
Published: September 2021

Abstract. Acute pulmonary embolism (APE) is a common, potentially life-threatening cardiovascular emergency, and represents the third leading cause of cardiovascular mortality after myocardial infarction and stroke. Risk stratification is important to guide the management of APE, as an early reperfusion strategy is associated with improved clinical outcomes in specific high-risk conditions. Pulmonary artery reperfusion is commonly achieved by systemic intravenous administration of thrombolytic drugs, but catheter-directed thrombolysis (CDThr) and interventional techniques of catheter-based embolectomy provide novel therapeutic approaches with an improved risk-benefit ratio. Future trials will help to determine when to use these different devices in massive or sub-massive APE, and which patient population is likely to benefit from interventional treatment.
CME: Hypokalzämie und Hypoparathyreoidismus CME-Fragen
Authors: Burget Lukas
Published: September 2021

Zusammenfassung. Dyselektrolytämien sind häufig, jedoch nicht auf Anhieb klar zuordenbar. Neben den Hyponatriämien spielen im klinischen Alltag vor allem Hyperkalzämien eine wichtige Rolle. Klinisch nicht weniger relevant sind Hypokalzämien und ein häufig zugrundeliegender primärer Hypoparathyreoidismus, welcher in den meisten Fällen iatrogen – im Rahmen einer Schilddrüsenoperation – bedingt ist. Das therapeutische Ziel umfasst neben einer adäquaten Kalziumeinstellung auch das Miterfassen und -therapieren der Sekundärkomplikationen, falls ein chronischer Hypoparathyreoidismus vorliegt.
Diurnal UT Variation of Low Latitude Geomagnetic Storms Using Six Indices
Authors: Balan N. , Ram S. Tulasi , Manu V. , Zhao Lingxin , Xing Zan‐Yang , Zhang Qing‐He
Published: September 2021

A quasi‐semidiurnal type pattern was observed earlier in the diurnal UT variation of the geomagnetic storms studied using mainly Kyoto Dst (disturbance storm‐time) index. However, the pattern has been argued as apparent due to uneven longitude distribution of the four Dst observatories. Unlike earlier studies, this paper investigates the diurnal UT variation of the storms automatically identified in six available indices including Kyoto Dst, USGS (United States Geological Survey) Dst, SymH (symmetric‐H), RC (ring current), Dcx (corrected extended Dst), and AER (Atmospheric and Environmental Research) in 50, 50, 36, 21, 5, and 7 years, respectively. The indices are derived using 4, 4, 12, 14, and 15 ground observatories (with maximum longitude separations of ∼120°, 120°, 70°, 110°, and 50°) and four DMSP (Defense Meteorology Satellite Program) satellites, respectively. The UT distribution of the storm intensity (minimum value of an index during the storm main phase) in all indices shows a striking quasi‐semidiurnal type variation with maxima around 06–08 UT and 21–23 UT and minima around 03–05 UT and 13–15 UT. Similar quasi‐semidiurnal variation is also observed in the computed values of the main energy input in the ring current. The variation correlates well with the variations of the dipole tilt angles μ and θ involved in the equinoctial hypothesis and Russell‐McPherron (RM) effect, respectively. These observations indicate that the quasi‐semidiurnal variation is real.
Spatial and Temporal Variability in Concentration‐Discharge Relationships at the Event Scale
Authors: Musolff A. , Zhan Q. , Dupas R. , Minaudo C. , Fleckenstein J. H. , Rode M. , Dehaspe J. , Rinke K.
Published: September 2021

The analysis of concentration‐discharge (C‐Q) relationships from low‐frequency observations is commonly used to assess solute sources, mobilization, and reactive transport processes at the catchment scale. High‐frequency concentration measurements are increasingly available and offer additional insights into event‐scale export dynamics. However, only few studies have integrated inter‐annual and event‐scale C‐Q relationships. Here, we analyze high‐frequency measurements of specific conductance (EC), nitrate (NO3‐N) concentrations and spectral absorbance at 254 nm (SAC254, as a proxy for dissolved organic carbon) over a two year period for four neighboring catchments in Germany ranging from more pristine forested to agriculturally managed settings. We apply an integrated method that adds a hysteresis term to the established power law C‐Q model so that concentration intercept, C‐Q slope and hysteresis can be characterized simultaneously. We found that inter‐event variability in C‐Q hysteresis and slope were most pronounced for SAC254 in all catchments and for NO3‐N in forested catchments. SAC254 and NO3‐N event responses in the smallest forested catchment were closely coupled and explainable by antecedent conditions that hint to a common near‐stream source. In contrast, the event‐scale C‐Q patterns of EC in all catchments and of NO3‐N in the agricultural catchment without buffer zones around streams were less variable and similar to the inter‐annual C‐Q relationship indicating a homogeneity of mobilization processes over time. Event‐scale C‐Q analysis thus added key insights into catchment functioning whenever the inter‐annual C‐Q relationship contrasted with event‐scale responses. Analyzing long‐term and event‐scale behavior in one coherent framework helps to disentangle these scattered C‐Q patterns.
Purple Bacteria Fix Nitrogen in Proterozoic-Analogue Lake
Authors: Cutts Elise
Published: September 2021

A new study challenges the assumption that cyanobacteria were the only major nitrogen fixers in the Proterozoic eon.
Impact of Chlorophyll Shading on the Peruvian Upwelling System
Authors: Echevin V. , Hauschildt J. , Colas F. , Thomsen S. , Aumont O.
Published: September 2021

The influence of chlorophyll shading on ocean dynamics has been usually disregarded in eastern boundary upwelling systems modeling studies in spite of their very high primary productivity. Here, we study how this effect impacts on the Peru upwelling system using a regional mesoscale‐resolving physical biogeochemical coupled model. We show that the shading effect leads to a surface cooling of up to 1°C on the shelf due to subsurface cooling of the source waters during their transit toward the shelf. The shading effect leads to a more realistic subsurface stratification, a slowdown of the alongshore currents, and a shoaling of the oxycline. Impacts on the regional model biases show that the shading effect needs to be taken into account in both physical and coupled physical‐biogeochemical regional models of upwelling systems.
Synergistic Effect of the 25–60‐day Tropical and Midlatitude Intraseasonal Oscillations on the Persistently Severe Yangtze Floods
Authors: Li Jianying , Zhai Panmao , Mao Jiangyu , Song Lili , Xiao Qingyao
Published: September 2021

Significant 25–60‐day intraseasonal oscillations (ISOs) in rainfall over the middle‐lower reaches of the Yangtze River (MLYR) are found for eight summers during 1979–2020. These 25–60‐day ISOs of MLYR rainfall account for 66.7% of persistently severe floods (PSFs) during 1979–2020, indicating their major role in inducing PSFs and the potential for extended‐range forecasting of PSFs. The 25–60‐day ISO in MLYR rainfall results from the synergistic effect of tropical and midlatitude ISOs. During the eight identified summers, more barotropic energy is transferred from summer‐mean to 25–60‐day circulation, thus forming a midlatitude ISO wave train, which cooperates with the tropical ISO in triggering twin vertical cells. Phase locking of ascending branch from the vertical cell induced by the tropical ISO with that from the reversed vertical cell triggered by the midlatitude ISO brings about the wet phase of 25–60‐day ISO of MLYR rainfall.
Jupiter's Auroral Radio Emissions Observed by Cassini: Rotational Versus Solar Wind Control, and Components Identification
Authors: Zarka P. , Magalhães F. P. , Marques M. S. , Louis C. K. , Echer E. , Lamy L. , Cecconi B. , Prangé R.
Published: September 2021

Reanalyzing Cassini radio observations performed during Jupiter's flyby of 2000–2001, we study the internal (rotational) versus external (solar wind) control of Jupiter's radio emissions, from kilometer to decameter wavelengths, and the relations between the different auroral radio components. For that purpose, we build a database of the occurrence of Jovian auroral radio components bKOM, HOM, and DAM observed by Cassini, and then frequency‐longitude stacked plots of the polarized intensity of these radio components. Comparing the results obtained inbound and outbound, as a function of the Observer's or Sun's longitude, we find that HOM & DAM are dominantly rotation‐modulated (i.e., emitted from searchlight‐like sources fixed in Jovian longitude), whereas bKOM is modulated more strongly by the solar wind than by the rotation (i.e., emitted from sources more active within a given Local Time sector). We propose a simple analytical description of these internal and external modulations and evaluate its main parameters (the amplitude of each control) for HOM + DAM and bKOM. Comparing Cassini and Nançay Decameter Array data, we find that HOM is primarily connected to the decameter emissions originating from the dusk sector of the Jovian magnetosphere. HOM and DAM components form a complex but stable pattern in the frequency‐longitude plane. HOM also seems to be related to the “lesser arcs” identified by Voyager. bKOM consists of a main part above 40 kHz in antiphase with HOM occurrence, and detached patches below 80 kHz in phase with HOM. The frequency‐longitude patterns formed by DAM, HOM and bKOM remain to be modeled.
Distinct amyloid and tau PET signatures are associated with diverging clinical and imaging trajectories in patients with amnestic syndrome of the hippocampal type
Authors: Lagarde Julien , Olivieri Pauline , Tonietto Matteo , Gervais Philippe , Comtat Claude , Caillé Fabien , Bottlaender Michel , Sarazin Marie
Published: September 2021

We aimed to investigate the amyloid and tau PET imaging signatures of patients with amnestic syndrome of the hippocampal type (ASHT) and study their clinical and imaging progression according to their initial PET imaging status. Thirty-six patients with a progressive ASHT and 30 controls underwent a complete neuropsychological assessment, 3 T brain MRI, [11C]-PiB and [18F]-Flortaucipir PET imaging. Subjects were clinically followed-up annually over 2 years, with a second 3 T MRI (n = 27 ASHT patients, n = 28 controls) and tau-PET (n = 20 ASHT patients) at the last visit. At baseline, in accordance with the recent biological definition of Alzheimer’s disease (AD), the AD PET signature was defined as the combination of (i) positive cortical amyloid load, and (ii) increased tau tracer binding in the entorhinal cortices and at least one of the following regions: amygdala, parahippocampal gyri, fusiform gyri. Patients who did not meet these criteria were considered to have a non-AD pathology (SNAP). Twenty-one patients were classified as AD and 15 as SNAP. We found a circumscribed tau tracer retention in the entorhinal cortices and/or amygdala in 5 amyloid-negative SNAP patients. At baseline, the SNAP patients were older and had lower ApoE ε4 allele frequency than the AD patients, but both groups did not differ regarding the neuropsychological testing and medial temporal lobe atrophy. During the 2-year follow-up, the episodic memory and language decline, as well as the temporo-parietal atrophy progression, were more pronounced in the AD sub-group, while the SNAP patients had a more pronounced progression of atrophy in the frontal lobes. Longitudinal tau tracer binding increased in AD patients but remained stable in SNAP patients. At baseline, distinct amyloid and tau PET signatures differentiated early AD and SNAP patients despite identical cognitive profiles characterized by an isolated ASHT and a similar degree of medial temporal atrophy. During the longitudinal follow-up, AD and SNAP patients diverged regarding clinical and imaging progression. Among SNAP patients, tau PET imaging could detect a tauopathy restricted to the medial temporal lobes, which was possibly explained by primary age-related tauopathy.
Identification of HMGCR as the anticancer target of physapubenolide against melanoma cells by in silico target prediction
Authors: Wang Hai-yan , Yu Pian , Chen Xi-sha , Wei Hui , Cao Shi-jie , Zhang Meng , Zhang Yi , Tao Yong-guang , Cao Dong-sheng , Qiu Feng , Cheng Yan
Published: September 2021

Physapubenolide (PB), a withanolide-type compound extracted from the traditional herb Physalis minima L., has been demonstrated to exert remarkable cytotoxicity against cancer cells; however, its molecular mechanisms are still unclear. In this study, we demonstrated that PB inhibited cell proliferation and migration in melanoma cells by inducing cell apoptosis. The anticancer activity of PB was further verified in a melanoma xenograft model. To explore the mechanism underlying the anticancer effects of PB, we carried out an in silico target prediction study, which combined three approaches (chemical similarity searching, quantitative structure-activity relationship (QSAR), and molecular docking) to identify the targets of PB, and found that PB likely targets 3-hydroxy-methylglutaryl CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway, which promotes cancer cell proliferation, migration, and metastasis. We further demonstrated that PB interacted with HMGCR, decreased its protein expression and inhibited the HMGCR/YAP pathway in melanoma cells. In addition, we found that PB could restore vemurafenib sensitivity in vemurafenib-resistant A-375 cells, which was correlated with the downregulation of HMGCR. In conclusion, we demonstrate that PB elicits anticancer action and enhances sensitivity to vemurafenib by targeting HMGCR.
Inflammatory conversion of quiescent osteoblasts by metastatic breast cancer cells through pERK1/2 aggravates cancer-induced bone destruction
Authors: Back Jungho , Nguyen Minh Nam , Li Lu , Lee Saelim , Lee Inkyu , Chen Fancheng , Gillinov Lauren , Chung Yeon-Ho , Alder Kareme D. , Kwon Hyuk-Kwon , Yu Kristin E. , Dussik Christopher M. , Hao Zichen , Flores Michael J. , Kim Yoseph , Ibe Izuchukwu K. , Munger Alana M. , Seo Sung Wook , Lee Francis Y.
Published: September 2021

Disruption of bone homeostasis caused by metastatic osteolytic breast cancer cells increases inflammatory osteolysis and decreases bone formation, thereby predisposing patients to pathological fracture and cancer growth. Alteration of osteoblast function induces skeletal diseases due to the disruption of bone homeostasis. We observed increased activation of pERK1/2 in osteolytic breast cancer cells and osteoblasts in human pathological specimens with aggressive osteolytic breast cancer metastases. We confirmed that osteolytic breast cancers with high expression of pERK1/2 disrupt bone homeostasis via osteoblastic ERK1/2 activation at the bone-breast cancer interface. The process of inflammatory osteolysis modulates ERK1/2 activation in osteoblasts and breast cancer cells through dominant-negative MEK1 expression and constitutively active MEK1 expression to promote cancer growth within bone. Trametinib, an FDA-approved MEK inhibitor, not only reduced breast cancer-induced bone destruction but also dramatically reduced cancer growth in bone by inhibiting the inflammatory skeletal microenvironment. Taken together, these findings suggest that ERK1/2 activation in both breast cancer cells and osteoblasts is required for osteolytic breast cancer-induced inflammatory osteolysis and that ERK1/2 pathway inhibitors may represent a promising adjuvant therapy for patients with aggressive osteolytic breast cancers by altering the shared cancer and bone microenvironment.
Corosolic acid inhibits cancer progression by decreasing the level of CDK19-mediated O-GlcNAcylation in liver cancer cells
Authors: Zhang Congcong , Niu Yongjie , Wang Zhixian , Xu Xin , Li Yan , Ma Lifang , Wang Jiayi , Yu Yongchun
Published: September 2021

Diabetes is an important risk factor for liver cancer, but its mechanism is unknown. Corosolic acid (CA) has been proven to have both hypoglycemic and antitumor effects, so revealing the function of CA can help us understand the relationship between diabetes and liver cancer. In previous studies, we confirmed that CA can effectively inhibit the expression of YAP, an important oncoprotein in HCC cells, and the proliferation of HCC cells. In addition, we also found that O-GlcNAcylation plays an indispensable role in HCC tumorigenesis. However, it is not clear whether CA can inhibit the effect of O-GlcNAcylation on HCC cells. In this study, the antitumor ability of CA was investigated by inhibiting the O-GlcNAcylation level and its corresponding mechanism. The results showed that HG (high glucose) could promote the proliferation of liver cancer cells, while CA could inhibit cell growth under HG conditions and tumor growth in a xenotransplantation model. CA can inhibit the activation of the HBP pathway and reduce the expression of YAP and OGT under HG conditions. Importantly, we found that CA can reduce YAP expression and O-GlcNAcylation by inhibiting the activity of CDK19. Overexpression of CDK19 partially reversed the CA-induced decrease in YAP and O-GlcNAcylation. This is the first evidence that CA can reduce the proliferative capacity of cells with high glucose levels and further inhibit tumor growth by inactivating the CDK19/YAP/O-GlcNAcylation pathway, suggesting that CA is a candidate drug for the development of treatments against diabetes-associated liver cancer.
A harmonized atlas of mouse spinal cord cell types and their spatial organization
Authors: Russ Daniel E. , Cross Ryan B. Patterson , Li Li , Koch Stephanie C. , Matson Kaya J. E. , Yadav Archana , Alkaslasi Mor R. , Lee Dylan I. , Le Pichon Claire E. , Menon Vilas , Levine Ariel J.
Published: September 2021

Single-cell RNA sequencing data can unveil the molecular diversity of cell types. Cell type atlases of the mouse spinal cord have been published in recent years but have not been integrated together. Here, we generate an atlas of spinal cell types based on single-cell transcriptomic data, unifying the available datasets into a common reference framework. We report a hierarchical structure of postnatal cell type relationships, with location providing the highest level of organization, then neurotransmitter status, family, and finally, dozens of refined populations. We validate a combinatorial marker code for each neuronal cell type and map their spatial distributions in the adult spinal cord. We also show complex lineage relationships among postnatal cell types. Additionally, we develop an open-source cell type classifier, SeqSeek, to facilitate the standardization of cell type identification. This work provides an integrated view of spinal cell types, their gene expression signatures, and their molecular organization.
Intrinsic nanostructure induced ultralow thermal conductivity yields enhanced thermoelectric performance in Zintl phase Eu2ZnSb2
Authors: Chen Chen , Feng Zhenzhen , Yao Honghao , Cao Feng , Lei Bing-Hua , Wang Yumei , Chen Yue , Singh David J. , Zhang Qian
Published: September 2021

The Zintl thermoelectric phase Eu2ZnSb2 has a remarkable combination of high mobility and low thermal conductivity that leads to good thermoelectric performance. The key feature of this compound is a crystal structure that has a Zn-site with a 50% occupancy. Here we use comparison of experimental thermal conductivity measurements and first principles thermal conductivity calculations to characterize the thermal conductivity reduction. We find that partial ordering, characterized by local order, but Zn-site disorder on longer scales, leads to an intrinsic nanostructuring induced reduction in thermal conductivity, while retaining electron mobility. This provides a direction for identifying Zintl compounds with ultralow lattice thermal conductivity and good electrical conductivity.
Ionic liquid facilitated melting of the metal-organic framework ZIF-8
Authors: Nozari Vahid , Calahoo Courtney , Tuffnell Joshua M. , Keen David A. , Bennett Thomas D. , Wondraczek Lothar
Published: September 2021

Hybrid glasses from melt-quenched metal-organic frameworks (MOFs) have been emerging as a new class of materials, which combine the functional properties of crystalline MOFs with the processability of glasses. However, only a handful of the crystalline MOFs are meltable. Porosity and metal-linker interaction strength have both been identified as crucial parameters in the trade-off between thermal decomposition of the organic linker and, more desirably, melting. For example, the inability of the prototypical zeolitic imidazolate framework (ZIF) ZIF-8 to melt, is ascribed to the instability of the organic linker upon dissociation from the metal center. Here, we demonstrate that the incorporation of an ionic liquid (IL) into the porous interior of ZIF-8 provides a means to reduce its melting temperature to below its thermal decomposition temperature. Our structural studies show that the prevention of decomposition, and successful melting, is due to the IL interactions stabilizing the rapidly dissociating ZIF-8 linkers upon heating. This understanding may act as a general guide for extending the range of meltable MOF materials and, hence, the chemical and structural variety of MOF-derived glasses.
Genomic sequencing of SARS-CoV-2 in Rwanda reveals the importance of incoming travelers on lineage diversity
Authors: Butera Yvan , Mukantwari Enatha , Artesi Maria , Umuringa Jeanne d’arc , O’Toole Áine Niamh , Hill Verity , Rooke Stefan , Hong Samuel Leandro , Dellicour Simon , Majyambere Onesphore , Bontems Sebastien , Boujemla Bouchra , Quick Josh , Resende Paola Cristina , Loman Nick , Umumararungu Esperance , Kabanda Alice , Murindahabi Marylin Milumbu , Tuyisenge Patrick , Gashegu Misbah , Rwabihama Jean Paul , Sindayiheba Reuben , Gikic Djordje , Souopgui Jacob , Ndifon Wilfred , Rutayisire Robert , Gatare Swaibu , Mpunga Tharcisse , Ngamije Daniel , Bours Vincent , Rambaut Andrew , Nsanzimana Sabin , Baele Guy , Durkin Keith , Mutesa Leon , Rujeni Nadine
Published: September 2021

COVID-19 transmission rates are often linked to locally circulating strains of SARS-CoV-2. Here we describe 203 SARS-CoV-2 whole genome sequences analyzed from strains circulating in Rwanda from May 2020 to February 2021. In particular, we report a shift in variant distribution towards the emerging sub-lineage A.23.1 that is currently dominating. Furthermore, we report the detection of the first Rwandan cases of the B.1.1.7 and B.1.351 variants of concern among incoming travelers tested at Kigali International Airport. To assess the importance of viral introductions from neighboring countries and local transmission, we exploit available individual travel history metadata to inform spatio-temporal phylogeographic inference, enabling us to take into account infections from unsampled locations. We uncover an important role of neighboring countries in seeding introductions into Rwanda, including those from which no genomic sequences were available. Our results highlight the importance of systematic genomic surveillance and regional collaborations for a durable response towards combating COVID-19.
Protocell arrays for simultaneous detection of diverse analytes
Authors: Zhang Yan , Kojima Taisuke , Kim Ge-Ah , McNerney Monica P. , Takayama Shuichi , Styczynski Mark P.
Published: September 2021

Simultaneous detection of multiple analytes from a single sample (multiplexing), particularly when done at the point of need, can guide complex decision-making without increasing the required sample volume or cost per test. Despite recent advances, multiplexed analyte sensing still typically faces the critical limitation of measuring only one type of molecule (e.g., small molecules or nucleic acids) per assay platform. Here, we address this bottleneck with a customizable platform that integrates cell-free expression (CFE) with a polymer-based aqueous two-phase system (ATPS), producing membrane-less protocells containing transcription and translation machinery used for detection. We show that multiple protocells, each performing a distinct sensing reaction, can be arrayed in the same microwell to detect chemically diverse targets from the same sample. Furthermore, these protocell arrays are compatible with human biofluids, maintain function after lyophilization and rehydration, and can produce visually interpretable readouts, illustrating this platform’s potential as a minimal-equipment, field-deployable, multi-analyte detection tool.
Structural basis for UFM1 transfer from UBA5 to UFC1
Authors: Kumar Manoj , Padala Prasanth , Fahoum Jamal , Hassouna Fouad , Tsaban Tomer , Zoltsman Guy , Banerjee Sayanika , Cohen-Kfir Einav , Dessau Moshe , Rosenzweig Rina , Isupov Michail N. , Schueler-Furman Ora , Wiener Reuven
Published: September 2021

Ufmylation is a post-translational modification essential for regulating key cellular processes. A three-enzyme cascade involving E1, E2 and E3 is required for UFM1 attachment to target proteins. How UBA5 (E1) and UFC1 (E2) cooperatively activate and transfer UFM1 is still unclear. Here, we present the crystal structure of UFC1 bound to the C-terminus of UBA5, revealing how UBA5 interacts with UFC1 via a short linear sequence, not observed in other E1-E2 complexes. We find that UBA5 has a region outside the adenylation domain that is dispensable for UFC1 binding but critical for UFM1 transfer. This region moves next to UFC1’s active site Cys and compensates for a missing loop in UFC1, which exists in other E2s and is needed for the transfer. Overall, our findings advance the understanding of UFM1’s conjugation machinery and may serve as a basis for the development of ufmylation inhibitors.
Structural and functional characterization of the bacterial biofilm activator RemA
Authors: Hoffmann Tamara , Mrusek Devid , Bedrunka Patricia , Burchert Fabiana , Mais Christopher-Nils , Kearns Daniel B. , Altegoer Florian , Bremer Erhard , Bange Gert
Published: September 2021

Bacillus subtilis can form structurally complex biofilms on solid or liquid surfaces, which requires expression of genes for matrix production. The transcription of these genes is activated by regulatory protein RemA, which binds to poorly conserved, repetitive DNA regions but lacks obvious DNA-binding motifs or domains. Here, we present the structure of the RemA homologue from Geobacillus thermodenitrificans, showing a unique octameric ring with the potential to form a 16-meric superstructure. These results, together with further biochemical and in vivo characterization of B. subtilis RemA, suggests that the protein can wrap DNA around its ring-like structure through a LytTR-related domain.