bluuebunny/crossref_metadata_2025 huggingface dataset:
Over-reflection of acoustic waves by supersonic exponential boundary layer flows
Authors: Zhang Y. , Görtz S. , Oberlack M.
Published: July 2022

The two-dimensional acoustic wave equation for inviscid compressible boundary layer flows, i.e. the Pridmore-Brown equation with an exponential velocity profile for homentropic flows, is studied for the reflection and over-reflection of acoustic waves based on the exact solution in terms of the confluent Heun function. The reflection coefficient$R$, which is the ratio of the amplitude of the reflected to that of the incoming acoustic wave, is determined as a function of the streamwise wavenumber$\alpha$, the Mach number$M$and the incident angle$\phi$of the acoustic waves. Over-reflection refers to$R>1$, i.e. the reflected wave has a larger amplitude than the incident wave. We prove that, in the supersonic context, energy is always transferred from the base flow to the reflected wave, i.e.$R<1$does not exist. Meanwhile, this fact is intimately linked to the critical layer. We show that the presence of the critical layer leads to an optimal energy exchange from the base flow into the acoustic wave, i.e. the critical layer ensures$R>1$. In our analysis, we observe a special phenomenon, resonant over-reflection, which is proven to be closely related to resonant frequencies$\omega _r$of unstable modes of the temporal stability of the base flow. At resonant frequencies of the first unstable mode, the over-reflection coefficient exhibits an unusual peak in an extremely narrow frequency interval. The maximum values of these peaks are largely synchronized with the variation of the growth rate$\omega _i$of the unstable modes. In addition, resonant over-reflection appears also at resonant frequencies of other higher unstable modes, but their peaks of the over-reflection coefficient are always smaller than that induced by the first unstable mode.
GROUPS WITH A LARGE PERMUTABLY EMBEDDED SUBGROUP
Authors: DE FALCO MARIA , DE GIOVANNI FRANCESCO , MUSELLA CARMELA
Published: July 2022

A group is called quasihamiltonian if all its subgroups are permutable, and we say that a subgroup Q of a group G is permutably embedded in G if
$\langle Q,g\rangle $
is quasihamiltonian for each element g of G. It is proved here that if a group G contains a permutably embedded normal subgroup Q such that
$G/Q$
is Černikov, then G has a quasihamiltonian subgroup of finite index; moreover, if G is periodic, then it contains a Černikov normal subgroup N such that
$G/N$
is quasihamiltonian. This result should be compared with theorems of Černikov and Schlette stating that if a group G is Černikov over its centre, then G is abelian-by-finite and its commutator subgroup is Černikov.
Identifying Patterns in the Structural Drivers of Intrastate Conflict
Authors: Moyer Jonathan D. , Matthews Austin S. , Rafa Mickey , Xiong Yutang
Published: July 2022

Quantitative methods have been used to: (1) better predict civil conflict onset; and (2) understand causal mechanisms to inform policy intervention and theory. However, an exploration of individual conflict onset cases illustrates great variation in the characteristics describing the outbreak of civil war, suggesting that there is not one single set of factors that lead to intrastate war. In this article, we use descriptive statistics to explore persistent clusters in the drivers of civil war onset, finding evidence that some arrangements of structural drivers cluster robustly across multiple model specifications (such as young, poorly developed states with anocratic regimes). Additionally, we find that approximately one-fifth of onset cases cannot be neatly clustered across models, suggesting that these cases are difficult to predict and multiple methods for understanding civil conflict onset (and state failure more generally) may be necessary.
Automorphism groups of endomorphisms of
Authors: Cai Julia , Hutz Benjamin , Mayer Leo , Weinreich Max
Published: July 2022

For any algebraically closed field K and any endomorphism f of
$\mathbb{P}^1(K)$
of degree at least 2, the automorphisms of f are the Möbius transformations that commute with f, and these form a finite subgroup of
$\operatorname{PGL}_2(K)$
. In the moduli space of complex dynamical systems, the locus of maps with nontrivial automorphisms has been studied in detail and there are techniques for constructing maps with prescribed automorphism groups that date back to Klein. We study the corresponding questions when K is the algebraic closure
$\bar{\mathbb{F}}_p$
of a finite field. We use the classification of finite subgroups of
$\operatorname{PGL}_2(\bar{\mathbb{F}}_p)$
to show that every finite subgroup is realizable as an automorphism group. To construct examples, we use methods from modular invariant theory. Then, we calculate the locus of maps over
$\bar{\mathbb{F}}_p$
of degree 2 with nontrivial automorphisms, showing how the geometry and possible automorphism groups depend on the prime p.
Molecular detection of Trypanosoma spp. and Hepatocystis parasite infections of bats in Northern Nigeria
Authors: Kamani J. , Atuman Y. J. , Oche D. A. , Shekaro A. , Werb O. , Ejotre I. , Schaer J.
Published: July 2022

Bats are mammalian hosts to a large diversity of eukaryotic protozoan blood parasites, including different genera of haemosporidians and diverse species of trypanosomes. Phylogenetic studies suggest that bats, particularly in Africa, have played an important role in the evolutionary histories of these parasite groups. However, our understanding of the diversity and distribution of chiropteran haemosporidians and trypanosomes in Africa remains tenuous. We investigated the prevalence and phylogenetic relationships of the blood parasites in different bat species in Northern Nigeria using molecular methods. A low prevalence of Hepatocystis parasites was detected in a potentially rare host species, the African straw-coloured fruit bat (Eidolon helvum) confirming yet another fruit bat species in the diverse range of African bat hosts. Trypanosome infections were identified in 3 different bat species. The trypanosomes of Mops cf. pumilus were recovered as a distinct lineage that is related to Trypanosoma erneyi, a species which is closely related to Trypanosoma dionisii and Trypanosoma cruzi. Nycteris cf. macrotis bats were infected with trypanosomes that are related to the distinct lineage of Trypanosoma cf. livingstonei parasites. Further, 2 different lineages of trypanosomes in E. helvum bats share highest nucleotide identities with Trypanosoma livingstonei and a group of Trypanosoma sp. parasites that are closely related to T. cf. livingstonei and T. livingstonei, respectively. The findings of this study confirm the notion that trypanosomes of African bats are phylogenetically diverse and that African bats might harbour a variety of yet undescribed trypanosome species.
“You have to work…but you can’t!”: Contradictions of the Active Labour Market Policies for Refugees and Asylum Seekers in the UK
Authors: CALO FRANCESCA , MONTGOMERY TOM , BAGLIONI SIMONE
Published: July 2022

The discourse of deservingness has been mobilised against certain groups in the UK society navigating UK labour markets, among them refugees and asylum seekers. These discourses, leading to the stigmatisation of the unemployed are coupled with an emphasis on the importance of individuals taking responsibility to develop their ‘employability’. Little attention has been paid to scrutinise the contrast between the deservingness rhetoric and policy making with the actual conditions newcomers, and in particular refugees and asylum seekers, are confronted with when seeking employment. Our paper fills such a gap by indicating key contradictions at the heart of labour market integration in the UK. On the one hand, the emphasis on deservingness is coupled with policy discourses that construct an environment shaped by welfare and labour market chauvinism. On the other hand, the policy architecture is fundamentally flawed in a number of ways in terms of the support mechanisms necessary to ensure that newcomers can successfully integrate into the labour market.
#YouAreWhatYouTweetCHHH: Identity and fricative epithesis in French-language tweets
Authors: Dalola Amanda
Published: July 2022

Phrase-final fricative epithesis (PFFE), often indicated in informal writing with a final-hor-ch, e.g.beaucoup_h, oui_ch, is a sociophonetic variable of Hexagonal French in which utterance-final vowels give way to intense fricative-like whistles. Production research has found PFFE to be used at equal rates among men and women, and perception research has found that native French speakers perceive it to mark either formal speech or intense affect. This research furthers the special issue’s line of inquiry on French variation in forms of digital media by extending the analysis to a sociophonetic variable with a robust life on Twitter. The study compares the pragmatic value of tweets containing PFFE with previously described values and then examines interactions of gender, hostword phrasal location and lexical frequency on its realization. 96.8% of PFFE occurrences in the 2060-token corpus were classified into the pragmatic categories of Formality and Intense Affect. Results suggest that PFFE has become a salient enough sociophonetic variable that 21st-century French users represent it graphically in their tweets, however, its usage is structurally more permissive than in spoken language, signaling that it has taken on an iconic value in digital spaces.
Écrire son vernaculaire: variation et normes communautaires dans les messages textes en français québécois
Authors: Blondeau Hélène , Tremblay Mireille
Published: July 2022

Cet article, qui porte sur les messages textes en français québécois, considère cette pratique langagière comme un lieu privilégié de l’expression du vernaculaire. L’analyse situe la langue des textos dans le débat qui a cours sur la diglossie et la variation en français. S’appuyant sur une analyse de textos tirés du corpus Texto4Science, l’article explique comment cette pratique vernaculaire s’appuie, comme l’oral familier, sur une grammaire qui se distingue de façon systématique du français de référence. De l’examen des données se dégage une grammaire à la fois variable et perméable. Enfin, l’article examine l’émergence d’une scripta vernaculaire et une néographie qui révèlent un effort délibéré de représenter des variantes vernaculaires.
Beratung zu Advance Care Planning in der ambulanten Pflege
Authors: Kirchner Änne , Langner Henriette , Meyer Gabriele , Schnakenberg Rieke , Silies Katharina , Hoffmann Falk , Köpke Sascha , Köberlein-Neu Juliane , Berg Almuth
Published: July 2022

Zusammenfassung. Hintergrund: StAdPlan ist eine multizentrische, Cluster-randomisierte kontrollierte Studie mit der Zielstellung, eine Intervention zu Advance Care Planning (ACP) für den Anwendungskontext der ambulanten Pflege in Deutschland zu entwickeln und zu evaluieren. Fragestellung/Ziel: In diesem Beitrag wird die Interventionsentwicklung unter Einbezug bestehender ACP-Konzepte und deren Anpassung auf die zeitlichen und personellen Ressourcen im System der ambulanten Pflege in Deutschland dargestellt. Pflegefachpersonen kommt dabei die Rolle zu, ältere pflegebedürftige Menschen und deren Angehörige im Rahmen von strukturierten Gesprächen für das Thema ACP zu sensibilisieren und die Nutzung bestehender Beratungsangebote zu fördern. Methoden: Die Interventionskomponenten wurden unter Anwendung des Behaviour Change Wheel (BCW) entwickelt. Ergebnisse: Die komplexe Intervention in Form eines niedrigschwelligen Beratungsangebotes richtet sich an Pflegebedürftige über 65 Jahre und ihre Angehörigen. Ein zweitägiges Schulungsangebot qualifiziert Pflegefachpersonen ambulanter Pflegedienste für leitfadengestützte Beratungsgespräche, die im häuslichen Umfeld der pflegebedürftigen Person, möglichst unter Einbeziehung Angehöriger, im Rahmen von mindestens zwei Terminen durchgeführt werden. Eine Broschüre ergänzt das Informationsangebot. Schlussfolgerungen: Das Vorgehen entlang des BCW-Modells war für Analyse, Beschreibung und Definition der spezifischen Funktionen der Intervention gut geeignet. Die Intervention wird in der anschließenden Studie auf ihre Effektivität untersucht.
Wohlbefinden von Kindern beobachten
Authors: Harring Dana , Schutter Sabrina
Published: July 2022

Zusammenfassung. Die Erhebung des Wohlbefindens von Kindern ist von standardisierten Beobachtungsinstrumenten geprägt. In diesem Beitrag wird das Potenzial eines ethnografisch-praxeologischen Zugangs für die Child Well-Being-Forschung untersucht. Anhand einer praxeologischen Rekonstruktion einer körperlichen Herstellungspraxis in einer Kindertageseinrichtung werden Potenziale und offene Fragen dieses analytischen Zugangs aufgezeigt. Durch die ethnografische Beobachtung rücken die Handlungsvollzüge bei der Herstellung von Wohlbefinden in den Fokus. Gleichzeitig lässt sich auch mit diesem Zugang die Problematik einer adultistischen Bewertung vorerst nicht aufheben.
Kindliches Wohlbefinden
Authors: Viernickel Susanne
Published: July 2022

Zusammenfassung. In der empirischen Forschung zu Bedingungen kindlichen Aufwachsens wird häufig auf das Konstrukt des kindlichen Wohlbefindens (Child Well-Being) zurückgegriffen. Mit diesem Einführungsbeitrag zum Schwerpunktheft soll der Versuch unternommen werden, die vielfältigen theoretischen Zugänge, Begriffsverwendungen und Merkmalszuschreibungen im Zusammenhang mit dem immer wieder als unscharf und diffus („fuzzy“, Betz et al., 2018 , S. 13) deklarierten Konzept des kindlichen Wohlbefindens zu systematisieren und bisherige Erträge ebenso wie Leerstellen zu markieren.
Constraining Martian Crustal Thickness with InSight Seismology
Authors: Rehnberg Morgan
Published: July 2022

The first seismic observations from Mars significantly reduce uncertainty in estimates of the Red Planet’s crustal structure.
Infrasound From Large Earthquakes Recorded on a Network of Balloons in the Stratosphere
Authors: Garcia Raphael F. , Klotz Adrien , Hertzog Albert , Martin Roland , Gérier Solène , Kassarian Ervan , Bordereau Jérôme , Venel Stéphanie , Mimoun David
Published: July 2022

The ground movements induced by seismic waves create acoustic waves propagating upward in the atmosphere, thus providing a practical solution to perform remote sensing of planetary interiors. However, a terrestrial demonstration of a seismic network based on balloon‐carried pressure sensors has not been provided. Here we present the first detection of seismic infrasound from a large magnitude quake on a balloon network. We demonstrate that quake's properties and planet's internal structure can be probed from balloon‐borne pressure records alone because these are generated by the ground movements at the planet surface below the balloon. Various seismic waves are identified, thus allowing us to infer the quake magnitude and location, as well as planetary internal structure. The mechanical resonances of balloon system are also observed. This study demonstrates the interest of planetary geophysical mission concepts based on seismic remote sensing with balloon platforms, and their interest to complement terrestrial seismic networks.
A Hybrid Optimization Framework for Seismic Full Waveform Inversion
Authors: Zhao Zeyu , Sen Mrinal K. , Denel Bertrand , Sun Dong , Williamson Paul
Published: July 2022

A hybrid optimization framework is proposed for full waveform inversion (FWI) problems by incorporating derivative information into the model update rule of a global optimization method called Very Fast Simulated Annealing (VFSA). The proposed optimization framework tackles the local minima issue of non‐linear inverse problems. Additionally, it can converge to the close neighborhood of the global solution from different starting points with an improved convergence speed compared to traditional global optimization methods. Applied to large‐scale FWI problems, the proposed framework greatly relaxes the issue of the dependence of FWI on starting models. Given a proper tuning and sufficient number of iterations, hybrid optimization based FWI can render a good background model, which is a good approximation to the ground truth, even with uninformative prior constraints and poor starting models. The output of hybrid optimization based FWI can be used as the starting model for a subsequent local optimization based FWI run to improve the spatial resolution of the result. The proposed hybrid optimization framework is very general, and can be applied to other linear and non‐linear problems that need optimization loops.
Effect of Tides on the Indonesian Seas Circulation and Their Role on the Volume, Heat and Salt Transports of the Indonesian Throughflow
Authors: Katavouta Anna , Polton Jeff A. , Harle James D. , Holt Jason T.
Published: July 2022

The effect of tides on the Indonesian Throughflow (ITF) is explored in a regional ocean model of South East Asia. Our model simulations, with and without tidal forcing, reveal that tides drive only a modest increase in the ITF volume, heat and salt transports toward the Indian Ocean. However, tides drive large regional changes in these transports through Lombok Strait, Ombai Strait and the Timor Sea, and regulate the partitioning of the ITF amongst them. The effect of tidal mixing on the salinity and temperature profiles within the Indonesian Seas drives a small decrease in the heat and salt transports toward the Indian Ocean in all three exit passages. In contrast, the tidal residual circulation due to the interaction between the tides and the topography and stratification (including the effects of tidal mixing on the circulation) leads to a large decrease in the transports toward the Indian Ocean through the Lombok and Ombai straits, but a large increase through the Timor Sea. Hence, the small net contribution from tides to the ITF's volume, heat and salt transports is due to a compensation between large, but opposing tidal residual transports at the combined Lombok and Ombai straits and in the Timor Sea. Our results indicate that explicit representation of tides, often missing in Earth system models, is necessary to accurately capture the ITF's pathway and so the tracer transport from the Pacific into the Indian Ocean.
Detecting and distinguishing indicators of risk for suicide using clinical records
Authors: Ahmedani Brian K. , Cannella Cara E. , Yeh Hsueh-Han , Westphal Joslyn , Simon Gregory E. , Beck Arne , Rossom Rebecca C. , Lynch Frances L. , Lu Christine Y. , Owen-Smith Ashli A. , Sala-Hamrick Kelsey J. , Frank Cathrine , Akinyemi Esther , Beebani Ganj , Busuito Christopher , Boggs Jennifer M. , Daida Yihe G. , Waring Stephen , Gui Hongsheng , Levin Albert M.
Published: July 2022

Health systems are essential for suicide risk detection. Most efforts target people with mental health (MH) diagnoses, but this only represents half of the people who die by suicide. This study seeks to discover and validate health indicators of suicide death among those with, and without, MH diagnoses. This case-control study used statistical modeling with health record data on diagnoses, procedures, and encounters. The study included 3,195 individuals who died by suicide from 2000 to 2015 and 249,092 randomly selected matched controls, who were age 18+ and affiliated with nine Mental Health Research Network affiliated health systems. Of the 202 indicators studied, 170 (84%) were associated with suicide in the discovery cohort, with 148 (86%) of those in the validation cohort. Malignant cancer diagnoses were risk factors for suicide in those without MH diagnoses, and multiple individual psychiatric-related indicators were unique to the MH subgroup. Protective effects across MH-stratified models included diagnoses of benign neoplasms, respiratory infections, and utilization of reproductive services. MH-stratified latent class models validated five subgroups with distinct patterns of indicators in both those with and without MH. The highest risk groups were characterized via high utilization with multiple healthcare concerns in both groups. The lowest risk groups were characterized as predominantly young, female, and high utilizers of preventive services. Healthcare data include many indicators of suicide risk for those with and without MH diagnoses, which may be used to support the identification and understanding of risk as well as targeting of prevention in health systems.
Impact of Anti-T-lymphocyte globulin dosing on GVHD and Immune reconstitution in matched unrelated myeloablative peripheral blood stem cell transplantation
Authors: Massoud Radwan , Klyuchnikov Evgeny , Gagelmann Nico , Zabelina Tatiana , Wolschke Christine , Ayuk Francis , Fritzsche-Friedland Ulrike , Zander Axel , Kröger Nicolaus
Published: July 2022

Data on the influence of different Anti-lymphocyte globulin (ATLG) doses on graft versus host disease (GVHD) incidence and immune reconstitution in matched unrelated (MUD) allogeneic Stem cell transplantation (allo-SCT) is limited. This retrospective study conducted at the University Medical-Center Hamburg compares GVHD and Immune reconstitution after myeloablative MUD (HLA 10/10) PBSC allogeneic stem cell transplant between 30 mg/Kg (n = 73) and 60 mg/Kg (n = 216) ATLG. Detailed phenotypes of T, B natural killer (NK), natural killer T (NKT) cells were analyzed by multicolor flow at day 30, 100, and 180 posttransplant. Neutrophil and platelet engraftments were significantly delayed in the 60 mg/kg group with a higher Cumulative incidence of Infections (67% vs 75% p = 0.049) and EBV (21% vs 41% p = 0.049) reactivation at day 100 in this group. In the 30 mg/kg group, we observed a faster reconstitution of naïve-B cells (p < 0.0001) and γδ T cells (p = 0.045) at day+30 and a faster naïve helper T-cell (p = 0.046), NK-cells (p = 0.035), and naïve B-cell reconstitution (p = 0.009) at day+180. There were no significant differences in aGVHD, cGVHD, NRM, RI, PFS, and OS between the groups. The choice of ATLG dose has significant impact on IR but not on GVHD after MUD-allo-SCT. Higher doses are associated with delayed engraftment and increased infections.
Targeting mitochondrial metabolism for precision medicine in cancer
Authors: Sainero-Alcolado Lourdes , Liaño-Pons Judit , Ruiz-Pérez María Victoria , Arsenian-Henriksson Marie
Published: July 2022

During decades, the research field of cancer metabolism was based on the Warburg effect, described almost one century ago. Lately, the key role of mitochondria in cancer development has been demonstrated. Many mitochondrial pathways including oxidative phosphorylation, fatty acid, glutamine, and one carbon metabolism are altered in tumors, due to mutations in oncogenes and tumor suppressor genes, as well as in metabolic enzymes. This results in metabolic reprogramming that sustains rapid cell proliferation and can lead to an increase in reactive oxygen species used by cancer cells to maintain pro-tumorigenic signaling pathways while avoiding cellular death. The knowledge acquired on the importance of mitochondrial cancer metabolism is now being translated into clinical practice. Detailed genomic, transcriptomic, and metabolomic analysis of tumors are necessary to develop more precise treatments. The successful use of drugs targeting metabolic mitochondrial enzymes has highlighted the potential for their use in precision medicine and many therapeutic candidates are in clinical trials. However, development of efficient personalized drugs has proved challenging and the combination with other strategies such as chemocytotoxic drugs, immunotherapy, and ketogenic or calorie restriction diets is likely necessary to boost their potential. In this review, we summarize the main mitochondrial features, metabolic pathways, and their alterations in different cancer types. We also present an overview of current inhibitors, highlight enzymes that are attractive targets, and discuss challenges with translation of these approaches into clinical practice. The role of mitochondria in cancer is indisputable and presents several attractive targets for both tailored and personalized cancer therapy.
Epigenetic modulators of B cell fate identified through coupled phenotype-transcriptome analysis
Authors: Kong Isabella Y. , Trezise Stephanie , Light Amanda , Todorovski Izabela , Arnau Gisela Mir , Gadipally Sreeja , Yoannidis David , Simpson Kaylene J. , Dong Xueyi , Whitehead Lachlan , Tempany Jessica C. , Farchione Anthony J. , Sheikh Amania A. , Groom Joanna R. , Rogers Kelly L. , Herold Marco J. , Bryant Vanessa L. , Ritchie Matthew E. , Willis Simon N. , Johnstone Ricky W. , Hodgkin Philip D. , Nutt Stephen L. , Vervoort Stephin J. , Hawkins Edwin D.
Published: July 2022

High-throughput methodologies are the cornerstone of screening approaches to identify novel compounds that regulate immune cell function. To identify novel targeted therapeutics to treat immune disorders and haematological malignancies, there is a need to integrate functional cellular information with the molecular mechanisms that regulate changes in immune cell phenotype. We facilitate this goal by combining quantitative methods for dissecting complex simultaneous cell phenotypic effects with genomic analysis. This combination strategy we term Multiplexed Analysis of Cells sequencing (MAC-seq), a modified version of Digital RNA with perturbation of Genes (DRUGseq). We applied MAC-seq to screen compounds that target the epigenetic machinery of B cells and assess altered humoral immunity by measuring changes in proliferation, survival, differentiation and transcription. This approach revealed that polycomb repressive complex 2 (PRC2) inhibitors promote antibody secreting cell (ASC) differentiation in both murine and human B cells in vitro. This is further validated using T cell-dependent immunization in mice. Functional dissection of downstream effectors of PRC2 using arrayed CRISPR screening uncovered novel regulators of B cell differentiation, includingMybl1,Myof,Gas7andAtoh8. Together, our findings demonstrate that integrated phenotype-transcriptome analyses can be effectively combined with drug screening approaches to uncover the molecular circuitry that drives lymphocyte fate decisions.
Aurora-A/FOXO3A/SKP2 axis promotes tumor progression in clear cell renal cell carcinoma and dual-targeting Aurora-A/SKP2 shows synthetic lethality
Authors: Li Pu , Chen Tingting , Kuang Peng , Liu Fujun , Li Zhongmin , Liu Fangfang , Wang Yu , Zhang Wenfeng , Cai Xiuyu
Published: July 2022

Renal cell carcinoma (RCC) is a common malignant tumor in the world. Histologically, most of RCC is classified as clear cell renal cell carcinoma (ccRCC), which is the most prevalent subtype. The overall survival of patients with ccRCC is poor, thus it is urgent to further explore its mechanism and target. S-phase kinase-associated protein 2 (SKP2) is overexpressed in a variety of human cancers and is associated with poor prognosis by enhancing tumor progression. However, it is unclear whether or how SKP2 is involved in ccRCC progression. Here, we reported that overexpression of SKP2 enhanced cell proliferation of ccRCC, while SKP2 depletion exhibited the opposite effect. Bioinformatic analyses found that SKP2 was positively correlated with Aurora-A (Aur-A) in ccRCC. The protein and mRNA levels of SKP2 were elevated or reduced by Aur-A overexpression or silencing, respectively. It was further found that Aur-A caused an increase phosphorylation of FOXO3A, which is a negatively transcription factor for SKP2. Interestingly, SKP2 mediated ubiquitylation and degradation of FOXO3A depend on the kinase activity of Aur-A. The combination of Aur-A inhibitor MLN8237 and SKP2 inhibitor SZL P1-41 showed a synergistic tumor growth inhibition in vivo and in vitro of ccRCC models. Thus, our data reveal that Aurora-A/FOXO3A/SKP2 axis promotes tumor progression in ccRCC, and the double inhibition of SKP2 and Aur-A shows significant synergistic effect, which indicates a potential new therapeutic strategy for ccRCC.
Novel roles of luteinizing hormone (LH) in tissue regeneration-associated functions in endometrial stem cells
Authors: Park Se-Ra , Kim Seong-Kwan , Kim Soo-Rim , Park Jeong-Ran , Lim Soyi , Hong In-Sun
Published: July 2022

Luteinizing hormone (LH) stimulates the synthesis and secretion of the key steroid hormone estrogen, which subsequently promotes ovarian follicular growth and development. Therefore, the administration of exogenous LH to achieve superovulation (multiple ovulations) and an LH surge is commonly used as the most effective therapeutic option in a majority of in vitro fertilization (IVF) clinics. However, a relatively low pregnancy rate (between 20% and 35%) is one of the most challenging aspects of LH-based infertility treatment. Furthermore, the major cause of this low pregnancy rate in LH-based infertility treatment remains unidentified. Recent studies have shown that endometrial stem cell loss or deficiency can significantly decrease tissue regeneration ability during the menstrual cycle and reduce endometrial receptivity. In this context, we postulated that the low pregnancy rates following LH-based ovarian hyperactivation may be the result of the adverse effects of consecutive exogenous LH administration on endometrial stem cells. To the best of our knowledge, this study revealed for the first time that in addition to its previously reported roles in stimulating ovarian functions through the pituitary-gonadal axis, LH brings about the extragonadal suppression of various tissue regeneration-associated functions in endometrial stem cells, such as self-renewal, migration ability, multilineage differentiation potential, and pluripotency/stemness, by inhibiting pro-survival Akt and ERK1/2 signaling pathways in vitro and in vivo, and as a consequence, it decreases the endometrial receptivity.
Single-cell profiling of immune cells after neoadjuvant pembrolizumab and chemotherapy in IIIA non-small cell lung cancer (NSCLC)
Authors: Hui Zhenzhen , Zhang Jiali , Ren Yulin , Li Xiaoling , Yan Cihui , Yu Wenwen , Wang Tao , Xiao Shanshan , Chen Yulong , Zhang Ran , Wei Feng , You Jian , Ren Xiubao
Published: July 2022

The combination of immune checkpoint inhibitors (ICIs) with chemotherapy (chemoimmunotherapy) in the neoadjuvant setting have achieved favorable clinical benefits in non-small cell lung cancer (NSCLC), but the mechanism of clinical responses remain unclear. We provide a rich resource of 186,477 individual immune cells from 48 samples of four treatment-naive and eight neoadjuvant chemoimmunotherapy treated IIIA NSCLC patients (responders versus non-responders) by single-cell RNA-seq and TCR-seq. We observed the synergistic increase of B cells and CD4+ T cells were associated with a positive therapeutic response of neoadjuvant chemoimmunotherapy. B cell IgG subclasses IgG1 and IgG3 played a critical role in anti-tumor immune response in tumor lesions, and this process was driven by increased IL-21 secreted by infiltrated T follicular helper (Tfh) cells after neoadjuvant chemoimmunotherapy. Furthermore, we uncovered several critical events for positive clinical outcomes, including the diminished activated TNFRSF4+ regulatory T cells (Tregs), increased LAMP3+ dendritic cells (DCs), and the expansion of intratumoral CD4+ T clones and peripheral C3-Cytotoxic CD8+ T clones. A validation cohort of 26 treatment-naive and 30 neoadjuvant chemoimmunotherapy treated IIIA/ IIIB NSCLC patients verified these findings. In total, our comprehensive study of the single-cell profile of immune cells provides insights into mechanisms underlying anti-PD-1-based therapies and identified potential predictive factors and therapeutic targets for improving the efficiency of neoadjuvant chemoimmunotherapy in NSCLC.
Freeze-derived heterogeneous structural color films
Authors: Miao Shuangshuang , Wang Yu , Sun Lingyu , Zhao Yuanjin
Published: July 2022

Structural colors have a demonstrated value in constructing various functional materials. Efforts in this area are devoted to developing stratagem for generating heterogeneous structurally colored materials with new architectures and functions. Here, inspired by icing process in nature and ice-templating technologies, we present freeze-derived heterogeneous structural color hydrogels with multiscale structural and functional features. We find that the space-occupying effect of ice crystals is helpful for tuning the distance of non-close-packed colloidal crystal nanoparticles, resulting in corresponding reflection wavelength shifts in the icing area. Thus, by effectively controlling the growth of ice crystals and photo-polymerizing them, structural color hydrogels with the desired structures and morphologies can be customized. Other than traditional monochromatic structure color hydrogels, the resultant hydrogels can be imparted with heterogeneous structured multi-compartment body and multi-color with designed patterns through varying the freezing area design. Based on these features, we have also explored the potential value of these heterotypic structural color hydrogels for information encryptions and decryptions by creating spatiotemporally controlled icing areas. We believe that these inverse ice-template structural color hydrogels will offer new routes for the construction and modulation of next generation smart materials with desired complex architectures.
Monomeric prefusion structure of an extremophile gamete fusogen and stepwise formation of the postfusion trimeric state
Authors: Feng Juan , Dong Xianchi , Su Yang , Lu Chafen , Springer Timothy A.
Published: July 2022

Here, we study the gamete fusogen HAP2 from Cyanidioschyzon merolae (Cyani), an extremophile red algae that grows at acidic pH at 45 °C. HAP2 has a trimeric postfusion structure with similarity to viral class II fusion proteins, but its prefusion structure has been elusive. The crystal structure of a monomeric prefusion state of Cyani HAP2 shows it is highly extended with three domains in the order D2, D1, and D3. Three hydrophobic fusion loops at the tip of D2 are each required for postfusion state formation. We followed by negative stain electron microscopy steps in the process of detergent micelle-stimulated postfusion state formation. In an intermediate state, two or three linear HAP2 monomers associate at the end of D2 bearing its fusion loops. Subsequently, D2 and D1 line the core of a trimer and D3 folds back over the exterior of D1 and D2. D3 is not required for formation of intermediate or postfusion-like states.
Desymmetrization of N-Cbz glutarimides through N-heterocyclic carbene organocatalysis
Authors: Hu Zhouli , Wei Chenlong , Shi Qianqian , Hong Xianfang , Liu Jinhua , Zhou Xiangui , Han Jinna , Cao Wei , Gupta Ashis Kumar , Zhang Xiaoxiang , Wei Donghui , Fu Zhenqian , Huang Wei
Published: July 2022

Over the past decade, the catalysis ofN-heterocyclic carbenes has achieved significant advances. In this area, aldehydes, enals, and esters, are commonly employed as starting materials through various catalytic activation modes. However, NHC-activated strategy of amide and its derivatives remains elusive. Described herein is the realization of asymmetric desymmetrization of N-Cbz glutarimides with alcohols through an imide C-N bond cleavage under NHC organocatalysis. A structurally diverse set of enantioenriched 4-amido esters is generated with acceptable yields and high enantioselectivities. This method features mild reaction conditions, excellent substrate scope, and excellent atom economy. DFT calculations have been performed to explore the detailed reaction mechanism and the origin of the enantioselectivity, which indicate that the strength of the C-H···O hydrogen bond and C–H⋯π interactions should be responsible for the stereoselectivity. The current strategy could open a door for efficient construction of (R)-Rolipram with excellent stereoselectivity.
A reference single-cell regulomic and transcriptomic map of cynomolgus monkeys
Authors: Qu Jiao , Yang Fa , Zhu Tao , Wang Yingshuo , Fang Wen , Ding Yan , Zhao Xue , Qi Xianjia , Xie Qiangmin , Chen Ming , Xu Qiang , Xie Yicheng , Sun Yang , Chen Dijun
Published: July 2022

Non-human primates are attractive laboratory animal models that accurately reflect both developmental and pathological features of humans. Here we present a compendium of cell types across multiple organs in cynomolgus monkeys (Macaca fascicularis) using both single-cell chromatin accessibility and RNA sequencing data. The integrated cell map enables in-depth dissection and comparison of molecular dynamics, cell-type compositions and cellular heterogeneity across multiple tissues and organs. Using single-cell transcriptomic data, we infer pseudotime cell trajectories and cell-cell communications to uncover key molecular signatures underlying their cellular processes. Furthermore, we identify various cell-specific cis-regulatory elements and construct organ-specific gene regulatory networks at the single-cell level. Finally, we perform comparative analyses of single-cell landscapes among mouse, monkey and human. We show that cynomolgus monkey has strikingly higher degree of similarities in terms of immune-associated gene expression patterns and cellular communications to human than mouse. Taken together, our study provides a valuable resource for non-human primate cell biology.
700,000 years of tropical Andean glaciation
Authors: Rodbell D. T. , Hatfield R. G. , Abbott M. B. , Chen C. Y. , Woods A. , Stoner J. S. , McGee D. , Tapia P. M. , Bush M. , Valero-Garcés B. L. , Lehmann S. B. , Mark S. Z. , Weidhaas N. C. , Hillman A. L. , Larsen D. J. , Delgado G. , Katz S. A. , Solada K. E. , Morey A. E. , Finkenbinder M. , Valencia B. , Rozas-Davila A. , Wattrus N. , Colman S. M. , Bustamante M. G. , Kück J. , Pierdominici S.
Published: July 2022

Our understanding of the climatic teleconnections that drove ice-age cycles has been limited by a paucity of well-dated tropical records of glaciation that span several glacial–interglacial intervals. Glacial deposits offer discrete snapshots of glacier extent but cannot provide the continuous records required for detailed interhemispheric comparisons. By contrast, lakes located within glaciated catchments can provide continuous archives of upstream glacial activity, but few such records extend beyond the last glacial cycle. Here a piston core from Lake Junín in the uppermost Amazon basin provides the first, to our knowledge, continuous, independently dated archive of tropical glaciation spanning 700,000 years. We find that tropical glaciers tracked changes in global ice volume and followed a clear approximately 100,000-year periodicity. An enhancement in the extent of tropical Andean glaciers relative to global ice volume occurred between 200,000 and 400,000 years ago, during sustained intervals of regionally elevated hydrologic balance that modified the regular approximately 23,000-year pacing of monsoon-driven precipitation. Millennial-scale variations in the extent of tropical Andean glaciers during the last glacial cycle were driven by variations in regional monsoon strength that were linked to temperature perturbations in Greenland ice cores1; these interhemispheric connections may have existed during previous glacial cycles.
Emerging signals of declining forest resilience under climate change
Authors: Forzieri Giovanni , Dakos Vasilis , McDowell Nate G. , Ramdane Alkama , Cescatti Alessandro
Published: July 2022

Forest ecosystems depend on their capacity to withstand and recover from natural and anthropogenic perturbations (that is, their resilience)1. Experimental evidence of sudden increases in tree mortality is raising concerns about variation in forest resilience2, yet little is known about how it is evolving in response to climate change. Here we integrate satellite-based vegetation indices with machine learning to show how forest resilience, quantified in terms of critical slowing down indicators3–5, has changed during the period 2000–2020. We show that tropical, arid and temperate forests are experiencing a significant decline in resilience, probably related to increased water limitations and climate variability. By contrast, boreal forests show divergent local patterns with an average increasing trend in resilience, probably benefiting from warming and CO2 fertilization, which may outweigh the adverse effects of climate change. These patterns emerge consistently in both managed and intact forests, corroborating the existence of common large-scale climate drivers. Reductions in resilience are statistically linked to abrupt declines in forest primary productivity, occurring in response to slow drifting towards a critical resilience threshold. Approximately 23% of intact undisturbed forests, corresponding to 3.32 Pg C of gross primary productivity, have already reached a critical threshold and are experiencing a further degradation in resilience. Together, these signals reveal a widespread decline in the capacity of forests to withstand perturbation that should be accounted for in the design of land-based mitigation and adaptation plans.
Myctobase, a circumpolar database of mesopelagic fishes for new insights into deep pelagic prey fields
Authors: Woods Briannyn , Trebilco Rowan , Walters Andrea , Hindell Mark , Duhamel Guy , Flores Hauke , Moteki Masato , Pruvost Patrice , Reiss Christian , Saunders Ryan A. , Sutton Caroline , Gan Yi-Ming , Van de Putte Anton
Published: July 2022

The global importance of mesopelagic fish is increasingly recognised, but they remain poorly studied. This is particularly true in the Southern Ocean, where mesopelagic fishes are both key predators and prey, but where the remote environment makes sampling challenging. Despite this, multiple national Antarctic research programs have undertaken regional sampling of mesopelagic fish over several decades. However, data are dispersed, and sampling methodologies often differ precluding comparisons and limiting synthetic analyses. We identified potential data holders by compiling a metadata catalogue of existing survey data for Southern Ocean mesopelagic fishes. Data holders contributed 17,491 occurrence and 11,190 abundance records from 4780 net hauls from 72 different research cruises. Data span across 37 years from 1991 to 2019 and include trait-based information (length, weight, maturity). The final dataset underwent quality control processes and detailed metadata was provided for each sampling event. This dataset can be accessed through Zenodo. Myctobase will enhance research capacity by providing the broadscale baseline data necessary for observing and modelling mesopelagic fishes.
Simulation of group testing scenarios can boost COVID-19 screening power
Authors: da Silva Vinicius Henrique , Goes Carolina Purcell , Trevisoli Priscila Anchieta , Lello Raquel , Clemente Luan Gaspar , de Almeida Talita Bonato , Petrini Juliana , Coutinho Luiz Lehmann
Published: July 2022

The COVID-19 has severely affected economies and health systems around the world. Mass testing could work as a powerful alternative to restrain disease dissemination, but the shortage of reagents is a limiting factor. A solution to optimize test usage relies on ‘grouping’ or ‘pooling’ strategies, which combine a set of individuals in a single reaction. To compare different group testing configurations, we developed the poolingr package, which performs an innovative hybrid in silico/in vitro approach to search for optimal testing configurations. We used 6759 viral load values, observed in 2389 positive individuals, to simulate a wide range of scenarios. We found that larger groups (>100) framed into multi-stage setups (up to six stages) could largely boost the power to detect spreaders. Although the boost was dependent on the disease prevalence, our method could point to cheaper grouping schemes to better mitigate COVID-19 dissemination through identification and quarantine recommendation for positive individuals.
Unconscious mind activates central cardiovascular network and promotes adaptation to microgravity possibly anti-aging during 1-year-long spaceflight
Authors: Otsuka Kuniaki , Cornelissen Germaine , Furukawa Satoshi , Shibata Koichi , Kubo Yutaka , Mizuno Koh , Aiba Tatsuya , Ohshima Hiroshi , Mukai Chiaki
Published: July 2022

The intrinsic cardiovascular regulatory system (β, 0.00013–0.02 Hz) did not adapt to microgravity after a 6-month spaceflight. The infraslow oscillation (ISO, 0.01–0.10 Hz) coordinating brain dynamics via thalamic astrocytes plays a key role in the adaptation to novel environments. We investigate the adaptive process of a healthy astronaut during a 12-month-long spaceflight by analyzing heart rate variability (HRV) in the LF (0.01–0.05 Hz) and MF1 (0.05–0.10 Hz) bands for two consecutive days on four occasions: before launch, at 1-month (ISS01) and 11-month (ISS02) in space, and after return to Earth. Alteration of β during ISS01 improved during ISS02 (P = 0.0167). During ISS01, LF and MF1 bands, reflecting default mode network (DMN) activity, started to increase at night (by 43.1% and 32.0%, respectively), when suprachiasmatic astrocytes are most active, followed by a 25.9% increase in MF1-band throughout the entire day during ISS02, larger at night (47.4%) than during daytime. Magnetic declination correlated positively with β during ISS01 (r = 0.6706, P < 0.0001) and ISS02 (r = 0.3958, P = 0.0095). Magnetic fluctuations may affect suprachiasmatic astrocytes, and the DMN involving ISOs and thalamic astrocytes may then be activated, first at night, then during the entire day, a mechanism that could perhaps promote an anti-aging effect noted in other investigations.
Exploratory analysis using machine learning of predictive factors for falls in type 2 diabetes
Authors: Suzuki Yasuhiro , Suzuki Hiroaki , Ishikawa Tatsuya , Yamada Yasunori , Yatoh Shigeru , Sugano Yoko , Iwasaki Hitoshi , Sekiya Motohiro , Yahagi Naoya , Hada Yasushi , Shimano Hitoshi
Published: July 2022

We aimed to investigate the status of falls and to identify important risk factors for falls in persons with type 2 diabetes (T2D) including the non-elderly. Participants were 316 persons with T2D who were assessed for medical history, laboratory data and physical capabilities during hospitalization and given a questionnaire on falls one year after discharge. Two different statistical models, logistic regression and random forest classifier, were used to identify the important predictors of falls. The response rate to the survey was 72%; of the 226 respondents, there were 129 males and 97 females (median age 62 years). The fall rate during the first year after discharge was 19%. Logistic regression revealed that knee extension strength, fasting C-peptide (F-CPR) level and dorsiflexion strength were independent predictors of falls. The random forest classifier placed grip strength, F-CPR, knee extension strength, dorsiflexion strength and proliferative diabetic retinopathy among the 5 most important variables for falls. Lower extremity muscle weakness, elevated F-CPR levels and reduced grip strength were shown to be important risk factors for falls in T2D. Analysis by random forest can identify new risk factors for falls in addition to logistic regression.