bluuebunny/crossref_metadata_2025 huggingface dataset:
Decomposition of Feynman integrals by multivariate intersection numbers
Authors: Frellesvig Hjalte , Gasparotto Federico , Laporta Stefano , Mandal Manoj K. , Mastrolia Pierpaolo , Mattiazzi Luca , Mizera Sebastian
Published: March 2021

Abstract

We present a detailed description of the recent idea for a direct decomposition of Feynman integrals onto a basis of master integrals by projections, as well as a direct derivation of the differential equations satisfied by the master integrals, employing multivariate intersection numbers. We discuss a recursive algorithm for the computation of multivariate intersection numbers, and provide three different approaches for a direct decomposition of Feynman integrals, which we dub the straight decomposition, the bottom-up decomposition, and the top-down decomposition. These algorithms exploit the unitarity structure of Feynman integrals by computing intersection numbers supported on cuts, in various orders, thus showing the synthesis of the intersection-theory concepts with unitarity-based methods and integrand decomposition. We perform explicit computations to exemplify all of these approaches applied to Feynman integrals, paving a way towards potential applications to generic multi-loop integrals.
Elliptic quantum curves of class $$ {\mathcal{S}}_k $$
Authors: Chen Jin , Haghighat Babak , Kim Hee-Cheol , Sperling Marcus
Published: March 2021

Abstract

Quantum curves arise from Seiberg-Witten curves associated to 4d$$ \mathcal{N} $$N= 2 gauge theories by promoting coordinates to non-commutative operators. In this way the algebraic equation of the curve is interpreted as an operator equation where a Hamiltonian acts on a wave-function with zero eigenvalue. We find that this structure generalises when one considers torus-compactified 6d$$ \mathcal{N} $$N= (1,0) SCFTs. The corresponding quantum curves are elliptic in nature and hence the associated eigenvectors/eigenvalues can be expressed in terms of Jacobi forms. In this paper we focus on the class of 6d SCFTs arising from M5 branes transverse to a ℂ2/ℤksingularity. In the limit where the compactified 2-torus has zero size, the corresponding 4d$$ \mathcal{N} $$N= 2 theories are known as class$$ {\mathcal{S}}_k $$Sk. We explicitly show that the eigenvectors associated to the quantum curve are expectation values of codimension 2 surface operators, while the corresponding eigenvalues are codimension 4 Wilson surface expectation values.
Bottom-quark production at hadron colliders: fully differential predictions in NNLO QCD
Authors: Catani Stefano , Devoto Simone , Grazzini Massimiliano , Kallweit Stefan , Mazzitelli Javier
Published: March 2021

Abstract

We report on the first fully differential calculation of the next-to-next-to-leading-order (NNLO) QCD radiative corrections to the production of bottom-quark pairs at hadron colliders. The calculation is performed by using the qT subtraction formalism to handle and cancel infrared singularities in real and virtual contributions. The computation is implemented in the Matrix framework, thereby allowing us to efficiently compute arbitrary infrared-safe observables in the four-flavour scheme. We present selected predictions for bottom-quark production at the Tevatron and at the LHC at different collider energies, and we perform some comparisons with available experimental results. We find that the NNLO corrections are sizeable, typically of the order of 25–35%, and they lead to a significant reduction of the perturbative uncertainties. Therefore, their inclusion is crucial for an accurate theoretical description of this process.
Implications of dark sector mixing on leptophilic scalar dark matter
Authors: Chakraborti Sreemanti , Islam Rashidul
Published: March 2021

Abstract

We propose a new viable outlook to the mixing between a singlet and a doublet leptonic dark sector fields. This choice relaxes the dark matter (DM) search constraints on the quintessential scalar singlet DM as well as presents new opportunities for its detection in the lab. The mixing produces an arbitrary mass difference between the two components of the extra doublet in a gauge-invariant way, without introducing any new scale of electroweak symmetry breaking in the theory. It also provides a useful handle to distinguish between the dark sector particles of different isospins, which is a challenging task other-wise. As the dark leptons coannihilate non-trivially, the mixing effectively enhances the viable parameter space for the relic density constraint. In low DM mass regime, our analysis shows that with a non-zero mixing, it is possible to relax the existing indirect search bounds on the upper limit of the DM-Standard Model coupling. From the analysis of the $$ 3\tau +{E}_T^{\mathrm{miss}} $$
3
τ
+

E
T
miss

and $$ \mathrm{\ell}\tau +{E}_T^{\mathrm{miss}} $$
ℓ
τ
+

E
T
miss

channels for LHC at $$ \sqrt{s} $$

s

= 13 TeV, we show that one ensures the presence of the mixing parameter between the dark sector particles of the theory by looking at the peak and tail positions of the kinematic distributions. Even with a tweak in the values of other free parameters within the viable parameter region, the distinct peak and tail positions of the kinematic distributions remains a constant feature of the model. While both the channels present us the opportunity to detect the mixing signature at the LHC/HL-LHC, the former gives better results in terms of a larger region of mixing parameter. From the fiducial cross section, the projected statistical significance for the integrated luminosity, $$ \mathcal{L} $$
L
= 3 ab−1, are shown for a combined parameter region obeying all the existing constraints, where there is the best possibility to detect such a signature.
Complement to thermodynamics of dyonic Taub-NUT-AdS spacetime
Authors: Mann Robert B. , Pando Zayas Leopoldo A. , Park Miok
Published: March 2021

Abstract

We examine the thermodynamics of Euclidean dyonic Taub-Nut/Bolt-AdS4 black holes for a variety of horizon geometries to understand how gauge field regularity conditions influence the thermodynamic relations. We find several distinct features that distinguish the NUT-charged case from its dyonic Reissner-Nordstrom counterpart. For the Nut solution, the gauge field vanishes at the horizon and so regularity is ensured. For the Bolt solution we find that the norm of the gauge field is required to vanish at the horizon in order to satisfy both regularity and the first law of thermodynamics. This regularity condition yields a constraint on the electric and magnetic charges and so reduces cohomogeneity of the system; for spherical horizons, the regularity condition removing the Misner string singularity further reduces cohomogeneity. We observe that bolt solutions with increasing electric charge have positive heat capacity, but upon turning on the magnetic charge to make the solution dyonic, we find that the properties of the uncharged one are retained, having both positive and negative heat capacity. We also study the extremal Bolt solution, finding that Misner string disappears at the horizon in the zero temperature limit. We find that the extremal solution has finite-temperature-like behaviour, with the electric potential playing a role similar to temperature.
A categorified Dold-Kan correspondence
Authors: Dyckerhoff Tobias
Published: March 2021

In this work, we establish a categorification of the classical Dold-Kan correspondence in the form of an equivalence between suitably defined $$\infty $$
∞
-categories of simplicial stable $$\infty $$
∞
-categories and connective chain complexes of stable $$\infty $$
∞
-categories. The result may be regarded as a contribution to the foundations of an emerging subject that could be termed categorified homological algebra.
Experimentelle Untersuchung von Einflussgrößen auf das Rasselgeräuschverhalten von Stirnrädern
Authors: Namhoff Christian , Kasten Marcel , Brimmers Jens , Brecher Christian
Published: March 2021

Die Reduzierung von Störgeräuschen spielt eine wesentliche Rolle im Entwicklungsprozess eines Automobils. Neben dem tonalen Getriebeheulen ist das impulsartige Rasselgeräusch in der Fahrerkabine relevant. Das Getrieberasseln entsteht durch eine Drehungleichförmigkeit im Triebstrang, die durch den ungleichförmigen Verbrennungsprozess des Verbrennungsmotors aufgeprägt wird. Die Zahnflanken heben bei Überschreitung einer bestimmten Winkelbeschleunigungsamplitude voneinander ab und bewegen sich innerhalb ihres Verdrehflankenspiels, sodass Schwingungsstöße entstehen. In diesem Bericht wird die experimentelle Untersuchung der Einflüsse Anregungsfrequenz, Schleppmoment und Schmierstoff auf das Rasselgeräuschverhalten von Stirnrädern vorgestellt. Die Rasselgrenze ist durch einen signifikanten Anstieg im Körperschall- und Drehbeschleunigungspegel sowie durch Impulse im Zeitverlauf des Körperschalls und der Drehbeschleunigung zu erkennen. Die Anregungsfrequenz der Drehzahlschwankung beeinflusst die Anzahl an Verdrehflankenstößen pro Umdrehung und führt tendenziell bei einer Zunahme zu einer verringerten Rasselgrenze. Nach Überschreiten der Rasselgrenze erfolgt eine Annäherung der Körperschallpegel von aufgeprägten Drehzahlschwankungen unterschiedlicher Anregungsfrequenzen und ab einer bestimmten Drehzahlschwankungsamplitude sind die Körperschallpegel miteinander vergleichbar. Bei steigendem Schleppmoment nimmt die Drehzahlschwankungsamplitude tendenziell zu, bei welcher die Prüfverzahnung anfängt zu rasseln. Die Rasselgrenze wird durch das Schleppmoment beeinflusst – nach dem Überschreiten der Rasselgrenze weichen jedoch weder die Körperschallpegel noch die Drehbeschleunigungspegel bei unterschiedlich wirkenden Schleppmomenten signifikant voneinander ab. Der Schmierstoff zeigt bei den gewählten Versuchsparametern den höchsten Einfluss auf das Rasselgeräuschverhalten der Prüfverzahnung beim Vergleich der Schmierstoffe SAE 0W-16 und SAE 85W-90. Die Körperschallverläufe weisen im Zeitbereich bei Betrachtung der Abklingkurven bei konstanter Drehzahlschwankungsamplitude auf eine höhere Dämpfung des Schmierstoffs SAE 85W-90 mit höherer Schmierstoffviskosität hin. Der Dämpfungseffekt des Öls nimmt mit zunehmender Anregungsfrequenz bei konstanter Drehzahlschwankungsamplitude ab.
Correction to: A Unifying View on SMT-Based Software Verification
Authors: Beyer Dirk , Dangl Matthias , Wendler Philipp
Published: March 2021

The article “A Unifying View on SMT-Based Software Verification”, written by Dirk Beyer, Matthias Dangl, and Philipp Wendler, was originally published Online First without Open Access
Hidden figures: epistemic costs and benefits of detecting (invisible) diversity in science
Authors: Peters Uwe
Published: March 2021

Demographic diversity might often be present in a group without group members noticing it. What are the epistemic effects if they do? Several philosophers and social scientists have recently argued that when individuals detect demographic diversity in their group, this can result in epistemic benefits even if that diversity doesn’t involve cognitive differences. Here I critically discuss research advocating this proposal, introduce a distinction between two types of detection of demographic diversity, and apply this distinction to the theorizing on diversity in science. Focusing on ‘invisible’ diversity (i.e., differences in, e.g., LGBTQ+, religious, or political orientation), I argue that in one common kind of group in science, if group members have full insight into their group’s diversity, this is likely to create epistemic costs. These costs can be avoided and epistemic benefits gained if group members only partly detect their group’s diversity. There is thus an epistemic reason for context-dependent limitations on scientists’ insight into the diversity of their group.
Assessment of selected major and trace elements in groundwater of Lagos based on land use and implication on human health
Authors: Odukoya Abiodun Mary , Ifarajinmi Wiiiiams Temitope
Published: March 2021

Sixty-seven (67) groundwater samples from different land use areas such as dumpsites, industrial, markets and residential all within Lagos, southwest Nigeria, were sampled and sent to ACME Laboratories, Ontario, Canada, for geochemical analysis to determine some essential and toxic elements using inductively coupled plasma-mass spectrometer method. The purpose was to establish baseline values for the geochemical composition of groundwater in some parts of Lagos as well as the health risk assessment. Based on essential elements, 83%, 80% and 100% of groundwater samples were deficient in Ca, Mg and Se, respectively, while 75%, 10%, 7% and 8% of samples can be categorised as soft, moderately hard, hard and very hard water, respectively. The soft water, as well as different deficiencies in water, had been linked to heart problems, impeded growth, fertility disorders and liver diseases. Concentrations of As, Cd, Cr, Pb, Ni and Fe were higher than recommended standards in 2.94%, 1.5%, 1.5%, 29.4%, 4.4% and 4.7% of groundwater samples, respectively. Groundwater in the study area can be classified between not contaminated (< 1) to very highly contaminated (CI > 5) based on the contamination index. Highly contaminated samples were within dumpsites and industrial areas. The land-use activities have a direct or indirect impact on groundwater quality. The apparent sources of groundwater pollutants include industrial discharge, effluents, leachates and municipal wastes. The result of total health risk index for both ingestion and dermal exposure to water showed values far > 1 for all the toxic elements and generally pose non-carcinogenic health risk hazards for child and adult population in the study area. THI for samples from residential, market, industrial and dumpsites showed mean values of (9.60 and 3.75), (14.17 and 5.37), (9.8 and 3.4) and 95.44 and 37.48) for child and adult population, respectively. The degree of contamination in groundwater showed the following trends: dumpsite > industrial > markets > residential in the study area.
Toolunterstützung für den Übungsbetrieb in der Datenbanklehre: Erfahrungen mit der Software Praktomat
Authors: Ehrlinger Christina , Fritsch Thomas , Fruth Michael , Lehner Franz , Scherzinger Stefanie
Published: March 2021

In diesem Artikel berichten wir über den erstmaligen Einsatz der Software Praktomat im Rahmen einer einführenden Datenbankvorlesung an der Universität Passau. Unser Ziel war es, den ca. 300 Studierenden aus Informatik und Wirtschaftsinformatik während des „Corona-Semesters“ die Möglichkeit zu bieten, Anfragen in relationaler Algebra und SQL im Selbststudium zu üben und dabei automatisierte Rückmeldungen zu bekommen. Insbesondere wollten wir kein neues E‑Learning-System von Grund auf implementieren, sondern auf einem bestehenden, quelloffenen Werkzeug aufsetzen. Wir beschreiben in diesem Artikel die notwendigen Anpassungen der Praktomat-Software, ursprünglich für die grundständige Programmierausbildung konzipiert. Wir evaluieren den Zufriedenheitserfolg unserer Studierenden und berichten weiter anekdotisch über die Erfahrungen der Studierenden und Lehrenden.
Homotopy theory of monoids and derived localization
Authors: Chuang Joe , Holstein Julian , Lazarev Andrey
Published: March 2021

We use derived localization of the bar and nerve constructions to provide simple proofs of a number of results in algebraic topology, both known and new. This includes a recent generalization of Adams’s cobar-construction to the non-simply connected case, and a new algebraic model for the homotopy theory of connected topological spaces as an $$\infty $$
∞
-category of discrete monoids.
Spontaneous Versus Controlled Mechanical Ventilation in Patients with Acute Respiratory Distress Syndrome
Authors: Aslam Tayyba Naz , Klitgaard Thomas Lass , Hofsø Kristin , Rasmussen Bodil Steen , Laake Jon Henrik
Published: March 2021

Purpose of Review

To review clinical evidence on whether or not to allow mechanically ventilated patients with acute respiratory distress syndrome (ARDS) to breathe spontaneously.

Recent Findings

Observational data (LUNG SAFE study) indicate that mechanical ventilation allowing for spontaneous breathing (SB) is associated with more ventilator-free days and a shorter stay in the intensive care unit without any effect on hospital mortality. A paediatric trial, comparing airway pressure release ventilation (APRV) and low-tidal volume ventilation, showed an increase in mortality in the APRV group. Conversely, in an unpublished trial comparing SB and controlled ventilation (NCT01862016), the authors concluded that SB is feasible but did not improve outcomes in ARDS patients.

A paucity of clinical trial data continues to prevent firm guidance on if or when to allow SB during mechanical ventilation in patients with ARDS. No published large randomised controlled trial exists to inform practice about the benefits and harms of either mode.
Messdatenbasierte Gefährdungsbeurteilung
Authors: Seidel David H. , Ellegast Rolf P. , Rieger Monika A. , Steinhilber Benjamin , Weber Britta
Published: March 2021

Hintergrund

Beobachtungsbasierte Methoden zur Gefährdungsbeurteilung physischer Belastungen im Bereich der oberen Extremität können durch subjektive Erfahrungen der Untersuchenden beeinflusst werden. Darüber hinaus ist eine Quantifizierung biomechanischer Belastungen, wie Zeitverläufe von Gelenkwinkeln, Winkelgeschwindigkeiten oder Kräften durch Beobachtungen, schwer möglich. Zur objektiven Quantifizierung von Expositionen im Rahmen von spezifischen Gefährdungsbeurteilungen eignen sich daher vor allem messtechnische Methoden, wobei die Auswahl der entsprechenden Methode herausfordernd sein kann.

Zielsetzung

Dieser Artikel soll Arbeitsschutzfachleute dabei unterstützen, aus der Bandbreite der unterschiedlichen Verfahren die geeignete messtechnische Methode für eine vorliegende Expositionssituation zu identifizieren.

Methoden

Ausgehend von einer Literaturübersicht wurden Messmethoden für die obere Extremität in Anlehnung an ein etabliertes Kategoriensystem hinsichtlich ihrer Komplexität klassifiziert. Zusätzlich werden Anwendungsbeispiele für alle Kategorien skizziert.

Ergebnisse

Dieser Artikel liefert eine Übersicht und Klassifizierung von unterschiedlichen messtechnischen Erfassungs- und Bewertungsmethoden arbeitsbezogener Muskel-Skelett-Belastungen, die in 3 Kategorien von einfach bis komplex eingeteilt werden.

Diskussion

Vereinfachte Sensorik in Kombination mit spezifischen Bewertungsansätzen kann zukünftig die objektive Gefährdungsbeurteilung physischer Belastungen unterstützen.
GIS-Based Multi-Criteria and Multi-Objective Evaluation for Sustainable Land-Use Planning (Case Study: Qaleh Ganj County, Iran) “Landuse Planning Using MCE and Mola”
Authors: Masoudi Malihe , Centeri Csaba , Jakab Gergely , Nel Lyndré , Mojtahedi Mehdi
Published: March 2021

Land evaluation is a key factor in land-use spatial planning, affecting both success and sustainability. This study showcases the value of using the multi-criteria evaluation (MCE) and multi-objective land allocation (MOLA) GIS decision-making tools determine the most favorable spatial development of various land-use types, for Qaleh Ganj County in Iran. Weighted linear combination (WLC) and ordered weighted averaging (OWA) were used to assess the potential of seven land uses based on predefined criteria. MOLA was also used for land-use zoning based on suitability. The results derived from these techniques indicate that the rangeland zone with 30.80% and the ecotourism zone with 22.9% have the highest suitability potential, and aquaculture with 0.26% and tourism with 0.24% have the lowest potential in Qaleh Ganj. Considering the 7 land uses and a lot of defined criteria, MCE and MOLA provided an automatic and flexible way of dealing with qualitative multi-dimensional environmental effects, factors, constraints and objectives. The combination of WLC and OWA helped to manage selection factors differently, as their level of risk and trade-off is different. The result can be considered as optimal suitability maps with an environmental preservation goal which can help to protect the natural environment of this area, and will also allow for continued economic development. The approach described in this study can help developing countries and the sensitive area facing environmental challenges due to rapid development. This approach and its application procedures can be applied to similar territorial contexts, where several territorial factors should be considered and taken into account.
Robust force and displacement control of an active landing gear for vibration reduction at touchdown and during taxiing
Authors: Pirooz Mehran , Mirmahdi Seyed Hossein , Khoogar Ahmad Reza
Published: March 2021

In this paper, a new approach is proposed to control the dynamic response of a landing gear system subjected to runway force, both on heavy landing conditions and at the taxiing process. The mathematical model of the system is used in a way that covers nonlinear dynamics characteristics of landing gear and nonlinear/nonaffine property of the external actuator. The operation of the landing gear system and its components are described briefly. The desired control system includes two different interior loops for displacement and force control. The inner loop determines the actuator force and the outer loop performs the displacement control. A lumped uncertainty is considered in both displacement and force control loops that represent uncertainties including parametric errors, measurement noises, unmodeled dynamics, disturbance due to runway excitation, and other disturbances. The direct method of Lyapunov is utilized for asymptotic stability analysis of the robust nonlinear control system (RNCS). This system is simulated in MATLAB software and the performance of the proposed controller is analyzed exactly. Besides, the results are compared with a passive system and conventional PID control. The comparison indicates that RNCS works better and more precisely. This method can reduce vibrations at touchdown and taxiing and effectively overcome uncertainty and provide well aircraft handling by decreasing the changes in tire force.
Urbanization, long-run growth, and the demographic transition
Authors: Adams Jonathan J.
Published: March 2021

Advanced economies undergo three transitions during their development: (1) transition from a rural to an urban economy, (2) transition from low-income growth to high-income growth, (3) transition from high fertility and mortality rates to low modern levels. The timings of these transitions are correlated in the historical development of most advanced economies. I consider a nonlinear model of endogenous long-run economic and demographic change, in which child quantity-quality substitution is driven by declining child mortality. Because the model captures the interactions between all three transitions, it is able to explain three additional empirical patterns: a declining urban-rural wage gap, a declining rural-urban family size ratio, and most surprisingly, that early urbanization slows development. This third prediction distinguishes the model from other theories of long-run growth, and I document evidence for it in cross-country data.
War Captives, Left-Behind Wives, and Buddhist Nuns: Female Migrants in Early Medieval China (4th–6th Century CE)
Authors: Huang Wen-Yi
Published: March 2021

Using received texts and excavated funerary epitaphs, this article examines the intricacies of gender and migration in early medieval China by exploring women's long-distance mobility from the fourth century to the sixth century, when what is now known as China was divided by the Northern Wei and a succession of four southern states—the Eastern Jin, Liu-Song, Southern Qi, and Liang. I focus on three types of migration in which women participated during this period: war-induced migration, family reunification, and religious journeys. Based on this analysis, I propose answers to two important questions: the connection between migration and the state, and textual representations of migrants. Though the texts under consideration are usually written in an anecdotal manner, the references to women, I argue, both reveals nuances in perceptions of womanhood at the time and elucidates the contexts within—and through—which long-distance travel became possible for women.
The quality of wine between innovation and tradition. A study of a changing ‘Mediterranean drinking culture’
Authors: Beccaria Franca , Pretto Albertina
Published: March 2021

Wine consumption is affected by intertwined needs generated by factors such as production and marketing methods, as well as by the individual's desire for social differentiation in a democratised mass drinking culture. Our study sought to determine whether consumption patterns have changed in the Italian province of Trentino and how such changes may have affected the meaning that wine drinkers living in this area assign to the concept of quality in wine. The paper presents a qualitative study (n=57 interviews) carried out in a wine producing region in north-east Italy. In addition to investigating the changes that have taken place in the area's wine drinking culture, the study also focuses on how consumers perceive and define wine quality. The findings show that economic, political and social factors have brought major changes in drinking culture and consumption over the last 50 years. In addition, changes in the wine industry have had a significant impact on how consumers’ views on wine quality and its key features have evolved. Nevertheless, the study found that some traditional aspects persist in the drinking culture and still determine the perception of quality.
Idea generation with Technology Semantic Network
Authors: Sarica Serhad , Song Binyang , Luo Jianxi , Wood Kristin L.
Published: March 2021

There are growing efforts to mine public and common-sense semantic network databases for engineering design ideation stimuli. However, there is still a lack of design ideation aids based on semantic network databases that are specialized in engineering or technology-based knowledge. In this study, we present a new methodology of using the Technology Semantic Network (TechNet) to stimulate idea generation in engineering design. The core of the methodology is to guide the inference of new technical concepts in the white space surrounding a focal design domain according to their semantic distance in the large TechNet, for potential syntheses into new design ideas. We demonstrate the effectiveness in general, and use strategies and ideation outcome implications of the methodology via a case study of flying car design idea generation.
Orexin A promotes progesterone secretion in luteinized granulose cells of Mongolian Ovis aries ovary by PRRT2 and ABCG1 genes
Authors: Xie Mengyuan , Han Dong , Xu Xiaojing
Published: March 2021

To study the role of orexin A in the reproductive regulation of Mongolian sheep, ovine ovarian granulosa cells were cultured in vitro. The cells were divided into groups after luteinization, the experimental group was given orexin A and the transcriptome was sequenced together with that of the control group. The different genes related to reproduction were screened out. qRT-PCR, western blot and enzyme-linked immunosorbent assay (ELISA) were used to verify the selected genes and detect the effect on progesterone secretion. In total, 123 differentially expressed genes were obtained by sequencing. Six genes with high expression related to reproduction (PRRT2, ABCG1, SOX4, TBX3, ID1 and ATP8) were screened. The results of qRT-PCR were consistent with those of sequencing; western blot and ELISA were used to verify the protein levels of steroidogenic acute regulatory protein (StAR) and its related PRRT2 and ABCG1, and to detect their effect on progesterone secretion. Validation results were consistent with those of qRT-PCR and sequencing. The experimental group was given orexin A and compared with the control group. Expression of PRRT2 protein was significantly increased (P < 0.05), ABCG1 protein expression was significantly decreased (P < 0.05), StAR expression was significantly increased (P < 0.05), and progesterone secretion was significantly increased (P < 0.05). The results showed that orexin A promoted the expression of StAR by upregulating PRRT2 and downregulating ABCG1, therefore affecting secretion of progesterone. Gene expression characteristics of orexin A affecting progesterone secretion were preliminarily explored; this study provides a theoretical basis for further study on signalling pathways and reproductive regulation in Mongolian sheep.
The Properties of Annually Laminated Stalagmites‐A Global Synthesis
Authors: Baker Andy , Mariethoz Gregoire , Comas‐Bru Laia , Hartmann Andreas , Frisia Silvia , Borsato Andrea , Treble Pauline C. , Asrat Asfawossen
Published: March 2021

Annually laminated speleothems have the potential to provide information on high‐frequency climate variability and, simultaneously, provide good chronological constraints. However, there are distinct types of speleothem annual laminae, from physical to chemical, and a common mechanism that links their formation has yet to be found. Here, we analyzed annually laminated stalagmites from 23 caves and 6 continents with the aim to find if there are common mechanisms underlying their development. Annually laminated stalagmites are least common in arid and semiarid climates, and most common in regions with a seasonality of precipitation. At a global scale, we observe faster growth rates with increasing mean annual temperature and decreasing latitude. Changepoints in average growth rates are infrequent and age‐depth relationships demonstrate that growth rates can be approximated to be constant. In general, annually laminated stalagmites are characterized by centennial‐scale stability in calcite precipitation due to a sufficiently large and well‐mixed water source, a time series spectrum showing first‐order autoregression due to mixing of stored water and annual recharged water, and an inter‐annual flickering of growth acceleration, bringing growth rates back to the long‐term mean. Climate forcing of growth rate variations is observed where a multi‐year climate signal is strong enough to be the dominant control on calcite growth rate variability, such that it retains a climate imprint after smoothing of this signal by mixing of stored water. In contrast, long‐term constant growth rate of laminated stalagmites adds further robustness to their unparalleled capacity to improve accuracy of chronology building.
Splenectomy improves liver fibrosis via tumor necrosis factor superfamily 14 (LIGHT) through the JNK/TGF-β1 signaling pathway
Authors: Liang Qing-shan , Xie Jian-Gang , Yu ChaoPing , Feng ZhuSheng , Ma JingChang , Zhang Yuan , Wang Dong , Lu JianGuo , Zhuang Ran , Yin Jikai
Published: March 2021

Splenectomy has been reported to improve liver fibrosis in patients with cirrhosis and hypersplenism. However, the mechanisms remain unclear. Tumor necrosis factor superfamily 14 (TNFSF14; also known as LIGHT) is highly expressed in the context of fibrosis and promotes disease progression in patients with fibrotic diseases such as pulmonary and skin fibrosis. Here, we determined whether splenectomy controls the production of LIGHT to improve liver fibrosis. Splenectomy reduced serum LIGHT levels in cirrhotic patients with hypersplenism and a ConA-induced liver fibrosis mouse model. Blocking LIGHT resulted in the downregulation of TGF-β1 in RAW264.7 cells. LIGHT treatment of RAW264.7 and JS1 cells in coculture regulated transforming growth factor-β1 (TGF-β1) expression through the activation of JNK signaling. Small interfering RNA-mediated silencing of lymphotoxin β receptor (LTβR) in macrophages resulted in pronounced decreases in the levels of fibrosis and αSMA in JS1 cells. These results indicated that LIGHT bound to LTβR and drove liver fibrosis in vitro. Blocking TGF-β1 abolished the effect of LIGHT in vitro. Furthermore, the administration of recombinant murine LIGHT protein-induced liver fibrosis with splenectomy, while blocking LIGHT without splenectomy improved liver fibrosis in vivo, revealing that the decrease in fibrosis following splenectomy was directly related to reduced levels of LIGHT. Thus, high levels of LIGHT derived from the spleen and hepatic macrophages activate JNK signaling and lead to increased TGF-β1 production in hepatic macrophages. Splenectomy attenuates liver fibrosis by decreasing the expression of LIGHT.
Effects of alpha-glucosidase-inhibiting drugs on acute postprandial glucose and insulin responses: a systematic review and meta-analysis
Authors: Alssema Marjan , Ruijgrok Carolien , Blaak Ellen E. , Egli Léonie , Dussort Pierre , Vinoy Sophie , Dekker Jacqueline M. , Denise Robertson M.
Published: March 2021

Background/objectives

Despite considerable literature supporting the potential health benefits of reducing postprandial glucose (PPG), and insulin (PPI) exposures, the size of a clinically relevant reduction is currently unknown. We performed a systematic review and meta-analysis to quantify effects of alpha-glucosidase-inhibiting (AGI) drugs on acute PPG and PPI responses.

Methods

We searched EMBASE and MEDLINE until March 13, 2018 for controlled studies using AGI drugs together with a standardized carbohydrate load or mixed meal. The mean incremental PPG and PPI levels were calculated as outcomes. Meta-analyses, stratified by diabetes state, were performed by using random effects models.

Results

The 66 included publications comprised 127 drug-control comparisons for PPG, and 106 for PPI, mostly testing acarbose or miglitol. The absolute effects on PPG were larger among individuals with diabetes (−1.5 mmol/l mean PPG [95% CI −1.9, −1.1] by acarbose, and −1.6 [−1.9, −1.4] by miglitol) as compared to individuals without diabetes (−0.4 [95% CI −0.5, −0.3] by acarbose, and −0.6 [−0.8, −0.4] by miglitol). Relative reductions in PPG by both drugs were similar for diabetic and non-diabetic individuals (43−54%). Acarbose and miglitol also significantly reduced mean PPI, with absolute and relative reductions being largest among individuals without diabetes.

Conclusions

The present meta-analyses provide quantitative estimates of reductions of PPG and PPI responses by AGI drugs in diabetes and non-diabetic individuals. These data can serve as benchmarks for clinically relevant reductions in PPG and PPI via drug or diet and lifestyle interventions.
OTS167 blocks FLT3 translation and synergizes with FLT3 inhibitors in FLT3 mutant acute myeloid leukemia
Authors: Eisfelder Bartholomew J. , Saygin Caner , Wynne Joseph , Colton Margaret W. , Fischietti Mariafausta , Beauchamp Elspeth M. , Cheng Jason X. , Odenike Olatoyosi , Roboz Gail , Alachkar Houda , Stock Wendy
Published: March 2021

Internal tandem duplication (-ITD) mutations of Fms-like tyrosine kinase 3 (FLT3) provide growth and pro-survival signals in the context of established driver mutations in FLT3 mutant acute myeloid leukemia (AML). Maternal embryonic leucine zipper kinase (MELK) is an aberrantly expressed gene identified as a target in AML. The MELK inhibitor OTS167 induces cell death in AML including cells with FLT3 mutations, yet the role of MELK and mechanisms of OTS167 function are not understood. OTS167 alone or in combination with tyrosine kinase inhibitors (TKIs) were used to investigate the effect of OTS167 on FLT3 signaling and expression in human FLT3 mutant AML cell lines and primary cells. We describe a mechanism whereby OTS167 blocks FLT3 expression by blocking FLT3 translation and inhibiting phosphorylation of eukaryotic initiation factor 4E–binding protein 1 (4E-BP1) and eukaryotic translation initiation factor 4B (eIF4B). OTS167 in combination with TKIs results in synergistic induction of FLT3 mutant cell death in FLT3 mutant cell lines and prolonged survival in a FLT3 mutant AML xenograft mouse model. Our findings suggest signaling through MELK is necessary for the translation and expression of FLT3-ITD, and blocking MELK with OTS167 represents a viable therapeutic strategy for patients with FLT3 mutant AML.
GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia
Authors: Zhou Cheng , Du Juan , Zhao Liang , Liu Wei , Zhao Tianming , Liang Hui , Fang Peng , Zhang Kaixuan , Zeng Hui
Published: March 2021

Acute myeloid leukemia (AML) is a hematological malignancy with high incidence and recurrence rates. Gene expression profiling has revealed that transcriptional overexpression of glioma‐associated oncogene 1 (GLI1), a vital gene in the Hedgehog (Hh) signaling pathway, occurs in poor-prognosis AML, and high levels of phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1) and AKT3 predict shorter overall survival in AML patients. In this study, we discovered that GLI1 overexpression promotes cell proliferation and reduces chemotherapy sensitivity in AML cells while knocking down GLI1 has the opposite effect. Moreover, GLI1 promoted cell cycle progression and led to elevated protein levels of cyclins and cyclin-dependent kinases (CDKs) in AML cells. By luciferase assays and co-immunoprecipitation, we demonstrated that the PI3K/AKT pathway is directly activated by GLI1. GLI1 overexpression significantly accelerates tumor growth and upregulated p-AKT, CDK4, and cyclinD3 in vivo. Notably, the GLI1 inhibitor GANT61 and the CDK4/6 inhibitor PD 0332991 had synergistic effects in promoting Ara-c sensitivity in AML cell lines and patient samples. Collectively, our data demonstrate that GLI1 reduces drug sensitivity by regulating cell cycle through the PI3K/AKT/GSK3/CDK pathway, providing a new perspective for involving GLI1 and CDK4/6 inhibitors in relapsed/refractory (RR) patient treatment.
Sodium iodate induces ferroptosis in human retinal pigment epithelium ARPE-19 cells
Authors: Liu Binghua , Wang Weiyan , Shah Arman , Yu Meng , Liu Yang , He Libo , Dang Jinye , Yang Li , Yan Mengli , Ying Yuling , Tang Zihuai , Liu Ke
Published: March 2021

Sodium iodate (SI) is a widely used oxidant for generating retinal degeneration models by inducing the death of retinal pigment epithelium (RPE) cells. However, the mechanism of RPE cell death induced by SI remains unclear. In this study, we investigated the necrotic features of cultured human retinal pigment epithelium (ARPE-19) cells treated with SI and found that apoptosis or necroptosis was not the major death pathway. Instead, the death process was accompanied by significant elevation of intracellular labile iron level, ROS, and lipid peroxides which recapitulated the key features of ferroptosis. Ferroptosis inhibitors deferoxamine mesylate (DFO) and ferrostatin-1(Fer-1) partially prevented SI-induced cell death. Further studies revealed that SI treatment did not alter GPX4 (glutathione peroxidase 4) expression, but led to the depletion of reduced thiol groups, mainly intracellular GSH (reduced glutathione) and cysteine. The study on iron trafficking demonstrated that iron influx was not altered by SI treatment but iron efflux increased, indicating that the increase in labile iron was likely due to the release of sequestered iron. This hypothesis was verified by showing that SI directly promoted the release of labile iron from a cell-free lysate. We propose that SI depletes GSH, increases ROS, releases labile iron, and boosts lipid damage, which in turn results in ferroptosis in ARPE-19 cells.
Evolution of combinatorial diversity in trans-acyltransferase polyketide synthase assembly lines across bacteria
Authors: Helfrich Eric J. N. , Ueoka Reiko , Chevrette Marc G. , Hemmerling Franziska , Lu Xiaowen , Leopold-Messer Stefan , Minas Hannah A. , Burch Adrien Y. , Lindow Steven E. , Piel Jörn , Medema Marnix H.
Published: March 2021

Trans-acyltransferase polyketide synthases (trans-AT PKSs) are bacterial multimodular enzymes that biosynthesize diverse pharmaceutically and ecologically important polyketides. A notable feature of this natural product class is the existence of chemical hybrids that combine core moieties from different polyketide structures. To understand the prevalence, biosynthetic basis, and evolutionary patterns of this phenomenon, we developed transPACT, a phylogenomic algorithm to automate global classification of trans-AT PKS modules across bacteria and applied it to 1782 trans-AT PKS gene clusters. These analyses reveal widespread exchange patterns suggesting recombination of extended PKS module series as an important mechanism for metabolic diversification in this natural product class. For three plant-associated bacteria, i.e., the root colonizer Gynuella sunshinyii and the pathogens Xanthomonas cannabis and Pseudomonas syringae, we demonstrate the utility of this computational approach for uncovering cryptic relationships between polyketides, accelerating polyketide mining from fragmented genome sequences, and discovering polyketide variants with conserved moieties of interest. As natural combinatorial hybrids are rare among the more commonly studied cis-AT PKSs, this study paves the way towards evolutionarily informed, rational PKS engineering to produce chimeric trans-AT PKS-derived polyketides.
In situ identification of the metallic state of Ag nanoclusters in oxidative dispersion
Authors: Li Rongtan , Xu Xiaoyan , Zhu Beien , Li Xiao-Yan , Ning Yanxiao , Mu Rentao , Du Pengfei , Li Mengwei , Wang Huike , Liang Jiajie , Chen Yongsheng , Gao Yi , Yang Bing , Fu Qiang , Bao Xinhe
Published: March 2021

Oxidative dispersion has been widely used in regeneration of sintered metal catalysts and fabrication of single atom catalysts, which is attributed to an oxidation-induced dispersion mechanism. However, the interplay of gas-metal-support interaction in the dispersion processes, especially the gas-metal interaction has not been well illustrated. Here, we show dynamic dispersion of silver nanostructures on silicon nitride surface under reducing/oxidizing conditions and during carbon monoxide oxidation reaction. Utilizing environmental scanning (transmission) electron microscopy and near-ambient pressure photoelectron spectroscopy/photoemission electron microscopy, we unravel a new adsorption-induced dispersion mechanism in such a typical oxidative dispersion process. The strong gas-metal interaction achieved by chemisorption of oxygen on nearly-metallic silver nanoclusters is the internal driving force for dispersion. In situ observations show that the dispersed nearly-metallic silver nanoclusters are oxidized upon cooling in oxygen atmosphere, which could mislead to the understanding of oxidation-induced dispersion. We further understand the oxidative dispersion mechanism from the view of dynamic equilibrium taking temperature and gas pressure into account, which should be applied to many other metals such as gold, copper, palladium, etc. and other reaction conditions.
Gain-switched semiconductor laser driven soliton microcombs
Authors: Weng Wenle , Kaszubowska-Anandarajah Aleksandra , He Jijun , Lakshmijayasimha Prajwal D. , Lucas Erwan , Liu Junqiu , Anandarajah Prince M. , Kippenberg Tobias J.
Published: March 2021

Dissipative Kerr soliton generation using self-injection-locked III-V lasers has enabled fully integrated hybrid microcombs that operate in turnkey mode and can access microwave repetition rates. Yet, continuous-wave-driven soliton microcombs exhibit low energy conversion efficiency and high optical power threshold, especially when the repetition frequencies are within the microwave range that is convenient for direct detection with off-the-shelf electronics. Here, by actively switching the bias current of injection-locked III-V semiconductor lasers with switching frequencies in the X-band and K-band microwave ranges, we pulse-pump both crystalline and integrated microresonators with picosecond laser pulses, generating soliton microcombs with stable repetition rates and lowering the required average pumping power by one order of magnitude to a record-setting level of a few milliwatts. In addition, we unveil the critical role of the phase profile of the pumping pulses, and implement phase engineering on the pulsed pumping scheme, which allows for the robust generation and the stable trapping of solitons on intracavity pulse pedestals. Our work leverages the advantages of the gain switching and the pulse pumping techniques, and establishes the merits of combining distinct compact comb platforms that enhance the potential of energy-efficient chipscale microcombs.
A scalable unified framework of total and allele-specific counts for cis-QTL, fine-mapping, and prediction
Authors: Liang Yanyu , Aguet François , Barbeira Alvaro N. , Ardlie Kristin , Im Hae Kyung
Published: March 2021

Genetic studies of the transcriptome help bridge the gap between genetic variation and phenotypes. To maximize the potential of such studies, efficient methods to identify expression quantitative trait loci (eQTLs) and perform fine-mapping and genetic prediction of gene expression traits are needed. Current methods that leverage both total read counts and allele-specific expression to identify eQTLs are generally computationally intractable for large transcriptomic studies. Here, we describe a unified framework that addresses these needs and is scalable to thousands of samples. Using simulations and data from GTEx, we demonstrate its calibration and performance. For example, mixQTL shows a power gain equivalent to a 29% increase in sample size for genes with sufficient allele-specific read coverage. To showcase the potential of mixQTL, we apply it to 49 GTEx tissues and find 20% additional eQTLs (FDR < 0.05, per tissue) that are significantly more enriched among trait associated variants and candidate cis-regulatory elements comparing to the standard approach.
Monitoring metallic sub-micrometric lithium structures in Li-ion batteries by in situ electron paramagnetic resonance correlated spectroscopy and imaging
Authors: Dutoit Charles-Emmanuel , Tang Mingxue , Gourier Didier , Tarascon Jean-Marie , Vezin Hervé , Salager Elodie
Published: March 2021

Monitoring the formation of dendrites or filaments of lithium is of paramount importance for Li-based battery technologies, hence the intense activities in designing in situ techniques to visualize their growth. Herein we report the benefit of correlating in situ electron paramagnetic resonance (EPR) spectroscopy and EPR imaging to analyze the morphology and location of metallic lithium in a symmetric Li/LiPF6/Li electrochemical cell during polarization. We exploit the variations in shape, resonance field and amplitude of the EPR spectra to follow, operando, the nucleation of sub-micrometric Li particles (narrow and symmetrical signal) that conjointly occurs with the fragmentation of bulk Li on the opposite electrode (asymmetrical signal). Moreover, in situ EPR correlated spectroscopy and imaging (spectral-spatial EPR imaging) allows the identification (spectral) and localization (spatial) of the sub-micrometric Li particles created by plating (deposition) or stripping (altered bulk Li surface). We finally demonstrate the possibility to visualize, via in situ EPR imaging, dendrites formed through the separator in the whole cell. Such a technique could be of great help in mastering the Li-electrolyte interface issues that plague the development of solid-state batteries.