bluuebunny/crossref_metadata_2025 huggingface dataset:
“All the pieces matter”
Authors: Ortiz García Javier
Published: September 2021

Este artículo aborda el problema de la traducción del lenguaje vulgar desde una perspectiva práctica. Para ello, se emplean ejemplos de tres episodios diferentes de la aclamada serieThe Wire, donde el uso de este tipo de lenguaje aparece en todos los estamentos sociales y profesionales de personajes. En primer lugar, se contextualiza la serie dentro del espectro televisivo del que procede, el estadounidense, y se analiza la importancia que en ella tiene el empleo del lenguaje vulgar. A continuación, se estudian las diferentes posibilidades estratégicas que el traductor puede emplear a la hora de traducir textos en los que aparece el lenguaje vulgar de manera reiterada. Por último, se examinan cualitativamente los tres ejemplos de la serie seleccionados y sus traducciones oficiales. Se concluye el estudio ofreciendo alternativas a esa traducción disponible en el mercado con el fin de ilustrar un posible visionado del programa más adecuado en el que se ha prestado especial atención al empleo del lenguaje vulgar traducido.
The expression of emotions in Kunbarlang and its neighbours in the multilingual context of western and central Arnhem Land
Authors: O’Keeffe Isabel , Singer Ruth , Coleman Carolyn
Published: September 2021

This paper explores how emotions are expressed in the endangered Gunwinyguan language Kunbarlang and compares these expressions to those in the neighbouring Gunwinyguan language Bininj Kunwok, and neighbouring languages from other language families, Mawng (Iwaidjan) and Ndjébbana (Maningridan). As well as considering body-based emotion expressions and the tropes (metaphors and metonymies) they instantiate, we consider the range of other (non-body-based) expressions and tropes available in each language. These provide an important point of comparison with the body-part expressions, which are limited to expressions based on noun incorporation in the Gunwinyguan languages and, correspondingly, a more limited range of tropes. By outlining and comparing the linguistic tropes used to express emotions in these four languages in the highly multilingual yet socioculturally unified context of western Arnhem Land, we aim to shed further light on the relationships between linguistic figurative features and conceptual representations of emotions.
Feeling through your chest
Authors: Bednall James
Published: September 2021

This article explores the expression and conceptualisation of emotions in Anindilyakwa (Gunwinyguan, north-east Arnhem Land). Fundamental to the emotional lexicon of this language is the widespread use of body parts, which frequently occur in figurative expressions. In this article I examine the primary body parts that occur in emotion descriptions in both literal (physical) and figurative expressions. Particular attention is given toyukudhukudha /-werrik- ‘chest’, the body part conceptualised as the primary site of emotion in Anindilyakwa and the most productive body-related morpheme used in emotion compounds. I consider the role of the chest and other productive body parts that occur in emotion compounds, and examine the metonymic and metaphorical devices that contribute to the expression of these emotional states. In doing so, I propose a number of overarching and widespread tropes that hold across different body-part compounds, and briefly contextualise these in relation to the emotion description systems of other closely-related (Gunwinyguan) languages.
Spatiotemporal evolution of sustainable development of China’s provinces: a modelling approach
Authors: Gao Junli , Shao Chaofeng , Chen Sihan , Zhang Xiaotong
Published: September 2021

Three sustainable development sub-indicators were established along with 49 indicators of sustainable development at the provincial level. We collected data for the key years of 2010, 2015, and 2018 and evaluated the sustainable development level of 31 provinces in China by using the best and worst value improved equal-weight TOPSIS method. With spatial autocorrelation and hotspot analysis, the spatial characteristics of the sustainable development level were studied. Grey correlation analysis and the offset degree index were also used to find out which indicators should be of most concern to improve the level of sustainable development. The results showed the following. (1) The level of sustainable development of China’s provinces is increasing, but there is a decrease from east to west. (2) In terms of sustainable development, the gap between the four major economic regions is narrowing. (3) The overall sustainable development level is highly consistent with the mainstream green development and the human development index, indicating that exploiting the driving force behind developing and improving the quality of development is the key to China’s sustainable development strategy. (4) Different measures should be taken to promote the realization of Sustainable Development Goals in different areas.
EGFR-mediated epidermal stem cell motility drives skin regeneration through COL17A1 proteolysis
Authors: Nanba Daisuke , Toki Fujio , Asakawa Kyosuke , Matsumura Hiroyuki , Shiraishi Ken , Sayama Koji , Matsuzaki Kyoichi , Toki Hiroshi , Nishimura Emi K.
Published: September 2021

Skin regenerative capacity declines with age, but the underlying mechanisms are largely unknown. Here we demonstrate a functional link between epidermal growth factor receptor (EGFR) signaling and type XVII collagen (COL17A1) proteolysis on age-associated alteration of keratinocyte stem cell dynamics in skin regeneration. Live-imaging and computer simulation experiments predicted that human keratinocyte stem cell motility is coupled with self-renewal and epidermal regeneration. Receptor tyrosine kinase array identified the age-associated decline of EGFR signaling in mouse skin wound healing. Culture experiments proved that EGFR activation drives human keratinocyte stem cell motility with increase of COL17A1 by inhibiting its proteolysis through the secretion of tissue inhibitor of metalloproteinases 1 (TIMP1). Intriguingly, COL17A1 directly regulated keratinocyte stem cell motility and collective cell migration by coordinating actin and keratin filament networks. We conclude that EGFR-COL17A1 axis–mediated keratinocyte stem cell motility drives epidermal regeneration, which provides a novel therapeutic approach for age-associated impaired skin regeneration.
Theoretical study on the favored alpha-decay half-lives of deformed nuclei
Authors: Hassanzad M. , Ghodsi O.N.
Published: September 2021

A systematic study on the α-decay half-lives of nuclei in the range

is performed by employing various versions of proximity potentials. To obtain more reliable results, deformation terms are included up to hexadecapole (

) in the spherical-deformed nuclear and Coulomb interaction potentials. First, the favored α-decay processes in this region are categorized as even-even, odd A, and odd-odd nuclei. Second, they are grouped into two transitions: ground state to ground state and ground state to isomeric states. Owing to the comparison of their root-mean-square deviations (RMSD's),

and

have the lowest values and better reproduce experimental data. Moreover, by considering preformation probability within the cluster formation model, the results validate the significant reduction in root-mean-square deviations obtained for different versions of proximity. Hence, the deviation between the calculated and experimental data is detracted.
Thermodynamic model of the activity of the comet 103P/Hartley*
Authors: Wesołowski Marcin
Published: September 2021

The paper presents three processes related to the dynamics of cometary particles. The following thermodynamic mechanisms were taken into account: quiet sublimation, emission of cometary matter via jet and migration of particles on the surface of the comet 103P/Hartley. Based on the first two mechanisms, the maximum particle size that can be lifted into the coma was determined. Additionally, in the case of a jet, the angle at which it is emitted from inside the cometary nucleus was determined. However, in the case of migration, the maximum width of individual belts within which a given particle can move was determined. In the context of the discussed mechanisms related to the activity of comet 103P/Hartley, the coefficient of friction and the structure of the solid or porous particles are of key importance.
DSC based Dual-Resunet for radio frequency interference identification
Authors: Zhang Yan-Jun , Li Yan-Zuo , Cheng Jun , Yan Yi-Hua
Published: September 2021

Radio frequency interference (RFI) will pollute the weak astronomical signals receivedby radio telescopes, which in return will seriously affect the time-domain astronomical observation and research. In this paper, we use a deep learning method to identify RFI in frequency spectrum data, and propose a neural network based on Unet that combines the principles of depthwise separable convolution and residual, named DSC Based Dual-Resunet. Compared with the existing Unet network, DSC Based Dual-Resunet performs better in terms ofaccuracy, F1 score, and MIoU, and is also better in terms of computation cost where the model size and parameter amount are 12.5% of Unet and the amount of computation is 38%ofUnet. The experimental results show that the proposed network is a high-performance and lightweight network, and it is hopeful to be applied to RFI identification of radio telescopes on a large scale.
Application of thermal gravimetric analysis and comparison of polyethylene films before and after exposure in various chemical solutions
Authors: Kojnoková T , Markovičová L , Nový F
Published: September 2021

In this paper, there are published experimental results of research in the field of polymers. The thermal analysis conveys information about changes in material effected by the melting of the material. The investigated material is low-density polyethylene (LD – PE). The LD – PE films were exposed to aggressive media with different values of potencia hydrogeni (pH). The experiment aims to apply thermal gravimetric analysis (TGA), one of the methods of thermal analysis. TGA monitors the weight of polyethylene films as a function of temperature. Original LD – PE film and the effect of media is evaluated based on TGA and evaluation of the surface morphology (macrostructure) after exposure. The largest weight loss is noticed in the original film without the influence of media. At 200 °C, the wax products are released from the material. During thermal analysis is observed a weight loss of up to 1 mg in the investigated film samples. LD – PE film after the effect of Coca-Cola has the highest decrease in mass and the most changed its macrostructure. LD – PE film after effect of Saponate has the lowest decrease in mass and its macrostructure is almost the same as the original LD – PE film after production technology.
The mechanical properties of coatings sprayed by electric arc for use in coal power plants
Authors: Šulcová P , Houdková Š , Duliškovič J
Published: September 2021

The components in coal power plants such as fire sides in boilers, preheaters, or heat exchangers are significantly mechanically and chemically stressed. The main stress originates from high temperature corrosion caused by the aggressive atmosphere inside the boiler, but other influences such as erosion and abrasion by coal and flying ash, heat shocks, etc. also have significant negative effect. One of the options for increasing the service life and improving the utility properties of these components is a thermal spray coating. Because the disassembly of these components is impossible, the mobile TWAS deposition technology was used. In this paper, different types of TWAS-sprayed coatings suitable for application in such environment are compared and evaluated. Two types of coating materials were evaluated, FeCr-based ones and NiCr-based ones, in terms of microstructure and mechanical properties such as hardness, adhesion, abrasion and erosion resistance. The SEM microscopy evaluation was used to evaluate the wear mechanism. It was found that the coatings with lower hardness but higher toughness resist the solid particle erosion better than hard but more brittle coatings. The experiences with the application of these coatings in selected areas on the fire side inside the boiler in the coal power plant are briefly reported.
Mechanical properties of additively manufactured builds from different 316L steel powders
Authors: Vavřík Jaroslav , Brázda Michal , Hodek Josef , Urbánek Miroslav , Prantl Antonín , Kiran Abhilash
Published: September 2021

In the present study, additively-manufactured (AM) specimens from 316L steel were investigated. The AM method used was Direct Energy Deposition (DED) where powder is fed continuously to a melt pool and is completely melted by high power laser. The melt pool rapidly solidifies on and beneath the substrate surface. To protect it from oxidation during deposition, argon is used as a shielding gas and is blown continuously to the melt pool. The DED process generates structures with minimum pores. 316L austenitic stainless steel was chosen for the experiments in order to avoid dealing with complex phase transformations during deposition. Four 316L powders supplied by four different companies were used and differences in the mechanical properties of the builds were examined. The process parameters were the same for each powder. There a number of studies on Selective Laser Melting (SLM) which explore the effects of powder properties on final mechanical properties of the builds. The underlying idea is to select a powder from a particular supplier to meet the customer required properties.
Investigation of thermal stability of Si0.7Ge0.3Si stacked multilayer with As ion-implantation
Authors: Wang Yanrong , Li Yongliang , Cheng Xiaohong , Wang Hanxiang , Yao Qide , Zhang Jing , Liu Wenkai , Wang Guilei , Yan Jiang , Wang Wenwu
Published: September 2021

The effect of As ion implantation on the stability of SiGe/Si multilayer was systematically studied. The atomic percentage of Ge in as-grown SiGe layer was 30% in this work. A thermally stable Si0.7Ge0.3/Si multilayer with As ion implantation was attained when the rapid thermal annealing (RTA) treatment temperature did not exceed 850 oC. Significant Ge diffusion was observed for the SiGe/Si multilayer with As ion implantation when the RTA temperature was 900 °C or above. However, minor Ge diffusion was attained for the SiGe/Si multilayer without As ion implantation when the RTA treatment temperature was 900 °C. Therefore, , compared with samples without As ion implantation, the stability window of the SiGe/Si multilayer with As ion implantation should be further reduced to 850 °C. As ion implantation plays a critical role in the stability of SiGe/Si multilayer, as it promotes the diffusion of Ge. Consequently, based on the stability of the SiGe/Si multilayer, the highest RTA treatment temperature of 850 °C is proposed for the gate-all-around (GAA) device fabrication process.
On the LS-category of product of Iwase’s manifolds
Authors: Dranishnikov Alexander
Published: September 2021

Iwase [Topology 42 (2003), pp. 701–713] has constructed two 16-dimensional manifolds

M
2

M_2

and

M
3

M_3

with LS-category 3 which are counter-examples to Ganea’s conjecture:

cat
⁡
(
M
×

S
n

)
=
cat
⁡
M
+
1

\operatorname {cat} (M\times S^n)=\operatorname {cat} M+1

. We show that the manifold

M
3

M_3

is a counter-example to the logarithmic law for the LS-category of the square of a manifold:

cat
⁡
(
M
×
M
)
=
2
cat
⁡
M

\operatorname {cat}(M\times M)=2\operatorname {cat} M

. Also we construct a map of degree one
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="f colon 2 left-parenthesis upper M 3 times upper S squared times upper S Superscript 14 Baseline right-parenthesis number-sign minus left-parenthesis upper M 2 times upper S squared times upper S Superscript 14 Baseline right-parenthesis right-arrow upper M 2 times upper M 3">

f
:
2
(

M
3

×

S
2

×

S

14

)
#
−
(

M
2

×

S
2

×

S

14

)
→

M
2

×

M
3

\begin{equation*} f:2(M_3\times S^2\times S^{14})\#-(M_2\times S^2\times S^{14})\to M_2\times M_3 \end{equation*}

which reduces Rudyak’s conjecture to the question whether

cat
⁡
(

M
2

×

M
3

)
≥
5

\operatorname {cat}(M_2\times M_3)\ge 5

and show that

cat
⁡
(

M
2

×

M
3

)
≥
4

\operatorname {cat}(M_2\times M_3)\ge 4

.
The Muskat problem with 𝐶¹ data
Authors: Chen Ke , Nguyen Quoc-Hung , Xu Yiran
Published: September 2021

In this paper we prove that the Cauchy problem of the Muskat equation is wellposed locally in time for any initial data in
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="ModifyingAbove upper C With dot Superscript 1 Baseline left-parenthesis double-struck upper R Superscript d Baseline right-parenthesis intersection upper L squared left-parenthesis double-struck upper R Superscript d Baseline right-parenthesis">

C
˙

1

(

R

d

)
∩

L
2

(

R

d

)

\dot C^1(\mathbb {R}^d)\cap L^2(\mathbb {R}^d)

.
Correlation Between Serum Total Bilirubin Levels and Blood Pressure Variability in Patients With Hypertension
Authors: Wang Jun , Xu Ya-nan , Tang Long , Zhang Jing-shui , Li Zhen , Shao Ming-liang , Hu Long , Wang Xian-ping
Published: September 2021

Background

To investigate the effect of serum total bilirubin levels on blood pressure and its variability in patients with hypertension.

Methods

This study was a retrospective observational study. A total of 189 subjects were recruited from September 2019 to March 2020. All hypertensive patients were scheduled for ambulatory blood pressure and a 24-hour dynamic electrocardiography. Standard deviations of 24-hour systolic and diastolic blood pressure were used as blood pressure variability indicators. A multiple linear regression was used to analyze the relationship between total bilirubin serum levels and blood pressure variability in hypertensive patients.

Results

All patients were divided into 3 groups according to tertile values of total bilirubin: low (≤12.2 µmol/l, n = 64), moderate (12.3–16.7 µmol/l, n = 64), and high (>16.8 µmol/l, n = 62) total bilirubin groups. Compared with low total bilirubin group, 24-hour mean systolic and diastolic blood pressure, 24-hour systolic blood pressure standard deviation, systolic blood pressure coefficient of variability, and 24-hour systolic blood pressure load were reduced in the moderate and high total bilirubin groups (all P < 0.05). Multiple linear regression analysis showed that female (B = −1.408, P = 0.013), age (B = 0.043, P = 0.035), diabetes (B = 2.624, P < 0.001), and moderate and high bilirubin grouping (B = −1.582, −3.079; both P < 0.05) were influencing factors of 24-hour systolic pressure standard deviation. Serum total bilirubin levels had no effect on the standard deviation of 24-hour diastolic blood pressure(P > 0.05).

Conclusions

In hypertensive patients, the total bilirubin serum level is an influencing factor for 24-hour systolic blood pressure variability.
MLIP causes recessive myopathy with rhabdomyolysis, myalgia and baseline elevated serum creatine kinase
Authors: Lopes Abath Neto Osorio , Medne Livija , Donkervoort Sandra , Rodríguez-García Maria Elena , Bolduc Véronique , Hu Ying , Guadagnin Eleonora , Foley A Reghan , Brandsema John F , Glanzman Allan M , Tennekoon Gihan I , Santi Mariarita , Berger Justin H , Megeney Lynn A , Komaki Hirofumi , Inoue Michio , Cotrina-Vinagre Francisco Javier , Hernández-Lain Aurelio , Martin-Hernández Elena , Williams Linford , Borell Sabine , Schorling David , Lin Kimberly , Kolokotronis Konstantinos , Lichter-Konecki Uta , Kirschner Janbernd , Nishino Ichizo , Banwell Brenda , Martínez-Azorín Francisco , Burgon Patrick G , Bönnemann Carsten G
Published: September 2021

Striated muscle needs to maintain cellular homeostasis in adaptation to increases in physiological and metabolic demands. Failure to do so can result in rhabdomyolysis. The identification of novel genetic conditions associated with rhabdomyolysis helps to shed light on hitherto unrecognized homeostatic mechanisms. Here we report seven individuals in six families from different ethnic backgrounds with biallelic variants in MLIP, which encodes the muscular lamin A/C-interacting protein, MLIP. Patients presented with a consistent phenotype characterized by mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis, and persistent basal elevated serum creatine kinase levels. The biallelic truncating variants were predicted to result in disruption of the nuclear localizing signal of MLIP. Additionally, reduced overall RNA expression levels of the predominant MLIP isoform were observed in patients’ skeletal muscle. Collectively, our data increase the understanding of the genetic landscape of rhabdomyolysis to now include MLIP as a novel disease gene in humans and solidifies MLIP’s role in normal and diseased skeletal muscle homeostasis.
Increased risk of diaphragmatic herniation following esophagectomy with a minimally invasive abdominal approach
Authors: Lee Adele Hwee Hong , Oo June , Cabalag Carlos S , Link Emma , Duong Cuong Phu
Published: September 2021

Objective

Diaphragmatic herniation is a rare complication following esophagectomy, associated with risks of aspiration pneumonia, bowel obstruction, and strangulation. Repair can be challenging due to the presence of the gastric conduit. We performed this systematic review and meta-analysis to determine the incidence and risk factors associated with diaphragmatic herniation following esophagectomy, the timing and mode of presentation, and outcomes of repair.

Methods

A systematic search using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines was performed using four major databases. A meta-analysis of diaphragmatic herniation incidence following esophagectomies with a minimally invasive abdominal (MIA) approach compared with open esophagectomies was conducted. Qualitative analysis was performed for tumor location, associated symptoms, time to presentation, and outcomes of postdiaphragmatic herniation repair.

Results

This systematic review consisted of 17,052 patients from 32 studies. The risk of diaphragmatic herniation was 2.74 times higher in MIA esophagectomy compared with open esophagectomy, with pooled incidence of 6.0% versus 3.2%, respectively. Diaphragmatic herniation was more commonly seen following surgery for distal esophageal tumors. Majority of patients (64%) were symptomatic at diagnosis. Presentation within 30 days of operation occurred in 21% of cases and is twice as likely to require emergent repair with increased surgical morbidity. Early diaphragmatic herniation recurrence and cardiorespiratory complications are common sequelae following hernia repair.

Conclusions

In the era of MIA esophagectomy, one has to be cognizant of the increased risk of diaphragmatic herniation and its sequelae. Failure to recognize early diaphragmatic herniation can result in catastrophic consequences. Increased vigilance and decreased threshold for imaging during this period is warranted.
Refraining from use diminishes cannabis-associated epigenetic changes in human sperm
Authors: Schrott Rose , Murphy Susan K , Modliszewski Jennifer L , King Dillon E , Hill Bendu , Itchon-Ramos Nilda , Raburn Douglas , Price Thomas , Levin Edward D , Vandrey Ryan , Corcoran David L , Kollins Scott H , Mitchell John T
Published: September 2021

Cannabis use alters sperm DNA methylation, but the potential reversibility of these changes is unknown. Semen samples from cannabis users and non-user controls were collected at baseline and again following a 77-day period of cannabis abstinence (one spermatogenic cycle). Users and controls did not significantly differ by demographics or semen analyses. Whole-genome bisulfite sequencing identified 163 CpG sites with significantly different DNA methylation in sperm between groups (P < 2.94 × 10−9). Genes associated with altered CpG sites were enriched with those involved in development, including cardiogenesis and neurodevelopment. Many of the differences in sperm DNA methylation between groups were diminished after cannabis abstinence. These results indicate that sustained cannabis abstinence significantly reduces the number of sperm showing cannabis-associated alterations at genes important for early development.
Major Reforms in Electricity Pricing: Evidence from a Quasi-Experiment
Authors: Labandeira Xavier , Labeaga José M , Teixidó Jordi J
Published: September 2021

The global energy mix and cost structure of the power industry are experiencing a redefinition. Many countries are revamping electricity-pricing systems to guarantee fixed-cost recovery, often by raising the fixed charge of two-part tariff schemes. However, a key assumption of two-part tariff schemes and associated fixed-cost recoveries is that consumers discriminate fixed from marginal costs. We conduct a quasi-experiment with data from a major electricity price reform recently implemented in Spain and find robust evidence indicating that consumers fail to distinguish between fixed and marginal costs. As a result, policymakers are not achieving the goal of cost recovery.
Mayotte seismic crisis: building knowledge in near real-time by combining land and ocean-bottom seismometers, first results
Authors: Saurel Jean-Marie , Jacques Eric , Aiken Chastity , Lemoine Anne , Retailleau Lise , Lavayssière Aude , Foix Océane , Dofal Anthony , Laurent Angèle , Mercury Nicolas , Crawford Wayne , Lemarchand Arnaud , Daniel Romuald , Pelleau Pascal , Bès de Berc Maxime , Dectot Grégoire , Bertil Didier , Roullé Agathe , Broucke Céleste , Colombain Alison , Jund Hélène , Besançon Simon , Guyavarch Pierre , Kowalski Philippe , Roudaut Mickaël , Apprioual Ronan , Battaglia Jean , Bodihar Soumya , Boissier Patrice , Bouin Marie Paule , Brunet Christophe , Canjamale Kévin , Catherine Philippe , Desfete Nicolas , Doubre Cécile , Dretzen Rémi , Dumouche Tom , Fernagu Philippe , Ferrazzini Valérie , Fontaine Fabrice R , Gaillot Arnaud , Géli Louis , Griot Cyprien , Grunberg Marc , Guzel Emre Can , Hoste-Colomer Roser , Lambotte Sophie , Lauret Frédéric , Léger Félix , Maros Emmanuel , Peltier Aline , Vergne Jérôme , Satriano Claudio , Tronel Frédéric , Van der Woerd Jérôme , Fouquet Yves , Jorry Stephan J , Rinnert Emmanuel , Thinon Isabelle , Feuillet Nathalie
Published: September 2021

The brutal onset of seismicity offshore Mayotte island North of the Mozambique Channel, Indian Ocean, that occurred in May 2018 caught the population, authorities and scientific community off guard. Around 20 potentially felt earthquakes were recorded in the first 5 d, up to magnitude Mw 5.9. The scientific community had little pre-existing knowledge of the seismic activity in the region due to poor seismic network coverage. During 2018 and 2019, the MAYOBS/REVOSIMA seismology group was progressively built between four French research institutions to improve instrumentation and data sets to monitor what we know now as an on-going exceptional submarine basaltic eruption. After the addition of 3 medium-band stations on Mayotte island and 1 on Grande Glorieuse island in early 2019, the data recovered from the Ocean Bottom Seismometers were regularly processed by the group to improve the location of the earthquakes detected daily by the land network. We first built a new local 1-D velocity model and established specific data processing procedures. The local 1.66 low VP/VS ratio we estimated is compatible with a volcanic island context. We manually picked about 125 000 P and S phases on land and sea bottom stations to locate more than 5000 events between February 2019 and May 2020. The earthquakes outline two separate seismic clusters offshore that we named Proximal and Distal. The Proximal cluster, located 10 km offshore Mayotte eastern coastlines, is 20–50 km deep and has a cylindrical shape. The Distal cluster start 5 km to the east of the Proximal cluster and extends below Mayotte's new volcanic edifice, from 50 to 25 km depth. The two clusters appear seismically separated, however our data set is insufficient to firmly demonstrate this.
Protective effects of a small-molecule inhibitor DDQ against tau-induced toxicities in a transgenic tau mouse model of Alzheimer’s disease
Authors: Vijayan Murali , George Mathew , Bunquin Lloyd E , Bose Chhanda , Reddy P Hemachandra
Published: September 2021

The purpose of our study is to determine DDQ (diethyl (3,4-dihydroxyphenethylamino) (quinolin-4-yl) methylphosphonate)—a newly discovered molecule that has been shown to protect against phosphorylated tau (p-tau) in Alzheimer’s disease (AD) pathogenesis. We used a well-studied tau (P301L) transgenic mouse model to achieve our goal. We administered DDQ into 12-month-old Tau mice, at 20 mg/kg body weight intraperitoneally two times per week for 2 months. We also assessed DDQ levels in the blood, skeletal muscle and brain using biochemical and molecular techniques. We investigated the mRNA and protein levels of mitochondrial dynamics, biogenesis, synaptic, p-tau and longevity genes sirtuins in DDQ-treated tau mice using real-time quantitative PCR (q-RT-PCR), immunoblotting and immunofluorescence techniques. Our extensive pharmacodynamics investigations revealed that skeletal muscle had the greatest peak levels of DDQ, followed by serum and brain. Interestingly, DDQ-treated tau mice had higher levels of mitochondrial fusion, biogenesis, synaptic genes and sirtuins than DDQ-untreated tau mice. In addition, DDQ-treated tau mice had lower levels of mitochondrial fission and p-tau than untreated tau mice. The current findings, combined with our prior findings, firmly show that DDQ possesses anti-aging, anti-amyloid-beta and anti-p-tau properties, making it a promising molecule for reducing age-related, amyloid-beta and p-tau-induced synaptic and mitochondrial toxicities in AD.
Mutations at a split codon in the GTPase-encoding domain of OPA1 cause dominant optic atrophy through different molecular mechanisms
Authors: Weisschuh Nicole , Marino Valerio , Schäferhoff Karin , Richter Paul , Park Joohyun , Haack Tobias B , Dell’Orco Daniele
Published: September 2021

Exonic (i.e. coding) variants in genes associated with disease can exert pathogenic effects both at the protein and mRNA level, either by altering the amino acid sequence or by affecting pre-mRNA splicing. The latter is often neglected due to the lack of RNA analyses in genetic diagnostic testing. In this study we considered both pathomechanisms and performed a comprehensive analysis of nine exonic nucleotide changes in OPA1, which is the major gene underlying autosomal dominant optic atrophy (DOA) and is characterized by pronounced allelic heterogeneity. We focused on the GTPase-encoding domain of OPA1, which harbors most of the missense variants associated with DOA. Given that the consensus splice sites extend into the exons, we chose a split codon, namely codon 438, for our analyses. Variants at this codon are the second most common cause of disease in our large cohort of DOA patients harboring disease-causing variants in OPA1. In silico splice predictions, heterologous splice assays, analysis of patient’s RNA when available, and protein modeling revealed different molecular outcomes for variants at codon 438. The wildtype aspartate residue at amino acid position 438 is directly involved in the dimerization of OPA1 monomers. We found that six amino acid substitutions at codon 438 (i.e. all substitutions of the first and second nucleotide of the codon) destabilized dimerization while only substitutions of the first nucleotide of the codon caused exon skipping. Our study highlights the value of combining RNA analysis and protein modeling approaches to accurately assign patients to future precision therapies.
Brain 5-HT1A Receptor PET Binding, Cortisol Responses to Stress, and the Familial Transmission of Suicidal Behavior
Authors: Melhem Nadine M , Zhong Yongqi , Miller Jeffrey M , Zanderigo Francesca , Ogden R Todd , Sublette M Elizabeth , Newell Madison , Burke Ainsley , Keilp John G , Lesanpezeshki Mohammad , Bartlett Elizabeth , Brent David A , Mann J John
Published: September 2021

Background

The serotonin 1A (5-HT1A) receptor has been implicated in depression and suicidal behavior. Lower resting cortisol levels are associated with higher 5-HT1A receptor binding, and both differentiate suicide attempters with depression. However, it is not clear whether 5-HT1A receptor binding and cortisol responses to stress are related to familial risk and resilience for suicidal behavior.

Methods

[11C]CUMI-101 positron emission tomography imaging to quantify regional brain 5-HT1A receptor binding was conducted in individuals considered to be at high risk for mood disorder or suicidal behavior on the basis of having a first- or second-degree relative(s) with an early onset mood disorder and history of suicidal behavior. These high-risk individuals were subdivided into the following groups: high risk resilient having no mood disorder or suicidal behavior (n = 29); high risk with mood disorder and no suicidal behavior history (n = 31); and high risk with mood disorder and suicidal behavior (n = 25). Groups were compared with healthy volunteers without a family history of mood disorder or suicidal behavior (n = 34). Participants underwent the Trier Social Stress Task (TSST). All participants were free from psychotropic medications at the time of the TSST and PET scanning.

Results

We observed no group differences in 5-HT1A receptor binding considering all regions simultaneously, nor did we observe heterogeneity of the effect of group across regions. These results were similar across outcome measures (BPND for all participants and BPp in a subset of the sample) and definitions of regions of interest (ROIs; standard or serotonin system-specific ROIs). We also found no group differences on TSST outcomes. Within the high risk with mood disorder and suicidal behavior group, lower BPp binding (β = −0.084, SE = 0.038, P = .048) and higher cortisol reactivity to stress (β = 9.25, 95% CI [3.27,15.23], P = .004) were associated with higher lethality attempts. There were no significant relationships between 5-HT1A binding and cortisol outcomes.

Conclusions

5-HT1A receptor binding in ROIs was not linked to familial risk or resilience protecting against suicidal behavior or mood disorder although it may be related to lethality of suicide attempt. Future studies are needed to better understand the biological mechanisms implicated in familial risk for suicidal behavior and how hypothalamic-pituitary-adrenal axis function influences such risk.
Critical Needs in Advancing Shigella Vaccines for Global Health
Authors: MacLennan Calman A , Talaat Kawsar R , Kaminski Robert W , Cohen Dani , Riddle Mark S , Giersing Birgitte K
Published: September 2021

Advancing new O-antigen-based Shigella vaccines is critically dependent on development of an international standard serum and harmonized ELISA, demonstration of field efficacy in young children in low- and middle-income countries, and early engagement with regulators and policy makers.
Role of Key Infectivity Parameters in the Transmission of Ebola Virus Makona in Macaques
Authors: de La Vega Marc Antoine , Wong Gary , Wei Haiyan , He Shihua , Bello Alexander , Fausther-Bovendo Hugues , Audet Jonathan , Tierney Kevin , Tran Kaylie , Soule Geoff , Racine Trina , Strong James E , Qiu Xiangguo , Kobinger Gary P
Published: September 2021

Many characteristics associated with Ebola virus disease remain to be fully understood. It is known that direct contact with infected bodily fluids is an associated risk factor, but few studies have investigated parameters associated with transmission between individuals, such as the dose of virus required to facilitate spread and route of infection. Therefore, we sought to characterize the impact by route of infection, viremia, and viral shedding through various mucosae, with regards to intraspecies transmission of Ebola virus in a nonhuman primate model. Here, challenge via the esophagus or aerosol to the face did not result in clinical disease, although seroconversion of both challenged and contact animals was observed in the latter. Subsequent intramuscular or intratracheal challenges suggest that viral loads determine transmission likelihood to naive animals in an intramuscular-challenge model, which is greatly facilitated in an intratracheal-challenge model where transmission from challenged to direct contact animal was observed consistently.
Influences on the assessment of resource- and animal-based welfare indicators in unweaned dairy calves for usage by farmers
Authors: Hayer Jason J , Nysar Dorit , Heinemann Céline , Leubner Caroline D , Steinhoff-Wagner Julia
Published: September 2021

Consumers, industrial stakeholders, and the legislature demand a stronger focus on animal welfare of all livestock at the farm level by using suitable indicators in self-assessments. In order to deduce farms’ animal welfare status reliably, factors that influence indicators’ results need to be identified. Hence, this study aimed to apply possible animal welfare indicators for unweaned dairy calves on conventional dairy farms with early cow–calf separation and evaluate influencing factors such as age and sex of calves or climatic conditions on the applied indicators’ results. An animal welfare assessment using 7 resource-based and 14 animal-based indicators was conducted at 42 typical Western German dairy farms (844 calves) in 2018 and 2019 by two observers. The effect of influencing factors was calculated by binary and ordinal logistic regressions and expressed as odds ratios. Although every unweaned calf was assessed during the farm visits, most farms had relatively few unweaned calves (average number of calves ± standard deviation = 20.1 ± 6.7 calves), with six farms having not more than 10 calves. The small sample sizes question the usage of those indicators to compare between farms and to set thresholds at the farm level. Only one assessed indicator (cleanliness core body) was not statistically affected by the evaluated influencing factors. Calf age was identified as the most decisive factor, as it affected 16 of 21 evaluated indicators, and calf age distribution on-farm varied greatly. Climatic conditions (ambient temperature and rainfall) influenced resource-based indicators such as access to concentrate and water or the cleanliness of feeding implements and bedding as well as animal-based cleanliness indicators and the occurrence of health-related impairments such as coughing and diarrhea. The authors found differences between calves on farms assessed by the different observers not only in resource-based hygiene indicators but also in animal-based indicators such as hyperthermia or hypothermia, highlighting the need for further evaluation of quality criteria in dairy calf welfare assessments. Nevertheless, animal welfare assessments by farmers themselves could be useful tools to sensitize farmers to animal welfare and thereby improve calves’ welfare.
Inactivation of the Wnt/β-catenin signaling contributes to the epithelial barrier dysfunction induced by sodium oxalate in canine renal epithelial cells
Authors: Ji Yun , Fang Shuting , Yang Ying , Wu Zhenlong
Published: September 2021

High oxalate consumption has been recognized as a risk factor for renal calcium oxalate stones in companion animals (dogs and cats). However, the cellular signaling involved in oxalate-induced dysfunction in renal tubular epithelial cells remains not fully elucidated. In this study, Mardin–Darby canine kidney (MDCK) cells, an epithelial cell line derived from canine kidney tubule, were tested for cell proliferation activity and barrier function after being exposed to sodium oxalate (NaOx). Further, the involvement of Wnt/β-catenin in NaOx-induced renal epithelial barrier dysfunction was evaluated. MDCK cells treated with NaOx exhibited reduction in cell proliferation and migration. Besides, NaOx exposure led to a decrease in transepithelial electrical resistance and an increase in paracellular permeability. The deleterious effects of NaOx on epithelial barrier function were related to the suppressed abundance of tight junction proteins including zonula occludens, occludin, and claudin-1. Of note, protein levels of β-catenin and phosphorylated (p)-β-catenin (Ser552) in MDCK cells were repressed by NaOx, indicating inhibitory effects on Wnt/β-catenin signaling. An inhibition of glycogen synthase kinase-3β (GSK-3β) by SB216763 enhanced the abundance of β-catenin and p-β-catenin (Ser552), and protected against epithelial barrier dysfunction in NaOx-treated MDCK cells. The results revealed a critical role of Wnt/β-catenin signaling in the epithelial barrier function of MDCK cells. Activation of Wnt/β-catenin signaling might be a potential therapeutic target for the treatment of oxalate-linked renal stones.
Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women: A Prospective Study and Meta-Analysis
Authors: Mori Nagisa , Keski-Rahkonen Pekka , Gicquiau Audrey , Rinaldi Sabina , Dimou Niki , Harlid Sophia , Harbs Justin , Van Guelpen Bethany , Aune Dagfinn , Cross Amanda J , Tsilidis Konstantinos K , Severi Gianluca , Kvaskoff Marina , Fournier Agnès , Kaaks Rudolf , Fortner Renée Turzanski , Schulze Matthias B , Jakszyn Paula , Sánchez Maria-Jose , Colorado-Yohar Sandra M , Ardanaz Eva , Travis Ruth , Watts Eleanor L , Masala Giovanna , Krogh Vittorio , Tumino Rosario , Sacerdote Carlotta , Panico Salvatore , Bueno-de-Mesquita Bas , Gram Inger Torhild , Waaseth Marit , Gunter Marc J , Murphy Neil
Published: September 2021

Background

Observational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results.

Methods

We investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone–binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided.

Results

In the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log2 1-unit increment = 1.17 [95% confidence interval = 1.00 to 1.38]; odds ratioquartile4-quartile1 = 1.33 [95% confidence interval = 0.89 to 1.97], Ptrend = .20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk.

Conclusion

Our observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women.
Prospective Welfare Analysis—Extending Willingness-To-Pay Assessment to Embrace Sustainability
Authors: Inderst Roman , Thomas Stefan
Published: September 2021

In this paper, we outline how a future change in consumers’ willingness-to-pay can be accounted for in a consumer welfare effects analysis in antitrust. Key to our solution is the prediction of preferences of new consumers and changing preferences of existing consumers in the future. The dimension of time is inextricably linked with that of sustainability. Taking into account the welfare of future cohorts of consumers, concerns for sustainability can therefore be integrated into the consumer welfare paradigm to a greater extent. As we argue in this paper, it is expedient to consider changes in consumers’ willingness-to-pay, in particular if society undergoes profound changes in such preferences, for example, caused by an increase in generally available information on environmental effects of consumption, and a rising societal awareness about how consumption can have irreversible impacts on the environment. We offer suggestions on how to conceptionalize and operationalize the projection of such consumers’ changing preferences in a “prospective welfare analysis.” This increases the scope of the consumer welfare paradigm and can help to solve conceptual issues regarding the integration of sustainability into antitrust enforcement while keeping consumer surplus as a quantitative gauge.
Structure, stability, and optical absorption spectra of small TinCx clusters: a first-principles approach
Authors: Gámez-Valenzuela Sergio , Alonso Julio A , Santoro Gonzalo , Martínez José I
Published: September 2021

Titanium carbide molecular clusters are thought to form in the circumstellar envelopes of carbon-rich asymptotic giant branch (AGB) stars but, to date, their detection has remained elusive. To facilitate the astrophysical identification of those clusters in AGB and post-AGB environments, the molecular structures and optical absorption spectra of small TinCx clusters, with n = 1–4 and x = 1–4, and some selected larger clusters, Ti3C8, Ti4C8, Ti6C13, Ti7C13, Ti8C12, Ti9C15, and Ti13C22, have been calculated. The density functional formalism, within the B3LYP approximation for electronic exchange and correlation, was used to find the lowest energy structures. Except the clusters having a single Ti atom, the rest exhibit three-dimensional structures. Those are formed by a Ti fragment surrounded in general by carbon dimers. The optical spectra of TinCx, computed by time-dependent density functional theory, using the corrected CAM-B3LYP functional, show absorption features in the visible and near-infrared regions which may help in the identification of these clusters in space. In addition, most of the clusters have sizable electric dipole moments, allowing their detection by radioastronomical observations.
Single-molecule conformational dynamics of a transcription factor reveals a continuum of binding modes controlling association and dissociation
Authors: Chen Wei , Lu Wei , Wolynes Peter G , Komives Elizabeth A
Published: September 2021

Binding and unbinding of transcription factors to DNA are kinetically controlled to regulate the transcriptional outcome. Control of the release of the transcription factor NF-κB from DNA is achieved through accelerated dissociation by the inhibitor protein IκBα. Using single-molecule FRET, we observed a continuum of conformations of NF-κB in free and DNA-bound states interconverting on the subseconds to minutes timescale, comparable to in vivo binding on the seconds timescale, suggesting that structural dynamics directly control binding kinetics. Much of the DNA-bound NF-κB is partially bound, allowing IκBα invasion to facilitate DNA dissociation. IκBα induces a locked conformation where the DNA-binding domains of NF-κB are too far apart to bind DNA, whereas a loss-of-function IκBα mutant retains the NF-κB conformational ensemble. Overall, our results suggest a novel mechanism with a continuum of binding modes for controlling association and dissociation of transcription factors.