bluuebunny/crossref_metadata_2025 huggingface dataset:
Islamic virtue-based ethics for artificial intelligence
Authors: Raquib Amana , Channa Bilal , Zubair Talat , Qadir Junaid
Published: June 2022

The twenty-first century technological advances driven by exponential rise of artificial intelligence (AI) technology have ushered in a new era that offers many of us hitherto unimagined luxuries and facilities. However, under the guise of this progressive discourse, particularly in the backdrop of current neo-liberal late-capitalist postmodern world, AI development also has prompted an increasingly uncertain ethical tomorrow. This paper aims to probe the question of ethics by exploring the true ramifications of AI and interrogating its various ethical dimensions. It questions the essential goodness that is attributed to unstinted AI development before elucidating the ethical repercussions of AI advancements and the aptness of the current market logics and business models that govern the tech-industry. The paper next positions a holistic Islamic virtue-based AI ethics framework grounded in the context of Islamic objectives (maqāṣid) as an alternative ethical system for AI governance. We argue that this distinctive Islamic virtue-based ethical approach, which can be used to explore AI-related ethical problems more holistically due to its ontological base and rich tradition while keeping in check undue influence from the current socio-politico-economic climate, can be a valuable addition to the global discourse on AI ethics.
Existence Results for Fractional Choquard Equations with Critical or Supercritical Growth
Authors: Hu Dongpo , Zheng Zhaowen , Liu Ming
Published: June 2022

In this paper, we study the following fractional Choquard equation with critical or supercritical growth $$\begin{aligned} \ (-\Delta )^su+V(x)u=f(x,u)+\lambda \left[ |x|^{-\mu }*|u|^p\right] p|u|^{p-2}u, \quad x \in {\mathbb {R}}^N, \end{aligned}$$

(
-
Δ
)

s

u
+
V

(
x
)

u
=
f

(
x
,
u
)

+
λ

|
x
|

-
μ

∗

|
u
|

p

p

|
u
|

p
-
2

u
,

x
∈

R

N

,

where $$0<s<1$$

0
<
s
<
1

, $$(-\Delta )^s$$

(
-
Δ
)

s

denotes the fractional Laplacian of order s, $$N>2s$$

N
>
2
s

, $$0<\mu <2s$$

0
<
μ
<
2
s

and $$p\ge 2_{\mu ,s}^*:=\frac{2N-\mu }{N-2s}$$

p
≥

2

μ
,
s

∗

:
=

2
N
-
μ

N
-
2
s

, which is the critical exponent in the sense of Hardy-Littlewood-Sobolev inequality. Under some suitable conditions, we prove that the equation admits a nontrivial solution for small $$\lambda >0$$

λ
>
0

by variational methods, which extends results in Bhattarai in J. Differ. Equ. 263, 3197–3229 (2017).
Challenges and threats to quality in scholarly knowledge production: views of selected stakeholders from 17 countries
Authors: Starkey Jesse C. , Koerber Amy , Cummins R. Glenn , Ardon-Dryer Karin , Eko Lyombe , Kee Kerk F.
Published: June 2022

This study applies Harvey and Green’s (1993) model of quality to scholarly knowledge production. Although studies of quality in higher education have been commonplace for decades, there is a gap in understanding quality in terms of research production from stakeholders’ perspectives. This study begins to fill that gap through a qualitative interview study of quality in the knowledge production process. Stakeholders in all parts of the scholarly knowledge production process, from 17 countries, are included in the data sample. Analysis of interview data extends Harvey and Green’s (1993) model into the realm of knowledge production. Definitions and challenges of quality in producing scholarly knowledge are discussed. The findings indicate a rift between the institutional view of quality and the individual perceptions of quality, suggesting the need for institutional policies that respond to stakeholders’ perceptions of quality in scholarly knowledge production and celebrate, rather than erase, epistemic diversity.
Incidental Questions as a Gatekeeping Doctrine
Authors: Papadaki Matina
Published: June 2022

In this essay, I discuss whether and to what extent the framing of the main dispute and incidental questions can have a gatekeeping function in relation to the jurisdiction and applicable law of a dispute settlement body. Recent cases have attached critical importance to the identification of the “real” main object of the dispute, and the “characterization” of claims to then determine which issues are incidental to the dispute, rather than focusing on which issues are within the tribunal's ratione materiae jurisdiction. Through an examination of selected case law, I argue that this “characterization approach” could in effect elevate a subjective framing of the “main” dispute to a jurisdictional gatekeeper. This approach introduces unnecessary evaluative determinations while obscuring normative clarity regarding the limits of consent-based jurisdiction and its relationship to incidentally applicable law.
Incidental Jurisdiction in International Adjudication and Incidental Determinations by International Organizations
Authors: Tzeng Peter
Published: June 2022

International courts and tribunals have developed two criteria for the exercise of incidental jurisdiction: necessity and ancillarity. Yet the question of whether to make an incidental determination is not unique to the adjudicatory context. International organizations sometimes confront it as well. And their practice in dealing with this question suggests that the criteria of necessity and ancillarity alone are insufficient for assessing whether an incidental determination should be made.
Prevalence and microbiological and genetic characteristics of multidrug-resistant Pseudomonas aeruginosa over three years in Qatar
Authors: Sid Ahmed Mazen A. , Abdel Hadi Hamad , Abu Jarir Sulieman , Ahmad Khan Faisal , Arbab Mohammed A. , Hamid Jemal M. , Alyazidi Mohammed A. , Al-Maslamani Muna A. , Skariah Sini , Sultan Ali A. , Al Khal Abdul Latif , Söderquist Bo , Ibrahim Emad Bashir , Jass Jana , Ziglam Hisham
Published: June 2022

Objectives:

Antimicrobial resistance (AMR) is a global priority with significant clinical and economic consequences. Multidrug-resistant (MDR) Pseudomonas aeruginosa is one of the major pathogens associated with significant morbidity and mortality. In healthcare settings, the evaluation of prevalence, microbiological characteristics, as well as mechanisms of resistance is of paramount importance to overcome associated challenges.

Methods:

Consecutive clinical specimens of P. aeruginosa were collected prospectively from 5 acute-care and specialized hospitals between October 2014 and September 2017, including microbiological, clinical characteristics and outcomes. Identification and antimicrobial susceptibility test were performed using the BD Phoenix identification and susceptibility testing system, matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF MS), and minimum inhibitory concentration (MIC) test strips. Overall, 78 selected MDR P. aeruginosa isolates were processed for whole-genome sequencing (WGS).

Results:

The overall prevalence of MDR P. aeruginosa isolates was 5.9% (525 of 8,892) and showed a decreasing trend; 95% of cases were hospital acquired and 44.8% were from respiratory samples. MDR P. aeruginosa demonstrated >86% resistance to cefepime, ciprofloxacin, meropenem, and piperacillin-tazobactam but 97.5% susceptibility to colistin. WGS revealed 29 different sequence types: 20.5% ST235, 10.3% ST357, 7.7% ST389, and 7.7% ST1284. ST233 was associated with bloodstream infections and increased 30-day mortality. All ST389 isolates were obtained from patients with cystic fibrosis. Encoded exotoxin genes were detected in 96.2% of isolates.

Conclusions:

MDR P. aeruginosa isolated from clinical specimens from Qatar has significant resistance to most agents, with a decreasing trend that should be explored further. Genomic analysis revealed the dominance of 5 main clonal clusters associated with mortality and bloodstream infections. Microbiological and genomic monitoring of MDR P. aeruginosa has enhanced our understanding of AMR in Qatar.
Between pronouns and R-expressions: Pronoun-like lexical noun phrases
Authors: Kučerová Ivona , Szczegielniak Adam
Published: June 2022

We discuss an empirical study that suggests a finer categorization of pronouns versus lexical noun phrases in terms of their feature valuation. We argue that not all lexical noun phrases have their ϕ-features valued from the lexicon. By investigating Polish politeness markers, we demonstrate that certain noun phrases can have their features (specifically, the person feature) valued in a manner parallel to feature valuation in free pronouns. The proposal thus refines our understanding of the categorial distinction between different types of nominals, and suggests that in addition to known morphological and syntactic variation in the domain of pronouns and lexical noun phrases, there is a more fine-tuned classification of feature valuation types.
Can You Keep a Secret? BS Conspiracy Theories and the Argument from Loose Lips
Authors: Ross Ryan
Published: June 2022

According to an argument that I will call the argument from loose lips, we can safely reject certain notorious conspiracy theories because they posit conspiracies that would be nearly impossible to keep secret. I distinguish between three versions of this argument: the epistemic argument, the alethic argument, and the statistical argument. I, then, discuss several limitations of the argument from loose lips. The first limitation is that only the statistical argument can be applied to new conspiracy theories. The second limitation is that no version of the argument suffices to rule out the existence of small initial conspiracies that have no need to add further conspirators. The third limitation is that no version of the argument is dialectically efficacious in the context of arguing with the relevant conspiracy theorists because nothing is said to address the alleged evidence that they cite.
Acoustic instability prediction of the flow through a circular aperture in a thick plate via an impedance criterion
Authors: Sierra-Ausin J. , Fabre D. , Citro V. , Giannetti F.
Published: June 2022

We investigate the mechanisms leading to acoustic whistling for a jet passing through a circular hole in a thick plate connecting two domains. Two generic situations are considered. In the first one, the upstream domain is a closed cavity while the downstream domain is open, leading to a class of conditionally unstable modes. In this case, the instability source lies in the recirculation region within the thickness of the plate, but coupling with a conveniently tuned resonator is needed to select the conditional instability range. In the second situation, the two regions, upstream and downstream of the hole, are considered as open, leading to a class of hydrodynamic modes where instability of the recirculation region is sufficient to generate self-oscillations without the need of any resonator. A matched asymptotic model, valid in the low Mach limit, is used to derive a global impedance of the system, combining the impedance of the hole and the modelled impedances of the upstream and downstream domains. It is shown that the knowledge of this global impedance along the real

$\omega$

-axis provides an instability criterion and a prediction of the eigenvalues of the full system. Validations against the solutions of the eigenvalue problem obtained from the linearized fully compressible formulation confirm the accuracy of the approach. Then, it is subsequently used to characterise the range of existence of instabilities as a function of the Reynolds number, the Mach number, the aspect ratio of the hole and (for the cavity configuration) the dimensionless volume of the cavity.
Integral relations for the skin-friction coefficient of canonical flows
Authors: Ricco Pierre , Skote Martin
Published: June 2022

We show that the Fukagata et al.'s (Phys. Fluids, vol. 14, no. 11, 2002, pp. 73–76) identity for free-stream boundary layers simplifies to the von Kármán momentum integral equation relating the skin-friction coefficient and the momentum thickness when the upper bound in the integrals used to obtain the identity is taken to be asymptotically large. If a finite upper bound is used, the terms of the identity depend spuriously on the bound itself. Differently from channel and pipe flows, the impact of the Reynolds stresses on the wall-shear stress cannot be quantified in the case of free-stream boundary layers because the Reynolds stresses disappear from the identity. The infinite number of alternative identities obtained by performing additional integrations on the streamwise momentum equation also all simplify to the von Kármán equation. Analogous identities are found for channel flows, where the relative influence of the physical terms on the wall-shear stress depends on the number of successive integrations, demonstrating that the laminar and turbulent contributions to the skin-friction coefficient are only distinguished in the original identity discovered by Fukagata et al. (Phys. Fluids, vol. 14, no. 11, 2002, pp. 73–76). In the limit of large number of integrations, these identities degenerate to the definition of skin-friction coefficient and a novel twofold-integration identity is found for channel and pipe flows. In addition, we decompose the skin-friction coefficient uniquely as the sum of the change of integral thicknesses with the streamwise direction, following the study of Renard & Deck (J. Fluid Mech., vol. 790, 2016, pp. 339–367). We utilize an energy thickness and an inertia thickness, which is composed of a thickness related to the mean-flow wall-normal convection and a thickness linked to the streamwise inhomogeneity of the mean streamwise velocity. The contributions of the different terms of the streamwise momentum equation to the friction drag are thus quantified by these integral thicknesses.
A model for the electric field-driven flow and deformation of a drop or vesicle in strong electrolyte solutions
Authors: Ma Manman , Booty Michael R. , Siegel Michael
Published: June 2022

A model is constructed to describe the flow field and arbitrary deformation of a drop or vesicle that contains and is embedded in an electrolyte solution, where the flow and deformation are caused by an applied electric field. The applied field produces an electrokinetic flow, which is set up on the charge-up time scale

$\tau _{*c}=\lambda _{*} a_{*}/D_{*}$

, where

$\lambda _{*}$

is the Debye screening length,

$a_{*}$

is the inclusion length scale and

$D_{*}$

is an ion diffusion constant. The model is based on the Poisson–Nernst–Planck and Stokes equations. These are reduced or simplified by forming the limit of strong electrolytes, for which dissolved salts are completely ionised in solution, together with the limit of thin Debye layers. Debye layers of opposite polarity form on either side of the drop interface or vesicle membrane, together forming an electrical double layer. Two formulations of the model are given. One utilises an integral equation for the velocity field on the interface or membrane surface together with a pair of integral equations for the electrostatic potential on the outer faces of the double layer. The other utilises a form of the stress-balance boundary condition that incorporates the double layer structure into relations between the dependent variables on the layers’ outer faces. This constitutes an interfacial boundary condition that drives an otherwise unforced Stokes flow outside the double layer. For both formulations relations derived from the transport of ions in each Debye layer give additional boundary conditions for the potential and ion concentrations outside the double layer.
What Motivates Emerging Economy Firms to Internationalize? A Replication and Extension of Ahsan et al. (2020) in the Context of China
Authors: Huang Can , Conde Felix , Cui Lin , Fu Yao
Published: June 2022

Ahsan, Sinha, and Srinivasan (2020) studied the motives of knowledge-intensive Indian firms’ international expansion based on resource-based considerations and the locational advantages offered by host countries. They identified firm characteristics associated with strategic asset-seeking, opportunity-seeking, and market-seeking motives. In this replication study, we examine Ahsan et al.'s (2020) model in the Chinese context. Based on our improved empirical model, our findings reveal some similarities but more importantly some key differences in the antecedents of internationalization motives between Indian and Chinese firms. Drawing on insights from prior studies, we propose that these differences can be attributed to differences in absorptive capacity, international expansion scales and patterns, ownership type, and the home institutional contexts in which Indian and Chinese firms operate. Overall, this replication study demonstrates the importance of contextualizing international business research.
UNDER THE IMPRESSION: MULTISPECTRAL IMAGING OF LORD FREDERICK CAMPBELL CHARTER XXI 5
Authors: Hudson Alison , Duffy Christina
Published: June 2022

Lord Frederick Campbell Charterxxi5 is the only surviving English document that still has an authentic, legible, pre-Conquest seal attached to it. The text purports to be a writ of Edward the Confessor (1003x5–1066) granting a slew of rights to Christ Church Cathedral, Canterbury. We examined the writ using multispectral imaging to recover layers of erased text.

Many scholars have noted that the text of the writ was altered on at least one occasion. Now, multispectral imaging confirms that there were multiple layers of erasures, even more than previously anticipated. The original writ may have been inscribed on reused parchment. This can be used as evidence for the conditions (and even the immense quantity) in which writs were produced during Edward’s reign. Alternatively – or additionally – the writ’s multiple alterations could suggest that it was rewritten repeatedly after the Conquest, during various phases of Canterbury’s post-Conquest property disputes. The results confirm Nicholas Brooks’ hypothesis that at one stage the text was altered from referring to the rights to the archbishop alone (in the singular), to instead refer to the whole community at Christ Church (in the plural). Taken together, these results reveal shifts in legal thinking in Canterbury between 1066 and 1100, while demonstrating the enduring authority of Edward the Confessor’s seal. These results also show the potential for using multispectral imaging to illuminate – literally – the history of manuscript production.
Contested duplicates: disputed negotiations surrounding ethnographic doppelgängers in German New Guinea, 1898–1914
Authors: Buschmann Rainer F.
Published: June 2022

The issue of duplicates and duplication in ethnographic collection is frequently regarded as a process that begins and ends in the museum as a fundamental act of the process of curating. In contrast, this article maintains, this practice occurred all along the chain of collecting, where indigenous artefacts operated as items of exchange in the context of the colonial encounter. Using the example of German New Guinea, the article maintains that epistemological concerns, as symbolic currency both in terms of inter-museum exchange and in terms of contributing to individual and institutional prestige, guiding ethnographic intuitions had little influence on colonial resident collectors. Colonial residents, who resented the heavy hand of colonial and museum officials in Berlin, infused duplication with their own desires, which included commercial gain or the conferment of the many German state decorations. The colonized indigenous population benefited from the increasing demand for their material culture, which provided valuable items and bargaining chips in the emerging colonial exchange. Duplicates are identified as doppelgängers to explore the political tensions that emerged in connection with duplication among museum officials and European and indigenous colonial residents.
Multistate outbreak of Salmonella Mbandaka infections linked to sweetened puffed wheat cereal – United States, 2018
Authors: Keaton Amelia A. , Schwensohn Colin A. , Brandenburg Joshua M. , Pereira Evelyn , Adcock Brandon , Tecle Selam , Hinnenkamp Rachel , Havens Jeff , Bailey Kim , Applegate Brad , Whitney Pamela , Gibson Deborah , Manion Kathy , Griffin Michelle , Ritter Joy , Biskupiak Carrie , Ajileye Kadri , Golwalkar Mugdha , Gosciminski Michael , Viveiros Brendalee , Caron Genevieve , McCullough Laine , Smith Lori , Vidyaprakash Eshaw , Doyle Matthew , Hardy Cerise , Elliot Elisa L. , Gieraltowski Laura B.
Published: June 2022

In May of 2018, PulseNet, the national molecular subtyping network for enteric pathogens, detected a multistate cluster of illnesses caused by an uncommon molecular subtype of Salmonella serovar Mbandaka. A case was defined as an illness in a person infected with the outbreak strain of Salmonella Mbandaka with illness onset on or after 3 March 2018 and before 1 September 2018. One-hundred thirty-six cases from 36 states were identified; 35 hospitalisations and no deaths were reported. Ill people ranged in age from <1 year to 95 years (median: 57 years). When standardised questionnaires did not generate a strong hypothesis, opened-ended interviews were performed. Sixty-three of 84 (75%) ultimately reported consuming or possibly consuming a specific sweetened puffed wheat cereal in the week before illness onset. Environmental sampling performed at the cereal manufacturing facility yielded the outbreak strain. The outbreak strain was also isolated from open cereal samples from ill people's homes and from a sealed retail sample. Due to these findings, the brand owner of the product issued a voluntary recall of the cereal on 14 June 2018. Additional investigation of the manufacturing facility identified persistent environmental contamination with Salmonella Mbandaka that was closely genetically related to other isolates in the outbreak. This investigation highlights the ability of Salmonella to survive in low-moisture environments, and the potential for prolonged outbreaks linked to products with long shelf lives and large distribution areas.
Distribution and habitat use of the endemic Yungas GuanPenelope bridgesiin the Southern Yungas of Argentina
Authors: TEJERINA SILVANA , BARDAVID SOFIA , POLITI NATALIA , BERNARDOS JAIME , PIDGEON ANNA , RIVERA LUIS OSVALDO
Published: June 2022

Identifying the factors that determine the spatial distribution and habitat use of species of conservation importance is essential to developing effective conservation and management strategies. As seed dispersers, guans play a key role in the regeneration of forests in South America and are threatened mainly by habitat loss and hunting pressure. The Yungas GuanPenelope bridgesi, an endemic species restricted to the Southern Yungas of Argentina and Bolivia, has been recently recognized as a separate species. To determine the conservation status of Yungas Guan, information on its distribution and habitat use is urgently needed. The objectives of our work were to 1) determine the potential distribution of the Yungas Guan in the Southern Yungas of Argentina and 2) assess the influence of environmental and anthropogenic covariables on habitat use of the species. We used records of Yungas Guan to model the potential distribution of the species with MaxEnt software and developed occupancy models to determine habitat use and influential elements of the landscape (puestos, urban areas, roads, rivers, and elevation). We obtained data on the presence of Yungas Guan with camera traps, with an effort of 6,990 camera trap-days. The total potential distribution of the species was 21,256 km2. We found that the habitat use by Yungas Guan increased with proximity to rivers and streams. The probability of habitat use was 0.27, with a range of 0.02–0.42. Of the total potential distribution area, 15,781 km2(81%) had a probability of habitat use greater than 0.2. This study is the first in determining the potential distribution of Yungas Guan in the Southern Yungas of Salta and Jujuy provinces in Argentina and highlights the importance of conducting analyses with occupancy models to assess the influence of environmental and anthropogenic variables and threats to cracid species.
Anxiety symptoms and associated functional impairment in children with CHD in a neurodevelopmental follow-up clinic
Authors: Cunningham Sean , Campbell Kathleen , Miller Thomas , Winter Sarah , Presson Angela , Ou Zhining , Glotzbach Kristi
Published: June 2022

Objectives:

To examine the prevalence of anxiety symptoms and associated functional impairment to adaptive skills among elementary-aged children with CHD and to determine the need for anxiety screening in this high-risk population.

Study design:

In a single-centre retrospective, cohort design, caregivers reported anxiety symptoms using Conner’s scales and functional impairment to adaptive skills using the Adaptive Behavior Assessment System. A total of 194 children were stratified across two cohorts: early elementary (ages 3–6 years) and late elementary (ages 6–14 years). Descriptive statistics summarised the frequency of anxiety symptoms and functional impairment. Spearman’s correlations compared anxiety symptoms to functional impairment of adaptive functioning. Univariable logistic regressions examined demographic and clinical characteristics associated with anxiety symptoms.

Results:

The majority of patients presented with anxiety, early elementary (63%), and late elementary cohorts (78%). Functional impairment was moderately correlated with anxiety symptoms in the early elementary cohort (rs = −.42, 95% CI [−0.58, −0.21], p = <.001). Greater anxiety symptoms were associated with lower cardiac complexity at primary age of surgery in the late elementary cohort (OR = 12.15, p = 0.019). Lesser anxiety symptoms were associated with having private insurance (OR = 0.25, p = 0.014).

Conclusion:

This study demonstrates anxiety symptoms are common and associated with functional impairment to adaptive functioning in younger children with CHD. No clear clinical predictors exist for anxiety symptoms or functional impairment; therefore, screening for anxiety symptoms may need to be added to standard clinical assessment of all children with CHD participating in neurodevelopmental follow-up.
“The Silent Partner”: Tonearms and Modular Masculinities in U.S. Midcentury Hi-Fi Culture
Authors: Smith-Biwer Kelli
Published: June 2022

Advertisements for audio equipment in midcentury magazines, such as High Fidelity and HiFi Review, shaped the constructions that determined how masculinity was modeled, embodied, and fashioned in the United States at midcentury. A hi-fi setup was a material expression of self and masculinity that could be ever tweaked, refashioned, and adjusted. Tonearms, however, were (and still are) delicate, troublesome, and, when improperly calibrated, capable of destroying record grooves. Manufacturers, advertisers, and magazine contributors who strategically gendered other technologies as masculine—such as amplifiers and speakers—struggled to imbue tonearms with the same virility, toughness, and power. If the hi-fi system served as an embodied simulacrum of the masculine self, then the tonearm was a necessary and omni-present symbolic point of gendered questioning in masculine identity formation. In this article, I argue that the tonearm is a site of fluidity and ambiguity within a modular masculine system, and I demonstrate that the discourses around tonearms in 1950s hi-fi magazines provide an alternative window into discussions of gender and sexuality in United States print culture. Through image analysis and close reading of advertisements and equipment reviews, I decentralize hegemonic masculinity and make room for readings that draw upon feminist and queer theory. More broadly, I submit that mid-twentieth-century hi-fi discourses do not produce a single brand of anxiously conforming maleness, but rather an array of modular masculinities.
Kinetic Energy Generation in Cross‐Equatorial Flow and the Somali Jet
Authors: Seshadri Ashwin K. , Dixit Vishal
Published: June 2022

In response to north‐south pressure gradients set by the annual march of the Sun, a cross‐equatorial flow that turns to become a low‐level Somali Jet at around 10°N is established in the lower troposphere over the Indian Ocean. This flow plays a fundamental role in the Indian monsoon. A mechanistic understanding of drivers of this flow is lacking. Here, we present a seasonal‐mean analysis of the kinetic energy (KE) budget of the low‐level flow using high spatiotemporal resolution ERA5 reanalysis to identify sources and sinks of KE. We find that the largest KE generation occurs around East African orography where the Somali Jet forms while significant KE is also generated over the Western Ghats and the Madagascar Island (“hot spots”). These regions are distant from core monsoon precipitation regions, suggesting that local circulations driven by condensation do not directly produce the bulk of KE during monsoons. A unique KE balance supports the generation of the Somali Jet, with KE generation balanced by nonlinear KE advection as it forms. Over oceans, KE generation occurs mainly due to cross‐isobaric meridional winds in the boundary layer (BL). In contrast, over the East African highlands and Western Ghats, KE generation maximizes just above the BL and mainly occurs due to the interaction of flow with orography. We propose a simple decomposition of lower tropospheric KE generation into contributions from surface pressure, orography, and free‐tropospheric gradients that corroborate the important role played by surface pressure gradients once adjusted for effects of orography.
Patterns and distribution of de novo mutations in multiplex Middle Eastern families
Authors: Kohailan Muhammad , Aamer Waleed , Syed Najeeb , Padmajeya Sujitha , Hussein Sura , Sayed Amira , Janardhanan Jyothi , Palaniswamy Sasirekha , El hajj Nady , Al-Shabeeb Akil Ammira , Fakhro Khalid A.
Published: June 2022

While de novo mutations (DNMs) are key to genetic diversity, they are also responsible for a high number of rare disorders. To date, no study has systematically examined the rate and distribution of DNMs in multiplex families in highly consanguineous populations. Leveraging WGS profiles of 645 individuals in 146 families, we implemented a combinatorial approach using 3 complementary tools for DNM discovery in 353 unique trio combinations. We found a total of 27,168 DNMs (median: 70 single-nucleotide and 6 insertion-deletions per individual). Phasing revealed around 80% of DNMs were paternal in origin. Notably, using whole-genome methylation data of spermatogonial stem cells, these DNMs were significantly more likely to occur at highly methylated CpGs (OR: 2.03; p value = 6.62 × 10−11). We then examined the effects of consanguinity and ethnicity on DNMs, and found that consanguinity does not seem to correlate with DNM rate, and special attention has to be considered while measuring such a correlation. Additionally, we found that Middle-Eastern families with Arab ancestry had fewer DNMs than African families, although not significant (p value = 0.16). Finally, for families with diseased probands, we examined the difference in DNM counts and putative impact across affected and unaffected siblings, but did not find significant differences between disease groups, likely owing to the enrichment for recessive disorders in this part of the world, or the small sample size per clinical condition. This study serves as a reference for DNM discovery in multiplex families from the globally under-represented populations of the Middle-East.
Interleukin-13 promotes cellular senescence through inducing mitochondrial dysfunction in IgG4-related sialadenitis
Authors: Zhu Mengqi , Min Sainan , Mao Xiangdi , Zhou Yuan , Zhang Yan , Li Wei , Li Li , Wu Liling , Cong Xin , Yu Guangyan
Published: June 2022

Immunoglobulin G4-related sialadenitis (IgG4-RS) is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood. The aim of this study was to explore the role and mechanism of interleukin-13 (IL-13) in the cellular senescence during the progress of IgG4-RS. We found that the expression of IL-13 and IL-13 receptor α1 (IL-13Rα1) as well as the number of senescent cells were significantly higher in the submandibular glands (SMGs) of IgG4-RS patients. IL-13 directly induced senescence as shown by the elevated activity of senescence-associated β-galactosidase (SA-β-gal), the decreased cell proliferation, and the upregulation of senescence markers (p53 and p16) and senescence-associated secretory phenotype (SASP) factors (IL-1β and IL-6) in SMG-C6 cells. Mechanistically, IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and mitochondrial-reactive oxygen species (mtROS), while decreased the mitochondrial membrane potential, ATP level, and the expression and activity of superoxide dismutase 2 (SOD2). Notably, the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger MitoTEMPO. Moreover, IL-13 increased the interaction between p-STAT6 and cAMP-response element binding protein (CREB)-binding protein (CBP) and decreased the transcriptional activity of CREB on SOD2. Taken together, our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6–CREB–SOD2-dependent pathway in IgG4-RS.
Clinical applications and utility of cell-free DNA-based liquid biopsy analyses in cervical cancer and its precursor lesions
Authors: Herbst Johanna , Pantel Klaus , Effenberger Katharina , Wikman Harriet
Published: June 2022

Human papilloma virus (HPV) is an infectious carcinogenic agent. Nearly all cervical cancers are positive for one of the high-risk HPV subtypes. Although the introduction of the HPV vaccines in many countries have shown tremendous positive effects on the incidence of both cervical intraepithelial lesions (CIN) and invasive cancer, the large majority of females worldwide are still not vaccinated. Patients with diagnosed high-grade CIN need a lifelong close monitoring of possible relapse or development of invasive cancer. Different blood-based liquid biopsy approaches have shown great promise as an easily obtainable minimally invasive tool for early detection and monitoring of disease. Among the different liquid biopsy approaches the clinical relevance of cell-free DNA (cfDNA) in cervical cancer has been best investigated. In cervical cancer, the DNA fragments can be of both, human as well as viral origin. Thus, the mutation and methylation status of genes related to carcinogenesis as well as the HPV status can be analysed in plasma from cervical cancer patients. This review describes recent advances in different cfDNA approaches for early detection and monitoring of cervical cancer and its precursor lesions.
β-blockers and breast cancer survival by molecular subtypes: a population-based cohort study and meta-analysis
Authors: Løfling L. Lukas , Støer Nathalie C. , Sloan Erica K. , Chang Aeson , Gandini Sara , Ursin Giske , Botteri Edoardo
Published: June 2022

Background

The association between use of β-blockers and breast cancer (BC) prognosis has been investigated in several observational studies, with conflicting results. We performed a nationwide cohort study and a meta-analysis to investigate the association, and assess if it varied between molecular subtypes of BC.

Methods

We identified women aged ≥50 years with BC diagnosed between 2004 and 2018 in Norway. We used Cox regression models to estimate the association between β-blocker use at diagnosis and BC-specific survival, overall and by molecular subtype. We performed a meta-analysis of observational studies that reported molecular subtype-specific estimates of this association.

Results

We included 30,060 women, of which 4461 (15%) used β-blockers. After a median follow-up of 5.1 years, 2826 (9%) died of BC. Overall, β-blocker use was not associated with BC-specific survival (hazard ratio [HR] = 1.07; 95% confidence interval [CI]: 0.97–1.19). We found an association only in triple-negative BC (TNBC) patients (HR = 0.66; 95% CI: 0.47–0.91). This was confirmed in the meta-analysis: β-blocker use was associated with progression/recurrence-free (HR = 0.58; 95% CI: 0.38–0.89) and BC-specific survival (HR = 0.74; 95% CI: 0.55–1.00) in TNBC patients only.

Conclusion

In our cohort of BC patients and in the meta-analysis, β-blocker use was associated with prolonged BC-specific survival only in TNBC patients.
Co-loaded lapatinib/PAB by ferritin nanoparticles eliminated ECM-detached cluster cells via modulating EGFR in triple-negative breast cancer
Authors: Wu Xinghan , Sheng Huan , Zhao Liping , Jiang Mingxia , Lou Han , Miao Yue , Cheng Ni , Zhang Weifen , Ding Dejun , Li Wentong
Published: June 2022

Cancer stem cell (CSC) cluster of triple-negative breast cancer (TNBC) is suggested to be responsible for therapy resistance, metastatic process and cancer recurrence, yet the sensitivity of CSC clusters of TNBC to ferroptosis remains elusive in a great measure. Current research revealed that epidermal growth factor receptor (EGFR) reinforced CD44-mediated TNBC cell clustering, whether blockade of EGFR has synergistic effects on erastin-induced tumor inhibition of CSC clusters is still poorly understood. Here, we found that fraction of CD24lowCD44high cells and size of tumor spheres clearly decreased following EGFR inhibition in TNBC cells. Inhibition of EGFR promoted expression of LC3B-II via YAP/mTOR signaling pathway, indicating that EGFR-mediated autophagy which contributed to ferroptosis. In order to further verify the protective effects of EGFR on ferroptosis induced by small molecules in TNBC cells, pseudolaric acid B (PAB) which led to ferroptosis of malignant cells was selected. In our experiment, lapatinib and PAB cotreatment inhibited TNBC cells viability and restrained formation of tumor spheres, accompanied with a high level of intracellular ROS. To target delivery lapatinib and PAB to TNBC cells, lapatinib/PAB@Ferritin (L/P@Ferritin) nanoparticles were prepared; results of in vitro and in vivo showed a higher tumor suppression efficiency of L/P@Ferritin, highlighting that it might provide a new perspective for treatment of CSC clusters of TNBC.
Promising prognostic value of Transglutaminase type 2 and its correlation with tumor-infiltrating immune cells in skin cutaneous melanoma
Authors: Muccioli Silvia , Ciaccio Roberto , Brillo Valentina , Leanza Luigi
Published: June 2022

Tissue Transglutaminases (TGs) are crosslinking enzymes with pleiotropic functions that have been linked to the development and progression of numerous cancers, with a recent focus on their ability to remodel the tumor microenvironment. Although several pieces of evidence demonstrated their importance in the regulation of the major signaling pathways that control oncogenesis, the correlation between TGs with clinical and pathological features remains controversial and to be further explored. Moreover, an assessment of the TGs alterations together with a functional analysis associated with clinical features and prognostic values are still lacking and would help to understand these intricacies, particularly in human cancers. In the present study, we processed data from numerous public datasets to investigate TGs distribution and prognostic signature in cancer patients. Here, we found that skin cutaneous melanoma (SKCM) shows the highest abundance of TGs mutations among the other human cancers. Interestingly, among all the TGs, TG2 is the only member whose expression is associated with a better overall survival in SKCM, although its expression increases with the worsening of the tumor phenotype. Our analysis revealed a strong positive association between TG2 expression and anti-tumoral immune response, which would explain the relationship between high mRNA levels and better overall survival. Our data suggest that TG2 may be presented as a new promising immune biomarker of prognosis in SKCM, which may contribute to identifying patients who would benefit the most from adjuvant immunotherapy.
HarmonizR enables data harmonization across independent proteomic datasets with appropriate handling of missing values
Authors: Voß Hannah , Schlumbohm Simon , Barwikowski Philip , Wurlitzer Marcus , Dottermusch Matthias , Neumann Philipp , Schlüter Hartmut , Neumann Julia E. , Krisp Christoph
Published: June 2022

Dataset integration is common practice to overcome limitations in statistically underpowered omics datasets. Proteome datasets display high technical variability and frequent missing values. Sophisticated strategies for batch effect reduction are lacking or rely on error-prone data imputation. Here we introduce HarmonizR, a data harmonization tool with appropriate missing value handling. The method exploits the structure of available data and matrix dissection for minimal data loss, without data imputation. This strategy implements two common batch effect reduction methods—ComBat and limma (removeBatchEffect()). The HarmonizR strategy, evaluated on four exemplarily analyzed datasets with up to 23 batches, demonstrated successful data harmonization for different tissue preservation techniques, LC-MS/MS instrumentation setups, and quantification approaches. Compared to data imputation methods, HarmonizR was more efficient and performed superior regarding the detection of significant proteins. HarmonizR is an efficient tool for missing data tolerant experimental variance reduction and is easily adjustable for individual dataset properties and user preferences.
Forest Fire Clustering for single-cell sequencing combines iterative label propagation with parallelized Monte Carlo simulations
Authors: Chen Zhanlin , Goldwasser Jeremy , Tuckman Philip , Liu Jason , Zhang Jing , Gerstein Mark
Published: June 2022

In the era of single-cell sequencing, there is a growing need to extract insights from data with clustering methods. Here, we introduce Forest Fire Clustering, an efficient and interpretable method for cell-type discovery from single-cell data. Forest Fire Clustering makes minimal prior assumptions and, different from current approaches, calculates a non-parametric posterior probability that each cell is assigned a cell-type label. These posterior distributions allow for the evaluation of a label confidence for each cell and enable the computation of “label entropies", highlighting transitions along developmental trajectories. Furthermore, we show that Forest Fire Clustering can make robust, inductive inferences in an online-learning context and can readily scale to millions of cells. Finally, we demonstrate that our method outperforms state-of-the-art clustering approaches on diverse benchmarks of simulated and experimental data. Overall, Forest Fire Clustering is a useful tool for rare cell type discovery in large-scale single-cell analysis.
EphB4 and ephrinB2 act in opposition in the head and neck tumor microenvironment
Authors: Bhatia Shilpa , Nguyen Diemmy , Darragh Laurel B. , Van Court Benjamin , Sharma Jaspreet , Knitz Michael W. , Piper Miles , Bukkapatnam Sanjana , Gadwa Jacob , Bickett Thomas E. , Bhuvane Shiv , Corbo Sophia , Wu Brian , Lee Yichien , Fujita Mayumi , Joshi Molishree , Heasley Lynn E. , Ferris Robert L. , Rodriguez Olga , Albanese Christopher , Kapoor Mohit , Pasquale Elena B. , Karam Sana D.
Published: June 2022

Differential outcomes of EphB4-ephrinB2 signaling offers formidable challenge for the development of cancer therapeutics. Here, we interrogate the effects of targeting EphB4 and ephrinB2 in head and neck squamous cell carcinoma (HNSCC) and within its microenvironment using genetically engineered mice, recombinant constructs, pharmacologic agonists and antagonists. We observe that manipulating the EphB4 intracellular domain on cancer cells accelerates tumor growth and angiogenesis. EphB4 cancer cell loss also triggers compensatory upregulation of EphA4 and T regulatory cells (Tregs) influx and their targeting results in reversal of accelerated tumor growth mediated by EphB4 knockdown. EphrinB2 knockout on cancer cells and vasculature, on the other hand, results in maximal tumor reduction and vascular normalization. We report that EphB4 agonism provides no additional anti-tumoral benefit in the absence of ephrinB2. These results identify ephrinB2 as a tumor promoter and its receptor, EphB4, as a tumor suppressor in HNSCC, presenting opportunities for rational drug design.
Near-zero-index ultra-fast pulse characterization
Authors: Jaffray Wallace , Belli Federico , Carnemolla Enrico G. , Dobas Catalina , Mackenzie Mark , Travers John , Kar Ajoy K. , Clerici Matteo , DeVault Clayton , Shalaev Vladimir M. , Boltasseva Alexandra , Ferrera Marcello
Published: June 2022

Transparent conducting oxides exhibit giant optical nonlinearities in the near-infrared window where their linear index approaches zero. Despite the magnitude and speed of these nonlinearities, a “killer” optical application for these compounds has yet to be found. Because of the absorptive nature of the typically used intraband transitions, out-of-plane configurations with short optical paths should be considered. In this direction, we propose an alternative frequency-resolved optical gating scheme for the characterization of ultra-fast optical pulses that exploits near-zero-index aluminium zinc oxide thin films. Besides the technological advantages in terms of manufacturability and cost, our system outperforms commercial modules in key metrics, such as operational bandwidth, sensitivity, and robustness. The performance enhancement comes with the additional benefit of simultaneous self-phase-matched second and third harmonic generation. Because of the fundamental importance of novel methodologies to characterise ultra-fast events, our solution could be of fundamental use for numerous research labs and industries.
Catalyst-free synthesis of sub-5 nm silicon nanowire arrays with massive lattice contraction and wide bandgap
Authors: Gao Sen , Hong Sanghyun , Park Soohyung , Jung Hyun Young , Liang Wentao , Lee Yonghee , Ahn Chi Won , Byun Ji Young , Seo Juyeon , Hahm Myung Gwan , Kim Hyehee , Kim Kiwoong , Yi Yeonjin , Wang Hailong , Upmanyu Moneesh , Lee Sung-Goo , Homma Yoshikazu , Terrones Humberto , Jung Yung Joon
Published: June 2022

The need for miniaturized and high-performance devices has attracted enormous attention to the development of quantum silicon nanowires. However, the preparation of abundant quantities of silicon nanowires with the effective quantum-confined dimension remains challenging. Here, we prepare highly dense and vertically aligned sub-5 nm silicon nanowires with length/diameter aspect ratios greater than 10,000 by developing a catalyst-free chemical vapor etching process. We observe an unusual lattice reduction of up to 20% within ultra-narrow silicon nanowires and good oxidation stability in air compared to conventional silicon. Moreover, the material exhibits a direct optical bandgap of 4.16 eV and quasi-particle bandgap of 4.75 eV with the large exciton binding energy of 0.59 eV, indicating the significant phonon and electronic confinement. The results may provide an opportunity to investigate the chemistry and physics of highly confined silicon quantum nanostructures and may explore their potential uses in nanoelectronics, optoelectronics, and energy systems.