bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics and near-optimal control in a stochastic rumor propagation model incorporating media coverage and Lévy noise
Authors: Huo Liang’an , Dong Yafang
Published: October 2021

The appearance of rumors intensifies people’s panic and affects social stability. How to control the spread of rumors has become an important issue which is worth studying. In order to more accurately reflect the actual situation in the real world, a stochastic model incorporating media coverage and Lévy noise is proposed to describe the dynamic process of rumor propagation. By introducing two control strategies of popular science education and media coverage in an emergency event, an near-optimal control problem that minimizes the influence and control cost of rumor propagation is proposed. Sufficient conditions for near-optimal control of the model are established by using a Hamiltonian function. Then the necessary conditions for near-optimal control are obtained by using the Pontryagin maximum principle. Finally, the effect of popular science education, media coverage and Lévy noise on rumor propagation process control is verified by numerical simulation.
Retinal Microvascular Caliber and Incident Depressive Symptoms: The Multi-Ethnic Study of Atherosclerosis
Authors: van Gennip April C E , Sedaghat Sanaz , Carnethon Mercedes R , Allen Norrina B , Klein Barbara E K , Cotch Mary Frances , Chirinos Diana A , Stehouwer Coen D A , van Sloten Thomas T
Published: October 2021

Cerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. The retina allows for visualization of a microvascular bed that shares similarities with the cerebral microvasculature. We investigated the associations between baseline retinal arteriolar and venular calibers (central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively) and incident depressive symptoms in the Multi-Ethnic Study of Atherosclerosis (MESA). We used longitudinal data on 4,366 participants (mean age = 63.2 years; 48.5% women, 28.4% Black) without baseline depressive symptoms. Depressive symptoms, defined as Center for Epidemiologic Studies Depression Scale score ≥16 and/or use of antidepressant medication, were determined between 2002 and 2004 (baseline; MESA visit 2) and at 3 follow-up examinations conducted every 1.5–2 years thereafter. Fundus photography was performed at baseline. After a mean follow-up period of 6.1 years, 21.9% (n = 958) had incident depressive symptoms. After adjustment for sociodemographic, lifestyle, and cardiovascular factors, a 1–standard-deviation larger baseline CRVE was associated with a higher risk of depressive symptoms (hazard ratio = 1.10, 95% confidence interval: 1.02, 1.17), and a 1–standard-deviation larger baseline CRAE was not statistically significantly associated with incident depressive symptoms (hazard ratio = 1.04, 95% confidence interval: 0.97, 1.11). In this study, larger baseline CRVE, but not CRAE, was associated with a higher incidence of depressive symptoms.
Emotion Word Development in Bilingual Children Living in Majority and Minority Contexts
Authors: Ahn Sunyoung , Chang Charles B
Published: October 2021

The lexicon of emotion words is fundamental to interpersonal communication. To examine how emotion word acquisition interacts with societal context, the present study investigated emotion word development in three groups of child Korean users aged 4–13 years: those who use Korean primarily outside the home as a majority language (MajKCs) or inside the home as a minority language (MinKCs), and those who use Korean both inside and outside the home (KCs). These groups, along with a group of L1 Korean adults, rated the emotional valence of 61 Korean emotion words varying in frequency, valence, and age of acquisition. Results showed KCs, MajKCs, and MinKCs all converging toward adult-like valence ratings by ages 11–13 years; unlike KCs and MajKCs, however, MinKCs did not show age-graded development and continued to diverge from adults in emotion word knowledge by these later ages. These findings support the view that societal context plays a major role in emotion word development, offering one reason for the intergenerational communication difficulties reported by immigrant families.
RNF126 is a positive regulator of TRAF3 ubiquitination
Authors: Kim Soomi , Park Kibeom , Oh Jung-Min , Kim Hongtae
Published: October 2021

Ubiquitination and deubiquitination of signaling molecules are critical regulatory mechanisms in various biological contexts such as inflammatory signaling and the DNA damage response. Thus, finely tuned regulation of protein ubiquitination is essential for maintaining cellular homeostasis. Here, we showed that the RING finger protein RNF126 interacts with TRAF3 and promotes its K63-linked polyubiquitination, which is a crucial step in the TRAF3-dependent antiviral response. We found that RNF126 also interacts with OTUB1, a deubiquitinating enzyme that negatively regulates K63-linked ubiquitination of TRAF3. RNF126 promotes ubiquitination of OTUB1, leading to reduced deubiquitinating activity toward TRAF3. Moreover, RNF126 promotes ubiquitination of OTUB1 on cysteine 91, which is reportedly required for its catalytic activity. Taken together, our results suggest that RNF126 positively regulates the antiviral response by directly promoting K63-linked polyubiquitination of TRAF3 and by reducing OTUB1 activity.
Clustering phosphate and iron-related markers and prognosis in dialysis patients
Authors: Morooka Hikaru , Tanaka Akihito , Inaguma Daijo , Maruyama Shoichi
Published: October 2021

Background

Hyperphosphatemia in patients undergoing dialysis is common and is associated with mortality. Recently, the link between phosphate metabolism and iron dynamics has received increasing attention. However, the association between this relationship and prognosis remains largely unexplored.

Methods

We conducted an observational study of patients who initiated dialysis in the 17 centers participating in the Aichi Cohort Study of the Prognosis in Patients Newly Initiated into Dialysis. Data were available on sex, age, use of phosphate binder, drug history, medical history and laboratory data. After excluding patients with missing values of phosphate, hemoglobin, ferritin and transferrin saturation, we used the Gaussian mixture model to divide the cohort into clusters based on phosphate, hemoglobin, logarithmic ferritin and transferrin saturation. We investigated the prognosis of patients in these clusters. The primary outcome was all-cause death. In each cluster, the prognostic impact of phosphate binder was also studied.

Results

The study included 1175 patients with chronic kidney disease who initiated dialysis between October 2011 and September 2013. Among them, 785 were men and 390 were women, with a mean ± SD age of 67.9 ± 13.0 years. The patients were divided into three clusters, and mortality was higher in cluster c than in cluster a (P = 0.005). Moreover, the use of phosphate binders was associated with a lower risk of all-cause death in two clusters (a and c) that were characterized by older age and higher prevalence of diabetes mellitus, among other things.

Conclusions

We used an unsupervised machine learning method to cluster patients, using phosphate, hemoglobin and iron-related markers. In two of the clusters, the oral use of a phosphate binder might improve prognosis.
Titin (TTN): from molecule to modifications, mechanics, and medical significance
Authors: Loescher Christine M , Hobbach Anastasia J , Linke Wolfgang A
Published: October 2021

The giant sarcomere protein titin is a major determinant of cardiomyocyte stiffness and contributor to cardiac strain sensing. Titin-based forces are highly regulated in health and disease, which aids in the regulation of myocardial function, including cardiac filling and output. Due to the enormous size, complexity, and malleability of the titin molecule, titin properties are also vulnerable to dysregulation, as observed in various cardiac disorders. This review provides an overview of how cardiac titin properties can be changed at a molecular level, including the role isoform diversity and post-translational modifications (acetylation, oxidation, and phosphorylation) play in regulating myocardial stiffness and contractility. We then consider how this regulation becomes unbalanced in heart disease, with an emphasis on changes in titin stiffness and protein quality control. In this context, new insights into the key pathomechanisms of human cardiomyopathy due to a truncation in the titin gene (TTN) are discussed. Along the way, we touch on the potential for titin to be therapeutically targeted to treat acquired or inherited cardiac conditions, such as HFpEF or TTN-truncation cardiomyopathy.
Methodology for the integration of a high-speed train in Maintenance 4.0
Authors: Bustos Alejandro , Rubio Higinio , Soriano-Heras Enrique , Castejon Cristina
Published: October 2021

The fourth industrial revolution is changing the way industries face their problems, including maintenance. The railway industry is moving to adopt this new industry model. The new trains are designed, manufactured, and maintained following an Industry 4.0 methodology, but most of the current trains in operation were not designed with this technological philosophy, so they must be adapted to it. In this paper, a new methodology for adapting a high-speed train to Industry 4.0 is proposed. That way, a train manufactured before this new paradigm can seize the advantages of Maintenance 4.0. This methodology is based on four stages (physical system, digital twin, information and communication technology infrastructure, and diagnosis) that comprise the required processes to digitalize a railway vehicle and that share information between them. The characteristics that the data acquisition and communication systems must fulfil are described, as well as the original signal processing techniques developed for analysing vibration signals. These techniques allow processing experimental data both in real time and deferred, according to actual maintenance requirements. The methodology is applied to determine the operating condition of a high-speed bogie by combining the signal processing of actual vibration measurements taken during the normal train operation and the data obtained from simulations of the digital twin. The combination of both (experimental data and simulations) allows establishing characteristic indicators that correspond to the normal running of the train and indicators that would correspond to anomalies in the behaviour of the train.
Transposon insertion mutation of Antarctic psychrotrophic fungus for red pigment production adaptive to normal temperature
Authors: Ding Lulu , Huang Hezhou , Lu Fengning , Lu Jian , Zhou Xiangshan , Zhang Yuanxing , Cai Menghao
Published: October 2021

Polar regions are rich in microbial and product resources. Geomyces sp. WNF-15A is an Antarctic psy chrotrophic filamentous fungus producing high quality red pigment with potential for industrial use. However, efficient biosynthesis of red pigment can only realize at low temperature, which brings difficult control and high cost for the large-scale fermentation. This study aims to develop transposon insertion mutation method to improve cell growth and red pigment production adaptive to normal temperature. Genetic manipulation system of this fungus was firstly developed by antibiotic marker screening, protoplast preparation and transformation optimization, by which transformation efficiency of ∼50% was finally achieved. Then transposable insertion systems were established using Helitron, Fot1, and Impala transposons. The transposition efficiency reached 11.9%, 9.4%, and 4.6%, respectively. Mutant MP1 achieved the highest red pigment production (OD520 of 39) at 14°C, which was 40% higher than the wild-type strain. Mutant MP14 reached a maximum red pigment production (OD520 of 14.8) at 20°C, which was about twofold of the wild-type strain. Mutants MP2 and MP10 broke the repression mechanism of red pigment biosynthesis in the wild-type and allowed production at 25°C. For cell growth, eight mutants grew remarkably better (12%∼30% biomass higher) than the wild-type at 25°C. This study established an efficient genetic manipulation and transposon insertion mutation platform for polar filamentous fungus. It provides reference for genetic breeding of psychrotrophic fungi from polar and other regions.
Getting on track for digital work: Digital transformation in an administrative court before and during COVID-19
Authors: Björkdahl Joakim , Kronblad Charlotta
Published: October 2021

This article analyses organizational change and new ways of working in one of our most institutionalized and professionalized contexts—the courts. Here, digital technologies and the implementation of digital work practices carry great promise as they enable more accessible and qualitative services to be produced more efficiently and effectively. While prior studies have shown that institutionalized and professionalized actors are reluctant to respond to change, attempts to change work practices through digital technologies remain understudied. In particular, we do not know how COVID-19 has influenced the motivation and implementation of digitalized work. This article draws on a large Swedish administrative court and its attempts to digitalize its work starting in 2018. We find that several barriers first inhibited a successful transformation of work practices. These barriers were connected to the institution of the court and the institutionalized profession of judges, which worked together in preventing organizational change. However, COVID-19 radically accelerated the digital implementation of work practices and gave rise to two separate re-assessment processes. The first established new motivations for digitalized work, and the second allowed for a new perception of value in digital work. These processes effectively broke down perceived barriers and substantially facilitated a more successful digital transformation of working practices.
Liposomal chrysin attenuates hepatic ischaemia-reperfusion injury: possible mechanism via inhibiting NLRP3 inflammasome
Authors: Huang Rui , Zhao Zizuo , Jiang Xujie , Li Weiwei , Zhang Lidan , Wang Bin , Tie Hongtao
Published: October 2021

Objectives

The chrysin has properties of low aqueous solubility, bioavailability and absorption, and its effect on hepatic ischaemia-reperfusion (HIR) remains unclear. Thus, we prepared a liposomal chrysin (LC) and explored its effect and potential mechanism on HIR.

Methods

A thin-film dispersion method was used to prepare LC, and a mouse HIR model was used. Mice were pre-treated with LC (100 mg/kg) or placebo by gavage feeding at 16.5 h, 8.5 h, 0.5 h before modelling.

Results

The average particle sizes, polydispersity index, zeta potential, encapsulation efficiency and drug loading of LC were 129 ± 13.53 nm, 0.265 ± 0.021, −34.46 ± 4.14 mV, 95.03 ± 2.17%, 16.4 ± 0.8%. The concentration of chrysin in plasma and liver tissue by LC administration increased 2.54 times and 1.45 times. LC pre-treatment reduced HIR-induced liver injury and inhibited cell apoptosis. Besides, LC pre-treatment decreased reactive oxygen species and malondialdehyde and inhibited the inflammation response indicated by lower IL-6, TNF-α, infiltration of neutrophils. Further, LC pre-treatment significantly decreased NLRP3 activation, evidenced by reduced cleaved caspase-3, NLRP3, ASC, cleaved caspase-1 and IL-1β expression.

Conclusions

LC has good biocompatibility, and it could attenuate HIR-induced injury. Its mechanism was associated with NLRP3 inflammasome inhibition, and LC might be an effective drug for treating and preventing HIR-induced injury.
Redrafting the Architecture of Daniel Traditions in the Hebrew Scriptures and Dead Sea Scrolls
Authors: Perrin Andrew B
Published: October 2021

For all the qualities that make the book of Daniel an odd fit in the Hebrew Bible—it is a bilingual hybrid of Aramaic and Hebrew traditions, has demonstrable compositional roots in the Second Temple period, and is attributed to a character of more recent ancestral memory—the book fits exceptionally well within a broader set of now-known Aramaic writings in the Dead Sea Scrolls. The texts and contexts of Daniel in view of these new discoveries, however, demand that we rethink the formation of Daniel traditions and transformations of Daniel as an emerging authoritative figure in ancient Jewish scribal culture. In this article, I apply a material philological approach to 4QDaniela–b (4Q112–4Q113), two Daniel manuscripts from Qumran that preserve the linguistic juncture between Dan. 7:28 and 8:1. I argue that the varied uses of physical space between these sections indicates a scribal understanding not necessarily of a unified book but of an early collection of Daniel traditions. In view of this possibility, the later Hebrew materials of Daniel 8–12 are then re-characterized as our earliest demonstrable Danielic pseudepigraphon in view of their documented redactional relationship to the foregoing Aramaic chapters. This, in turn, provides a fresh way of approaching the so-called Aramaic Pseudo-Daniel (4Q243–4Q245) fragments among the Qumran Aramaic texts simply as Danielic traditions in their own integrity.
IDH wild-type grade 2 diffuse astrocytomas: prognostic factors and impact of treatments within molecular subgroups
Authors: Rudà Roberta , Bruno Francesco , Ius Tamara , Silvani Antonio , Minniti Giuseppe , Pace Andrea , Lombardi Giuseppe , Bertero Luca , Pizzolitto Stefano , Pollo Bianca , Conti Nibali Marco , Pellerino Alessia , Migliore Enrica , Skrap Miran , Bello Lorenzo , Soffietti Riccardo
Published: October 2021

Background

Prognostic factors and role of treatments are not well known in isocitrate dehydrogenase (IDH) wild-type (wt) grade 2 astrocytomas. The aim of this study was to define in these tumors clinical features, molecular characteristics, and prognostic factors, with particular focus on molecular subgroups defined by cIMPACT-NOW update 3.

Methods

We analyzed 120 patients with confirmed diagnosis of grade 2 IDHwt astrocytoma according to WHO 2016, collected from seven Italian centers between 1999 and 2017.

Results

Median PFS and OS of the whole cohort were 18.9 and 32.6 months. Patients older than 40 years and patients with modest contrast enhancement on MRI had a shorter PFS and OS. Gross total resection yielded superior PFS and OS over non-gross total resection. PFS and OS of patients with either pTERT mutation or EGRF amplification were significantly shorter. The prognostic value of age, contrast enhancement on MRI, and extent of surgery was different within the molecular subgroups. Gross total resection was associated with increased PFS (not reached versus 14 months, p = 0.023) and OS (117.9 versus 20 months, p = 0.023) in patients without EGFR amplification, and with increased OS in those without pTERT mutation (NR vs 53.7 months, p = 0.05). Conversely, for patients with EGFR amplification or pTERT mutation, gross total resection did not yield a significant survival benefit.

Conclusion

Patients without EGFR amplification and pTERT mutation could be observed after gross total resection.
Characteristics of the lunar samples returned by the Chang’E-5 mission
Authors: Li Chunlai , Hu Hao , Yang Meng-Fei , Pei Zhao-Yu , Zhou Qin , Ren Xin , Liu Bin , Liu Dawei , Zeng Xingguo , Zhang Guangliang , Zhang Hongbo , Liu Jianjun , Wang Qiong , Deng Xiangjin , Xiao Caijin , Yao Yonggang , Xue Dingshuai , Zuo Wei , Su Yan , Wen Weibin , Ouyang Ziyuan
Published: October 2021

Forty-five years after the Apollo and Luna missions returned lunar samples, China's Chang’E-5 (CE-5) mission collected new samples from the mid-latitude region in the northeastern Oceanus Procellarum of the Moon. Our study shows that 95% of CE-5 lunar soil sizes are found to be within the range of 1.40–9.35 μm, while 95% of the soils by mass are within the size range of 4.84–432.27 μm. The bulk density, true density and specific surface area of CE-5 soils are 1.2387 g/cm3, 3.1952 g/cm3 and 0.56 m2/g, respectively. Fragments from the CE-5 regolith are classified into igneous clasts (mostly basalt), agglutinate and glass. A few breccias were also found. The minerals and compositions of CE-5 soils are consistent with mare basalts and can be classified as low-Ti/low-Al/low-K type with lower rare-earth-element contents than materials rich in potassium, rare earth element and phosphorus. CE-5 soils have high FeO and low Mg index, which could represent a new class of basalt.
Flavonoids naringenin chalcone, naringenin, dihydrotricin, and tricin are lignin monomers in papyrus
Authors: Rencoret Jorge , Rosado Mario J , Kim Hoon , Timokhin Vitaliy I , Gutiérrez Ana , Bausch Florian , Rosenau Thomas , Potthast Antje , Ralph John , del Río José C
Published: October 2021

Recent studies demonstrate that several polyphenolic compounds produced from beyond the canonical monolignol biosynthetic pathways can behave as lignin monomers, participating in radical coupling reactions and being incorporated into lignin polymers. Here, we show various classes of flavonoids, the chalconoid naringenin chalcone, the flavanones naringenin and dihydrotricin, and the flavone tricin, incorporated into the lignin polymer of papyrus (Cyperus papyrus L.) rind. These flavonoids were released from the rind lignin by Derivatization Followed by Reductive Cleavage (DFRC), a chemical degradative method that cleaves the β-ether linkages, indicating that at least a fraction of each was integrated into the lignin as β-ether-linked structures. Due to the particular structure of tricin and dihydrotricin, whose C-3ʹ and C-5ʹ positions at their B-rings are occupied by methoxy groups, these compounds can only be incorporated into the lignin through 4ʹ–O–β bonds. However, naringenin chalcone and naringenin have no substituents at these positions and can therefore form additional carbon–carbon linkages, including 3ʹ– or 5ʹ–β linkages that form phenylcoumaran structures not susceptible to cleavage by DFRC. Furthermore, Nuclear Magnetic Resonance analysis indicated that naringenin chalcone can also form additional linkages through its conjugated double bond. The discovery expands the range of flavonoids incorporated into natural lignins, further broadens the traditional definition of lignin, and enhances the premise that any phenolic compound present at the cell wall during lignification could be oxidized and potentially integrated into the lignin structure, depending only on its chemical compatibility. This study indicates that papyrus lignin has a unique structure, as it is the only lignin known to date that integrates such a diversity of phenolic compounds from different classes of flavonoids. This discovery will open up new ways to engineer and design lignins with specific properties and for enhanced value.
Entrepreneurial Human Capital and Firm Dynamics
Authors: Queiró Francisco
Published: October 2021

This article shows that entrepreneurial human capital is a key driver of firm dynamics using administrative panel data on the universe of firms and workers in Portugal. Firms started by more educated entrepreneurs are larger at entry and exhibit higher life cycle growth. Consistent with an effect on growth, the thickness of the right tail of the size distribution increases with entrepreneur schooling. The evidence points to several underlying mechanisms, with technology adoption playing the most important part. I develop and estimate a model of firm dynamics that can parsimoniously account for these findings and use it to draw aggregate implications. Accounting for the effect of entrepreneurial human capital on firm dynamics can substantially increase aggregate returns to schooling and the fraction of cross-country income differences explained by human and physical capital.
The modulatory effect of bee honey against diethyl nitrosamine and carbon tetrachloride instigated hepatocellular carcinoma in Wistar rats
Authors: Abouzed Tarek Kamal , Eldomany Ehab B , Khatab Shymaa A , Aldhahrani Adil , Gouda Wael M , Elgazzar Ahmed M , Soliman Mohamed Mohamed , Kassab Mohmed Atef , El-Shazly Samir Ahmed , Althobaiti Fayez , Dorghamm Doaa Abdallha
Published: October 2021

Hepatocellular carcinoma (HCC) is a serious threat to human health that has attracted substantial interest. The purpose of this study was to investigate the modulatory effect of bee honey against induced HCC by diethylnitrosamine/carbon tetrachloride (DEN/CCl4) in rats. HCC was induced by a single intraperitoneal dose of DEN (200 mg/kg B.W). Two weeks later, CCl4 (1 ml/kg) was intraperitoneally injected (three times a week). Bee honey was administered orally at 2 g/rat before and after the induction of HCC. The results showed that bee honey administration significantly increased body weight, decreased liver weight, and relative liver weight compared to those in the HCC-induced group. Moreover, a significant decrease in serum alpha-fetoprotein (AFP) as well as AST, ALT, GGT, ALP activities were observed in bee honey administration rats compared with those in HCC-induced group. Also, the hepatic MDA was significantly decreased; in addition, SOD, CAT, and GPx activities were significantly increased in groups treated with bee honey compared with those in the HCC group. The hepatic histopathology alterations caused by DEN/CCl4 injection were ameliorated by bee honey treatment. Likewise, the mRNA expression levels of tumor necrosis factor-alpha (TNF-α), transforming growth factor (TGF-β1), intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), glypican (GP-3), thioredoxin (TRX), and glutaredoxin (GRX) were downregulated, and caspase-3 was upregulated by bee honey treatment compared with untreated HCC-induced group. In conclusion, bee honey has remarkable beneficial effects against HCC induced in rats through its antioxidant, anti-inflammatory, antifibrotic, and antimetastatic effects.

Practical Applications

The current study confirmed that honey has the potential to act as an antimetastatic factor. Bee honey supplementation either before or after combined injection of DEN/CCl4 exhibited inhibitory and ameliorative effects against DEN/CCl4-induced HCC through its antioxidant, antiproliferative, anti-metastatic, antifibrotic, and apoptosis properties. To our knowledge, this is the first study to describe the molecular mechanisms underlying honey’s effects against DEN/CCl4-induced HCC in rats.
A high-fidelity human cervical muscle finite element model for motion and injury studies
Authors: Li Fan , Li Honggeng , Lei Kang , Zhang Biao , Su Sicheng , Hu Wei , Cao Yingchun , Nie Jin
Published: October 2021

Active muscle response is a key factor in the motion and injury of the human head and neck. Due to the limitations of experimentation and the shortcomings of previous finite element models, the influence of material parameters of cervical muscle on motions of the head and neck during a car crash have not been comprehensively investigated. In the present work, a model of the cervical muscle in a 50th-percentile adult male was constructed. The muscles were modelled using solid finite elements, with a nonlinear-elastic and viscoelastic material and a Hill material modelling the passive and active parts of each muscle, respectively. The head dynamic responses of the model were validated using results obtained from volunteer sled tests. The influence of the material parameters of a muscle on head and neck motions were determined. Our key finding was that the greater the stiffness and the contraction strength of the neck muscles, the smaller the rotation angle of the head and the neck, and, hence, the lower the risk of head and neck injury to occupants in a car crash.
Simulations reveal that different responses to cell crowding determine the expansion of
p53
and
Notch
mutant clones in squamous epithelia
Authors: Kostiou Vasiliki , Hall Michael W. J. , Jones Philip H. , Hall Benjamin A.
Published: October 2021

During ageing, normal epithelial tissues progressively accumulate clones carrying mutations that increase mutant cell fitness above that of wild-type cells. Such mutants spread widely through the tissues, yet despite this cellular homeostasis and functional integrity of the epithelia are maintained. Two of the genes most commonly mutated in human skin and oesophagus are
p53
and
Notch1
, both of which are also recurrently mutated in cancers of these tissues. From observations taken in human and mouse epithelia, we find that clones carrying
p53
and
Notch
pathway mutations have different clone dynamics which can be explained by their different responses to local cell crowding.
p53
mutant clone growth in mouse epidermis approximates a logistic curve, but feedbacks responding to local crowding are required to maintain tissue homeostasis. We go on to show that the observed ability of
Notch
pathway mutant cells to displace the wild-type population in the mouse oesophageal epithelium reflects a local density feedback that affects both mutant and wild-type cells equally. We then show how these distinct feedbacks are consistent with the distribution of mutations observed in human datasets and are suggestive of a putative mechanism to constrain these cancer-associated mutants.
Ultrastructure expansion microscopy in
Trypanosoma brucei
Authors: Kalichava Ana , Ochsenreiter Torsten
Published: October 2021

The recently developed ultrastructure expansion microscopy (U-ExM) technique allows us to increase the spatial resolution within a cell or tissue for microscopic imaging through the physical expansion of the sample. In this study, we validate the use of U-ExM in
Trypanosoma brucei
measuring the expansion factors of several different compartments/organelles and thus verify the isotropic expansion of the cell. We furthermore demonstrate the use of this sample preparation protocol for future studies by visualizing the nucleus and kDNA, as well as proteins of the cytoskeleton, the basal body, the mitochondrion and the endoplasmic reticulum. Lastly, we discuss the challenges and opportunities of U-ExM.
Malaria, COVID-19 and angiotensin-converting enzyme 2: what does the available population data say?
Authors: De A. , Dash M. , Tiwari A. , Sinha A.
Published: October 2021

The etiopathogenesis of COVID-19 and its differential geographic spread suggest some populations are apparently ‘less affected’ through many host-related factors that involve angiotensin-converting enzyme 2 (ACE2) protein, which is also the entry receptor for SARS-CoV-2. The role of ACE2 has been well studied in COVID-19 but not in the context of malaria and COVID-19. We have previously suggested how malaria might intersect with COVID-19 through
ACE2
mutation and here we evaluate the currently available data that could provide a link between the two diseases. Based on the existing global and Indian data on malaria, COVID-19 and the suggested
ACE2
mutation, the association could not be examined robustly, neither accepting nor refuting the suggested hypothesis. We strongly recommend targeted evaluation of this hypothesis through carefully designed robust molecular epidemiological studies.
Structured time-delay models for dynamical systems with connections to Frenet–Serret frame
Authors: Hirsh Seth M. , Ichinaga Sara M. , Brunton Steven L. , Nathan Kutz J. , Brunton Bingni W.
Published: October 2021

Time-delay embedding and dimensionality reduction are powerful techniques for discovering effective coordinate systems to represent the dynamics of physical systems. Recently, it has been shown that models identified by dynamic mode decomposition on time-delay coordinates provide linear representations of strongly nonlinear systems, in the so-called Hankel alternative view of Koopman (HAVOK) approach. Curiously, the resulting linear model has a matrix representation that is approximately antisymmetric and tridiagonal; for chaotic systems, there is an additional forcing term in the last component. In this paper, we establish a new theoretical connection between HAVOK and the Frenet–Serret frame from differential geometry, and also develop an improved algorithm to identify more stable and accurate models from less data. In particular, we show that the sub- and super-diagonal entries of the linear model correspond to the intrinsic curvatures in the Frenet–Serret frame. Based on this connection, we modify the algorithm to promote this antisymmetric structure, even in the noisy, low-data limit. We demonstrate this improved modelling procedure on data from several nonlinear synthetic and real-world examples.
Universal self-similar attractor in the bending-driven levelling of thin viscous films
Authors: Pedersen Christian , Salez Thomas , Carlson Andreas
Published: October 2021

We study theoretically and numerically the bending-driven levelling of thin viscous films within the lubrication approximation. We derive Green’s function of the linearized thin-film equation and further show that it represents a universal self-similar attractor at long times. As such, the rescaled perturbation of the film profile converges in time towards the rescaled Green’s function, for any summable initial perturbation profile. In addition, for stepped axisymmetric initial conditions, we demonstrate the existence of another, short-term and one-dimensional-like self-similar regime. We also characterize the convergence time towards the long-term universal attractor in terms of the relevant physical and geometrical parameters, and provide the local hydrodynamic fields and global elastic energy in the universal regime as functions of time. Finally, we extend our analysis to the nonlinear thin-film equation through numerical simulations.
Drift of elastic floating ice sheets by waves and current, part I: single sheet
Authors: Kostikov Vasily K. , Hayatdavoodi Masoud , Ertekin R. C.
Published: October 2021

The drift motion of a freely floating deformable ice sheet in shallow water subjected to incident nonlinear waves and uniform current is studied by use of the Green–Naghdi theory for the fluid motion and the thin plate theory for an elastic sheet. The nonlinear wave- and current-induced forces are obtained by integrating the hydrodynamic pressure around the body. The oscillations and translational motion of the sheet are then determined by substituting the flow-induced forces into the equation of motion of the body. The resulting governing equations, boundary and matching conditions are solved in two dimensions with a finite difference technique. The surge and drift motions of the sheet are analysed in a broad range of body parameters and various wave-current conditions. It is demonstrated that wavelength to sheet length ratio plays an important role in the drift response of the floating sheet, while the sheet mass and rigidity have comparatively less impact. It is also observed that while the presence of the ambient current changes the drift speed significantly (almost linearly), it has little to no effect on its oscillations. However, under the same ambient current, the drift speed changes remarkably by the wave period (or wavelength).
On a class ofq-orthogonal polynomials and theq-Riemann–Hilbert problem
Authors: Joshi Nalini , Lasic Latimer Tomas
Published: October 2021

We give an explicit solution of aq-Riemann–Hilbert problem that arises in the theory of orthogonal polynomials, prove that it is unique and deduce several properties. In particular, we describe the asymptotic behaviour of zeros in the limit as the degree of the polynomial approaches infinity.
General relativity’s energy and positivity: a brief history
Authors: Deser S.
Published: October 2021

I give a brief review of the search for a proper definition of energy in General Relativity (GR), a far from trivial quest, which was only completed after four and a half decades. The equally (or perhaps more) difficult task of establishing its positivity—it was to take another 15 plus years—will then be summarized. Extension to cosmological GR is included. Mention is made of some recent offshoots. An invitation to submit a review to the Proceedings of the Royal Society prompts revisiting a subject of central importance both to GR and to my own past research—its energy definition and positivity. While there are no loose ends left, a summary may be of some use to students and non-experts. Exposure to introductory GR is useful. We will divide this survey into two unequal parts: first, the original GR without a cosmological constant, then extend it to the rather different two cases of

Λ
≠
0

.
Viscoplastic plates
Authors: Ball Thomasina V. , Balmforth Neil J.
Published: October 2021

An asymptotic model is constructed to describe the bending of thin sheets, or plates, of viscoplastic fluid described by the Herschel–Bulkley constitutive law, which incorporates the von Mises yield condition and a nonlinear viscous stress. The model reduces to a number of previous ones from plasticity theory and viscous fluid mechanics in various limits. It is characterized by a yield criterion proposed by Ilyushin which compactly combines the effect of the bending moment and in-plane stress tensors through three particular invariants. The model is used to explore the bending of loaded flat plates, the deflection of impulsively driven circular plates, and the tension-controlled deflection of loaded beams.
WNT/β-catenin dependant alteration of cortical neurogenesis in a human stem cell model of SETBP1 disorder
Authors: Cardo Lucia F. , Li Meng
Published: October 2021

Disruptions of SETBP1 (SET binding protein 1) on 18q12.3 by heterozygous gene deletion or loss-of-function variants cause SETBP1 disorder. Clinical features are frequently associated with moderate to severe intellectual disability, autistic traits and speech and motor delays. Despite SETBP1 association with neurodevelopmental disorders, little is known about its role in brain development. Using CRISPR/CAS9 genome editing technology, we generated a SETBP1 deletion model in human embryonic stem cells (hESCs), and examined the effects of SETBP1-deficiency in in vitro derived neural progenitors (NPCs) and neurons using a battery of cellular assays, genome wide transcriptomic profiling and drug-based phenotypic rescue.

SETBP1-deficient NPCs exhibit protracted proliferation and distorted layer-specific neuronal differentiation with overall decrease in neurogenesis. Genome wide transcriptome profiling and protein biochemical analysis showed that SETBP1 deletion led to enhanced activation of WNT/β-catenin signaling. Crucially, treatment of the SETBP1-deficient NPCs with a small molecule WNT inhibitor XAV939 restored hyper canonical β-catenin activity and rescued cortical neuronal differentiation.

Our study establishes a novel regulatory link between SETBP1 and WNT/β-catenin signaling during human cortical neurogenesis and provides mechanistic insights into structural abnormalities and potential therapeutic avenues for SETBP1 disorder.
gp130/STAT3 signaling is required for homeostatic proliferation and anabolism in postnatal growth plate and articular chondrocytes
Authors: Liu Nancy Q. , Lin Yucheng , Li Liangliang , Lu Jinxiu , Geng Dawei , Zhang Jiankang , Jashashvili Tea , Buser Zorica , Magallanes Jenny , Tassey Jade , Shkhyan Ruzanna , Sarkar Arijita , Lopez Noah , Wang Liming , Petrigliano Frank A. , Van Handel Ben , Lyons Karen , Evseenko Denis
Published: October 2021

Growth of long bones and vertebrae is maintained postnatally by a long-lasting pool of progenitor cells. Little is known about the molecular mechanisms that regulate the output and maintenance of the cells that give rise to mature cartilage. Here we demonstrate that postnatal chondrocyte-specific deletion of a transcription factor Stat3 results in severely reduced proliferation coupled with increased hypertrophy, growth plate fusion, stunting and signs of progressive dysfunction of the articular cartilage. This effect is dimorphic, with females more strongly affected than males. Chondrocyte-specific deletion of the IL-6 family cytokine receptor gp130, which activates Stat3, phenocopied Stat3-deletion; deletion of Lifr, one of many co-receptors that signals through gp130, resulted in a milder phenotype. These data define a new molecular circuit that regulates chondrogenic cell maintenance and output and reveals a novel, hitherto unrecognized function of IL-6 cytokines in the skeletal system with direct implications for skeletal development and regeneration.
Hippocampus-striatum wiring diagram revealed by directed stepwise polysynaptic tracing
Authors: Du Wenqin Rita , Li Elizabeth , Guo Jun , Chen Yuh-tarng , Oh So Jung , Samuel Aspen , Li Ying , Oyibo Hassana K , Xu Wei
Published: October 2021

The hippocampus and the striatum represent two major systems in the brain for learning, memory and navigation. Although they were traditionally considered as two parallel systems responsible for distinct types of learning or navigation, increasing evidence indicates a close synergetic or competitive interaction between them. Both the hippocampus and the striatum consist of multiple anatomical and functional domains. Besides the limited direct projection from the hippocampus to the ventral striatum, most of the functional interaction between them may be mediated by polysynaptic projections. Polysynaptic connectivity has been difficult to examine due to a lack of methods to continuously track the pathways in a controlled manner. Here we developed a novel approach for directed stepwise polysynaptic tracing by reconstituting a replication-deficient retrograde transneuronal virus – pseudorabies virus lacking gene IE180 (PRVΔIE). We minimized PRV neurotoxicity by temporally restricting viral replication; and enabled both anatomical tracing and functional analysis of the circuits. With these tools, we delineated a hippocampus-striatum wiring diagram, which consists of pathways from specific functional domains in the hippocampus to corresponding domains in the striatum via distinct intermediate regions. This polysynaptic wring diagram provides a structural foundation for further elucidation of the interaction between the hippocampus and the stratum in multiple brain functions.

Significance Statement

We created a new method for controlled stepwise tracing of polysynaptic neuronal circuits which also enables functional analysis of the circuits. With this method, we revealed the polysynaptic wiring diagram between the hippocampus and the striatum, two major brain structures centrally involved in learning, memory and spatial navigation. This wiring diagram demonstrates how specific anatomical domains in the hippocampus are connected to the specific domains in the striatum via distinct intermediate brain regions; thus it will help to elucidate the functional interaction between these two major memory and navigation systems. Our new method can be broadly applied to many other brain circuits for anatomical and functional analysis.
Revealing the early stages of carbamazepine crystallization by cryoTEM and 3D electron diffraction
Authors: Broadhurst Edward T. , Xu Hongyi , Parsons Simon , Nudelman Fabio
Published: October 2021

Time-resolved carbamazepine crystallization from wet ethanol has been monitored using a combination of cryoTEM and 3D electron diffraction. Carbamazepine is shown to crystallize exclusively as a dihydrate after 180 s. When the timescale was reduced to 30 s, three further polymorphs could be identified. At 20 s, the development of early stage carbamazepine dihydrate was observed through phase separation. This work reveals two possible crystallization pathways present in this active pharmaceutical ingredient.
3′,5′-Dichloro-N,N-diphenyl-[1,1′-biphenyl]-4-amine
Authors: Patel Dinesh G. , Cox Jordan M. , Bender Branden M. , Benedict Jason B.
Published: October 2021

The title triphenylamine derivative, C24H17Cl2N, featuring a 3,5-dichloro-1,1′-biphenyl moiety has been synthesized and structurally characterized. The molecular structure shows rotations of the phenyl rings in the range of 37–40° from the amine plane. In the crystal, the molecules interact by van der Waals interactions.
The use of an analytic hierarchy process to evaluate the flexibility and adaptability in architecture
Authors: De Paris Sabine , Lacerda Lopes Carlos Nuno , Neuenfeldt Junior Alvaro
Published: October 2021

Purpose

Investigation of housing adaptability is related to understanding factors that influence project transformation. Factors may be associated with the design and project stage as also alternative uses to existing buildings. To structure methodology for criteria analysis of adaptability, the research aims to verify the importance level of factors related to adaptability and flexibility context in architecture.

Design/methodology/approach

Employing a multicriteria analysis and a diagnosis performed with architecture professionals, criteria importance identified in a bibliographic survey is contacted.

Findings

With harmonious results, key elements highlighted in the diagnosis are discussed. Adaptability and flexibility are mainly related to balance in the design of spaces and their connections, so the user can have control administrating the organization of their habitat.

Originality/value

As a complex subject, involving legal, social and cultural issues, the multicriteria method supports the scientific analysis of data. The results can be used in a practical case study as assessment of housing adaptability and flexibility, as a useful tool to decision support in architectural project.
Knowledge search strategies and corporate entrepreneurship: evidence from China's high-tech firms
Authors: Ye Jiangfeng , Jiang Yingna , Hao Bin , Feng Yanan
Published: October 2021

Purpose

This study aims to explore the impact of search breadth and depth on corporate entrepreneurship (CE) through the mediating effect of opportunity discovery under the consideration of the technological environmental dynamism as a moderating factor.

Design/methodology/approach

This study adopts a quantitative method, collecting 246 questionnaires from high-tech firms in the national industrial park of the Yangtze River Delta zone in China. The authors examine the hypotheses using multiple hierarchical regressions and conduct Sobel and bootstrapping tests to further assess the mediating and moderated mediating effects of the variables.

Findings

The results indicate that both the relationship between search breadth and CE and the relationship between search depth and CE are mediated by opportunity discovery. The authors further show that technological environmental dynamism positively moderates the indirect effect of knowledge search breadth on CE and negatively moderates the indirect effect of knowledge search depth and CE.

Originality/value

This study provides a valuable theoretical framework for entrepreneurship literature by differentiating the effects of search depth and search breadth on the promotion of CE in established firms and pioneers the examination of the mediating role of opportunity discovery and the moderating role of technological environmental dynamism in these links as well.