bluuebunny/crossref_metadata_2025 huggingface dataset:
Degenerative lamellar macular holes: tractional development and morphological alterations
Authors: Bringmann Andreas , Unterlauft Jan Darius , Wiedemann Renate , Barth Thomas , Rehak Matus , Wiedemann Peter
Published: January 2021

Purpose

The development of degenerative lamellar macular holes (DLH) is largely unclear. This study was aimed at documenting with spectral-domain optical coherence tomography the tractional development and morphological alterations of DLH.

Methods

A retrospective case series of 44 eyes of 44 patients is described.

Results

The development of DLH is preceded for months or years by tractional deformations of the fovea due to the action of contractile epiretinal membranes (ERM) and/or the partially detached posterior hyaloid, or by cystoid macular edema (CME). DLH may develop after a tractional stretching and thickening of the foveal center, from a foveal pseudocyst, after a detachment of the foveola from the retinal pigment epithelium, a disruption of the foveal structure due to CME, and after surgical treatment of tractional lamellar or full-thickness macular holes (FTMH). The foveal configuration of a DLH can be spontaneously reestablished after short transient episodes of CME and a small FTMH. A DLH can evolve to a FTMH by traction of an ERM. Surgical treatment of a DLH may result in an irregular regeneration of the foveal center without photoreceptors.

Conclusions

Tractional forces play an important role in the development of DLH and in the further evolution to FTMH. It is suggested that a DLH is the result of a retinal wound repair process after a tractional disruption of the Müller cell cone and a degeneration of Henle fibers, to prevent a further increase in the degenerative cavitations.
Work, Childcare, or Both? Experimental Evidence on the Efficacy of Childcare Subsidies in Raising Parental Labor Supply
Authors: Zangger Christoph , Widmer Janine , Gilgen Sandra
Published: January 2021

As a policy tool aimed at raising parental labor supply, childcare subsidies come with high expectations. Using data from a factorial survey conducted in the City of Bern, Switzerland, we examine whether childcare subsidies reach their goal. Because of the simultaneity of the decision to take up a job and arranging childcare, we experimentally alter hypothetical income (e.g., gross earnings from a job, income from other sources) as well as aspects of the childcare setting including subsidy levels. Using an alternative-specific conditional logit model, we show that subsidies have the expected effect of increasing parents’ labor supply. Moreover, the results from simulations based on the estimated utility function show that varying subsidy levels have different effects on subgroups of parents. Subsidies are especially efficient in raising the labor supply of low-status parents, and especially for women. We also find that subsidies already have the desired effect at 25% of total childcare costs and that the marginal utility of higher subsidy levels decreases beyond that threshold. Subsidies covering 25% of the total costs for childcare lead to an approximately 2 h per week increase in the labor supply of women.
Moments of Moments and Branching Random Walks
Authors: Bailey E. C. , Keating J. P.
Published: January 2021

We calculate, for a branching random walk $$X_n(l)$$

X
n

(
l
)

to a leaf l at depth n on a binary tree, the positive integer moments of the random variable $$\frac{1}{2^{n}}\sum _{l=1}^{2^n}e^{2\beta X_n(l)}$$

1

2
n

∑

l
=
1

2
n

e

2
β

X
n

(
l
)

, for $$\beta \in {\mathbb {R}}$$

β
∈
R

. We obtain explicit formulae for the first few moments for finite n. In the limit $$n\rightarrow \infty $$

n
→
∞

, our expression coincides with recent conjectures and results concerning the moments of moments of characteristic polynomials of random unitary matrices, supporting the idea that these two problems, which both fall into the class of logarithmically correlated Gaussian random fields, are related to each other.
An adaptive MCMC method for Bayesian variable selection in logistic and accelerated failure time regression models
Authors: Wan Kitty Yuen Yi , Griffin Jim E.
Published: January 2021

Bayesian variable selection is an important method for discovering variables which are most useful for explaining the variation in a response. The widespread use of this method has been restricted by the challenging computational problem of sampling from the corresponding posterior distribution. Recently, the use of adaptive Monte Carlo methods has been shown to lead to performance improvement over traditionally used algorithms in linear regression models. This paper looks at applying one of these algorithms (the adaptively scaled independence sampler) to logistic regression and accelerated failure time models. We investigate the use of this algorithm with data augmentation, Laplace approximation and the correlated pseudo-marginal method. The performance of the algorithms is compared on several genomic data sets.
Robust fitting for generalized additive models for location, scale and shape
Authors: Aeberhard William H. , Cantoni Eva , Marra Giampiero , Radice Rosalba
Published: January 2021

The validity of estimation and smoothing parameter selection for the wide class of generalized additive models for location, scale and shape (GAMLSS) relies on the correct specification of a likelihood function. Deviations from such assumption are known to mislead any likelihood-based inference and can hinder penalization schemes meant to ensure some degree of smoothness for nonlinear effects. We propose a general approach to achieve robustness in fitting GAMLSSs by limiting the contribution of observations with low log-likelihood values. Robust selection of the smoothing parameters can be carried out either by minimizing information criteria that naturally arise from the robustified likelihood or via an extended Fellner–Schall method. The latter allows for automatic smoothing parameter selection and is particularly advantageous in applications with multiple smoothing parameters. We also address the challenge of tuning robust estimators for models with nonlinear effects by proposing a novel median downweighting proportion criterion. This enables a fair comparison with existing robust estimators for the special case of generalized additive models, where our estimator competes favorably. The overall good performance of our proposal is illustrated by further simulations in the GAMLSS setting and by an application to functional magnetic resonance brain imaging using bivariate smoothing splines.
Non-invariant submanifolds of locally decomposable golden Riemannian manifolds
Authors: Gök Mustafa , Kılıç Erol
Published: January 2021

In this paper, we investigate any non-invariant submanifold of a locally decomposable golden Riemannian manifold in the case that the rank of the set of tangent vector fields of the induced structure on the submanifold by the golden structure of the ambient manifold is less than or equal to the codimension of the submanifold.
Security trends in Internet of Things: a survey
Authors: Rachit  , Bhatt Shobha , Ragiri Prakash Rao
Published: January 2021

The Internet of Things (IoT) is a network of embedded devices that are uniquely identifiable and have embedded software required to communicate between the transient states. The purpose of this study is to explore discrete IoT security challenges pertaining to currently deployed IoT standards and protocols. We have presented a detailed review in this study that focuses on IoT's imminent security aspects, covering identification of risks pertaining to the current IoT system, novel security protocols, and security projects proffered in recent years. This work presents an updated review of the IoT architecture in the protocols and standards that are proffered for the next-gen IoT systems. A security-specific comparative analysis of protocols, standards, and proffered security models are presented as per IoT security requirements. This study elicits the need for standardization at the communication and data audit level, which exposes the hardware, software, and data to various threats and attacks. Our study reveals a need for protocols that are competent enough to be accorded for over one threat vector. This paper provides an insight into the latest security research trends, which will prove beneficial in the development of IoT security. The research outcomes can benefit the research community in IoT by integrating IoT-based devices' best security aspects.
AI, Norms, Big Data, and the Law
Authors: HYDÉN Håkan
Published: January 2021

This is an overview article regarding artificial intelligence (AI) and its potential normative implications. Technology has always had inherent normative consequences not least due to AI and the use of algorithms. There is a crucial difference between algorithms in a technical sense and from a social-science perspective. It is a question of different orders of normativity—the first related to the algorithm as a technical instruction and the second to the consequences springing from the first order. I call these last-mentioned normsalgo norms. These are embedded in the technology and determined by the design of the AI. The outcome is an empirical question. AI andalgo normsare moving targets, which call for a novel scientific approach that relates to advanced practice. Law actualizes primarily for preventive reasons in relation to negative aspects of the new technology. No major regulatory scheme for AI exists. In the article, I point out some areas that raise the need for legal regulation. Finally, I comment on three main challenges for the digital development in relation to AI: (1) the energy costs; (2) the singularity point; and (3) the governance problems.
Ethnic and Immigrant Variations in the Time Trends of Dementia and Parkinsonism
Authors: Wong Jessica J. , Kwong Jeffrey C. , Tu Karen , Butt Debra A. , Wilton Andrew S. , Shah Baiju R. , Murray Brian J. , Kopp Alexander , Chen Hong
Published: January 2021

Objective:

We assessed long-term incidence and prevalence trends of dementia and parkinsonism across major ethnic and immigrant groups in Ontario.

Methods:

Linking administrative databases, we established two cohorts (dementia 2001–2014 and parkinsonism 2001–2015) of all residents aged 20 to 100 years with incident diagnosis of dementia (N = 387,937) or parkinsonism (N = 59,617). We calculated age- and sex-standardized incidence and prevalence of dementia and parkinsonism by immigrant status and ethnic groups (Chinese, South Asian, and the General Population). We assessed incidence and prevalence trends using Poisson regression and Cochran–Armitage trend tests.

Results:

Across selected ethnic groups, dementia incidence and prevalence were higher in long-term residents than recent or longer-term immigrants from 2001 to 2014. During this period, age- and sex-standardized incidence of dementia in Chinese, South Asian, and the General Population increased, respectively, among longer-term immigrants (by 41%, 58%, and 42%) and long-term residents (28%, 7%, and 4%), and to a lesser degree among recent immigrants. The small number of cases precluded us from assessing parkinsonism incidence trends. For Chinese, South Asian, and the General Population, respectively, prevalence of dementia and parkinsonism modestly increased over time among recent immigrants but significantly increased among longer-term immigrants (dementia: 134%, 217%, and 117%; parkinsonism: 55%, 54%, and 43%) and long-term residents (dementia: 97%, 132%, and 71%; parkinsonism: 18%, 30%, and 29%). Adjustment for pre-existing conditions did not appear to explain incidence trends, except for stroke and coronary artery disease as potential drivers of dementia incidence.

Conclusion:

Recent immigrants across major ethnic groups in Ontario had considerably lower rates of dementia and parkinsonism than long-term residents, but this difference diminished with longer-term immigrants.
Psychological contract breach and voluntary turnover among newcomers: the role of supervisor trustworthiness and negative affectivity
Authors: Lapointe Émilie , Vandenberghe Christian
Published: January 2021

This article looks at the relationship between psychological contract breach and voluntary turnover among newcomers, using supervisor trustworthiness as a mediator and negative affectivity as a moderator. Relying on data from 243 newcomers, psychological contract breach was found to be negatively related to the three dimensions of supervisor trustworthiness, i.e., ability, benevolence, and integrity. Supervisor integrity further mediated a positive relationship between psychological contract breach and voluntary turnover measured 8 months later. Psychological contract breach interacted with negative affectivity such that it was less negatively related to dimensions of supervisor trustworthiness at high levels of negative affectivity. The indirect relationship of psychological contract breach to voluntary turnover as mediated by supervisor integrity was also weaker at high levels of negative affectivity. We discuss the implications of these findings for research and practice.
Topological complexity of real Grassmannians
Authors: Pavešić Petar
Published: January 2021

We use some detailed knowledge of the cohomology ring of real Grassmann manifolds Gk(ℝn) to compute zero-divisor cup-length and estimate topological complexity of motion planning for k-linear subspaces in ℝn. In addition, we obtain results about monotonicity of Lusternik–Schnirelmann category and topological complexity of Gk(ℝn) as a function of n.
Spatial variation of East Asian winter monsoon evolution between northern and southern China since the last glacial maximum
Authors: Li Qin , Wu Haibin , Cheng Jun , Zhu Shuya , Zhang Chunxia , Wu Jianyu , Lin Yating , Li Pei , Ren Xiangbin , Zhao Deai , Zhang Yan
Published: January 2021

The East Asian winter monsoon (EAWM) is one of the most dynamic components of the global climate system. Although poorly understood, knowledge of long-term spatial differences in EAWM variability during the glacial–interglacial cycles is important for understanding the dynamic processes of the EAWM. We reconstructed the spatiotemporal characteristics of the EAWM since the last glacial maximum (LGM) using a comparison of proxy records and long-term transient simulations. A loess grain-size record from northern China (a sensitive EAWM proxy) and the sea surface temperature gradient of an EAWM index in sediments of the southern South China Sea were compared. The data–model comparison indicates pronounced spatial differences in EAWM evolution, with a weakened EAWM since the LGM in northern China but a strengthened EAWM from the LGM to the early Holocene, followed by a weakening trend, in southern China. The model results suggest that variations in the EAWM in northern China were driven mainly by changes in atmospheric carbon dioxide (CO2) concentration and Northern Hemisphere ice sheets, whereas orbital insolation and ice sheets were important drivers in southern China. We propose that the relative importance of insolation, ice sheets, and atmospheric CO2for EAWM evolution varied spatially within East Asia.
Abdominal obesity and risk of CVD: a dose–response meta-analysis of thirty-one prospective studies
Authors: Xue Ran , Li Qianwen , Geng Yaping , Wang Hao , Wang Fudi , Zhang Shenshen
Published: January 2021

This meta-analysis aimed to study the relationship between abdominal obesity and the risk of CVD by waist circumference (WC), waist:hip ratio (WHR) and waist:height ratio (WHtR). We systematically searched PubMed, Embase and Web of Science. Prospective studies that estimated cardiovascular events by WC, WHR and WHtR were included in this study. Pooled relative risks with 95 % CI were calculated using random effects models. A total of thirty-one studies were included in the meta-analysis, including 669 560 participants and 25 214 cases. Compared the highest with the lowest category of WC, WHR and WHtR, the summary risk ratios were 1·43 (95 % CI, 1·30, 1·56, P < 0·001), 1·43 (95 % CI, 1·33, 1·54, P < 0·001) and 1·57 (95 % CI, 1·37, 1·79, P < 0·001), respectively. The linear dose–response analysis revealed that the risk of CVD increased by 3·4 % for each 10 cm increase of WC, and by 3·5 and 6·0 % for each 0·1 unit increase of WHR and WHtR in women, respectively. In men, the risk of CVD increased by 4·0 % for each 10 cm increase of WC, and by 4·0 and 8·6 % for each 0·1 unit increase of WHR and WHtR, respectively. Collectively, abdominal obesity is associated with an increased risk of CVD. WC, WHR and WHtR are good indicators for the prediction of CVD.
EVOLVING ETHNOGRAPHIES IN PLINY THE ELDER'S TRANSDANUBIAN EXEGESIS (HN4.80–1)
Authors: Hart Timothy C.
Published: January 2021

In sections 4.80 and 4.81 of theHistoria Naturalis, Pliny the Elder describes the peoples living beyond the Danube River in his own day in the later first centuryc.e.:

(4.80) ab eo in plenum quidem omnes Scytharum sunt gentes, uariae tamen litori adposita tenuere, alias Getae, Daci Romanis dicti, alias Sarmatae, Graecis Sauromatae, eorumque Hamaxobii aut Aorsi, alias Scythae degeneres et a seruis orti aut Trogodytae, mox Alani et Rhoxolani; superiora autem inter Danuuium et Hercynium saltum usque ad Pannonica hiberna Carnunti Germanorumque ibi confinium, campos et plana Iazyges Sarmatae, montes uero et saltus pulsi ab iis Daci ad Pathissum amnem. (4.81) a Maro, siue Duria est a Suebis regnoque Vanniano dirimens eos, auersa Basternae tenent aliique inde Germani. […] Scytharum nomen usquequaque transiit in Sarmatas atque Germanos. nec aliis prisca illa durauit appellatio quam qui extremi gentium harum, ignoti prope ceteris mortalibus, degunt.
Catalan focus markers as discourse particles
Authors: TROTZKE ANDREAS , MAYOL LAIA
Published: January 2021

In this paper, we investigate focus markers in Catalan that can take on discourse-particle readings. We focus on two Catalan elements that have not been studied from a formal linguistics perspective so far: the focus adverbprecisament‘precisely’ and the focus particletambé‘also’. We demonstrate that these elements feature interpretations that we identify as a type of meaning familiar from discourse particles in languages other than Catalan. After having outlined the basic distribution and interpretative effects of these particles, we analyze the semantics and pragmatics ofprecisamentandtambéwithin a probabilistic argumentative framework, and we then conclude the paper by comparing the observations and analyses we have pointed out for Catalan to other languages that feature a discourse-particle reading of similar focus markers.
Increases in depression and anxiety symptoms in adolescents and young adults during the COVID-19 pandemic
Authors: Hawes Mariah T. , Szenczy Aline K. , Klein Daniel N. , Hajcak Greg , Nelson Brady D.
Published: January 2021

Background

The coronavirus [coronavirus disease 2019 (COVID-19)] pandemic has introduced extraordinary life changes and stress, particularly in adolescents and young adults. Initial reports suggest that depression and anxiety are elevated during COVID-19, but no prior study has explored changes at the within-person level. The current study explored changes in depression and anxiety symptoms from before the pandemic to soon after it first peaked in Spring 2020 in a sample of adolescents and young adults (N = 451) living in Long Island, New York, an early epicenter of COVID-19 in the U.S.

Methods

Depression (Children's Depression Inventory) and anxiety symptoms (Screen for Child Anxiety Related Symptoms) were assessed between December 2014 and July 2019, and, along with COVID-19 experiences, symptoms were re-assessed between March 27th and May 15th, 2020.

Results

Across participants and independent of age, there were increased generalized anxiety and social anxiety symptoms. In females, there were also increased depression and panic/somatic symptoms. Multivariable linear regression indicated that greater COVID-19 school concerns were uniquely associated with increased depression symptoms. Greater COVID-19 home confinement concerns were uniquely associated with increased generalized anxiety symptoms, and decreased social anxiety symptoms, respectively.

Conclusions

Adolescents and young adults at an early epicenter of the COVID-19 pandemic in the U.S. experienced increased depression and anxiety symptoms, particularly amongst females. School and home confinement concerns related to the pandemic were independently associated with changes in symptoms. Overall, this report suggests that the COVID-19 pandemic is having multifarious adverse effects on the mental health of youth.
Different Prevention and Treatment Strategies for Knee Osteoarthritis (KOA) with Various Lower Limb Exoskeletons – A Comprehensive Review
Authors: Zhou Xin , Liu Geng , Han Bing , Li Hui , Zhang Li , Liu Xiaoli
Published: January 2021

It was reported that about 10% of people suffer from painful knee arthritis, and a quarter of them were severely disabled. The core activities of daily living were severely limited by knee osteoarthritis (KOA). In order to reduce knee pain and prolong the life of the knee joint, there has been an increasing demand on the development of exoskeletons, for prevention and treatment. The course of KOA was closely related to the biomechanics of knee joint, and the pathogenesis was summarized based on the biomechanics of knee joint. For the prevention and clinical treatment, exoskeletons are classified into three categories: prevention, treatment, and rehabilitation after the operation. Furthermore, the design concepts, actuators, sensors, control strategies, and evaluation criteria were presented. Finally, the shortcomings and limitations were summarized. It is useful for researchers to develop suitable exoskeletons in the future.
Integration of conflict resolution automation and vertical situation display for on-ground air traffic control operations
Authors: Trapsilawati Fitri , Chen Chun-Hsien , Wickens Chris D. , Qu Xingda
Published: January 2021

Both conflict resolution aid (CRA) and vertical situation display (VSD) systems may contribute to air traffic control (ATC) operations. However, their effectiveness still needs to be examined before being widely adopted in ATC facilities. This study aims to examine empirically the use of CRA and VSD as well as the systems’ interaction in ATC operations. It was found that CRA benefited conflict resolution performance by 13⋅7% and lowered workload by 46⋅4% compared with manually performing the task. The VSD could also reduce the air traffic controllers’ (ATCOs) workload and improve their situation awareness. Ultimately, when the first CRA failure occurred, the situation awareness supported by VSD offset the performance decrements by 30%. The findings from this study demonstrate that integrating VSD with CRA would benefit ATC operations, regardless of the CRA's imperfection.
Ecological and environmental factors affecting the foraging activity of the White-bellied Heron Ardea insignis (Hume, 1878) in Bhutan
Authors: KHANDU PEMA , GALE GEORGE A. , BUMRUNGSRI SARA
Published: January 2021

White-bellied Heron Ardea insignis (WBH) is critically endangered, but we lack data on many aspects of its basic ecology and threats to the species are not clearly understood. The goal of this study was to analyse WBH foraging microhabitat selection, foraging behaviour, and prey preferences in two river basins (Punatsangchhu and Mangdechhu) in Bhutan which are likely home to one of the largest remaining populations of WBH. We also explored the relationship between the relative abundance of the WBH and prey biomass catch per unit effort within four foraging river microhabitats (pool, pond, riffle and run). Prey species were sampled in 13 different 100-m thalweg lengths of the rivers using cast nets and electrofishing gear. Riffles and pools were the most commonly used microhabitats; relative abundance was the highest in riffles. The relative abundance of WBH and prey biomass catch per unit effort (CPUE) also showed a weak but significant positive correlation (rs = 0.22). The highest biomass CPUE was observed in riffles while the lowest was found in the ponds. From the 97 prey items caught by the WBH, 95% of the prey were fish. The WBH mainly exploited three genera of fish (Garra, Salmo, and Schizothorax) of which Schizothorax (64%) was the most frequently consumed. This study provides evidence in support of further protection of critical riverine habitat and fish resources for this heron. Regular monitoring of sand and gravel mining, curbing illegal fishing, habitat restoration/mitigation, and developing sustainable alternatives for local people should be urgently implemented by the government and other relevant agencies. Further study is also required for understanding the seasonal variation and abundance of its prey species in their prime habitats along the Punatsangchhu and Mangdechhu basins.
Embryonic development of the fire-eye-tetra Moenkhausia oligolepis (Characiformes: Characidae)
Authors: dos Santos Raquel Santos , Rodrigues Jeane Rodrigues , Cordeiro Jhennifer Gomes , Tercya Hadda , Leite Marissol , Costa Bruna Patrícia Dutra , da Silva Costa Raphael , Maximino Caio , Siqueira-Silva Diógenes Henrique de
Published: January 2021

This study describes the embryonic development of Moenkhausia oligolepis in laboratory conditions. After fertilization, the embryos were collected every 10 min up to 2 h, then every 20 min up to 4 h, and afterwards every 30 min until hatching. The fertilized eggs of M. oligolepis measured approximately 0.85 ± 0.5 mm and had an adhesive surface. Embryonic development lasted 14 h at 25ºC through the zygote, cleavage, blastula, gastrula, neurula, and segmentation phases. Hatching occurred in embryos around the 30-somites stage. The present results contribute only the second description of embryonic development to a species from the Moenkhausia genus, being also the first for this species. Such data are of paramount importance considering the current conflicting state of this genus phylogenetic classification and may help taxonomic studies. Understanding the biology of a species that is easily managed in laboratory conditions and has an ornamental appeal may assist studies in its reproduction to both supply the aquarium market and help the species conservation in nature. Moreover, these data enable the use of M. oligolepis as a model species in biotechnological applications, such as the germ cell transplantation approach.
Perioperative and long-term management of Fontan patients
Authors: Al-Shawk May , Banjoko Adeolu , Axiaq Ariana , Amin Kiran , Harky Amer
Published: January 2021

A Fontan circulation requires a series of three-staged operations aimed to palliate patients with single-ventricle CHD. Currently, the most frequent technique is the extracardiac total cavopulmonary connection, an external conduit connecting the IVC and right pulmonary artery, bypassing the right side of the heart. Fontan candidates must meet strict criteria; they are assessed utilising both cardiac catheterisation and cardiac magnetic resonance. Postoperatively, treatment protocols prioritise antibiotic prophylaxis, diuretics, angiotensin-converting enzyme inhibitors, anticoagulation, and oxygen therapy with fluid restriction and a low-fat diet. These measures aim to reduce length of stay in the ICU and hospital by preventing acute complications such as infection, venous thromboembolism, low cardiac output, pleural effusion, and acute kidney injury. Late complications of a Fontan procedure include circulation failure, protein-losing enteropathy, plastic bronchitis, and Fontan-associated liver disease. The definitive management is cardiac transplantation, with promising innovations in selective embolisation of lymphatic vessels and Fontan-specific ventricular assist devices. Further research assessing current protocols in the perioperative management of Fontan patients would be beneficial for standardising current practice and improving outcomes.
Fancy Footwork: Furniture Patterns Going to and from Gandhāra
Authors: SRINIVASAN DORIS METH
Published: January 2021

This paper is the first assessment of the different sources and shapes in a selection of Gandhāran furniture. Two main types of furniture legs are discussed. These are thought to be originally wooden legs attached to chairs, stools, and beds that are depicted in Kushan sculpture from Gandhāran. The two types are defined by their decoration. The first type is the geometric, lathe-turned furniture leg, the second type of leg is carved, not lathe-turned and depicts figures. The foreign origins of both types are traced and analyzed. A list, plus illustrations of reliefs showing representative contexts for each type, is given. Several heretofore unpublished reliefs are included. In some cases the Gandhāran examples can be interpreted as well as their developments into Central Asian furniture types.
NEW CONSTRUCTIONS OF SELF-COMPLEMENTARY CAYLEY GRAPHS
Authors: LI CAI HENG , RAO GUANG , SONG SHU JIAO
Published: January 2021

Vertex-primitive self-complementary graphs were proved to be affine or in product action by Guralnicket al.[‘On orbital partitions and exceptionality of primitive permutation groups’,Trans. Amer. Math. Soc.356(2004), 4857–4872]. The product action type is known in some sense. In this paper, we provide a generic construction for the affine case and several families of new self-complementary Cayley graphs are constructed.
SOME INNOCENT QUESTIONS ABOUT LANGUAGE
Authors: Lyon Ardon
Published: January 2021

Philosophers and others often believe that a language used to talk about usage in a particular language should not be mixed with use of that language itself. I argue below that this opinion is mistaken.
A PHILOSOPHER WORKS FROM HOME: DIARIES OF A PHILOSOPHICAL ROMP THROUGH VAST TERRITORIES, SOMETIMES CROSSING OVER INTO UNCHARTED REGIONS OCCUPIED BY OTHER PEOPLE
Authors: Thalos Mariam
Published: January 2021

This is my impersonation of a philosopher working from home, which aims at making lively a few worthy philosophical questions. The old is new again, as each generation confronts its own challenges and demons, in its own context.
The difference a wire makes: planning law, public Orthodox Judaism and urban space in Australia
Authors: Riedel Mareike
Published: January 2021

This paper considers a planning dispute that surrounded the construction of a Jewish religious installation (called an eruv) in the public urban space of an Australian suburb. The aim of this case-study is to examine the role of law in regulating Jewish difference – a topic that has to date received little attention in the socio-legal literature concerned with the governance of religious diversity. In analysing residents’ objections to the eruv, the paper explores long-standing anxieties about Jewish particularity in Australia and beyond as they surfaced in opposition to the eruv. It shows how the law continues to exclude certain forms of Jewish difference that are perceived as transgressing dominant religious and racial norms. Moreover, the paper highlights the particular ways in which planning law assigned value to these anxieties and legitimised the marginalisation of Orthodox Jews, emphasising the significance of local law as a site for exclusion and inequality.
The Paradox of the Thai Middle Class in Democratisation
Authors: Lertchoosakul Kanokrat
Published: January 2021

The relationship of the bourgeoisie and democratisation has been inconsistent across the history of democracy. This work offers an alternative explanation taking the example of the Thai middle class, which had promoted democracy, turned against it. From the democratic transition of 1973 until the present day, the Thai middle class has played contradictory roles in the democratisation of the country. This work investigates the effects of democratic institution-building after regime change and the efforts to consolidate democracy in the middle class. This work proposes two major observations. The first is the failure of the middle class to establish themselves in democratic institutions and processes in either the legislature/executive, political parties, local government or structured interest groups. They have learned of the uncertainty of free elections and how the elected executives have benefitted other classes but not them. The second regards the missing prerequisite of democracy. Insufficient understanding of majority rules and two-turnover elections, caused the middle class who were disappointed with the outcome of democratic regimes and systems to easily turn away from democracy.
Serotonin receptor 4 in the hippocampus modulates mood and anxiety
Authors: Karayol Remzi , Medrihan Lucian , Warner-Schmidt Jennifer L. , Fait Ben W. , Rao Meghana N. , Holzner Eva B. , Greengard Paul , Heintz Nathaniel , Schmidt Eric F.
Published: January 2021

Serotonin receptor 4 (5-HT4R) plays an important role in regulating mood, anxiety, and cognition, and drugs that activate this receptor have fast-acting antidepressant (AD)-like effects in preclinical models. However, 5-HT4R is widely expressed throughout the central nervous system (CNS) and periphery, making it difficult to pinpoint the cell types and circuits underlying its effects. Therefore, we generated a Cre-dependent 5-HT4R knockout mouse line to dissect the function of 5-HT4R in specific brain regions and cell types. We show that the loss of functional 5-HT4R specifically from excitatory neurons of hippocampus led to robust AD-like behavioral responses and an elevation in baseline anxiety. 5-HT4R was necessary to maintain the proper excitability of dentate gyrus (DG) granule cells and cell type-specific molecular profiling revealed a dysregulation of genes necessary for normal neural function and plasticity in cells lacking 5-HT4R. These adaptations were accompanied by an increase in the number of immature neurons in ventral, but not dorsal, dentate gyrus, indicating a broad impact of 5-HT4R loss on the local cellular environment. This study is the first to use conditional genetic targeting to demonstrate a direct role for hippocampal 5-HT4R signaling in modulating mood and anxiety. Our findings also underscore the need for cell type-based approaches to elucidate the complex action of neuromodulatory systems on distinct neural circuits.
Prenatal androgen exposure causes a sexually dimorphic transgenerational increase in offspring susceptibility to anxiety disorders
Authors: Risal Sanjiv , Manti Maria , Lu Haojiang , Fornes Romina , Larsson Henrik , Benrick Anna , Deng Qiaolin , Cesta Carolyn E. , Rosenqvist Mina A. , Stener-Victorin Elisabet
Published: January 2021

If and how obesity and elevated androgens in women with polycystic ovary syndrome (PCOS) affect their offspring’s psychiatric health is unclear. Using data from Swedish population health registers, we showed that daughters of mothers with PCOS have a 78% increased risk of being diagnosed with anxiety disorders. We next generated a PCOS-like mouse (F0) model induced by androgen exposure during late gestation, with or without diet-induced maternal obesity, and showed that the first generation (F1) female offspring develop anxiety-like behavior, which is transgenerationally transmitted through the female germline into the third generation of female offspring (F3) in the androgenized lineage. In contrast, following the male germline, F3 male offspring (mF3) displayed anxiety-like behavior in the androgenized and the obese lineages. Using a targeted approach to search for molecular targets within the amygdala, we identified five differentially expressed genes involved in anxiety-like behavior in F3 females in the androgenized lineage and eight genes in the obese lineage. In mF3 male offspring, three genes were dysregulated in the obese lineage but none in the androgenized lineage. Finally, we performed in vitro fertilization (IVF) using a PCOS mouse model of continuous androgen exposure. We showed that the IVF generated F1 and F2 offspring in the female germline did not develop anxiety-like behavior, while the F2 male offspring (mF2) in the male germline did. Our findings provide evidence that elevated maternal androgens in PCOS and maternal obesity may underlie the risk of a transgenerational transmission of anxiety disorders in children of women with PCOS.
Dual RNA 3’-end processing of H2A.X messenger RNA maintains DNA damage repair throughout the cell cycle
Authors: Griesbach Esther , Schlackow Margarita , Marzluff William F. , Proudfoot Nick J.
Published: January 2021

Phosphorylated H2A.X is a critical chromatin marker of DNA damage repair (DDR) in higher eukaryotes. However, H2A.X gene expression remains relatively uncharacterised. Replication-dependent (RD) histone genes generate poly(A)- mRNA encoding new histones to package DNA during replication. In contrast, replication-independent (RI) histone genes synthesise poly(A)+ mRNA throughout the cell cycle, translated into histone variants that confer specific epigenetic patterns on chromatin. Remarkably H2AFX, encoding H2A.X, is a hybrid histone gene, generating both poly(A)+ and poly(A)- mRNA isoforms. Here we report that the selective removal of either mRNA isoform reveals different effects in different cell types. In some cells, RD H2A.X poly(A)- mRNA generates sufficient histone for deposition onto DDR associated chromatin. In contrast, cells making predominantly poly(A)+ mRNA require this isoform for de novo H2A.X synthesis, required for efficient DDR. This highlights the importance of differential H2A.X mRNA 3’-end processing in the maintenance of effective DDR.
Regulatory protein HilD stimulates Salmonella Typhimurium invasiveness by promoting smooth swimming via the methyl-accepting chemotaxis protein McpC
Authors: Cooper Kendal G. , Chong Audrey , Kari Laszlo , Jeffrey Brendan , Starr Tregei , Martens Craig , McClurg Molly , Posada Victoria R. , Laughlin Richard C. , Whitfield-Cargile Canaan , Garry Adams L. , Bryan Laura K. , Little Sara V. , Krath Mary , Lawhon Sara D. , Steele-Mortimer Olivia
Published: January 2021

In the enteric pathogen Salmonella enterica serovar Typhimurium, invasion and motility are coordinated by the master regulator HilD, which induces expression of the type III secretion system 1 (T3SS1) and motility genes. Methyl-accepting chemotaxis proteins (MCPs) detect specific ligands and control the direction of the flagellar motor, promoting tumbling and changes in direction (if a repellent is detected) or smooth swimming (in the presence of an attractant). Here, we show that HilD induces smooth swimming by upregulating an uncharacterized MCP (McpC), and this is important for invasion of epithelial cells. Remarkably, in vitro assays show that McpC can suppress tumbling and increase smooth swimming in the absence of exogenous ligands. Expression of mcpC is repressed by the universal regulator H-NS, which can be displaced by HilD. Our results highlight the importance of smooth swimming for Salmonella Typhimurium invasiveness and indicate that McpC can act via a ligand-independent mechanism when incorporated into the chemotactic receptor array.
Non-invasive suppression of essential tremor via phase-locked disruption of its temporal coherence
Authors: Schreglmann Sebastian R. , Wang David , Peach Robert L. , Li Junheng , Zhang Xu , Latorre Anna , Rhodes Edward , Panella Emanuele , Cassara Antonino M. , Boyden Edward S. , Barahona Mauricio , Santaniello Sabato , Rothwell John , Bhatia Kailash P. , Grossman Nir
Published: January 2021

Aberrant neural oscillations hallmark numerous brain disorders. Here, we first report a method to track the phase of neural oscillations in real-time via endpoint-corrected Hilbert transform (ecHT) that mitigates the characteristic Gibbs distortion. We then used ecHT to show that the aberrant neural oscillation that hallmarks essential tremor (ET) syndrome, the most common adult movement disorder, can be transiently suppressed via transcranial electrical stimulation of the cerebellum phase-locked to the tremor. The tremor suppression is sustained shortly after the end of the stimulation and can be phenomenologically predicted. Finally, we use feature-based statistical-learning and neurophysiological-modelling to show that the suppression of ET is mechanistically attributed to a disruption of the temporal coherence of the aberrant oscillations in the olivocerebellar loop, thus establishing its causal role. The suppression of aberrant neural oscillation via phase-locked driven disruption of temporal coherence may in the future represent a powerful neuromodulatory strategy to treat brain disorders.
Single cell transcriptomic analysis of human pluripotent stem cell chondrogenesis
Authors: Wu Chia-Lung , Dicks Amanda , Steward Nancy , Tang Ruhang , Katz Dakota B. , Choi Yun-Rak , Guilak Farshid
Published: January 2021

The therapeutic application of human induced pluripotent stem cells (hiPSCs) for cartilage regeneration is largely hindered by the low yield of chondrocytes accompanied by unpredictable and heterogeneous off-target differentiation of cells during chondrogenesis. Here, we combine bulk RNA sequencing, single cell RNA sequencing, and bioinformatic analyses, including weighted gene co-expression analysis (WGCNA), to investigate the gene regulatory networks regulating hiPSC differentiation under chondrogenic conditions. We identify specific WNTs and MITF as hub genes governing the generation of off-target differentiation into neural cells and melanocytes during hiPSC chondrogenesis. With heterocellular signaling models, we further show that WNT signaling produced by off-target cells is responsible for inducing chondrocyte hypertrophy. By targeting WNTs and MITF, we eliminate these cell lineages, significantly enhancing the yield and homogeneity of hiPSC-derived chondrocytes. Collectively, our findings identify the trajectories and molecular mechanisms governing cell fate decision in hiPSC chondrogenesis, as well as dynamic transcriptome profiles orchestrating chondrocyte proliferation and differentiation.
Deep learning encodes robust discriminative neuroimaging representations to outperform standard machine learning
Authors: Abrol Anees , Fu Zening , Salman Mustafa , Silva Rogers , Du Yuhui , Plis Sergey , Calhoun Vince
Published: January 2021

Recent critical commentaries unfavorably compare deep learning (DL) with standard machine learning (SML) approaches for brain imaging data analysis. However, their conclusions are often based on pre-engineered features depriving DL of its main advantage — representation learning. We conduct a large-scale systematic comparison profiled in multiple classification and regression tasks on structural MRI images and show the importance of representation learning for DL. Results show that if trained following prevalent DL practices, DL methods have the potential to scale particularly well and substantially improve compared to SML methods, while also presenting a lower asymptotic complexity in relative computational time, despite being more complex. We also demonstrate that DL embeddings span comprehensible task-specific projection spectra and that DL consistently localizes task-discriminative brain biomarkers. Our findings highlight the presence of nonlinearities in neuroimaging data that DL can exploit to generate superior task-discriminative representations for characterizing the human brain.
Evaluation of microalgae polysaccharides as biostimulants of tomato plant defense using metabolomics and biochemical approaches
Authors: Rachidi Farid , Benhima Redouane , Kasmi Yassine , Sbabou Laila , Arroussi Hicham El
Published: January 2021

Microalgal polysaccharides (PSs) may be an effective elicitor agent that can efficiently protect plants against biotic stresses. In this study, wee investigates, the effect of PS obtained from microalgae and cyanobacteria (D. salina MS002, P. tricorontum MS023, Porphyridium sp. MS081, Desmodesmus sp., D. salina MS067 and A. platensis MS001) on the biochemical and metabolomics markers linked to defense pathways in tomato plants. The phenylalanine ammonia lyase (PAL), chitinase, 1,3-beta-glucanase and peroxidase (POX) activities have been improved in tomato plants leaves treated by polysaccharides extracted from P. triocnutum (238.26%); Desmodesmus sp. (19.95%); P. triocnutum (137.50%) and Porphyridium sp. (47.28%) respectively. For proteins, polyphenols and H2O2, the maximum effect was induced by D. salina 067 (55.01%), Porphyridium sp. (3.97%) and A. platensis (35.08%) respectively. On the other hand, Gas Chromatography-mass spectrometry (GC–MS) metabolomics analysis showed that PSs induced the modification of metabolite profile involved in the wax construction of tomato leaves, such as fatty acids, alkanes, alkenes and phytosterol. PS treatments improved the accumulation of fatty acids C16:3, C18:2 and C18:3 released from the membrane lipids as precursors of oxylipin biosynthesis which are signaling molecules of plant defense. In addition, PS treatment induced the accumulation of C18:0 and Azelaic acid which is a regulator of salicylic acid-dependent systemic acquired resistance. However, molecular and metabolic studies can determine more precisely the mode of action of microalgal polysaccharides as biostimulants/elicitors plant defense.
1H-NMR metabolomics reveals a multitarget action of Crithmum maritimum ethyl acetate extract in inhibiting hepatocellular carcinoma cell growth
Authors: Gnocchi Davide , Del Coco Laura , Girelli Chiara Roberta , Castellaneta Francesca , Cesari Gianluigi , Sabbà Carlo , Fanizzi Francesco Paolo , Mazzocca Antonio
Published: January 2021

Hepatocellular carcinoma (HCC) is nowadays the sixth cause of tumour-related deceases worldwide, estimated to become the third in Western countries by 2030. New drugs for HCC treatment still have many adverse effects. Several lines of evidence indicate that plant metabolites offer concrete opportunities for developing new therapeutic strategies for many diseases, including cancer. We previously reported that ethyl acetate extract of a spontaneous edible plant harvested in Apulia, Crithmum maritimum, significantly inhibited cell growth in HCC cells. By 1H-NMR spectroscopy, here we show that Crithmum maritimum ethyl acetate extract counteracts the Warburg effect, by reducing intracellular lactate, inhibits protein anabolism, by decreasing amino acid level, and affects membrane biosynthesis by lowering choline and phosphocholine. Also, we observed an effect on lipid homeostasis, with a reduction in triglycerides, cholesterol, monounsaturated fatty acids (MUFA), and diunsaturated fatty acids (DUFA), and an increase in polyunsaturated fatty acids (PUFA). Taken together, these data demonstrate that Crithmum maritimum-induced cytostasis is exerted through a multi-effect action, targeting key metabolic processes in HCC cells. Overall, our findings highlight the role of Crithmum maritimum as a promising tool for the prevention and the improvement of the therapeutic options for HCC and other types of tumours.
An absorbance method for analysis of enzymatic degradation kinetics of poly(ethylene terephthalate) films
Authors: Zhong-Johnson En Ze Linda , Voigt Christopher A. , Sinskey Anthony J.
Published: January 2021

Increased interest in poly(ethylene terephthalate) (PET)-degrading enzymes (PETases) have generated efforts to find mutants with improved catalytic activity and thermostability. Here, we present a simple and fast method to determine relative enzyme kinetics through bulk absorbance measurements of released products over time. A thermostable variant of PETase from Ideonella sakaiensis was engineered (R280A S121E D186H N233C S282C) with a denaturation temperature of 69.4 ± 0.3 °C. This was used to assess the method’s ability to determine relative enzyme kinetics across variants and reveal structure–function relationships. Measurements at 24 and 72 h at 400 nM of enzyme suggest that the mutations improved catalytic rates 5- to 7-fold. On the contrary, kinetic analyses of the thermostable variant and wild-type reveal different reaction trajectories despite similar maximum catalytic rates, resulting in higher product accumulation from the thermostable variant over time. The results of the assay support the necessity for kinetic measurements to determine relationships between sequence and function for IsPETase and other PET hydrolases.