bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling and treating GRIN2A developmental and epileptic encephalopathy in mice
Authors: Amador Ariadna , Bostick Christopher D , Olson Heather , Peters Jurrian , Camp Chad R , Krizay Daniel , Chen Wenjuan , Han Wei , Tang Weiting , Kanber Ayla , Kim Sukhan , Teoh JiaJie , Sah Megha , Petri Sabrina , Paek Hunki , Kim Ana , Lutz Cathleen M , Yang Mu , Myers Scott J , Bhattacharya Subhrajit , Yuan Hongjie , Goldstein David B , Poduri Annapurna , Boland Michael J , Traynelis Stephen F , Frankel Wayne N
Published: April 2020

NMDA receptors play crucial roles in excitatory synaptic transmission. Rare variants in GRIN2A encoding the GluN2A subunit are associated with a spectrum of disorders, ranging from mild speech and language delay to intractable neurodevelopmental disorders, including but not limited to developmental and epileptic encephalopathy. A de novo missense variant, p.Ser644Gly, was identified in a child with this disorder, and Grin2a knock-in mice were generated to model and extend understanding of this intractable childhood disease. Homozygous and heterozygous mutant mice exhibited altered hippocampal morphology at 2 weeks of age, and all homozygotes exhibited lethal tonic-clonic seizures by mid-third week. Heterozygous adults displayed susceptibility to induced generalized seizures, hyperactivity, repetitive and reduced anxiety behaviours, plus several unexpected features, including significant resistance to electrically-induced limbic seizures and to pentylenetetrazole induced tonic-clonic seizures. Multielectrode recordings of neuronal networks revealed hyperexcitability and altered bursting and synchronicity. In heterologous cells, mutant receptors had enhanced NMDA receptor agonist potency and slow deactivation following rapid removal of glutamate, as occurs at synapses. NMDA receptor-mediated synaptic currents in heterozygous hippocampal slices also showed a prolonged deactivation time course. Standard anti-epileptic drug monotherapy was ineffective in the patient. Introduction of NMDA receptor antagonists was correlated with a decrease in seizure burden. Chronic treatment of homozygous mouse pups with NMDA receptor antagonists significantly delayed the onset of lethal seizures but did not prevent them. These studies illustrate the power of using multiple experimental modalities to model and test therapies for severe neurodevelopmental disorders, while revealing significant biological complexities associated with GRIN2A developmental and epileptic encephalopathy.
Medial Prefrontal Cortex Represents the Object-Based Cognitive Map When Remembering an Egocentric Target Location
Authors: Zhang Bo , Naya Yuji
Published: April 2020

A cognitive map, representing an environment around oneself, is necessary for spatial navigation. However, compared with its constituent elements such as individual landmarks, neural substrates of coherent spatial information, which consists in a relationship among the individual elements, remain largely unknown. The present study investigated how the brain codes map-like representations in a virtual environment specified by the relative positions of three objects. Representational similarity analysis revealed an object-based spatial representation in the hippocampus (HPC) when participants located themselves within the environment, while the medial prefrontal cortex (mPFC) represented it when they recollected a target object’s location relative to their self-body. During recollection, task-dependent functional connectivity increased between the two areas implying exchange of self-location and target location signals between the HPC and mPFC. Together, the object-based cognitive map, whose coherent spatial information could be formed by objects, may be recruited in the HPC and mPFC for complementary functions during navigation, which may generalize to other aspects of cognition, such as navigating social interactions.
Neural Pattern Similarity Unveils the Integration of Social Information and Aversive Learning
Authors: Undeger Irem , Visser Renée M , Olsson Andreas
Published: April 2020

Attributing intentions to others’ actions is important for learning to avoid their potentially harmful consequences. Here, we used functional magnetic resonance imaging multivariate pattern analysis to investigate how the brain integrates information about others’ intentions with the aversive outcome of their actions. In an interactive aversive learning task, participants (n = 33) were scanned while watching two alleged coparticipants (confederates)—one making choices intentionally and the other unintentionally—leading to aversive (a mild shock) or safe (no shock) outcomes to the participant. We assessed the trial-by-trial changes in participants’ neural activation patterns related to observing the coparticipants and experiencing the outcome of their choices. Participants reported a higher number of shocks, more discomfort, and more anger to shocks given by the intentional player. Intentionality enhanced responses to aversive actions in the insula, anterior cingulate cortex, inferior frontal gyrus, dorsal medial prefrontal cortex, and the anterior superior temporal sulcus. Our findings indicate that neural pattern similarities index the integration of social and threat information across the cortex.
Predominant Qualities Evoked by Quinine, Sucrose, and Capsaicin Associate With PROP Bitterness, but not TAS2R38 Genotype
Authors: Nolden Alissa A , McGeary John E , Hayes John E
Published: April 2020

Genetic variability in the ability to taste thiourea compounds has been studied for 80+ years. Over the last 3 decades, many studies have reported perceived intensity of concentrated propylthiouracil (PROP) associates with greater intensity from a broad range of stimuli, including nonbitter tastants, irritants, and retronasally delivered odorants. Thus, PROP phenotype has become a common measure of individual differences in orosensation. Much, but not all, of the phenotypic variation in PROP bitterness is explained by TAS2R38 polymorphisms. While differences in PROP bitterness are clearly due to genetic variation, mechanistically it is challenging to envision how this receptor (narrowly tuned to the N–C=S moiety) relates to overall orosensory response. Here, we report data for 200+ individuals who had been genotyped for TAS2R38 and phenotyped for PROP in a laboratory setting. Participants also reported the intensity of quinine, capsaicin, and sucrose on a general Labeled Magnitude Scale. Our data recapitulate earlier reports associating PROP bitterness with the intensity of the predominant qualities of sucrose, quinine, and capsaicin; however, we also find correlations between the intensities of sucrose, quinine, and capsaicin were much stronger with each other than with PROP. As expected, TAS2R38 diplotype did not associate with the intensity of sucrose, quinine, or capsaicin. The strength of PROP–capsaicin and PROP–sucrose relationships increased after grouping participants by TAS2R38 diplotype, with the greatest increases in association observed within homozygotes. Collectively, this suggests the suprathreshold intensity of PROP is a confounded phenotype that captures both genetic variation specific to N–C=S compounds and overall orosensation.
First Reported Nosocomial Outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 in a Pediatric Dialysis Unit
Authors: Schwierzeck Vera , König Jens Christian , Kühn Joachim , Mellmann Alexander , Correa-Martínez Carlos Luis , Omran Heymut , Konrad Martin , Kaiser Thomas , Kampmeier Stefanie
Published: April 2020

Background

Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was initially detected in China in December 2019. Currently, in Germany >140 000 cases of COVID-19 are confirmed. Here we report a nosocomial outbreak of SARS-CoV-2 infections in the pediatric dialysis unit of the University Hospital Münster (UHM).

Methods

Single-step real-time reverse-transcription polymerase chain reaction (rRT-PCR) from nasopharyngeal swabs was used to diagnose the index patient and identify infected contacts. Epidemiological links were analyzed by patient interviews and medical record reviews. In addition, each contact was assessed for exposure to the index case and monitored for clinical symptoms. Cycle threshold (Ct) values of all positive test results were compared between symptomatic and asymptomatic cases.

Results

Forty-eight cases were involved in this nosocomial outbreak. Nine contact cases developed laboratory-confirmed COVID-19 infections. Two SARS-CoV-2–positive cases remained clinically asymptomatic. Eleven cases reported flulike symptoms without positive results. Ct values were significantly lower in cases presenting typical COVID-19 symptoms, suggesting high viral shedding (P = .007).

Conclusions

Person-to-person transmission was at the heart of a hospital outbreak of SARS-CoV-2 between healthcare workers (HCWs) and patients in the pediatric dialysis unit at UHM. Semiquantitative rRT-PCR results suggest that individuals with high viral load pose a risk to spread SARS-CoV-2 in the hospital setting. Our epidemiological observation highlights the need to develop strategies to trace and monitor SARS-CoV-2–infected HCWs to prevent COVID-19 outbreaks in the hospital setting.
The Federal Reserve’s Dollar Swap Lines and the European Central Bank during the global financial crisis of 2007–09
Authors: Carré Emmanuel , Le Maux Laurent
Published: April 2020

Although the literature has studied the role of the Federal Reserve as the global lender of last resort in 2007–09, many aspects of the Dollar Swap Lines to the European Central Bank need further exploration. Accordingly, we provide original evidence about the auction operations, allotted amounts and interest rates with regard to the Federal Reserve’s dollar swaps and the European Central Bank’s dollar provision. More specifically, we examine the demand side of the Dollar Swap Lines (whereas the existing literature mentions the supply side only) and we scrutinise the interest rate (whereas the literature concentrates on volumes) set by the Federal Reserve, and also the rate set by the European Central Bank. Our findings cast light on the nature of the relationship between the Federal Reserve and the European Central Bank. Finally, we contribute to the literature on the global lender of last resort by coining the notion of the financial dilemma, under the dollar system within a framework of globalised financial markets.
Early Postoperative Endoscopic Recurrence in Crohn’s Disease Is Characterised by Distinct Microbiota Recolonisation
Authors: Machiels Kathleen , Pozuelo del Río Marta , Martinez-De la Torre Adrian , Xie Zixuan , Pascal Andreu Victòria , Sabino João , Santiago Alba , Campos David , Wolthuis Albert , D’Hoore André , De Hertogh Gert , Ferrante Marc , Manichanh Chaysavanh , Vermeire Séverine
Published: April 2020

Background and Aims

Intestinal microbiota dysbiosis is implicated in Crohn’s disease [CD] and may play an important role in triggering postoperative disease recurrence [POR]. We prospectively studied faecal and mucosal microbial recolonisation following ileocaecal resection to identify the predictive value of recurrence-related microbiota.

Methods

Mucosal and/or faecal samples from 121 CD patients undergoing ileocaecal resection were collected at predefined time points before and after surgery. Ileal biopsies were collected from 39 healthy controls. POR was defined by a Rutgeerts score ≥i2b. The microbiota was evaluated by 16S rRNA sequencing. Prediction analysis was performed using C5.0 and Random Forest algorithms.

Results

The mucosa-associated microbiota in CD patients was characterised by a depletion of butyrate-producing species (false discovery rate [FDR] <0.01) and enrichment of Proteobacteria [FDR = 0.009] and Akkermansia spp. [FDR = 0.02]. Following resection, a mucosal enrichment of Lachnospiraceae [FDR <0.001] was seen in all patients but in POR patients, also Fusobacteriaceae [FDR <0.001] increased compared with baseline. Patients without POR showed a decrease of Streptococcaceae [FDR = 0.003] and Actinomycineae [FDR = 0.06]. The mucosa-associated microbiota profile had good discriminative power to predict POR, and was superior to clinical risk factors. At Month 6, patients experiencing POR had a higher abundance of taxa belonging to Negativicutes [FDR = 0.04] and Fusobacteria [FDR = 0.04] compared with patients without POR.

Conclusions

Microbiota recolonisation after ileocaecal resection is different between recurrence and non-recurrence patients, with Fusobacteria as the most prominent player driving early POR. These bacteria involved in the early recolonisation and POR represent a promising therapeutic strategy in the prevention of disease recurrence.
Alphabetical Author Order, Intellectual Collaboration and High-Skilled Migration
Authors: Li Wenchao , Yi Junjian
Published: April 2020

We study the consequences of alphabetical author order in economics for job placements of economists, based on a context that enables a clean identification. Results using two different data sets both show that, relative to Chinese physicists and statisticians, Chinese economists with surname initials located later in the alphabet tend not to stay in the US and are more likely to work in China. Such effects of surname initials on job placements are clearly identified and represent a result of alphabetical author order, because in Chinese culture, names are seldom listed alphabetically in contexts other than joint publications in international economics journals.
Hot stuff. Anatomy of the sex market at the dawn of the twentieth century
Authors: Mortas Pauline
Published: April 2020

Drawing on a rich legal dossier on a violation of obscenity laws (the Trafford affair), this article studies the formation of a sex market in early twentieth-century Paris. Books and erotic photographs, contraceptives, sex toys and remedies for increasing sexual potency: the diversity of these products relating to sexual practices is clearly revealed by the case. The dossier demonstrates how this commercial enterprise drew on the benefits of industrialization, mass media and globalization for building its client-base and developing a transnational dimension. It also allows us to understand the strategies deployed to keep the sale of these objects clandestine, in a context where they were increasingly overseen by the authorities, revealing innovative forms of commercial exchange, based on an epistolary transvestism.
Peacekeeping Deployments and Mutinies in African Sending States
Authors: Schiel Rebecca , Powell Jonathan , Daxecker Ursula
Published: April 2020

Research on host-country effects of peacekeeping deployments has highlighted destabilizing consequences for contributing states, suggesting that deployments can increase the willingness and ability of soldiers to mutiny or attempt coups. Yet others expect that peacekeeping contributions may bring a variety of benefits, including improved civilian control of the armed forces. We reconcile these conflicting assessments in two ways. First, we identify important differences across peacekeeping organizations. Missions undertaken by the United Nations (UN) are generally better funded and equipped, invoke selection criteria that should produce fewer grievances than missions operated by regional organizations, and may be more risk averse. The benefits or hazards of peacekeeping can thus vary substantially, leading to different consequences for organizations. Second, the pros and cons of peacekeeping can incentivize mutinies and coups differently. When grievances are present, financial incentives of peacekeeping may prompt soldiers to prefer mutiny over coups to avoid being disqualified from future participation. We assess these expectations for African states’ participation in UN and non-UN peacekeeping operations from 1990 to 2011. We find no evidence that UN peacekeeping deployments increase mutiny risk, while non-UN deployments have a positive effect on the occurrence of mutiny. These findings remain robust across a large number of model specifications.
Twist1 induces chromosomal instability (CIN) in colorectal cancer cells
Authors: Khot Maithilee , Sreekumar Dyuthi , Jahagirdar Sanika , Kulkarni Apoorva , Hari Kishore , Faseela Elangoli Ebrahimkutty , Sabarinathan Radhakrishnan , Jolly Mohit Kumar , Sengupta Kundan
Published: April 2020

Twist1 is a basic helix-loop-helix transcription factor, essential during early development in mammals. While Twist1 induces epithelial-to-mesenchymal transition (EMT), here we show that Twist1 overexpression enhances nuclear and mitotic aberrations. This is accompanied by an increase in whole chromosomal copy number gains and losses, underscoring the role of Twist1 in inducing chromosomal instability (CIN) in colorectal cancer cells. Array comparative genomic hybridization (array CGH) analysis further shows sub-chromosomal deletions, consistent with an increased frequency of DNA double strand breaks (DSBs). Remarkably, Twist1 overexpression downmodulates key cell cycle checkpoint factors—Bub1, BubR1, Mad1 and Mad2—that regulate CIN. Mathematical simulations using the RACIPE tool show a negative correlation of Twist1 with E-cadherin and BubR1. Data analyses of gene expression profiles of patient samples from The Cancer Genome Atlas (TCGA) reveal a positive correlation between Twist1 and mesenchymal genes across cancers, whereas the correlation of TWIST1 with CIN and DSB genes is cancer subtype-specific. Taken together, these studies highlight the mechanistic involvement of Twist1 in the deregulation of factors that maintain genome stability during EMT in colorectal cancer cells. Twist1 overexpression enhances genome instability in the context of EMT that further contributes to cellular heterogeneity. In addition, these studies imply that Twist1 downmodulates nuclear lamins that further alter spatiotemporal organization of the cancer genome and epigenome. Notwithstanding their genetic background, colorectal cancer cells nevertheless maintain their overall ploidy, while the downstream effects of Twist1 enhance CIN and DNA damage enriching for sub-populations of aggressive cancer cells.
The effect of social participation on income-related inequality in health outcome among Chinese older adults
Authors: Sun Jian , Lyu Xiaoyin , Lyu Shoujun , Zhao Rui
Published: April 2020

Background

This study aimed to investigate the effect of social participation on income-related inequality in health outcome among older adults in China.

Methods

The panel data used in this study were sourced from the 2011 and 2014 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Furthermore, this study employed a concentration index to assess the income-related inequality in health outcome. Moreover, this study used the decomposition method of concentration index to analyse the effect of social participation on income-related inequality in health outcome.

Results

The total concentration index of Instrumental Activity of Daily Living (IADL) status decreased from 0.0257 in 2011 to 0.0172 in 2014. Furthermore, the total concentration index of psychological health decreased from 0.0309 in 2011 to 0.0269 in 2014. The decomposition analysis indicates that social participation made a major contribution to the pro-rich inequality in IADL status. Moreover, the results also indicate that social participation made a minor contribution to the pro-rich inequality in psychological health.

Conclusions

This study demonstrated that overall there were pro-rich inequalities in IADL status and psychological health among older adults in China. Moreover, social participation made a major contribution to the pro-rich inequality in IADL status, while it made a minor contribution to the pro-rich inequality in psychological health.
Optimization of flucloxacillin dosing regimens in critically ill patients using population pharmacokinetic modelling of total and unbound concentrations
Authors: Jager Nynke G L , van Hest Reinier M , Xie Jiao , Wong Gloria , Ulldemolins Marta , Brüggemann Roger J M , Lipman Jeffrey , Roberts Jason A
Published: April 2020

Background

Initial appropriate anti-infective therapy is associated with improved outcomes in patients with severe infections. In critically ill patients, altered pharmacokinetic (PK) behaviour is common and known to influence the achievement of PK/pharmacodynamic targets.

Objectives

To describe population PK and optimized dosing regimens for flucloxacillin in critically ill patients.

Methods

First, we developed a population PK model, estimated between-patient variability (BPV) and identified covariates that could explain BPV through non-linear mixed-effects analysis, using total and unbound concentrations obtained from 35 adult critically ill patients treated with intermittent flucloxacillin. Second, we validated the model using external datasets from two different countries. Finally, frequently prescribed dosing regimens were evaluated using Monte Carlo simulations.

Results

A two-compartment model with non-linear protein binding was developed and validated. BPV of the maximum binding capacity decreased from 42.2% to 30.4% and BPV of unbound clearance decreased from 88.1% to 71.6% upon inclusion of serum albumin concentrations and estimated glomerular filtration rate (eGFR; by CKD-EPI equation), respectively. PTA (target of 100%fT>MIC) was 91% for patients with eGFR of 33 mL/min and 1 g q6h, 87% for patients with eGFR of 96 mL/min and 2 g q4h and 71% for patients with eGFR of 153 mL/min and 2 g q4h.

Conclusions

For patients with high creatinine clearance who are infected with moderately susceptible pathogens, therapeutic drug monitoring is advised since there is a risk of underexposure to flucloxacillin. Due to the non-linear protein binding of flucloxacillin and the high prevalence of hypoalbuminaemia in critically ill patients, dose adjustments should be based on unbound concentrations.
Rationale of a loading dose initiation for hydroxychloroquine treatment in COVID-19 infection in the DisCoVeRy trial
Authors: Lê Minh Patrick , Peiffer-Smadja Nathan , Guedj Jeremie , Néant Nadège , Mentré France , Ader Florence , Yazdanpanah Yazdan , Peytavin Gilles
Published: April 2020

Around the world, several dose regimens of hydroxychloroquine have been used for COVID-19 infection treatment, with the objective of identifying a short-term course. Hydroxychloroquine was found to decrease the viral replication in a concentration-dependent manner in vitro and to be more active when added prior to the viral challenge. A loading dose is used to rapidly attain a target drug concentration, which is usually considered as approximately the steady-state concentration. With a loading dose, the minimum effective concentration is reached much more rapidly than when using only the maintenance dose from the start. Thus, we propose a hydroxychloroquine sulphate dose regimen of 400 mg twice daily at Day 1 then 400 mg once daily from Day 2 to Day 10. We aim to evaluate this in the C-20-15 DisCoVeRy trial.
Dr. Agent: Clinical predictive model via mimicked second opinions
Authors: Gao Junyi , Xiao Cao , Glass Lucas M , Sun Jimeng
Published: April 2020

Objective

Prediction of disease phenotypes and their outcomes is a difficult task. In practice, patients routinely seek second opinions from multiple clinical experts for complex disease diagnosis. Our objective is to mimic such a practice of seeking second opinions by training 2 agents with different focuses: the primary agent studies the most recent visit of the patient to learn the current health status, and then the second-opinion agent considers the entire patient history to obtain a more global view.

Materials and Methods

Our approach Dr. Agent augments recurrent neural networks with 2 policy gradient agents. Moreover, Dr. Agent is customized with various patient demographics information and learns a dynamic skip connection to focus on the relevant information over time. We trained Dr. Agent to perform 4 clinical prediction tasks on the publicly available MIMIC-III (Medical Information Mart for Intensive Care) database: (1) in-hospital mortality prediction, (2) acute care phenotype classification, (3) physiologic decompensation prediction, and (4) forecasting length of stay. We compared the performance of Dr. Agent against 4 baseline clinical predictive models.

Results

Dr. Agent outperforms baseline clinical prediction models across all 4 tasks in terms of all metrics. Compared with the best baseline model, Dr. Agent achieves up to 15% higher area under the precision-recall curve on different tasks.

Conclusions

Dr. Agent can comprehensively model the long-term dependencies of patients’ health status while considering patients’ demographics using 2 agents, and therefore achieves better prediction performance on different clinical prediction tasks.
Determination of Bromate Ions in Drinking Water by Derivatization with 2-Methyl-2-Butene, Dispersive Liquid-Liquid Extraction and Gas Chromatography-Electron Capture Detection
Authors: Nabi Mehdi , Ghoreishi Sayed Mehdi , Behpour Mohsen
Published: April 2020

Background

A simple, rapid, selective and sensitive sample preparation and derivatization method was performed for determination of bromate ions in water by means of dispersive liquid-liquid extraction (DLLE) by gas chromatography-electron capture detection (GC-ECD). This method is based on 2-methyl-2-butene derivatization by bromine produced from bromate ions in acidic medium and extraction by n-hexane.

Objective

Derivatizing agent: It is cheap and available and it has high efficiency in reaction with Br2. Simplicity: Preparation and extraction process don't need to any specific equipment and procedure is completely simple and fast. Limit of detection: DL is as low as 0.43 µg/L.

Methods

Various effective factors on the derivatization and extraction efficiency, such as amount of derivatizing agent, volume of extraction solvent, bromide concentration, volume and concentration of sulfuric acid, type and volume of extracting and dispersing solvent, ionic strength, storage time before extraction and ECD makeup-gas flow rate were investigated.

Results

Under the optimum conditions, the method had a linear calibration curve ranging from 1.0 to 200.0 µg/L for bromate ions with a determination coefficient (R2) of 0.994 and the detection limit was 0.43 µg/L. The recovery percent and relative standard deviation for the determination of 1.0, 5.0 and 50.0 µg/L bromate ion was between 90 and 110%, and 3.0 and 8.0% (n = 3), respectively.

Conclusions

Finally, the method was successfully applied for the preconcentration and determination of bromate ions in water samples, and satisfactory results were obtained.

Highlights

(1) Fast, easy, accurate and economical innovative analysis of bromate ions in water and wastewater. (2) Determination of inorganic ion by GC-ECD after derivatization (3) Low detection limit (4) Optimization of different method parameters to obtain accurate results based on requirements of international standards, specifically ISO/IEC 17025.
Defining Hate Speech
Authors: Fino Audrey
Published: April 2020

This article looks at the international criminal law on hate speech that falls short of direct and public incitement to commit genocide. Using the most egregious form of hate speech that has been prosecuted as an international crime — that of direct and public incitement to genocide — as a baseline, the author analyses the legal parameters of hate speech as persecution (a crime against humanity) and hate speech as instigation (a mode of liability). In so doing, the author critically reviews the International Residual Mechanism for the International Criminal Tribunals’ (IRMCT) appeal judgment in the Šešelj case (Šešelj Appeal Judgment) in the light of prior case law of the International Military Tribunal of Nuremberg (IMT) and the International Criminal Tribunals for Rwanda and the former Yugoslavia (ICTR and ICTY respectively). The author submits that a plain reading of the Šešelj Appeal Judgment supports the view that it is only the more extreme form of incitement to violence, incitement to commit crimes, followed by actual violent acts, that may constitute hate speech amounting to the crime of persecution: incitement to discrimination or incitement to hatred as such do not qualify. Whether ‘incitement to violence’ absent the commission of crimes could qualify as persecution (a crime against humanity) remains an unsettled point. With regard to hate speech as instigation, the Šešelj Appeal Judgment’s restatement and application of the law causes less controversy: the substantial causal connection required for instigation was found to be direct in the circumstances of that case — even though directness is not a legal requirement for instigation. The author concludes that both these interpretations of hate speech are consistent with the earlier ad hoc tribunals’ jurisprudence and, more generally, with international human rights law which, with some controversial exceptions, allows criminalization only of the most extreme forms of incitement to violence.
Modeling the Putative Ancient Distribution of Aedes togoi (Diptera: Culicidae)
Authors: Peach Daniel A H , Matthews Benjamin J
Published: April 2020

The coastal rock pool mosquito, Aedes (Tanakius) togoi (Theobald) (Diptera: Culicidae), is found in coastal east Asia in climates ranging from subtropical to subarctic. However, a disjunct population in the Pacific Northwest of North America has an ambiguous heritage. Two potential models explain the presence of Ae. togoi in North America: ancient Beringian dispersal or modern anthropogenic introduction. Genetic studies have thus far proved inconclusive. Here we described the putative ancient distribution of Ae. togoi habitat in east Asia and examined the climatic feasibility of a Beringian introduction into North America using modern distribution records and ecological niche modeling of bioclimatic data from the last interglacial period (~120,000 BP), the last glacial maximum (~21,000 BP), and the mid-Holocene (~6000 BP). Our results suggest that suitable climatic conditions existed for Ae. togoi to arrive in North America through natural dispersal as well as to persist there until present times. Furthermore, we find that ancient distributions of suitable Ae. togoi habitat in east Asia may explain the genetic relationships between Ae. togoi populations identified in other studies. These findings indicate the utility of ecological niche modeling as a complementary tool for studying insect phylogeography.
Performance of Trichopria drosophilae (Hymenoptera: Diapriidae), a Generalist Parasitoid of Drosophila suzukii (Diptera: Drosophilidae), at Low Temperature
Authors: Colombari Fernanda , Tonina Lorenzo , Battisti Andrea , Mori Nicola
Published: April 2020

Survival and parasitism activity of Trichopria drosophilae Perkins adults, a cosmopolitan parasitoid of Drosophila spp., were studied under laboratory conditions using five constant temperatures at the lower range known for this enemy, from 4 to 20°C in 4°C increments. Drosophila suzukii Matsumura, an invasive pest of small fruits, was used as a host. Commercially available adult parasitoids were provided with 1) food and D. suzukii pupae; 2) food and no D. suzukii pupae; 3) no food and no pupae. The results show that adult females of T. drosophilae lived longer than males, and both generally benefitted from food supply. The highest level of survival was observed between 8 and 12°C for fed insects, irrespective of whether they were offered host pupae or not. The absence of food led to the highest mortality, but the parasitoid demonstrated considerably resistance to prolonged starvation. Successful parasitism increased steadily with temperature and reached the highest value at 20°C. Conversely, D. suzukii emergence rate was high after exposure of pupae to parasitoids at 4°C, while pupal mortality increased strongly with temperature until 12°C. The findings indicate that T. drosophilae is well adapted to the relatively cold conditions experienced in early spring and in autumn or at high elevations, when the host pupae could be largely available. The long lifespan of the adults and the ability to parasitize the host at low temperature make T. drosophilae potentially useful for the biocontrol of D. suzukii.
Risk Estimation with a Time-Varying Probability of Zero Returns
Authors: Sucarrat Genaro , Grønneberg Steffen
Published: April 2020

The probability of an observed financial return being equal to zero is not necessarily zero, or constant. In ordinary models of financial return, however, for example, autoregressive conditional heteroskedasticity, stochastic volatility, Generalized Autoregressive Score, and continuous-time models, the zero probability is zero, constant, or both, thus frequently resulting in biased risk estimates (volatility, value-at-risk [VaR], expected shortfall [ES], etc.). We propose a new class of models that allows for a time-varying zero probability that can either be stationary or nonstationary. The new class is the natural generalization of ordinary models of financial return, so ordinary models are nested and obtained as special cases. The main properties (e.g., volatility, skewness, kurtosis, VaR, ES) of the new model class are derived as functions of the assumed volatility and zero-probability specifications, and estimation methods are proposed and illustrated. In a comprehensive study of the stocks at New York Stock Exchange, we find extensive evidence of time-varying zero probabilities in daily returns, and an out-of-sample experiment shows that corrected risk estimates can provide significantly better forecasts in a large number of instances.
Hematologic adaptation to the subterranean environment by the naked mole-rat, Heterocephalus glaber (Ctenohystrica: Heterocephalidae)
Authors: Holtze Susanne , Koch Rosie , Hildebrandt Thomas Bernd , Lemma Alemayehu , Szafranski Karol , Platzer Matthias , Alemayehu Fitsum , Goeritz Frank , Braude Stan
Published: April 2020

One method burrowing animals are hypothesized to use in adapting to the presumed hypoxic subterranean environment is increasing the oxygen-carrying capacity of blood. A number of recent studies have examined hematologic parameters in laboratory-reared naked mole-rats, but not in animals living under natural atmospheric conditions. To our knowledge, blood chemistry parameters have never been systematically assessed in a fossorial mammal. In this study we examined the blood of wild naked mole-rats in Kenya and Ethiopia to determine whether their blood chemistry differs significantly from naked mole-rats born and living in captivity. We also compared our results to published values for hystricomorphs, other subterranean rodents, and surface-dwelling rodents of similar size.
Internal exposure rate conversion coefficients and absorbed fractions of mouse for 137Cs, 134Cs and 90Sr contamination in body
Authors: Endo Satoru , Matsutani Yuki , Kajimoto Tsuyoshi , Tanaka Kenichi , Suzuki Masatoshi
Published: April 2020

The aim of this study was to determine parameters for estimating the internal exposure of all organs in mouse experiments from the radioactivity concentration in organs. The estimation of internal exposure rate conversion coefficients and absorbed fractions for 137Cs, 134Cs and 90Sr by the Particle and Heavy Ion Transport code System (PHITS) with a voxel-based mouse phantom is presented. The geometry of the voxel phantom is constructed from computer tomography images of a mouse 9 cm in length weighing 23.9 g. The voxel-based mouse phantom has the following organs: brain, skull, heart, lungs, liver, stomach, spleen, kidneys, bladder, testis and tissue (tissue and other organs). Gamma- and beta-rays from 137Cs, 134Cs and 90Sr sources in each source organ are generated and scored for every target organ. The internal exposure rate conversion coefficients and absorbed fractions are calculated from deposition energies in each target organ from each source organ and are used to generate an internal exposure rate conversion coefficient matrix and an absorbed fraction matrix. The absorbed fractions of beta-rays in the source organs are roughly 0.5–0.8 for 137Cs and 134Cs, and the absorbed fractions of gamma-rays are <0.04 for 137Cs and <0.03 for 134Cs. The internal exposure rate conversion coefficient matrix is defined using the absorbed fractions. The calculated internal exposure rate coefficient matrix is tested under a uniform radioactivity concentration of 1 Bq/kg for 137Cs, 134Cs and 90Sr. The estimated internal exposure rates in the mouse whole body for 137Cs, 134Cs and 90Sr are 3.28 × 10−3, 2.55 × 10−3 and 1.20 × 10−2 μGy/d, respectively. These values are very similar to those for an ellipsoid frog (31.4 g) and an ellipsoid crab egg mass (12.6 g) reported in ICRP Publication 108.
Sette’s calculus P1 and some hierarchies of paraconsistent systems
Authors: Ciuciura Janusz
Published: April 2020

The necessary condition for a calculus to be paraconsistent is that its consequence relation is not explosive. This results in rejection of the principle of ex contradictione sequitur quodlibet. In 1973, Sette presented a calculus, denoted as $P^1$, which is paraconsistent only at the atomic level, i.e. $\alpha $ and ${\sim }\alpha $ yield any $\beta $ if, and only if the formula $\alpha $ is not a propositional variable. The calculus has been viewed as one of the noteworthy paraconsistent calculi since then. The objective of this paper is to propose a new semantics for Sette’s calculus and present some hierarchies of the paraconsistent calculi, which are based on $P^1$. We demonstrate that $P^1$ is sound and complete with respect to the semantics and so are all the calculi under consideration.
Multicenter evaluation of three different MALDI-TOF MS systems for identification of clinically relevant filamentous fungi
Authors: Sun Yue , Guo Jian , Chen Rong , Hu Liang , Xia Qihang , Wu Wenjuan , Wang Jinghua , Hu Fupin
Published: April 2020

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) holds promise as a potential tool for clinical identification of filamentous fungi. However, due to the lack of an appropriate extraction protocol and the difficulty of database building, the identification power of each system differs. In this study, we selected 126 clinical mould isolates comprising 28 species identified using internal transcribed spacer (ITS) sequencing as the reference method to evaluate three MALDI-TOF MS systems. When using cultures and sample preparation as recommended by the respective vendors, of the 126 strains tested, VITEK MS identified 121 (96.0%) to species-level and 124 (98.4%) to genus-level; Biotyper identified 53 (42.1%) to species-level and 54 (42.9%) to genus-level; Autof identified 74 (58.7%) to species-level and 76 (60.3%) to genus-level. For the Autof system, the tube extraction method recommended by the vendor performed better (59%) than the on-plate lysis (51%). Our study demonstrates that MALDI-TOF MS systems can successfully identify most clinically relevant fungi, while performance is still highly dependent on the database and sample preparation protocol.
High-redshift cosmology with oxygen lines from Hα surveys
Authors: Fonseca José , Camera Stefano
Published: April 2020

A new generation of cosmological experiments will spectroscopically detect the Hα line from emission-line galaxies at optical/near-infrared frequencies. Other emission lines will also be present, which may come from the same Hα sample or constitute a new galaxy sample altogether. Our goal is to assess the value, for cosmological investigation, of galaxies at z ≳ 2 present in Hα galaxy surveys and identifiable by the highly redshifted ultraviolet and optical lines – namely the O ii line and the O iii doublet in combination with the Hβ line. We use state-of-the-art luminosity functions to estimate the number density of O iii + Hβ and O ii ELGs. We study the constraining power of these high-redshift galaxy samples on cosmological parameters such as the baryon acoustic oscillation (BAO) amplitude, H(z), DA(z), fσ8(z), and bσ8(z) for different survey designs. We present a strong science case for extracting the O iii + Hβ sample, which we consider as an independent probe of the Universe in the redshift range 2−3. Moreover, we show that the O ii sample can be used to measure the BAO and growth of structure above z = 3; albeit it may be shot-noise dominated, it will none the less provide valuable tomographic information. We discuss the scientific potential of a sample of galaxies, which, so far, has been mainly considered as a contaminant in Hα galaxy surveys. Our findings indicate that planed Hα surveys should include the extraction of these oxygen-line samples in their pipeline, to enhance their scientific impact on cosmology.
Most stars (and planets?) are born in intense radiation fields
Authors: Lee Eve J , Hopkins Philip F
Published: April 2020

Protostars and young stars are strongly spatially ‘clustered’ or ‘correlated’ within their natal giant molecular clouds. We demonstrate that such clustering leads to the conclusion that the incident bolometric radiative flux upon a random young star/disc is enhanced (relative to volume-averaged fluxes) by a factor that increases with the total stellar mass of the complex. Because the Galactic cloud mass function is top-heavy, the typical star in our Galaxy experienced a much stronger radiative environment than those forming in well-observed nearby (but relatively small) clouds, exceeding fluxes in the Orion Nebular Cluster by factors of ≳30. Heating of the circumstellar disc around a median young star is dominated by this external radiation beyond $\sim \! 50$ au. And if discs are not well shielded by ambient dust, external ultraviolet irradiation can dominate over the host star down to sub-au scales. Another consequence of stellar clustering is an extremely broad Galaxy-wide distribution of incident flux (spanning >10 decades), with half the Galactic star formation in a substantial ‘tail’ towards even more intense background radiation. We also show that the strength of external irradiation is amplified superlinearly in high-density environments such as the Galactic Centre, starbursts, or high-redshift galaxies.
Understanding the Early Evolutionary Stages of a Tandem Drosophilamelanogaster-Specific Gene Family: A Structural and Functional Population Study
Authors: Clifton Bryan D , Jimenez Jamie , Kimura Ashlyn , Chahine Zeinab , Librado Pablo , Sánchez-Gracia Alejandro , Abbassi Mashya , Carranza Francisco , Chan Carolus , Marchetti Marcella , Zhang Wanting , Shi Mijuan , Vu Christine , Yeh Shudan , Fanti Laura , Xia Xiao-Qin , Rozas Julio , Ranz José M
Published: April 2020

Gene families underlie genetic innovation and phenotypic diversification. However, our understanding of the early genomic and functional evolution of tandemly arranged gene families remains incomplete as paralog sequence similarity hinders their accurate characterization. The Drosophila melanogaster-specific gene family Sdic is tandemly repeated and impacts sperm competition. We scrutinized Sdic in 20 geographically diverse populations using reference-quality genome assemblies, read-depth methodologies, and qPCR, finding that ∼90% of the individuals harbor 3–7 copies as well as evidence of population differentiation. In strains with reliable gene annotations, copy number variation (CNV) and differential transposable element insertions distinguish one structurally distinct version of the Sdic region per strain. All 31 annotated copies featured protein-coding potential and, based on the protein variant encoded, were categorized into 13 paratypes differing in their 3′ ends, with 3–5 paratypes coexisting in any strain examined. Despite widespread gene conversion, the only copy present in all strains has functionally diverged at both coding and regulatory levels under positive selection. Contrary to artificial tandem duplications of the Sdic region that resulted in increased male expression, CNV in cosmopolitan strains did not correlate with expression levels, likely as a result of differential genome modifier composition. Duplicating the region did not enhance sperm competitiveness, suggesting a fitness cost at high expression levels or a plateau effect. Beyond facilitating a minimally optimal expression level, Sdic CNV acts as a catalyst of protein and regulatory diversity, showcasing a possible evolutionary path recently formed tandem multigene families can follow toward long-term consolidation in eukaryotic genomes.
Behavioural aspects of microhabitat segregation of different age stages in the wetland land snail Vertigo moulinsiana (Eupulmonata: Vertiginidae) in the laboratory
Authors: Książkiewicz-Parulska Zofia
Published: April 2020

This laboratory study investigated behavioural differences between adults and juveniles of the wetland land snail species Vertigo moulinsiana with respect to temperature and humidity. Juveniles of V. moulinsiana, for example, tend to remain within the shaded, humid and cool layer of the litter, while adults usually climb above wet vegetation to a height of over 2 m. Adults are thus exposed to greater variation in temperature and humidity than juveniles. My experiments showed that adults of V. moulinsiana remain active longer than juveniles when subject to high temperature (36 °C) and low relative humidity (RH 30%). Conversely, juveniles stay active longer than adults in high humidity (22 °C, RH 100%). A short period of starvation lengthened the time needed for the juveniles to become active after dormancy, possibly indicating a different response between adults and juveniles to lack of nutritional reserves. These behavioural differences to food availability and the risk of water loss correspond to the microhabitat differences observed between adults and juveniles in the wild.
Can a digital slide scanner and viewing technique assist the visual scoring for the cytokinesis-block micronucleus cytome assay?
Authors: Jaunay Emma L , Dhillon Varinderpal S , Semple Susan J , Simpson Bradley S , Deo Permal , Fenech Michael
Published: April 2020

The cytokinesis-block micronucleus cytome (CBMNcyt) assay is a comprehensive method to measure DNA damage, cytostasis and cytotoxicity caused by nutritional, radiation and chemical factors. A slide imaging technique has been identified as a new method to assist with the visual scoring of cells for the CBMNcyt assay. A NanoZoomer S60 Digital Pathology slide scanner was used to view WIL2-NS cells treated with hydrogen peroxide (H2O2) and measure CBMNcyt assay biomarkers using a high-definition desktop computer screen. The H2O2-treated WIL2-NS cells were also scored visually using a standard light microscope, and the two visual scoring methods were compared. Good agreement was found between the scoring methods for all DNA damage indices (micronuclei, nucleoplasmic bridges and nuclear buds) and nuclear division index with correlation R values ranging from 0.438 to 0.789, P < 0.05. Apoptotic and necrotic cell frequency was lower for the NanoZoomer scoring method, but necrotic frequency correlated well with the direct visual microscope method (R = 0.703, P < 0.0001). Considerable advantages of the NanoZoomer scoring method compared to direct visual microscopy includes reduced scoring time, improved ergonomics and a reduction in scorer fatigue. This study indicates that a digital slide scanning and viewing technique may assist with visual scoring for the CBMNcyt assay and provides similar results to conventional direct visual scoring.