| 1. |
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| 2. |
- Zamora, Juan Carlos, et al.
(author)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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In: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Journal article (peer-reviewed)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 3. |
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| 4. |
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| 5. |
- da Silva, DA, et al.
(author)
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Vibronic coupling in the ground and excited states of the naphthalene cation
- 2004
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In: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; :15, s. 1702-1703
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Journal article (peer-reviewed)abstract
- The hole - vibrational coupling in naphthalene is studied using high-resolution gas-phase photoelectron spectroscopy and density functional theory calculations (DFT), and a remarkable increase of the coupling with low-frequency vibrations is observed in the excited states.
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| 6. |
- Abel, I, et al.
(author)
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Overview of the JET results with the ITER-like wall
- 2013
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
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Journal article (peer-reviewed)abstract
- Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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| 7. |
- Baroni de Moraes, Marcia Terezinha, et al.
(author)
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Phenotyping of Lewis and secretor HBGA from saliva and detection of new FUT2 gene SNPs from young children from the Amazon presenting acute gastroenteritis and respiratory infection
- 2019
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In: Infection, Genetics and Evolution. - : ELSEVIER SCIENCE BV. - 1567-1348 .- 1567-7257. ; 70, s. 61-66
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Journal article (peer-reviewed)abstract
- The Histo-blood group antigens (HBGA) are host genetic factors associated with susceptibility to rotavirus (RV) and human norovirus (HuNoV), the major etiological agents of viral acute gastroenteritis (AGE) worldwide. The FUT2 gene expressing the alpha-1, 2-L- fucosyltransferase enzyme is important for gut HBGA expression, and also provides a composition of the phenotypic profile achieved through mutations occurring in populations with different evolutionary histories; as such, it can be considered a genetic population marker. In this study, Lewis and secretor HBGA phenotyping was performed using 352 saliva samples collected from children between three months and five years old born in the Amazon (Brazil, Venezuela and English Guyana) presenting AGE or acute respiratory infection (ARI), the latter considered as control samples. The total of children phenotyped as secretors was 323, corresponding to 91.80%. From these, 207 (58.80%) had a Le (a + b +) profile. The HBGA profiles were equally found in children with AGE as well as with ARI. The rs1047781 of the FUT2 gene was not detected in DNA from saliva cells with a Le (a + b +) profile. However, mutations not yet described in the FUT2 gene were observed: missense 325A amp;gt; T, 501C amp;gt; T, 585C amp;gt; T, 855A amp;gt; T and missense substitutions 327C amp;gt; T [S (Ser) amp;gt; C (Cys)], 446 T amp;gt; C [L(Leu) amp;gt; P(Pro)], 723C amp;gt; A [N(Asn) amp;gt; K(Lys)], 724A amp;gt; T [I(Ile) amp;gt; F(Phe)], 736C amp;gt; A [H(His) amp;gt; N(Asn)]. The SNP distribution in the FUT2 gene of the analyzed samples was very similar to that described in Asian populations, including indigenous tribes.
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| 8. |
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| 9. |
- Caetano, Joao Pedro, et al.
(author)
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Influence of malocclusion on sleep bruxism and orofacial pain : data from a study in school children
- 2024
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In: Clinical Oral Investigations. - : Springer. - 1432-6981 .- 1436-3771. ; 28:2
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Journal article (peer-reviewed)abstract
- Objectives This cross-sectional school-based study explored the influence of malocclusion on temporomandibular disorders (TMD) pain complaints, and whether this association would be mediated by sleep bruxism in a representative sample of 7- to 8-year-old children. Methods Path analysis estimated direct, indirect, and total effects of occlusal features on sleep bruxism and TMD pain in 7- to 8-year-old children. Occlusal features were assessed with Dental Aesthetic Index (DAI), orofacial pain complaints using the TMD pain screener, possible sleep bruxism based on self-reports, and probable sleep bruxism based on self-reports combined with clinical findings. Structural equation modeling analyzed data with confounding factors. Results From 580 participants, possible sleep bruxism was observed in 136 children (31.5%), probable sleep bruxism in 30 children (6.7%), and TMD pain complaints in 78 children (13.8%). Malocclusion had no direct effect on either possible sleep bruxism [standardized coefficient (SC) 0.000; p = 0.992], or TMD pain complaints (SC - 0.01; p = 0.740). When probable sleep bruxism was set as the mediator of interest, malocclusion did not directly affect probable sleep bruxism (SC 0.01; p = 0.766), nor TMD pain complaints (SC - 0.02; p = 0.515). A direct effect of probable sleep bruxism on TMD pain complaints was observed with an SC of 0.60 (p < 0.001). However, in neither case, malocclusion indirectly affected TMD pain complaints via bruxism. Conclusion Malocclusion in 7- to 8-year-old children did not directly influence possible or probable sleep bruxism or TMD pain complaints. Instead, probable sleep bruxism was strongly associated with TMD pain complaints. Clinical significance The impact of occlusal features on TMD pain complaints and bruxism has been a long-standing controversy in dentistry. However, the scientific literature linking this association may be inconsistent, mainly due to biased sample selection methods with inadequate consideration of confounders. Further research should try to identify additional risk factors for TMD pain in addition to probable sleep bruxism in children.
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| 10. |
- Callaway, EM, et al.
(author)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Journal article (peer-reviewed)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 11. |
- Cantelli, Carina Pacheco, et al.
(author)
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Norovirus infection and HBGA host genetic susceptibility in a birth community-cohort, Rio de Janeiro, Brazil
- 2020
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In: Infection, Genetics and Evolution. - : ELSEVIER. - 1567-1348 .- 1567-7257. ; 82
-
Journal article (peer-reviewed)abstract
- Norovirus has emerged as an important viral agent of acute pediatric gastroenteritis, with a growing genetic diversity reported in the last decades. Histo-blood group antigens (HBGAs) present on the surface of enterocytes are susceptibility factors for norovirus infection and differ between populations which could affects the epidemiology and evolution of these viruses. This study investigated the frequency, incidence and genetic diversity of noroviruses in a cohort of rotavirus A vaccinated children in association to the host HBGA (Secretor/Lewis) genetic susceptibility profile. Norovirus genogroups I and II (GI/GII) were screened by RT-qPCR in 569 stool samples from 132 children followed-up from birth to 11 months of age during 2014-2018. Noroviruses were identified in 21.2% of children enrolled in this study, with a norovirus detection rate of 5.6% (32/569), in 17.1% and 4.7% of acute diarrheic episodes (ADE) and non-ADE, respectively. The norovirus incidence was 5.8 infections per 100 child-months. Partial nucleotide sequencing characterized six different norovirus genotypes, with GII.4 Sydney 2012 being detected in 50% associated with three different polymerase genotypes (GII.31, GII.P16 and GII.P4 New Orleans 2009). FUT3 genotyping was yielded seven new mutations in this population. A significant association between symptomatic norovirus infection and secretor profile could be inferred.
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| 12. |
- Cantelli, Carina Pacheco, et al.
(author)
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Rotavirus A shedding and HBGA host genetic susceptibility in a birth community-cohort, Rio de Janeiro, Brazil, 2014-2018
- 2020
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In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 10:1
-
Journal article (peer-reviewed)abstract
- Recent studies have investigated whether the human histo-blood group antigen (HBGAs) could affect the effectiveness of the oral rotavirus vaccines, suggesting secretor positive individuals develop a more robust response. We investigated the Rotavirus A (RVA) shedding in association with the host susceptibility profile in children from a birth community-cohort in Rio de Janeiro, Brazil, from 2014 to 2018. A total of 132 children were followed-up between 0 to 11-month-old, stool samples were collected before/after the 1(st)/2(nd) RV1 vaccination doses and saliva samples were collected during the study. RVA shedding was screened by RT-qPCR and G/P genotypes determined by multiplex RT-PCR and/or Sanger nucleotide sequencing. The sequencing indicated an F167L amino acid change in the RV1 VP8* P[8] in 20.5% of shedding follow-ups and these mutant subpopulations were quantified by pyrosequencing. The HBGA/secretor status was determined and 80.3% of the children were secretors. Twenty-one FUT2 gene SNPs were identified and two new mutations were observed. The mutant F167L RV1 VP8* P[8] was detected significantly more in Le (a+b+) secretors (90.5%) compared to non-secretors and even to secretors Le (a-b+) (9.5%). The study highlights the probable association between RV1 shedding and HBGAs as a marker for evaluating vaccine strain host susceptibility.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Da Lio, Mauro, et al.
(author)
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A Mental Simulation Approach for Learning Neural-Network Predictive Control (in Self-Driving Cars)
- 2020
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In: IEEE Access. - : IEEE. - 2169-3536. ; 8, s. 192041-192064
-
Journal article (peer-reviewed)abstract
- This paper presents a novel approach to learning predictive motor control via mental simulations. The method, inspired by learning via mental imagery in natural Cognition, develops in two phases: first, the learning of predictive models based on data recorded in the interaction with the environment; then, at a deferred time, the synthesis of inverse models via offline episodic simulations. Parallelism with human-engineered control-theoretic workflow (mathematical modeling the direct dynamics followed by optimal control inversion) is established. Compared to the latter human-directed synthesis, the mental simulation approach increases autonomy: a robotic agent can learn predictive models and synthesize inverse ones with a large degree of independence. Human modeling is still needed but limited to providing efficient templates for the forward and inverse neural networks and a few other directives. One could consider these templates as the efficient brain network typologies that evolution produced to permit live beings quickly and efficiently learning. The structure of the neural networks both forward and inverse ones; is made of interpretable local models which follows the cerebellar organization (and are also similar to local model approaches known in the literature). We demonstrate the learning of a first-round model (contrasted to Model Predictive Control) for lateral vehicle dynamics. Then, we demonstrate a second learning iteration, where the forward/inverse neural models are significantly improved.
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| 19. |
- Da Lio, Mauro, et al.
(author)
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Exploiting Dream-Like Simulation Mechanisms to Develop Safer Agents for Automated Driving The "Dreams4Cars" EU Research and Innovation Action
- 2017
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In: 2017 IEEE 20th International Conference on Intelligent Transportation Systems (ITSC). - : IEEE. - 9781538615263 - 9781538615270
-
Conference paper (peer-reviewed)abstract
- Automated driving needs unprecedented levels of reliably and safety before marked deployment. The average human driver fatal accident rate is 1 every 100 million miles. Automated vehicles will have to provably best these figures. This paper introduces the notion of dream-like mechanisms as a simulation technology to produce a large number of hypothetical design and test scenarios - especially focusing on variations of more frequent dangerous and near miss events. Grounded in the simulation hypothesis of cognition, we show here some principles for effective simulation mechanisms and an artificial cognitive system architecture that can learn from the simulated situations.
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| 20. |
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| 21. |
- Da Silva, Maycon R., et al.
(author)
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Identification of two additional behaviorally active gland constituents of female Diatraea saccharalis (Fabricius) (Lepidoptera Crambidae)
- 2021
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In: Journal of the Brazilian Chemical Society. - : Sociedade Brasileira de Quimica (SBQ). - 0103-5053. ; 32:1, s. 225-230
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Journal article (peer-reviewed)abstract
- The sugarcane borer, Diatraea saccharalis (Fabricius), is the major pest insect attacking sugarcane crops in Brazil. Population control by insecticide treatment is not efficient due to simultaneous presence of all developmental stages of the insect throughout the year, and alternative control methods are needed. Two female-produced sex pheromone components, (Z,E)-hexadeca-9,11-dienal and (Z)- hexadec-11-enal, have previously been reported to elicit antennal activity and behavioral response of males in flight tunnel experiments. However, the attractiveness of these compounds in field tests has been very low. In this study, two additional female-produced compounds in D. saccharalis eliciting consistent antennal response in males were identified as (Z)-hexadec-9-enal and hexadecanal. In flight tunnel assays, the behavioral response to a quaternary blend was significantly higher when compared with the previously identified binary blend. Subtracting (Z)-hexadec-9-enal or hexadecanal from the full blend did not reduce attraction, indicating redundancy in the communication channel. We conclude that additional compounds are part of the sex pheromone of D. saccharalis, which may improve the efficiency of trap lures for monitoring of this pest.
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| 22. |
- de Moraes, Marcia Terezinha Baroni, et al.
(author)
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G6P[8] Rotavirus a Possessing a Wa-like VP3 Gene from a Child with Acute Gastroenteritis Living in the Northwest Amazon Region
- 2023
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In: Pathogens. - : MDPI. - 2076-0817. ; 12:7
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Journal article (peer-reviewed)abstract
- The introduction of rotavirus A (RVA) vaccines has considerably reduced the RVA-associated mortality among children under 5 years of age worldwide. The ability of RVA to reassort gives rise to different combinations of surface proteins G (glycoprotein, VP7) and P (protease sensitive, VP4) RVA types infecting children. During the epidemiological surveillance of RVA in the Northwest Amazon region, an unusual rotavirus genotype G6P[8] was detected in feces of a 2-year-old child with acute gastroenteritis (AGE) that had been vaccinated with one dose of Rotarix(& REG;) (RV1). The G6P[8] sample had a DS-1-like constellation with a Wa-like VP3 gene mono-reassortment similar to equine-like G3P[8] that has been frequently detected in Brazil previously. The results presented here reinforce the evolutionary dynamics of RVA and the importance of constant molecular surveillance.
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| 23. |
- de Moraes, Marcia Terezinha Baroni, et al.
(author)
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Molecular Epidemiology of Sapovirus in Children Living in the Northwest Amazon Region
- 2021
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In: Pathogens. - : MDPI. - 2076-0817. ; 10:8
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Journal article (peer-reviewed)abstract
- Sapovirus is an important etiological agent of acute gastroenteritis (AGE), mainly in children under 5 years old living in lower-income communities. Eighteen identified sapovirus genotypes have been observed to infect humans. The aim of this study was to identify sapovirus genotypes circulating in the Amazon region. Twenty-eight samples were successfully genotyped using partial sequencing of the capsid gene. The genotypes identified were GI.1 (n = 3), GI.2 (n = 7), GII.1 (n = 1), GII.2 (n = 1), GII.3 (n = 5), GII.5 (n = 1), and GIV.1 (n = 10). The GIV genotype was the most detected genotype (35.7%, 10/28). The phylogenetic analysis identified sapovirus genotypes that had no similarity with other strains reported from Brazil, indicating that these genotypes may have entered the Amazon region via intense tourism in the Amazon rainforest. No association between histo-blood group antigen expression and sapovirus infection was observed.
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| 24. |
- Ekbom, K, et al.
(author)
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Age at onset and sex ratio in cluster headache: observations over three decades
- 2002
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 22:2, s. 94-100
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Journal article (peer-reviewed)abstract
- Five hundred and fifty-four patients with episodic cluster headache (ECH) and chronic cluster headache (CCH) were examined between 1963 and 1997. Mean age at onset was significantly higher in women with CCH compared with women with ECH and in men with ECH or CCH. In women with CCH age at onset was evenly distributed from 10 to 69 years, whereas in men with CCH and in both sexes with ECH, there was a peak when they were in their 20s. In women with ECH a second peak of onset occurred in their 50s. Although not statistically significant, primary CCH started later in women (mean 50.8 years) than secondary CCH (mean 35.5 years). There was a significant variation in the male : female ratio with respect to age at onset, being largest between 30 and 49 years of age (ECH 7.2 : 1; CCH 11.0 : 1) and lowest after 50 (ECH 2.3 : 1; CCH 0.6 : 1). During the observation period of more than 30 years there was a trend towards a decreasing male preponderance; the male: female ratio was significantly higher among patients with onset before rather than after 1970. The proportion of episodic vs. chronic CH did not change during the study period. The nature of the sex- and age-related pattern of cluster headache onset remains to be elucidated but mechanisms associated with sex hormone regulation, perhaps of hypothalamic origin, may be involved, as well as environmental factors related to lifestyle.
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| 25. |
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| 26. |
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| 27. |
- Ekbom, K, et al.
(author)
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Periods of cluster headache induced by nitrate therapy and spontaneous remission of angina pectoris during active clusters
- 2004
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 24:2, s. 92-98
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Journal article (peer-reviewed)abstract
- Glyceryl trinitrate (GTN) is known to induce single extra attacks of cluster headache (CH) during active cluster periods, most probably via actions of nitric oxide (NO). Induction of whole periods of CH by organic nitrates has, however, attracted little attention in the literature. We report on eight patients with episodic CH and coexistent effort-induced angina pectoris. Cases 1-6 had been free of their headaches for many years but got recurrence of CH within a few weeks after the administration of long-acting organic nitrates (isosorbide-dinitrate, isosorbide-5-mononitrate or slow-release GTN) aimed at treating their chest pains. These nitrate-induced headache periods were more severe and had a longer duration than the previous spontaneous ones. Furthermore, one of the subjects and two additional cases experienced a marked reduction of their anginal attacks during successive CH periods. Exercise time to effort-induced angina was increased in all three patients and one of them revealed a markedly elevated threshold for eliciting ischaemic cardiac symptoms by standardized physical exercise on a cycle ergometer. We hypothesize whether extra CH periods elicited by sustained nitrate therapy and remission of angina pectoris during active clusters are caused by central mechanisms involving inhibition of sympathetic tone and effects on both cranial vessels and cardiac functions.
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| 28. |
- Fodor, Gábor, et al.
(author)
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An Overview of Device-to-Device Communications Technology Components in METIS
- 2016
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In: IEEE Access. - : Institute of Electrical and Electronics Engineers (IEEE). - 2169-3536. ; 4, s. 3288-3299
-
Journal article (peer-reviewed)abstract
- As the standardization of network-assisted deviceto-device (D2D) communications by the 3 rd Generation Partnership Project progresses, the research community has started to explore the technology potential of new advanced features that will largely impact the performance of 5G networks. For 5G, D2D is becoming an integrative term of emerging technologies that take advantage of the proximity of communicating entities in licensed and unlicensed spectra. The European 5G research project Mobile and Wireless Communication Enablers for the 2020 Information Society (METIS) has identified advanced D2D as a key enabler for a variety of 5G services, including cellular coverage extension, social proximity and communicating vehicles. In this paper, we review the METIS D2D technology components in three key areas of proximal communications – network-assisted multi-hop, full-duplex, and multi-antenna D2D communications – and argue that the advantages of properly combining cellular and ad hoc technologies help to meet the challenges of the information society beyond 2020.
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| 29. |
- Fodor, G., et al.
(author)
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An Overview of Device-to-Device Communications Technology Components in METIS
- 2016
-
In: IEEE Access. - : Institute of Electrical and Electronics Engineers (IEEE). - 2169-3536 .- 2169-3536. ; 4, s. 3288-3299
-
Journal article (peer-reviewed)abstract
- As the standardization of network-assisted device-to-device (D2D) communications by the Third Generation Partnership Project progresses, the research community has started to explore the technology potential of new advanced features that will largely impact the performance of 5G networks. For 5G, D2D is becoming an integrative term of emerging technologies that take an advantage of the proximity of communicating entities in licensed and unlicensed spectra. The European 5G research project Mobile and Wireless Communication Enablers for the 2020 Information Society (METIS) has identified advanced D2D as a key enabler for a variety of 5G services, including cellular coverage extension, social proximity, and communicating vehicles. In this paper, we review the METIS D2D technology components in three key areas of proximal communications-network-assisted multi-hop, full-duplex, and multi-antenna D2D communications-and argue that the advantages of properly combining cellular and ad hoc technologies help to meet the challenges of the information society beyond 2020.
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| 30. |
- Fritzson, Ingela, et al.
(author)
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Inhibition of Human DHODH by 4-Hydroxycoumarins, Fenamic Acids, and N-(Alkylcarbonyl)anthranilic Acids Identified by Structure-Guided Fragment Selection
- 2010
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In: ChemMedChem. - : Wiley. - 1860-7187 .- 1860-7179. ; 5:4, s. 608-617
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Journal article (peer-reviewed)abstract
- A strategy that combines virtual screening and structureguided selection of fragments was used to identify three unexplored classes of human DHODH inhibitor compounds: 4-hydroxycoumarins, fenamic acids, and N-(alkylcarbonyl)anthranilic acids. Structure-guided selection of fragments targeting the inner subsite of the DHODH ubiquinone binding site made these findings possible with screening of fewer than 300 fragments in a DHODH assay. Fragments from the three inhibitor classes identified were subsequently chemically expanded to target an additional subsite of hydrophobic character. All three classes were found to exhibit distinct structure–activity relationships upon expansion. The novel N-(alkylcarbonyl anthranilic acid class shows the most promising potency against human DHODH, with IC50 values in the low nanomolar range. The structure of human DHODH in complex with an inhibitor of this class is presented.
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| 31. |
- Hoes, J. N., et al.
(author)
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EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases
- 2007
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 66:12, s. 1560-1567
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Journal article (peer-reviewed)abstract
- Objective: To develop evidence-based recommendations for the management of systemic glucocorticoid ( GC) therapy in rheumatic diseases. Methods: The multidisciplinary guideline development group from 11 European countries, Canada and the USA consisted of 15 rheumatologists, 1 internist, 1 rheumatologist-epidemiologist, 1 health professional, 1 patient and 1 research fellow. The Delphi method was used to agree on 10 key propositions related to the safe use of GCs. A systematic literature search of PUBMED, EMBASE, CINAHL, and Cochrane Library was then used to identify the best available research evidence to support each of the 10 propositions. The strength of recommendation was given according to research evidence, clinical expertise and perceived patient preference. Results: The 10 propositions were generated through three Delphi rounds and included patient education, risk factors, adverse effects, concomitant therapy ( ie, non-steroidal anti-inflammatory drugs, gastroprotection and cyclo-oxygenase-2 selective inhibitors, calcium and vitamin D, bisphosphonates) and special safety advice ( ie, adrenal insufficiency, pregnancy, growth impairment). Conclusion: Ten key recommendations for the management of systemic GC-therapy were formulated using a combination of systematically retrieved research evidence and expert consensus. There are areas of importance that have little evidence ( ie, dosing and tapering strategies, timing, risk factors and monitoring for adverse effects, perioperative GC-replacement) and need further research; therefore also a research agenda was composed.
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| 32. |
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| 33. |
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| 34. |
- Jansen, Jurgen, et al.
(author)
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Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine
- 2007
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 92:6, s. 2378-2381
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Journal article (peer-reviewed)abstract
- Context: T-3 action in neurons is essential for brain development. Recent evidence indicates that monocarboxylate transporter 8 (MCT8) is important for neuronal T-3 uptake. Hemizygous mutations have been identified in the X-linked MCT8 gene in boys with severe psychomotor retardation and elevated serum T-3 levels. Objective: The objective of this study was to determine the functional consequences of MCT8 mutations regarding transport of T-3. Design: MCT8 function was studied in wild-type or mutant MCT8-transfected JEG3 cells by analyzing: 1) T-3 uptake, 2) T-3 metabolism in cells cotransfected with human type 3 deiodinase, 3) immunoblotting, and 4) immunocytochemistry. Results: The mutations identified in MCT8 comprise four deletions (24.5 kb, 2.4 kb, 14 bp, and 3 bp), three missense mutations (Ala224Val, Arg271His, and Leu471Pro), a nonsense mutation (Arg245stop), and a splice site mutation (94 amino acid deletion). All tested mutants were inactive in uptake and metabolism assays, except MCT8 Arg271His, which showed approximately 20% activity vs. wild-type MCT8. Conclusion: These findings support the hypothesis that the severe psychomotor retardation and elevated serum T-3 levels in these patients are caused by inactivation of the MCT8 transporter, preventing action and metabolism of T-3 in central neurons.
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| 35. |
- Knaapen, M, et al.
(author)
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Establishing a core outcome set for treatment of uncomplicated appendicitis in children: study protocol for an international Delphi survey
- 2019
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In: BMJ open. - : BMJ. - 2044-6055. ; 9:5, s. e028861-
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Journal article (peer-reviewed)abstract
- Appendicitis is a global disease affecting roughly 1 in every 12 people in the world, with the highest incidence between ages 10 and 19 years. To date, a wide variety of health outcomes have been reported in randomised controlled trials and meta-analyses evaluating treatments for appendicitis. This is especially the case in studies comparing non-operative treatment with operative treatment. A set of standard outcomes, to be reported in all future trials, is needed to allow for adequate comparison and interpretation of clinical trial results and to make data pooling possible. This protocol describes the development of such a global core outcome set (COS) to allow unified reporting of treatment interventions in children with acute uncomplicated appendicitis.Methods and analysisWe use current international standard methodology for the development and reporting of this COS. Its development consists of three phases: (1) an update of the most recent systematic review on outcomes reported in uncomplicated paediatric appendicitis research to identify additional outcomes, (2) a three-step global Delphi study to identify a set of core outcomes for which there is consensus between parents and (paediatric) surgeons and (3) an expert meeting to finalise the COS and its definitions. Children and young people will be involved through their parents during phase 2 and will be engaged directly using a customised face-to-face approach.Ethics and disseminationThe medical research ethics committee of the Academic Medical Center Amsterdam has approved the study. Each participating country/research group will ascertain ethics board approval. Electronic informed consent will be obtained from all participants. Results will be presented in peer-reviewed academic journals and at (international) conferences.Trial registration numberCOMET registration: 1119
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| 36. |
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| 37. |
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| 38. |
- Kunz, G, et al.
(author)
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Naturally occurring mutations in the thrombomodulin gene leading to impaired expression and function
- 2002
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In: Blood. - 1528-0020. ; 99:10, s. 3646-3653
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Journal article (peer-reviewed)abstract
- Sporadic mutations in the thrombomodulin (TM) gene occur in patients with both arterial and venous thrombosis, but the effects of these mutations on expression and function are largely unexplored. Full-length wild-type TM complementary DNA (cDNA) was incorporated into vector pcDNA6 for transfection into COS-7 cells for transient expression. Mutagenesis was performed to create 7 TM mutants with natural mutations either previously identified (Ala25Thr, Gly6lAla, Asp468Tyr, Pro477Ser, Pro483Leu) or reported here (an 11-base pair [bp] deletion, del791-801, leading to STOP306, and a missense mutation, Arg385Ser). Four mutations were found to detrimentally affect the level of expression of the TM protein. Of the missense mutations, 3 had reduced expression compared to wild-type TM (100%), Arg385Ser (50.2% +/- 5%, P < .001), Pro477Ser (76.8% +/-11%, P <.001), Pro483Leu (82.1% +/- 8%, P < .007). No TM protein expression could be detected on the cell surface for mutation del791-801. The cofactor activity of TM in protein C activation was also evaluated. The Michaelis constant (K,) for wild-type thrombin-TM complex was 634 +/- 6 nmol/L. Two mutants, with Arg385Ser and Pro477Ser, had Increased (P < .0001) K, 2967 +/- 283 nM, and 2342 +/- 219 nM, respectively, demonstrating impaired function of the thrombin-TM complex. This work presents biochemical evidence that certain (but not all) natural mutations In the TM gene reduce expression and impair function of the protein on the cell surface, and helps clarify the suggested contribution that these mutations might make to the risk of thromboembolic disease.
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| 39. |
- Lança, Telma, et al.
(author)
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IRF8 deficiency induces the transcriptional, functional, and epigenetic reprogramming of cDC1 into the cDC2 lineage
- 2022
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In: Immunity. - : Elsevier BV. - 1074-7613 .- 1097-4180. ; 55:8, s. 11-1447
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Journal article (peer-reviewed)abstract
- Conventional dendritic cells (cDCs) consist of two major functionally and phenotypically distinct subsets, cDC1 and cDC2, whose development is dependent on distinct sets of transcription factors. Interferon regulatory factor 8 (IRF8) is required at multiple stages of cDC1 development, but its role in committed cDC1 remains unclear. Here, we used Xcr1-cre to delete Irf8 in committed cDC1 and demonstrate that Irf8 is required for maintaining the identity of cDC1. In the absence of Irf8, committed cDC1 acquired the transcriptional, functional, and chromatin accessibility properties of cDC2. This conversion was independent of Irf4 and was associated with the decreased accessibility of putative IRF8, Batf3, and composite AP-1-IRF (AICE)-binding elements, together with increased accessibility of cDC2-associated transcription-factor-binding elements. Thus, IRF8 expression by committed cDC1 is required for preventing their conversion into cDC2-like cells.
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| 40. |
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| 41. |
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| 42. |
- Narciso-da-Rocha, Carlos, et al.
(author)
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Diversity and antibiotic resistance of Acinetobacter spp. in water from the source to the tap.
- 2013
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In: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 0175-7598 .- 1432-0614. ; 97:1, s. 329-340
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Journal article (peer-reviewed)abstract
- Acinetobacter spp. are ubiquitous bacteria in the environment. Acinetobacter spp. isolated from a municipal drinking water treatment plant and from connected tap water were identified to the species level on the basis of rpoB gene partial sequence analysis. Intraspecies variation was assessed based on the analysis of partial sequences of housekeeping genes (rpoB, gyrB, and recA). Antibiotic resistance was characterized using the disk diffusion method and isolates were classified as wild or non-wild type (non-WT), according to the observed phenotype. The strains of Acinetobacter spp. were related to 11 different validly published species, although three groups of isolates, presenting low rpoB sequence similarities with previously described species, may represent new species. Most of the isolates were related to the species A. johnsonii and A. lwoffii. These two groups, as well as others related to the species A. parvus and A. tjernbergiae, were detected in the water treatment plant and in tap water. Other strains, related to the species A. pittii and A. beijerinckii, were isolated only from tap water. Most of the isolates (80%) demonstrated wild type (WT) to all of the 12 antibiotics tested. Non-WT for tetracycline, meropenem, and ceftazidime, among others, were observed in water treatment plant or in tap water samples. Although, in general, this study suggests a low prevalence of acquired antibiotic resistance in water Acinetobacter spp., the potential of some species to acquire and disseminate resistance via drinking water is suggested.
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| 43. |
- Olivares, Alberto Ignacio Olivares, et al.
(author)
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Epidemiology of enteric virus infections in children living in the Amazon region
- 2021
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In: International Journal of Infectious Diseases. - : Elsevier Science Ltd. - 1201-9712 .- 1878-3511. ; 108, s. 494-502
-
Journal article (peer-reviewed)abstract
- Objectives: To verify the frequency of viruses causing acute gastroenteritis (AGE) in association with the histo-blood group antigen (HBGA) and Rotarix (TM) vaccination coverage in children from the Amazon region. Design: Fecal and saliva samples were collected from children with AGE (n = 485) and acute respiratory infection (ARI) (n = 249) clinical symptoms. Rotavirus A (RVA), norovirus, human adenovirus (HAdV), and sapovirus (SaV) were verified in feces by molecular detection. Saliva samples were used for HBGA phenotyping/FUT3 genotyping. Blood group types, clinical aspects and Rotarix (TM) RVA vaccination data were recorded. Results: Norovirus remained the most prevalently detected cause of AGE (38%, 184/485 and ARI 21.3%, 53/249). High HAdV frequencies were observed in AGE children (28.6%, 139/485) and ARI children (37.3%, 93/249). RVA was the third most prevalent virus causing AGE (22.7%, 110/485 and ARI 19.3%, 48/249) and a low RV1 coverage (61%, 448/734) was verified. The SaV frequencies were lower (7.2%, 35/485 for AGE and 6.8%, 17/249 for ARI). Secretor children were HBGA susceptible to HAdV infection (OR 1.5, 95% CI 1.0-2.3; P = 0.04) but not to RVA, norovirus or SaV infection. Conclusions: Norovirus could be considered the main etiological agent of AGE. No association was verified for HBGA susceptibility to RVA, norovirus and SaV. Secretor children showed a slight susceptibility to HAdV infection and the Le (a-b-) heterogeneous SNPs on the FUT3 gene. (C) 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
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| 44. |
- Plebe, Alice, et al.
(author)
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Human-inspired autonomous driving : A survey
- 2024
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In: Cognitive Systems Research. - : Elsevier. - 2214-4366 .- 1389-0417. ; 83
-
Research review (peer-reviewed)abstract
- Autonomous vehicles promise to revolutionize society and improve the daily life of many, making them a coveted aim for a vast research community. To enable complex reasoning in autonomous vehicles, researchers are exploring new methods beyond traditional engineering approaches, in particular the idea of drawing inspiration from the only existing being able to drive: the human. The mental processes behind the human ability to drive can inspire new approaches with the potential to bridge the gap between artificial drivers and human drivers. In this review, we categorize and evaluate existing work on autonomous driving influenced by cognitive science, neuroscience, and psychology. We propose a taxonomy of the various sources of inspiration and identify the potential advantages with respect to traditional approaches. Although these human-inspired methods have not yet reached widespread adoption, we believe they are critical to the future of fully autonomous vehicles.
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| 45. |
- Romanelli, F, et al.
(author)
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Overview of the JET results
- 2011
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
-
Journal article (peer-reviewed)abstract
- Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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| 46. |
- Sanso, M, et al.
(author)
-
Cdk9 and H2Bub1 signal to Clr6-CII/Rpd3S to suppress aberrant antisense transcription
- 2020
-
In: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 48:13, s. 7154-7168
-
Journal article (peer-reviewed)abstract
- Mono-ubiquitylation of histone H2B (H2Bub1) and phosphorylation of elongation factor Spt5 by cyclin-dependent kinase 9 (Cdk9) occur during transcription by RNA polymerase II (RNAPII), and are mutually dependent in fission yeast. It remained unclear whether Cdk9 and H2Bub1 cooperate to regulate the expression of individual genes. Here, we show that Cdk9 inhibition or H2Bub1 loss induces intragenic antisense transcription of ∼10% of fission yeast genes, with each perturbation affecting largely distinct subsets; ablation of both pathways de-represses antisense transcription of over half the genome. H2Bub1 and phospho-Spt5 have similar genome-wide distributions; both modifications are enriched, and directly proportional to each other, in coding regions, and decrease abruptly around the cleavage and polyadenylation signal (CPS). Cdk9-dependence of antisense suppression at specific genes correlates with high H2Bub1 occupancy, and with promoter-proximal RNAPII pausing. Genetic interactions link Cdk9, H2Bub1 and the histone deacetylase Clr6-CII, while combined Cdk9 inhibition and H2Bub1 loss impair Clr6-CII recruitment to chromatin and lead to decreased occupancy and increased acetylation of histones within gene coding regions. These results uncover novel interactions between co-transcriptional histone modification pathways, which link regulation of RNAPII transcription elongation to suppression of aberrant initiation.
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| 47. |
- Serra Filho, L. A., et al.
(author)
-
Double-GEM based thermal neutron detector prototype
- 2022
-
In: Journal of Instrumentation. - : IOP Publishing Ltd. - 1748-0221. ; 17:9
-
Journal article (peer-reviewed)abstract
- The Helium-3 shortage and the growing interest in neutron science constitute a driving factor in developing new neutron detection technologies. In this work, we report the development of a double-GEM detector prototype that uses a (B4C)-B-10 layer as a neutron converter material. GEANT4 simulations were performed predicting an efficiency of (3.14 +/- 0.10)%, agreeing within 2.7 sigma with the experimental and analytic detection efficiencies obtained by the detector when tested in a 41.8 meV thermal neutron beam. The detector is position sensitive, equipped with a 256+256 strip readout connected to resistive chains, and achieves a spatial resolution better than 3 mm. The gain stability over time was also measured with a fluctuation of about 0.2% h(-1) of the signal amplitude. A simple data acquisition with only 5 electronic channels is sufficient to operate this detector.
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| 48. |
- Svensson, DA, et al.
(author)
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A note on cluster headache in a population-based twin register
- 2003
-
In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 23:5, s. 376-380
-
Journal article (peer-reviewed)abstract
- Evidence of a familial risk factor in cluster headache is accumulating and studies of twin concordance may resolve family resemblance into genetic and environmental influences. The past literature on cluster headache in twins comprises a few case reports of concordant monozygotic pairs. Swedish twin pairs with a diagnosis of cluster headache were selected through a cross-match of national registers of twin births and hospitalizations. Seventeen discordant twin pairs were found, in which it was possible to verify cluster headache status in 11 complete pairs (two monozygotic, four dizygotic, and five unlike-sexed pairs). In both members of a female monozygotic pair, migraine without aura developed after birth of the first child and remitted by menopause, whereas post-menopausal development of chronic cluster headache occurred in only one of them. The importance of individual specific factors for cluster headache was demonstrated. However, to explain familial aggregation a larger sample of affected twin pairs is necessary.
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| 49. |
- Svensson, DA, et al.
(author)
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Genetic and environmental influences on expression of recurrent headache as a function of the reporting age in twins
- 2002
-
In: Twin research : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1369-0523. ; 5:4, s. 277-286
-
Journal article (peer-reviewed)abstract
- To explore age-related mechanisms in the expression of recurrent headache, we evaluated whether genetic and environmental influences are a function of the reporting age using questionnaire information that was gathered in 1973 for 15- to 47-year-old Swedish twins (n =12,606 twin pairs). Liability to mixed headache (mild migraine and tension-type headache) was explained by non-additive genetic influences (49%) in men aged from 15 to 30 years and additive genetic plus shared environmental influences (28%) in men aged from 31 to 47 years. In women, the explained proportion of variance, which was mainly due to additive genetic effects, ranged from 61% in adolescent twins to 12% in twins aged from 41 to 47 years, whereas individual specific environmental variance was significantly lower in twins aged from 15 to 20 years than in twins aged from 21 to 30 years. Liability to migrainous headache (more severe migraine) was explained by non-addi-tive genetic influences in men, 32% in young men and 45% in old men, while total phenotypic variance was significantly lower in young men than in old men. In women, the explained proportion of variance ranged from 91% in the youngest age group to 37% in the oldest age group, with major contributions from non-additive effects in young and old women (15–20 years and 41–47 years, respectively) and additive genetic effects in intermediate age groups (21–40 years). While total variance showed a positive age trend, genetic variance tended to be stable across age groups, whereas individual specific environmental variance was significantly lower in adolescent women as compared to older women.
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| 50. |
- Svensson, DA, et al.
(author)
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Genetic and environmental influences on recurrent headaches in eight to nine-year-old twins
- 1999
-
In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 19:10, s. 866-872
-
Journal article (peer-reviewed)abstract
- The major objective of the present study was to estimate genetic and environmental influences on recurrent headaches in prepubescent twins. A nationwide cohort of 8 to 9-year-old Swedish twins ( n = 1,480) was screened for nonsymptomatic and recurrent headaches through a questionnaire mailed to their parents (75% response frequency). Among positives, 79% of headaches were classified as migraine or tension-type headache in close accordance with the International Headache Society criteria. The prevalences of migraine and nonmigrainous headaches were 2.4% and 11.3%, respectively, and without significant differences between the sexes or zygosity types. Inheritance on liability to recurrent headaches was estimated to 70% (a2 = 0.70, 95% CI = 0.54 − 0.82) for boys and girls but the genetic effect was found to be uncorrelated between the sexes. We conclude that genetic and individual specific effects are important for recurrent headaches of migrainous and nonmigrainous types in prepubescent children, and that different genetic etiologies might exist for boys and girls.
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