Autism spectrum disorders are a group of highly heritable neurodevelopmental disorders with a complex genetic etiology. The International Molecular Genetic Study of Autism Consortium previously ...identified linkage loci on chromosomes 7 and 2, termed AUTS1 and AUTS5, respectively. In this study, we performed a high-density association analysis in AUTS1 and AUTS5, testing more than 3000 single nucleotide polymorphisms (SNPs) in all known genes in each region, as well as SNPs in non-genic highly conserved sequences. SNP genotype data were also used to investigate copy number variation within these regions. The study sample consisted of 127 and 126 families, showing linkage to the AUTS1 and AUTS5 regions, respectively, and 188 gender-matched controls. Further investigation of the strongest association results was conducted in an independent European family sample containing 390 affected individuals. Association and copy number variant analysis highlighted several genes that warrant further investigation, including IMMP2L and DOCK4 on chromosome 7. Evidence for the involvement of DOCK4 in autism susceptibility was supported by independent replication of association at rs2217262 and the finding of a deletion segregating in a sib-pair family.
This paper deals with a new transformation and fusion of digital input patterns used to train and test feedforward neural network for a wound-rotor three-phase induction machine windings ...short-circuit diagnosis. The single type of short-circuits tested by the proposed approach is based on turn-to-turn fault which is known as the first stage of insulation degradation. Used input/output data have been binary coded in order to reduce the computation complexity. A new procedure, namely addition and mean of the set of same rank, has been implemented to eliminate the redundancy due to the periodic character of input signals. However, this approach has a great impact on the statistical properties on the processed data in terms of richness and of statistical distribution. The proposed neural network has been trained and tested with experimental signals coming from six current sensors implemented around a setup with a prime mover and a 5.5 kW wound-rotor three-phase induction generator. Both stator and rotor windings have been modified in order to sort out first and last turns in each phase. The experimental results highlight the superiority of using this new procedure in both training and testing modes.
Abstract
Creation of electrons and positrons from light alone is a basic prediction of quantum electrodynamics, but yet to be observed. Our simulations show that the required conditions are ...achievable using a high-intensity two-beam laser facility and an advanced target design. Dual laser irradiation of a structured target produces high-density
γ
rays that then create > 10
8
positrons at intensities of 2 × 10
22
Wcm
−2
. The unique feature of this setup is that the pair creation is primarily driven by the linear Breit-Wheeler process (
γ
γ
→
e
+
e
−
), which dominates over the nonlinear Breit-Wheeler and Bethe-Heitler processes. The favorable scaling with laser intensity of the linear process prompts reconsideration of its neglect in simulation studies and also permits positron jet formation at experimentally feasible intensities. Simulations show that the positrons, confined by a quasistatic plasma magnetic field, may be accelerated by the lasers to energies >200 MeV.
Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal disease entity in four families with a ...combination of SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss of FAT1 results in decreased cell adhesion and migration in fibroblasts and podocytes and the decreased migration is partially reversed by a RAC1/CDC42 activator. Podocyte-specific deletion of Fat1 in mice induces abnormal glomerular filtration barrier development, leading to podocyte foot process effacement. Knockdown of Fat1 in renal tubular cells reduces migration, decreases active RAC1 and CDC42, and induces defects in lumen formation. Knockdown of fat1 in zebrafish causes pronephric cysts, which is partially rescued by RAC1/CDC42 activators, confirming a role of the two small GTPases in the pathogenesis. These findings provide new insights into the pathogenesis of SRNS and tubulopathy, linking FAT1 and RAC1/CDC42 to podocyte and tubular cell function.
Brazil's natural grasslands under attack Overbeck, Gerhard E; Toma, Tiago S P; da Silveira-Filho, Ricardo R ...
Science (American Association for the Advancement of Science),
2024-Apr-12, Letnik:
384, Številka:
6692
Journal Article
Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD ...pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials.
•Clinical target volume definition in radiotherapy is challenging.•The contribution of computational methods is discussed.•Goals are automation, consistency, and ultimately improvements.•Image ...segmentation algorithms can automate the process in parts.•Mathematical models may quantitatively describe tumor progression patterns.
Treatment planning in radiotherapy distinguishes three target volume concepts: the gross tumor volume (GTV), the clinical target volume (CTV), and the planning target volume (PTV). Over time, GTV definition and PTV margins have improved through the development of novel imaging techniques and better image guidance, respectively. CTV definition is sometimes considered the weakest element in the planning process. CTV definition is particularly complex since the extension of microscopic disease cannot be seen using currently available in-vivo imaging techniques. Instead, CTV definition has to incorporate knowledge of the patterns of tumor progression. While CTV delineation has largely been considered the domain of radiation oncologists, this paper, arising from a 2019 ESTRO Physics research workshop, discusses the contributions that medical physics and computer science can make by developing computational methods to support CTV definition. First, we overview the role of image segmentation algorithms, which may in part automate CTV delineation through segmentation of lymph node stations or normal tissues representing anatomical boundaries of microscopic tumor progression. The recent success of deep convolutional neural networks has also enabled learning entire CTV delineations from examples. Second, we discuss the use of mathematical models of tumor progression for CTV definition, using as example the application of glioma growth models to facilitate GTV-to-CTV expansion for glioblastoma that is consistent with neuroanatomy. We further consider statistical machine learning models to quantify lymphatic metastatic progression of tumors, which may eventually improve elective CTV definition. Lastly, we discuss approaches to incorporate uncertainty in CTV definition into treatment plan optimization as well as general limitations of the CTV concept in the case of infiltrating tumors without natural boundaries.
We investigated the susceptibility of an Italian population of Culex pipiens mosquitoes to Zika virus (ZIKV) infection, tested in parallel with Aedes aegypti, as a positive control. We analysed ...mosquitoes at 0, 3, 7, 10, 14, 20 and 24 days after an infectious blood meal. Viral RNA was detected in the body of Cx. pipiens up to three days post-infection, but not at later time points. Our results indicate that Cx. pipiens is not susceptible to ZIKV infection.
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