811 research outputs found
Association of Factor V Secretion with Protein Kinase B Signaling in Platelets from Horses with Atypical Equine Thrombasthenia.
BackgroundTwo congenital bleeding diatheses have been identified in Thoroughbred horses: Glanzmann thrombasthenia (GT) and a second, novel diathesis associated with abnormal platelet function in response to collagen and thrombin stimulation.Hypothesis/objectivesPlatelet dysfunction in horses with this second thrombasthenia results from a secretory defect.AnimalsTwo affected and 6 clinically normal horses.MethodsEx vivo study. Washed platelets were examined for (1) expression of the αIIb-β3 integrin; (2) fibrinogen binding capacity in response to ADP and thrombin; (3) secretion of dense and α-granules; (4) activation of the mammalian target of rapamycin (mTOR)-protein kinase B (AKT) signaling pathway; and (5) cellular distribution of phosphatidylinositol-4-phosphate-3-kinase, class 2B (PIK3C2B) and SH2 containing inositol-5'-phosphatase 1 (SHIP1).ResultsPlatelets from affected horses expressed normal amounts of αIIb-β3 integrin and bound fibrinogen normally in response to ADP, but bound 80% less fibrinogen in response to thrombin. α-granules only released 50% as much Factor V as control platelets, but dense granules released their contents normally. Protein kinase B (AKT) phosphorylation was reduced after thrombin activation, but mTOR Complex 2 (mTORC2) and phosphoinositide-dependent kinase 1 (PDK1) signaling were normal. SH2-containing inositol-5'-phosphatase 1 (SHIP1) did not localize to the cytoskeleton of affected platelets and was decreased overall consistent with reduced AKT phosphorylation.Conclusions and clinical significanceDefects in fibrinogen binding, granule secretion, and signal transduction are unique to this thrombasthenia, which we designate as atypical equine thrombasthenia
HeteroGenius: A Framework for Hybrid Analysis of Heterogeneous Software Specifications
Nowadays, software artifacts are ubiquitous in our lives being an essential
part of home appliances, cars, cell phones, and even in more critical
activities like aeronautics and health sciences. In this context software
failures may produce enormous losses, either economical or, in the worst case,
in human lives. Software analysis is an area in software engineering concerned
with the application of diverse techniques in order to prove the absence of
errors in software pieces. In many cases different analysis techniques are
applied by following specific methodological combinations that ensure better
results. These interactions between tools are usually carried out at the user
level and it is not supported by the tools. In this work we present
HeteroGenius, a framework conceived to develop tools that allow users to
perform hybrid analysis of heterogeneous software specifications.
HeteroGenius was designed prioritising the possibility of adding new
specification languages and analysis tools and enabling a synergic relation of
the techniques under a graphical interface satisfying several well-known
usability enhancement criteria. As a case-study we implemented the
functionality of Dynamite on top of HeteroGenius.Comment: In Proceedings LAFM 2013, arXiv:1401.056
MoCheQoS: Automated Analysis of Quality of Service Properties of Communicating Systems
We present MoCheQoS, a tool to analyse quality of service (QoS) properties of
message-passing systems. Building on the logic and the choreographic model we
defined in recently published work, MoCheQoS implements a bounded model
checking algorithm. We discuss strengths and weaknesses of MoCheQoS through
some case studies.Comment: 29 page
Bionomics and taxonomy of leafhopper Sophonia orientalis (Homoptera: Cicadellidae), a Pacific pest species in the Macaronesian Archipelagos
The leafhopper Sophonia orientalis (Matsumura) (Homoptera: Cicadellidae) is native
to Asia, but it has been recently introduced to the Hawaii Archipelago, CA and French Polynesia.
Although this extremely polyphagous species is considered to be a threat to all native plants of Hawaii
and to many economically important cropping cultures, its taxonomy remains obscure. Most literature
referred to this species as Sophonia rufofascia (Kuoh & Kuoh), but recently it has been shown that
previous records of this species correspond to S. orientalis. In this study, S. orientalis is recorded from
northeastern Atlantic archipelagos of Madeira and Canaries, with the Þrst collection made in 2000
representing the Þrst record of this species for Macaronesia. Diagnosis of the species together with
information on the karyotype and structure of testes and ovaries is given. The number of chromosomes
is 2n 16 X0 (males) and 2n 16 XX (females), and each testis and ovaryis composed of six follicles
and six ovarioles, respectively. In Madeira, S. orientalis was found on 28 plant species, including native
and endemic plants, but it also was associated with important crops such as vineyards. The presence
of adults and nymphs during most of the year suggests that this species has several annual generations.
Owing to the suitable climate and the presence of a great number of host plants, its potential for
detrimental effects to Madeira ecosystems is considered to be great, and the proximity of Madeira and
Canary Islands to the European land mass suggests that this pest may spread.info:eu-repo/semantics/publishedVersio
On the construction of explosive relation algebras
Fork algebras are an extension of relation algebras obtained by extending the
set of logical symbols with a binary operator called fork. This class of
algebras was introduced by Haeberer and Veloso in the early 90's aiming at
enriching relation algebra, an already successful language for program
specification, with the capability of expressing some form of parallel
computation.
The further study of this class of algebras led to many meaningful results
linked to interesting properties of relation algebras such as representability
and finite axiomatizability, among others. Also in the 90's, Veloso introduced
a subclass of relation algebras that are expansible to fork algebras, admitting
a large number of non-isomorphic expansions, referred to as explosive relation
algebras.
In this work we discuss some general techniques for constructing algebras of
this type
Evidence for TTAGG telomere repeats and rRNA gene clusters in leafhoppers of the genus Alebra (Hemiptera: Auchenorrhyncha: Cicadellidae)
The leafhopper genus Alebra Fieber, 1872 comprises a complex of morphologically similar species. The chromosome
complements (karyotypes) of five Alebra species, i.e. A. albostriella, A. coryli, A. viridis, A. wahlbergi and a new, yet undescribed
species, provisionally named Taxon 1, were here investigated, three of these species (A. coryli, A. viridis, and Taxon 1) for the first
time. The techniques applied included standard chromosome staining, fluorescence in situ hybridization (FISH) for mapping of 18S
rDNA and telomeric repeats (in every species), C-banding, AgNOR-banding and CMA3
/DAPI- staining (in A. viridis). The species
have a holokinetic type of chromosomes, as in other hemipterans. Karyotypes of all species are remarkably conserved with 2n = 22 +
X(0)/XX (male/female), one large and 10 medium pairs of autosomes and the X chromosome similar in size to larger chromosomes
within this group. In every species, FISH identified the “classical” insect telomere repeat of TTAGG and rRNA gene clusters located
on the homologues of a medium-sized pair of autosomes, presumably number 5. Thus, speciation in Alebra has apparently not involved
significant karyotypic changes. In A. viridis, rDNA sites were both Ag- and CMA3
-positive and were located at an interstitial position.
C-banding revealed heterochromatic bands in the X chromosome and also in all but four pairs of autosomes, the bands were located at
one telomere of a chromosome. C-bands were positive for CMA3
and negative for DAPI, suggesting that C-heterochromatin is mainly
enriched in GC-pairs.info:eu-repo/semantics/publishedVersio
Equitable modelling of brain imaging by counterfactual augmentation with morphologically constrained 3D deep generative models
We describe CounterSynth, a conditional generative model of diffeomorphic deformations that induce label-driven, biologically plausible changes in volumetric brain images. The model is intended to synthesise counterfactual training data augmentations for downstream discriminative modelling tasks where fidelity is limited by data imbalance, distributional instability, confounding, or underspecification, and exhibits inequitable performance across distinct subpopulations. Focusing on demographic attributes, we evaluate the quality of synthesised counterfactuals with voxel-based morphometry, classification and regression of the conditioning attributes, and the Fréchet inception distance. Examining downstream discriminative performance in the context of engineered demographic imbalance and confounding, we use UK Biobank and OASIS magnetic resonance imaging data to benchmark CounterSynth augmentation against current solutions to these problems. We achieve state-of-the-art improvements, both in overall fidelity and equity. The source code for CounterSynth is available at https://github.com/guilherme-pombo/CounterSynth
Functional consequences of seven novel mutations in the CYP11B1 Gene: four mutations associated with nonclassic and three mutations causing classic 11 -Hydroxylase Deficiency
Context: Steroid 11β-hydroxylase (CYP11B1) deficiency (11OHD) is the second most common form of congenital adrenal hyperplasia (CAH). Cases of nonclassic 11OHD are rare compared with the incidence of nonclassic 21-hydroxylase deficiency.
Objective: The aim of the study was to analyze the functional consequences of seven novel CYP11B1 mutations (p.M88I, p.W116G, p.P159L, p.A165D, p.K254_A259del, p.R366C, p.T401A) found in three patients with classic 11OHD, two patients with nonclassic 11OHD, and three heterozygous carriers for CYP11B1 mutations.
Methods: We conducted functional studies employing a COS7 cell in vitro expression system comparing wild-type (WT) and mutant CYP11B1 activity. Mutants were examined in a computational three-dimensional model of the CYP11B1 protein.
Results: All mutations (p.W116G, p.A165D, p.K254_A259del) found in patients with classic 11OHD have absent or very little 11β-hydroxylase activity relative to WT. The mutations detected in patients with nonclassic 11OHD showed partial functional impairment, with one patient being homozygous (p.P159L; 25% of WT) and the other patient compound heterozygous for a novel mild p.M88I (40% of WT) and the known severe p.R383Q mutation. The two mutations detected in heterozygous carriers (p.R366C, p.T401A) also reduced CYP11B1 activity by 23 to 37%, respectively.
Conclusion: Functional analysis results allow for the classification of novel CYP11B1 mutations as causative for classic and nonclassic 11OHD, respectively. Four partially inactivating mutations are predicted to result in nonclassic 11OHD. These findings double the number of mild CYP11B1 mutations previously described as associated with mild 11OHD. Our data are important to predict phenotypic expression and provide important information for clinical and genetic counseling i
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