In response to agonist stimulation, the αllbβ3 integrin on platelets is converted to an active conformation that binds fibrinogen and mediates platelet aggregation. This process contributes to both ...normal hemostasis and thrombosis. Activation of αllbβ3 is believed to occur in part via engagement of the β3 cytoplasmic tail with talin; however, the role of the αllb tail and its potential binding partners in regulating αllbβ3 activation is less clear. We report that calcium and integrin binding protein 1 (CIB1), which interacts directly with the αllb tail, is an endogenous inhibitor of αllbβ3 activation; overexpression of CIB1 in megakaryocytes blocks agonist-induced αllbβ3 activation, whereas reduction of endogenous CIB1 via RNA interference enhances activation. CIB1 appears to inhibit integrin activation by competing with talin for binding to αllbβ, thus providing a model for tightly controlled regulation of αllbβ3 activation.
In response to agonist stimulation, the alphaIIbbeta3 integrin on platelets is converted to an active conformation that binds fibrinogen and mediates platelet aggregation. This process contributes to ...both normal hemostasis and thrombosis. Activation of alphaIIbbeta3 is believed to occur in part via engagement of the beta3 cytoplasmic tail with talin; however, the role of the alphaIIb tail and its potential binding partners in regulating alphaIIbbeta3 activation is less clear. We report that calcium and integrin binding protein 1 (CIB1), which interacts directly with the alphaIIb tail, is an endogenous inhibitor of alphaIIbbeta3 activation; overexpression of CIB1 in megakaryocytes blocks agonist-induced alphaIIbbeta3 activation, whereas reduction of endogenous CIB1 via RNA interference enhances activation. CIB1 appears to inhibit integrin activation by competing with talin for binding to alphaIIbbeta3, thus providing a model for tightly controlled regulation of alphaIIbbeta3 activation.
In response to agonist stimulation, the alphaIIb{szligbeta}3 integrin on platelets is converted to an active conformation that binds fibrinogen and mediates platelet aggregation. This process ...contributes to both normal hemostasis and thrombosis. Activation of alphaIIb{szligbeta}3 is believed to occur in part via engagement of the {szligbeta}3 cytoplasmic tail with talin; however, the role of the alphaIIb tail and its potential binding partners in regulating alphaIIb{szligbeta}3 activation is less clear. We report that calcium and integrin binding protein 1 (CIB1), which interacts directly with the alphaIIb tail, is an endogenous inhibitor of alphaIIb{szligbeta}3 activation; overexpression of CIB1 in megakaryocytes blocks agonist-induced alphaIIb{szligbeta}3 activation, whereas reduction of endogenous CIB1 via RNA interference enhances activation. CIB1 appears to inhibit integrin activation by competing with talin for binding to alphaIIb{szligbeta}3, thus providing a model for tightly controlled regulation of alphaIIb{szligbeta}3 activation.
The mechanical properties of polycrystalline metals are governed by the interaction of defects that are generated by deformation within the 3D microstructure. In materials that deform by slip, the ...plasticity is usually highly heterogeneous within the microstructure. Many experimental tools can be used to observe the results of slip events at the free surface of a sample; however, there are only a few methods for imaging these events in the bulk. In this article, the imaging of bulk slip events within the 3D microstructure are enabled by the combined use of X-ray diffraction contrast tomography and topotomography. Correlative measurements between high-resolution digital image correlation, X-ray diffraction contrast tomography, topotomography and phase contrast tomography are performed during deformation of Ti-7Al to investigate the sensitivity of the X-ray topotomography method for the observation of slip events in the bulk. Much larger neighborhoods of grains were able to be mapped than in previous studies, enabling quantitative measurements of slip transmission. Significant differences were observed between surface and bulk grains, indicating the need for 3D observations of plasticity to better understand deformation in polycrystalline materials.
Asthmaexpert, an expert system (ES), was produced at the special request of several clinicians in order to better understand the medical decisions made clinical experts in managing an asthmatic ...patient. We describe and evaluate this knowledge base, focusing mainly on assessment of the severity of asthma. After compiling data from a patient, Asthmaexpert assesses the severity of the disease and identifies the trigger factors involved, suggests any further investigations that may be required, and offers a treatment strategy. Implemented with Nexpert and Hypercard, it runs on a MacIntosh personal computer. The validation stage involved eight clinical experts who provided 20 case report forms (CRF) with their conclusions about management of asthma. The CRF were then programmed into the ES, which provided its own conclusions about the same subjects. Afterward, all the experts evaluated the conclusions given by ES or by their colleagues in a double-blind manner. One hundred twenty-seven CRF were available. The reliability of the experts' opinions was good, with a substantial consensus between them when assessing severity scores (kappa = 0.27 to 0.54). There was no difference in concordance of opinions on severity scores either between the experts who designed the system and ES or between the other experts and ES (weighted kappa = 0.72 and 0.69, respectively). Experts judged that the severity scores given by ES were as good as those proposed by their colleagues, and that the overall conclusions given by ES were as good as or better than those given by their colleagues. The conclusions drawn by ES were given a good rating.
"Asthmaexpert" was produced at the special request of several clinicians in order to obtain a better understanding of the medical decisions taken by clinical experts in the management of asthmatic ...patients. In order to assess the severity of asthma, a new score called Artificial Intelligence score (AI score), produced by Asthmaexpert, was compared with three other scores (Aas, Hargreave and Brooks). One hundred patients were enrolled prospectively in the study during their first consultation in the out-patient clinic. Distribution of severity level according to the different scores was studied, and the reliability between AI and other scores was evaluated by Kappa and MacNemar tests. Correlations with functional parameters were performed. The AI score assessed higher levels of severity than the other scores (Kappa = 18, 28 and 10% for Aas, Hargreave and Brooks, respectively) with significant MacNemar test in all cases. There was a significant correlation between AI score and forced expiratory volume in one second (FEV1) (r = 0.73). These data indicate that the AI score is a severity score which defines higher levels of severity than the chosen scores. Correlations for functional parameters are good. This score appears easy to use for the first consultation of an asthmatic patient.
We retrospectively studied the outcome of pregnancy in 62 cases of absent end diastolic flow (AEDF) of umbilical artery Doppler flow velocity waveform. The history of pregnancies revealed that nearly ...all were of high risk. Many cases presented cerebral (65%) or uterine (55.5%) Doppler flow abnormalities, or both (38%). We noted 10 fetal deaths and decided 7 pregnancy terminations. Malformation and chromosomal defect rate was 16%. We noted 44 (71%) live-births, a very high rate of cesarean section (86%), prematurity (75%), small for gestational age (39%). Forty-five percent of the neonates had a 1-min Apgar score under 7, which dropped to 27% at 5 min. Neonate mortality rate was 6.9% and the total mortality rate was 34% (21/62). Morbidity was significant (7 cases with severe morbidity, 2 cases with chromosomal abnormality of poor prognosis). We compared different sub-groups with a view to looking for some prenatal factors which predict poor neonatal outcome in case of AEDF.
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