Alzheimer prediction from connected speech extracts : assessment of generalisation to new data

co-direction : Simona BrambatiPlusieurs avancées utilisant le discours obtenu de la tâche de description d’image ont été réalisées dans la détection de la maladie d’Alzheimer (AD). L’utilisation de caractéristiques linguistiques et acoustiques sélectionnées manuellement ainsi que l’utilisation de méthodologies d’apprentissage profond ont montré des résultats très prometteurs dans la classification des patients avec AD. Dans ce mémoire, nous comparons les deux méthodologies sur la scène Cookie Theft du Boston Aphasia Examination en entrainant des modèles avec des caractéristiques sélectionnées à partir des extraits textuels et audio ainsi que sur un modèle d’apprentissage profond BERT. Nos modèles sont entrainés sur l’ensemble de données ADReSS challenge plus récent et évaluées sur l’ensemble de données CCNA et vice versa pour mesurer la généralisation des modèles sur des exemples jamais vus dans des ensembles de données différents. Une évaluation détaillée de l’interprétabilité des modèles est effectuée pour déterminer si les modèles ont bien appris les représentations reliées à la maladie. Nous observons que les modèles ne performent pas bien lorsqu’ils sont évalués sur différents ensembles de données provenant du même domaine. Les représentations apprises des modèles entrainés sur les deux ensembles de données sont très différentes, ce qui pourrait expliquer le bas niveau de performance durant l’étape d’évaluation. Même si nous démontrons l’importance des caractéristiques linguistiques sur la classification des AD vs contrôle, nous observons que le meilleur modèle est BERT avec un niveau d’exactitude de 62.6% sur les données ADReSS challenge et 66.7% sur les données CCNA.Many advances have been made in the early diagnosis of Alzheimer’s Disease (AD) using connected speech elicited from a picture description task. The use of hand built linguistic and acoustic features as well as Deep Learning approaches have shown promising results in the classification of AD patients. In this research, we compare both approaches on the Cookie Theft scene from the Boston Aphasia Examination with models trained with features derived from the text and audio extracts as well as a Deep Learning approach using BERT. We train our models on the newer ADReSS challenge dataset and evaluate on the CCNA dataset and vice versa in order to asses the generalisation of the trained model on unseen examples from a different dataset. A thorough evaluation of the interpretability of the models is performed to see how well each of the models learn the representations related to the disease. It is observed that the models do not perform well when evaluated on a different dataset from the same domain. The selected and learned representations from the models trained on either dataset are very different and may explain the low performance in the evaluation step. While we demonstrate the importance of linguistic features in the classification of AD vs non-AD, we find the best overall model is BERT which achieves a test accuracy of 62.6% on the ADRess challenge dataset and 66.7% on the CCNA dataset

A guanosine 5′-triphosphate-dependent protein kinase is localized in the outer envelope membrane of pea chloroplasts

A guanosine 5-triphosphate (GTP)-dependent protein kinase was detected in preparations of outer chloroplast envelope membranes of pea (Pisum sativum L.) chloroplasts. The protein-kinase activity was capable of phosphorylating several envelope-membrane proteins. The major phosphorylated products were 23- and 32.5-kilo-dalton proteins of the outer envelope membrane. Several other envelope proteins were labeled to a lesser extent. Following acid hydrolysis of the labeled proteins, most of the label was detected as phosphoserine with only minor amounts detected as phosphothreonine. Several criteria were used to distinguish the GTP-dependent protein kinase from an ATP-dependent kinase also present in the outer envelope membrane. The ATP-dependent kinase phosphorylated a very different set of envelope-membrane proteins. Heparin inhibited the GTP-dependent kinase but had little effect upon the ATP-dependent enzyme. The GTP-dependent enzyme accepted phosvitin as an external protein substrate whereas the ATP-dependent enzyme did not. The outer membrane of the chloroplast envelope also contained a phosphotransferase capable of transferring labeled phosphate from [-32P]GTP to ADP to yield (-32P]ATP. Consequently, addition of ADP to a GTP-dependent protein-kinase assay resulted in a switch in the pattern of labeled products from that seen with GTP to that typically seen with ATP

District administrator perspectives of current and ideal approaches to identifying and supporting student social, emotional, and behavioral needs

IntroductionLeadership support has been identified as a key facilitator to successful implementation of school-based initiatives. School leadership contributions to student academic success and school reform have been documented, but less work has focused on the effects of leadership on school mental health initiatives such as social, emotional, and behavioral (SEB) screening. Few studies have investigated administrator knowledge and support for SEB screening or compared their current and ideal approaches to SEB screening, both of which are important to informing directions for implementation supports.MethodsUsing a nationally representative sample of U.S. public school districts, we investigated tensions between school district administrators’ (n = 1,330) current and ideal approaches to SEB screening within the current study. We fit binomial and multinomial logistic regression models to determine predictors of positive, negative, or no tensions based on the administrators’ current approach to SEB screening, administrators’ beliefs about the role of schools in student SEB concerns, and district demographics.ResultsNearly half of administrators (46.7%) reported using an approach to SEB screening that was not their ideal approach. Higher beliefs scores commonly predicted administrator desire for more proactive approaches, whereas district characteristics yielded varied results.DiscussionResults call for targeted next steps, including implementation supports, funding, and knowledge building aligned with administrator and district characteristics

The distribution of calmodulin in living mitotic cells

Calmodulin has been labeled with rhodamine isothiocyanate (CaM-RITC) and used as a probe for the location of calmodulin in vivo. CaM-RITC retains its capacity to regulate the activity of brain phosphodiesterase in a Ca2+-dependent manner in vitro, indicating that the labeled protein is still active. After injection into living mammalian cells CaM-RITC incorporates rapidly into the mitotic spindle; the details of its localization there mimic closely the distribution of Calmodulin seen by immunofluorescence. In interphase cells the CaM-RITC is excluded from the nucleus, but shows no region of specific concentration within the cytoplasm. Neither a 2-fold increase in cellular CaM nor the injection of anti CaM has any observable effect on the progress of mitosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25048/1/0000476.pd

Povećanje letalnog učinka bleomicina na stanice HeLa i V79 s pomoću pčelinjeg otrova

This study investigated possible growth-inhibiting effects of bee venom applied alone or in combination with a cytotoxic drug bleomycin on HeLa and V79 cells in vitro based on clone formation, cell counting, and apoptosis. Melittin, the key component of bee venom, is a potent inhibitor of calmodulin activity, and also a potent inhibitor cell growth and clonogenicity. Intracellular accumulation of melittin correlates with the cytotoxicity of antitumour agents. Previous studies indicated that some calcium antagonists and calmodulin inhibitors enhanced intracellular levels of antitumor agents by inhibiting their outward transport. In this study, treatment of exponentially growing HeLa and V79 cells with bleomycin caused a dose-dependent decrease in cell survival due to DNA damage. This lethal effect was potentiated by adding a non-lethal dose of the bee venom. By preventing repair of damaged DNA, bee venom inhibited recovery from potentially lethal damage induced by bleomycin in V79 and HeLa cells. Apoptosis, necrosis, and lysis were presumed as possible mechanisms by which bee venom inhibited growth and clonogenicity of V79 cells. HeLa cells, on the other hand, showed greater resistance to bee venom. Our findings suggest that bee venom might find a therapeutic use in enhancing cytotoxicity of antitumour agent bleomycin.U uvjetima in vitro istražen je inhibitorni učinak pčelinjeg otrova, samog ili združenog s citostatikom bleomicinom, na rast stanica HeLa i V79. Rabljene su sljedeće metode: brojenje stanica, metoda klonskog rasta i apoptoza. Poznato je da neki antagonisti kalcija i kalmodulinski inhibitori povisuju unutarstaničnu razinu protutumorskih lijekova inhibirajući njihov prijenos iz stanice. Unutarstanična akumulacija melitina izravno povećava citotoksični učinak protutumorskog lijeka. Obrada stanica HeLa i V79 u eksponencijalnoj fazi rasta bleomicinom uzrokuje oštećenje DNA ovisno o dozi te smanjenje broja živih stanica. Uočeno je da se letalni učinak bleomicina može pojačati dodatkom neletalne doze pčelinjeg otrova. Pčelinji otrov pritom inhibira popravak nastalih oštećenja u stanicama HeLa i V79 te sprječava oporavak stanica tretiranih bleomicinom. Apoptoza, nekroza i liza mogući su mehanizmi kojima pčelinji otrov inhibira rast i stvaranje kolonija stanica V79, dok HeLa-stanice pokazuju pojačanu otpornost na pčelinji otrov. Istraživanje također potvrđuje mogućnost uporabe pčelinjeg otrova u povećanju citotoksičnosti bleomicina

Activity and regulation by growth factors of calmodulin-dependent protein kinase III (elongation factor 2-kinase) in human breast cancer

Calmodulin-dependent protein kinase III (CaM kinase III, elongation factor-2 kinase) is a unique member of the Ca2+/CaM-dependent protein kinase family. Activation of CaM kinase III leads to the selective phosphorylation of elongation factor 2 (eEF-2) and transient inhibition of protein synthesis. Recent cloning and sequencing of CaM kinase III revealed that this enzyme represents a new superfamily of protein kinases. The activity of CaM kinase III is selectively activated in proliferating cells; inhibition of the kinase blocked cells in G0/G1-S and decreased viability. To determine the significance of CaM kinase III in breast cancer, we measured the activity of the kinase in human breast cancer cell lines as well as in fresh surgical specimens. The specific activity of CaM kinase III in human breast cancer cell lines was equal to or greater than that seen in a variety of cell lines with similar rates of proliferation. The specific activity of CaM kinase III was markedly increased in human breast tumour specimens compared with that of normal adjacent breast tissue. The activity of this enzyme was regulated by breast cancer mitogens. In serum-deprived MDA-MB-231 cells, the combination of insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) stimulated cell proliferation and activated CaM kinase III to activities observed in the presence of 10% serum. Inhibition of enzyme activity blocked cell proliferation induced by growth factors. In MCF-7 cells separated by fluorescence-activated cell sorting, CaM kinase III was increased in S-phase over that of other phases of the cell cycle. In summary, the activity of Ca2+/CaM-dependent protein kinase III is controlled by breast cancer mitogens and appears to be constitutively activated in human breast cancer. These results suggest that CaM kinase III may contribute an important link between growth factor/receptor interactions, protein synthesis and the induction of cellular proliferation in human breast cancer. © 1999 Cancer Research Campaig

Human neutrophil phosphodiesterase

Extracts of human neutrophils were examined for phosphodiesterase activity using a radiochemical assay. As reported by other investigators, both high- and low- K m forms of the enzyme were found. Although calmodulin could be measured in these extracts, human neutrophil phosphodiesterase proved not to be calmodulin dependent. Activity of the neutrophil phosphodiesterase was also not altered by physiologic concentrations of indomethacin, p -bromophenacyl bromide, eicosatetraenoic acid, or eicosatetraynoic acid, all inhibitors of arachidonic acid metabolism. These results are relevant to stimulus-secretion coupling in neutrophils, wherein calmodulin-dependent reactions play a vital role.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44535/1/10753_2004_Article_BF00916094.pd