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Search Results: 1 - 10 of 487541 matches for " John A. Dani "
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Nicotinic Receptor Activity Alters Synaptic Plasticity
John A. Dani
The Scientific World Journal , 2001, DOI: 10.1100/tsw.2001.74
Cocaine inhibition of nicotinic acetylcholine receptors influences dopamine release
Alexandra Acevedo-Rodriguez,Mariella De Biasi,John A. Dani
Frontiers in Synaptic Neuroscience , 2014, DOI: 10.3389/fnsyn.2014.00019
Abstract: Nicotinic acetylcholine receptors (nAChRs) potently regulate dopamine (DA) release in the striatum and alter cocaine's ability to reinforce behaviors. Since cocaine is a weak nAChR inhibitor, we hypothesized that cocaine may alter DA release by inhibiting the nAChRs in DA terminals in the striatum and thus contribute to cocaine's reinforcing properties primarily associated with the inhibition of DA transporters. We found that biologically relevant concentrations of cocaine can mildly inhibit nAChR-mediated currents in midbrain DA neurons and consequently alter DA release in the dorsal and ventral striatum. At very high concentrations, cocaine also inhibits voltage-gated Na channels in DA neurons. Furthermore, our results show that partial inhibition of nAChRs by cocaine reduces evoked DA release. This diminution of DA release via nAChR inhibition more strongly influences release evoked at low or tonic stimulation frequencies than at higher (phasic) stimulation frequencies, particularly in the dorsolateral striatum. This cocaine-induced shift favoring phasic DA release may contribute to the enhanced saliency and motivational value of cocaine-associated memories and behaviors.
Bayesian Optimization of Text Representations
Dani Yogatama,Noah A. Smith
Computer Science , 2015,
Abstract: When applying machine learning to problems in NLP, there are many choices to make about how to represent input texts. These choices can have a big effect on performance, but they are often uninteresting to researchers or practitioners who simply need a module that performs well. We propose an approach to optimizing over this space of choices, formulating the problem as global optimization. We apply a sequential model-based optimization technique and show that our method makes standard linear models competitive with more sophisticated, expensive state-of-the-art methods based on latent variable models or neural networks on various topic classification and sentiment analysis problems. Our approach is a first step towards black-box NLP systems that work with raw text and do not require manual tuning.
Blood–brain barrier P-glycoprotein function in healthy subjects and Alzheimer's disease patients: effect of polymorphisms in the ABCB1 gene
Dani?lle ME van Assema, Mark Lubberink, Patrizia Rizzu, John C van Swieten, Robert C Schuit, Jonas Eriksson, Philip Scheltens, Matthias Koepp, Adriaan A Lammertsma, Bart NM van Berckel
EJNMMI Research , 2012, DOI: 10.1186/2191-219x-2-57
Abstract: Thirty-two healthy subjects and seventeen patients with Alzheimer's disease underwent 60-min dynamic (R)-[11C]verapamil PET scans. The binding potential of (R)-[11C]verapamil was assessed using a previously validated constrained two-tissue plasma input compartment model and used as outcome measure. DNA was isolated from frozen blood samples and C1236T, G2677T/A and C3435T single-nucleotide polymorphisms were amplified by polymerase chain reaction.In healthy controls, binding potential did not differ between subjects without and with one or more T present in C1236T, G2677T and C3435T. In contrast, patients with Alzheimer's disease with one or more T in C1236T, G2677T and C3435T had significantly higher binding potential values than patients without a T. In addition, there was a relationship between binding potential and T dose in C1236T and G2677T.In Alzheimer's disease patients, C1236T, G2677T/A and C3435T single-nucleotide polymorphisms may be related to changes in P-glycoprotein function at the blood–brain barrier. As such, genetic variations in ABCB1 might contribute to the progression of amyloid-beta deposition in the brain.P-glycoprotein (Pgp) is a 170 kDa membrane-bound efflux transporter located in several organs throughout the body with an excretory and/or barrier function, such as the liver, kidneys, intestine, placenta, testes and the blood–brain barrier (BBB) [1]. At the BBB, Pgp is highly expressed and has an important function in the transport of a wide variety of endogenous and exogenous substances out of the brain into the bloodstream [2]. Pgp has been shown to play a role in amyloid-beta clearance from the brain and, as such, has been hypothesized to be involved in the pathogenesis of Alzheimer's disease (AD) [3]. Recently, BBB Pgp dysfunction in AD patients was shown using the Pgp substrate tracer (R)-11C]verapamil and positron emission tomography (PET) [4].Pgp is encoded in the ABCB1 gene (formerly known as the multidrug resistance (MDR1) gene), wh
Comparison of Perfusion Weighted Magnetic Resonance Imaging and Single Photon Emission Computed Tomography for Assessment of Cerebrovascular Reserve in Symptomatic Carotid Territory Stenosis  [PDF]
Stephen T. McSorley, Krishna A. Dani, Jim Patterson, David Brennan, Donald M. Hadley, Keith Muir
Open Journal of Radiology (OJRad) , 2012, DOI: 10.4236/ojrad.2012.23013
Abstract: Background: Perfusion Weighted Magnetic Resonance Imaging (PW-MRI) and HMPAO Single Photon Emission Computed Tomography (SPECT) are both cerebral perfusion measurement techniques. Imaging before and after acetazolamide administration can assess cerebrovascular reserve in symptomatic haemodynamic cerebrovascular disease. We compared SPECT and PW-MRI parameters in this patient group. Methods: We identified 10 patients with haemody-namically induced symptoms and intra- or extra-cranial arterial stenoses with back-to-back acetazolamide challenge SPECT and PW-MRI, 4 of whom had resting studies. Regions of interest (ROIs) were applied to parameter maps using an ASPECTS template and perfusion parameters expressed relative to contralateral ROIs, giving 118 challenge and 48 resting ROIs. Results: SPECT relative cerebral blood flow (rCBF) correlated with PW-MRI time to peak (TTP) (r = ?0.568), mean transit time (MTT) (r = ?0.317), regional cerebral blood flow (rCBF) (r = 0.299) and cerebral blood volume (CBV) (r = 0.224). Bias between SPECT and PW-MRI rCBF was small (?0.018) with wide limits of agreement and a systematic measurement error. Pre- to post-acetazolamide PW-MRI rCBF change showed poor sensitivity and specificity for detecting change in SPECT rCBF. SPECT and PW-MRI rCBF had stronger correlation and smaller bias in unilateral stenosis than with bilateral stenosis. Conclusion: Systematic bias between techniques limits interchange- ability in cerebrovascular reserve measurement in patients with cerebrovascular stenosis.
Some New Product Cordial Graphs
Samir K. Vaidya,Nilesh A. Dani
Journal of Applied Computer Science & Mathematics , 2010,
Abstract: We present here product cordial labeling for thegraphs obtained by joining apex vertices of two stars, shells andwheels to a new vertex. We extend these results for k copies ofstars, shells and wheels.
Periodontal Management of Non Healing Endodontic Lesion
Nitin H. Dani,Shahabe A. Saquib
Indian Journal of Dental Advancements , 2011,
Abstract: The fact that the periodontium is anatomically interrelated with the dental pulp by virtue of apical foramina and lateral canals creates pathways for exchange of noxious agents between the two tissue compartments when either or both of the tissues are diseased. Proper diagnosis of the various disorders affecting the periodontium and the pulp is important to exclude unnecessary and even detrimental treatment. This is a clinical case report of an enododontic-periodontic lesion in relation to lower left central incisor. Root canal treatment has been done with the respected tooth six months ago, but the lesion showed no sign of healing resulting in draining sinus and increasing pocket depth. Radiographic examination revealed overobturation of gutta-percha with peri-radicular pathology. Periodontal flap surgery was performed and the defect was filled with bone graft mixed with Platelet rich plasma (PRP) and covered by platelet rich fibrin (PRF). Patient reviewed for six months which showed uneventful healing and no recurrence of the lesion.
Inhaled Nitric Oxide in preterm infants: a systematic review and individual patient data meta-analysis
Lisa M Askie, Roberta A Ballard, Gary Cutter, Carlo Dani, Diana Elbourne, David Field, Jean-Michel Hascoet, Anna Hibbs, John P Kinsella, Jean-Christophe Mercier, Wade Rich, Michael D Schreiber, Pimol Srisuparp, Nim V Subhedar, Krisa P Van Meurs, Merryn Voysey, Keith Barrington, Richard A Ehrenkranz, Neil Finer, the Meta-Analysis of Preterm Patients on inhaled Nitric Oxide (MAPPiNO) Collaboration
BMC Pediatrics , 2010, DOI: 10.1186/1471-2431-10-15
Abstract: The Meta-Analysis of Preterm Patients on inhaled Nitric Oxide (MAPPiNO) Collaboration will perform an individual patient data meta-analysis to answer these important clinical questions. Studies will be included if preterm infants receiving assisted ventilation are randomized to receive inhaled Nitric Oxide or to a control group. The individual patient data provided by the Collaborators will be analyzed on an intention-to-treat basis where possible. Binary outcomes will be analyzed using log-binomial regression models and continuous outcomes will be analyzed using linear fixed effects models. Adjustments for trial differences will be made by including the trial variable in the model specification.Thirteen (13) trials, with a total of 3567 infants are eligible for inclusion in the MAPPiNO systematic review. To date 11 trials (n = 3298, 92% of available patients) have agreed to participate. Funding was successfully granted from Ikaria Inc as an unrestricted grant. A collaborative group was formed in 2006 with data collection commencing in 2007. It is anticipated that data analysis will commence in late 2009 with results being publicly available in 2010.Approximately 8-13% of infants are born prematurely across developed countries. Preterm delivery accounts for 75-80% of all neonatal morbidity and mortality [1,2]. Although survival rates have markedly improved in recent decades, premature infants requiring assisted ventilation are still at significant risk of both pulmonary and cerebral injury.An estimated 75% of the infants with a birth weight less than 1000 grams develop respiratory distress syndrome (RDS), and nearly 30% are still oxygen dependent at a postmenstrual age of 36 weeks [3]. The commonest definition of chronic lung disease (CLD) is oxygen dependency or respiratory support at 36 weeks postmenstrual age. Infants with severe CLD remain at high risk for pulmonary morbidity and mortality during the first two years of life [4]. In addition, long-term neurodevel
The Complete Genome Sequence of Cupriavidus metallidurans Strain CH34, a Master Survivalist in Harsh and Anthropogenic Environments
Paul J. Janssen,Rob Van Houdt,Hugo Moors,Pieter Monsieurs,Nicolas Morin,Arlette Michaux,Mohammed A. Benotmane,Natalie Leys,Tatiana Vallaeys,Alla Lapidus,Sébastien Monchy,Claudine Médigue,Safiyh Taghavi,Sean McCorkle,John Dunn,Dani?l van der Lelie,Max Mergeay
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010433
Abstract: Many bacteria in the environment have adapted to the presence of toxic heavy metals. Over the last 30 years, this heavy metal tolerance was the subject of extensive research. The bacterium Cupriavidus metallidurans strain CH34, originally isolated by us in 1976 from a metal processing factory, is considered a major model organism in this field because it withstands milli-molar range concentrations of over 20 different heavy metal ions. This tolerance is mostly achieved by rapid ion efflux but also by metal-complexation and -reduction. We present here the full genome sequence of strain CH34 and the manual annotation of all its genes. The genome of C. metallidurans CH34 is composed of two large circular chromosomes CHR1 and CHR2 of, respectively, 3,928,089 bp and 2,580,084 bp, and two megaplasmids pMOL28 and pMOL30 of, respectively, 171,459 bp and 233,720 bp in size. At least 25 loci for heavy-metal resistance (HMR) are distributed over the four replicons. Approximately 67% of the 6,717 coding sequences (CDSs) present in the CH34 genome could be assigned a putative function, and 9.1% (611 genes) appear to be unique to this strain. One out of five proteins is associated with either transport or transcription while the relay of environmental stimuli is governed by more than 600 signal transduction systems. The CH34 genome is most similar to the genomes of other Cupriavidus strains by correspondence between the respective CHR1 replicons but also displays similarity to the genomes of more distantly related species as a result of gene transfer and through the presence of large genomic islands. The presence of at least 57 IS elements and 19 transposons and the ability to take in and express foreign genes indicates a very dynamic and complex genome shaped by evolutionary forces. The genome data show that C. metallidurans CH34 is particularly well equipped to live in extreme conditions and anthropogenic environments that are rich in metals.
Differential Dynamics of ATR-Mediated Checkpoint Regulators
Dani?l O. Warmerdam,Roland Kanaar,Veronique A. J. Smits
Journal of Nucleic Acids , 2010, DOI: 10.4061/2010/319142
Abstract: The ATR-Chk1 checkpoint pathway is activated by UV-induced DNA lesions and replication stress. Little was known about the spatio and temporal behaviour of the proteins involved, and we, therefore, examined the behaviour of the ATRIP-ATR and Rad9-Rad1-Hus1 putative DNA damage sensor complexes and the downstream effector kinase Chk1. We developed assays for the generation and validation of stable cell lines expressing GFP-fusion proteins. Photobleaching experiments in living cells expressing these fusions indicated that after UV-induced DNA damage, ATRIP associates more transiently with damaged chromatin than members of the Rad9-Rad1-Hus1 complex. Interestingly, ATRIP directly associated with locally induced UV damage, whereas Rad9 bound in a cooperative manner, which can be explained by the Rad17-dependent loading of Rad9 onto damaged chromatin. Although Chk1 dissociates from the chromatin upon UV damage, no change in the mobility of GFP-Chk1 was observed, supporting the notion that Chk1 is a highly dynamic protein. 1. Introduction Eukaryotic cells are continuously threatened by DNA damage caused by environmental factors and intracellular metabolic processes. To protect themselves against these potential threats, cells have developed DNA damage checkpoint and repair mechanisms, which help to ensure transmission of an intact genome. Cell cycle checkpoints and DNA repair mechanisms together determine the ultimate faith of the cell after suffering DNA damage. Activation of the DNA damage checkpoint involves the activation of transducer kinases ATR/ATM and subsequently the effector kinases Chk1/Chk2 [1]. So-called mediator proteins, including Claspin and BRCA1, were additionally discovered, and function either in the recruitment of substrates to DNA lesions or as scaffolds on which protein complexes are assembled [2, 3]. In response to a variety of DNA damaging agents like UV light and replication stress, the ATR-mediated checkpoint pathway is activated. Biochemical data indicates that ATRIP, in complex with ATR, binds to RPA-coated single stranded DNA (ssDNA) [4]. Independently, the Rad17-RFC complex is also recruited to sites of damage. The Rad17-RFC protein complex facilitates the loading of the Rad9-Rad1-Hus1 (9-1-1 complex) sliding clamp onto the DNA [5–7]. Subsequently, TopBP1 is recruited to DNA lesions by binding to the Rad9 subunit of the 9-1-1 complex, thereby locating near the ATRIP-ATR heterodimer. Through an interaction with TopBP1, ATR becomes fully active, resulting in the activation of effector kinase Chk1 and subsequent checkpoint arrest
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