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Search Results: 1 - 10 of 737994 matches for " John Noel M. Via?a "
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Illuminating the role of cholinergic signaling in circuits of attention and emotionally salient behaviors
Antonio Luchicchi,Bernard Bloem,John Noel M. Viaa,Lorna W. Role
Frontiers in Synaptic Neuroscience , 2014, DOI: 10.3389/fnsyn.2014.00024
Abstract: Acetylcholine (ACh) signaling underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. Alterations in ACh signaling are involved in the pathophysiology of multiple neuropsychiatric disorders. In the central nervous system, ACh transmission is mainly guaranteed by dense innervation of select cortical and subcortical regions from disperse groups of cholinergic neurons within the basal forebrain (BF; e.g., diagonal band, medial septal, nucleus basalis) and the pontine-mesencephalic nuclei, respectively. Despite the fundamental role of cholinergic signaling in the CNS and the long standing knowledge of the organization of cholinergic circuitry, remarkably little is known about precisely how ACh release modulates cortical and subcortical neural activity and the behaviors these circuits subserve. Growing interest in cholinergic signaling in the CNS focuses on the mechanism(s) of action by which endogenously released ACh regulates cognitive functions, acting as a neuromodulator and/or as a direct transmitter via nicotinic and muscarinic receptors. The development of optogenetic techniques has provided a valuable toolbox with which we can address these questions, as it allows the selective manipulation of the excitability of cholinergic inputs to the diverse array of cholinergic target fields within cortical and subcortical domains. Here, we review recent papers that use the light-sensitive opsins in the cholinergic system to elucidate the role of ACh in circuits related to attention and emotionally salient behaviors. In particular, we highlight recent optogenetic studies which have tried to disentangle the precise role of ACh in the modulation of cortical-, hippocampal- and striatal-dependent functions.
Impacts of waveforms on the fluid flow, wall shear stress, and flow distribution in cerebral aneurysms and the development of a universal reduced pressure  [PDF]
Noel M. Naughton, Brian D. Plourde, John R. Stark, Simona Hodis, John P. Abraham
Journal of Biomedical Science and Engineering (JBiSE) , 2014, DOI: 10.4236/jbise.2014.71002

The hydrodynamics of aneurysm blood flow is thought to be a critical factor in the evolution and potential rupture of blood vessel walls. The ability to predict which aneurysms may grow or rupture has eluded researchers and practicing clinicians. On the other hand, it is expected that local flow patterns, pressures, and wall shear stress play a role in the aneurysm life. In this study, the impact of waveform on these parameters was studied. A baseline waveform, taken from a patient, was applied to an aneurysm geometry. Then the waveform was modified by increasing and decreasing both the flowrates and the cardiac rate. In total, seven cases were investigated. It was found that there were remarkable similarities in the patterns of flow and wall stresses for the cases. These similarities existed throughout the cardiac cycle. It was also found that there was a reduced pressure variable that provides a universal relationship that characterizes all of the cases. It was seen that the maximum wall shear occurs at the neck of the aneurysm and scales with the peak systolic velocity. Finally, it is shown that the flow distribution to the multiple outlets does not appreciably depend on the details of the inlet waveform. All cases had a flow distribution that was within 2%.

Evolution of an Agriculture-Associated Disease Causing Campylobacter coli Clade: Evidence from National Surveillance Data in Scotland
Samuel K. Sheppard,John F. Dallas,Daniel J. Wilson,Norval J. C. Strachan,Noel D. McCarthy,Keith A. Jolley,Frances M. Colles,Ovidiu Rotariu,Iain D. Ogden,Ken J. Forbes,Martin C. J. Maiden
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015708
Abstract: The common zoonotic pathogen Campylobacter coli is an important cause of bacterial gastroenteritis worldwide but its evolution is incompletely understood. Using multilocus sequence type (MLST) data of 7 housekeeping genes from a national survey of Campylobacter in Scotland (2005/6), and a combined population genetic-phylogenetics approach, we investigated the evolutionary history of C. coli. Genealogical reconstruction of isolates from clinical infection, farm animals and the environment, revealed a three-clade genetic structure. The majority of farm animal, and all disease causing genotypes belonged to a single clade (clade 1) which had comparatively low synonymous sequence diversity, little deep branching genetic structure, and a higher number of shared alleles providing evidence of recent clonal decent. Calibration of the rate of molecular evolution, based on within-species genetic variation, estimated a more rapid rate of evolution than in traditional estimates. This placed the divergence of the clades at less than 2500 years ago, consistent with the introduction of an agricultural niche having had an effect upon the evolution of the C. coli clades. Attribution of clinical isolate genotypes to source, using an asymmetric island model, confirmed that strains from chicken and ruminants, and not pigs or turkeys, are the principal source of human C. coli infection. Taken together these analyses are consistent with an evolutionary scenario describing the emergence of agriculture-associated C. coli lineage that is an important human pathogen.
Cerebellar Purkinje cells incorporate immunoglobulins and immunotoxins in vitro: implications for human neurological disease and immunotherapeutics
Kenneth E Hill, Susan A Clawson, John W Rose, Noel G Carlson, John E Greenlee
Journal of Neuroinflammation , 2009, DOI: 10.1186/1742-2094-6-31
Abstract: To assess Purkinje cell uptake of immunoglobulins, organotypic cultures of rat cerebellum incubated with rat IgGs, human IgG, fluorescein-conjugated IgG, and rat IgM were studied by confocal microscopy in real time and following fixation. An IgG-daunorubicin immunotoxin was used to determine whether conjugation of pharmacological agents to IgG could be used to achieve Purkinje cell-specific drug delivery.IgG uptake was detected in Purkinje cell processes after 4 hours of incubation and in Purkinje cell cytoplasm and nuclei by 24-48 hours. Uptake could be followed in real time using IgG-fluorochrome conjugates. Purkinje cells also incorporated IgM. Intracellular immunoglobulin did not affect Purkinje cell viability, and Purkinje cells cleared intracellular IgG or IgM within 24-48 hours after transfer to media lacking immunoglobulins. The IgG-daunomycin immunotoxin was also rapidly incorporated into Purkinje cells and caused extensive, cell-specific death within 8 hours. Purkinje cell death was not produced by unconjugated daunorubicin or control IgG.Purkinje cells in rat organotypic cultures incorporate and clear host (rat) and non-host (human or donkey) IgG or IgM, independent of the immunoglobulin's reactivity with Purkinje cell antigens. This property permits real-time study of immunoglobulin-Purkinje cell interaction using fluorochrome IgG conjugates, and can allow Purkinje cell-specific delivery of IgG-conjugated pharmacological agents. Antibodies to intracellular Purkinje cell proteins could potentially be incorporated intracellularly to produce cell injury. Antibodies used therapeutically, including immunotoxins, may also be taken up and cause Purkinje cell injury, even if they do not recognize Purkinje cell antigens.Antibodies to cytoplasmic components of cerebellar Purkinje cells have been repeatedly described in sera and cerebrospinal fluid (CSF) of patients developing paraneoplastic cerebellar degeneration in the setting of systemic cancer, as well as in s
Abnormal hCG levels in a patient with treated stage I seminoma: a diagnostic dilemma
Noel J Aherne, Cormac A Small, Gerard P McVey, David A Fitzpatrick, John G Armstrong
World Journal of Surgical Oncology , 2008, DOI: 10.1186/1477-7819-6-68
Abstract: The patient was a bodybuilder, and following a negative metastatic work – up, admitted to injecting exogenous beta hCG. This was done to reduce withdrawal symptoms from androgen abuse. The patient remains well eight years post diagnosis.This case highlights the need for surgical oncologists to conduct vigilant screening of young male patients with a history of testicular germ cell tumours and who may indulge in steroid abuse.Testicular cancer accounts for 1% of all male cancers [1], and while the incidence has doubled in the last twenty years, the overall 5 – year survival is in the order of 99%. Among urologists and radiation oncologists, the follow – up of patients with testicular malignancies requires meticulous screening for distant metastases and careful surveillance with tumour marker measurement. These include alpha – foetoprotein (AFP) and beta human chorionic gonadotrophin (hCG), used to supplement clinical and radiologic evaluation. This case report details only the second published case of false positive beta hCG due to exogenous hCG administration [2].A 26 year old man presented to the urology service with a left testicular swelling. Clinical examination, followed by testicular ultrasound confirmed the presence of a testicular tumour. After a negative metastatic work – up, the patient proceeded to a left inguinal orchidectomy. This was followed by prophylactic para – aortic nodal irradiation to a total dose of 25 Gray (Gy) in 17 fractions. He then had a five year period of routine surveillance with clinical examination, tumour marker evaluation and annual computed tomographic (CT) scan. After five years a routine beta hCG was measured at 28.5 mIU/mL (normal 1.0 – 5.3 mIU/mL) and this raised concern regarding recurrence of his seminoma. This instigated a complete re – staging with CT Thorax/Abdomen/Pelvis and further metastatic work – up. These were all normal.On further consultation, the patient admitted to self – administering intramuscular Nandrolone,
The effects of progesterone on breast tissue
Desreux J,Delansorne R,Foidart J-M,Noel A
Journal für Menopause , 2001,
Duffy Antigen Receptor for Chemokine (DARC) Polymorphisms and Its Involvement in Acquisition of Inhibitory Anti-Duffy Binding Protein II (DBPII) Immunity
Flávia A. Souza-Silva, Letícia M. Torres, Jessica R. Santos-Alves, Michaelis Loren Tang, Bruno A. M. Sanchez, Tais N. Sousa, Cor J. F. Fontes, Paulo A. Nogueira, Roberto S. Rocha, Cristiana F. A. Brito, John H. Adams, Flora S. Kano, Luzia H. Carvalho
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0093782
Abstract: The Plasmodium vivax Duffy binding protein (PvDBP) and its erythrocytic receptor, the Duffy antigen receptor for chemokines (DARC), are involved in the major P. vivax erythrocyte invasion pathway. An open cohort study to analyze DARC genotypes and their relationship to PvDBP immune responses was carried out in 620 volunteers in an agricultural settlement of the Brazilian Amazon. Three cross-sectional surveys were conducted at 6-month intervals, comprising 395, 410, and 407 subjects, respectively. The incidence rates of P. vivax infection was 2.32 malaria episodes per 100 person-months under survey (95% confidence interval [CI] of 1.92-2.80/100 person-month) and, of P. falciparum, 0.04 per 100 person-months (95% CI of 0.007–0.14/100 person-month). The distribution of DARC genotypes was consistent with the heterogeneous ethnic origins of the Amazon population, with a predominance of non-silent DARC alleles: FY*A > FY*B. The 12-month follow-up study demonstrated no association between DARC genotypes and total IgG antibodies as measured by ELISA targeting PvDBP (region II, DBPII or regions II–IV, DBPII-IV). The naturally acquired DBPII specific binding inhibitory antibodies (BIAbs) tended to be more frequent in heterozygous individuals carrying a DARC-silent allele (FY*BES). These results provide evidence that DARC polymorphisms may influence the naturally acquired inhibitory anti-Duffy binding protein II immunity.
Simultaneous feature selection and parameter optimisation using an artificial ant colony: case study of melting point prediction
Noel M O'Boyle, David S Palmer, Florian Nigsch, John BO Mitchell
Chemistry Central Journal , 2008, DOI: 10.1186/1752-153x-2-21
Abstract: Starting from an initial set of 203 descriptors, the WAAC algorithm selected a PLS model with 68 descriptors which has an RMSE on an external test set of 46.6°C and R2 of 0.51. The number of components chosen for the model was 49, which was close to optimal for this feature selection. The selected SVM model has 28 descriptors (cost of 5, ε of 0.21) and an RMSE of 45.1°C and R2 of 0.54. This model outperforms a kNN model (RMSE of 48.3°C, R2 of 0.47) for the same data and has similar performance to a Random Forest model (RMSE of 44.5°C, R2 of 0.55). However it is much less prone to bias at the extremes of the range of melting points as shown by the slope of the line through the residuals: -0.43 for WAAC/SVM, -0.53 for Random Forest.With a careful choice of objective function, the WAAC algorithm can be used to optimise machine learning and regression models that suffer from overfitting. Where model parameters also need to be tuned, as is the case with support vector machine and partial least squares models, it can optimise these simultaneously. The moving probabilities used by the algorithm are easily interpreted in terms of the best and current models of the ants, and the winnowing procedure promotes the removal of irrelevant descriptors.Quantitative Structure-Activity and Structure-Property Relationship (QSAR and QSPR) models are based upon the idea, first proposed by Hansch [1], that a molecular property can be related to physicochemical descriptors of the molecule. A QSAR model for prediction must be able to generalise well to give accurate predictions on unseen test data. Although it is true in general that the more descriptors used to build a model, the better the model predicts the training set data, such a model typically has very poor predictive ability when presented with unseen test data, a phenomenon known as overfitting [2]. Feature selection refers to the problem of selecting a subset of the descriptors which can be used to build a model with optimal pred
Pilomatrix carcinoma presenting as an extra axial mass: clinicopathological features
Noel J Aherne, David A Fitzpatrick, David Gibbons, John G Armstrong
Diagnostic Pathology , 2008, DOI: 10.1186/1746-1596-3-47
Abstract: We report the case of a 41 year old mentally retarded male who had a longstanding lesion in the left neck for approximately fifteen years previously diagnosed as a pilomatrixoma. He presented with severe headache, falls and visual disturbance and a biopsy showed pilomatrix carcinoma of the occipital region which, on computed tomography ( CT ) invaded the occipital bone, the cerebellum and the left temporal lobe. At his initial presentation he had a craniotomy and subtotal excision of the lesion but received no adjuvant therapy. After an early intracranial recurrence he had further debulking and adjuvant external beam radiotherapy. He has had no further intracranial recurrence after three and a half years of follow-up. Here we present the pathological features of this uncommon tumour.Pilomatrix carcinomas are the aggressive variant of pilomatrixomas, a type of hair matrix tumour. Although initially thought to be benign when first described by Malherbe and Chenantais [1], as early as 1927 Gromiko [2] noted that some tumours had biologically aggressive behaviour. In 1980, Lopansri and Mihm [3] reviewed six cases of biologically aggressive pilomatrixoma. They found that the major discriminators of malignancy when compared to pilomatrixomas were the presence of hyperchromatic, vesicular basaloid cells with numerous mitoses and infiltration into adjacent tissue or blood vessels. They are characterised by sheets and islands of proliferating atypical basaloid cells with an infiltrating border. This case demonstrates an unusual pattern of local spread into the cranial cavity.A 41 year old male presented with a cutaneous tumour in the left posterior triangle of the neck which had been present for at least fifteen years. He had a history of mild mental retardation, bilateral undescended testes and had undergone appendicectomy as a child. He was otherwise well and in fulltime employment. He had multiple prior resections of the neck lesion which revealed benign pilomatrixoma. Th
Aggregate Planning for a Large Food Manufacturer with High Seasonal Demand
Flávia M. Takey,Marco A. Mesquita
Brazilian Journal of Operations & Production Management , 2010,
Abstract: This study was motivated by the poor inventory management performance in a Brazilian food company with a high seasonal demand. It was clearly recognized that the best inventory management would depend on improvements in demand forecasting and in the production planning process itself. In order to deal with the identified problems, an aggregate production planning model based on linear programming has been developed. The model determines the monthly production rates and inventory levels of finished products as well as the work-force requirements to accomplish productions plans. A simple disaggregating method, which searches for equal run out times, translates the aggregate plans into a detailed master production schedule for a shorter horizon of three months. With the effective usage of this model, and improvements in the demand forecasting processes, a global reduction of inventory levels of both raw materials and final products can be achieved.
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