498 research outputs found

    Machine-Part cell formation through visual decipherable clustering of Self Organizing Map

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    Machine-part cell formation is used in cellular manufacturing in order to process a large variety, quality, lower work in process levels, reducing manufacturing lead-time and customer response time while retaining flexibility for new products. This paper presents a new and novel approach for obtaining machine cells and part families. In the cellular manufacturing the fundamental problem is the formation of part families and machine cells. The present paper deals with the Self Organising Map (SOM) method an unsupervised learning algorithm in Artificial Intelligence, and has been used as a visually decipherable clustering tool of machine-part cell formation. The objective of the paper is to cluster the binary machine-part matrix through visually decipherable cluster of SOM color-coding and labelling via the SOM map nodes in such a way that the part families are processed in that machine cells. The Umatrix, component plane, principal component projection, scatter plot and histogram of SOM have been reported in the present work for the successful visualization of the machine-part cell formation. Computational result with the proposed algorithm on a set of group technology problems available in the literature is also presented. The proposed SOM approach produced solutions with a grouping efficacy that is at least as good as any results earlier reported in the literature and improved the grouping efficacy for 70% of the problems and found immensely useful to both industry practitioners and researchers.Comment: 18 pages,3 table, 4 figure

    Astrocytic Ion Dynamics: Implications for Potassium Buffering and Liquid Flow

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    We review modeling of astrocyte ion dynamics with a specific focus on the implications of so-called spatial potassium buffering, where excess potassium in the extracellular space (ECS) is transported away to prevent pathological neural spiking. The recently introduced Kirchoff-Nernst-Planck (KNP) scheme for modeling ion dynamics in astrocytes (and brain tissue in general) is outlined and used to study such spatial buffering. We next describe how the ion dynamics of astrocytes may regulate microscopic liquid flow by osmotic effects and how such microscopic flow can be linked to whole-brain macroscopic flow. We thus include the key elements in a putative multiscale theory with astrocytes linking neural activity on a microscopic scale to macroscopic fluid flow.Comment: 27 pages, 7 figure

    Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models

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    The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example during chromosome organization. Describing phenomena that cover such diverse length, and also time scales, requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA, and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure

    Immunohistochemical localization and mRNA expression of aquaporins in the macula utriculi of patients with Meniere’s disease and acoustic neuroma

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    Meniere’s disease is nearly invariably associated with endolymphatic hydrops (the net accumulation of water in the inner ear endolymphatic space). Vestibular maculae utriculi were acquired from patients undergoing surgery for Meniere’s disease and acoustic neuroma and from autopsy (subjects with normal hearing and balance). Quantitative immunostaining was conducted with antibodies against aquaporins (AQPs) 1, 4, and 6, Na+K+ATPase, Na+K+2Cl co-transporter (NKCC1), and α-syntrophin. mRNA was extracted from the surgically acquired utricles from subjects with Meniere’s disease and acoustic neuroma to conduct quantitative real-time reverse transcription with polymerase chain reaction for AQP1, AQP4, and AQP6. AQP1 immunoreactivity (−IR) was located in blood vessels and fibrocytes in the underlying stroma, without any apparent alteration in Meniere’s specimens when compared with acoustic neuroma and autopsy specimens. AQP4-IR localized to the epithelial basolateral supporting cells in Meniere’s disease, acoustic neuroma, and autopsy. In specimens from subjects with Meniere’s disease, AQP4-IR was significantly decreased compared with autopsy and acoustic neuroma specimens. AQP6-IR occurred in the sub-apical vestibular supporting cells in acoustic neuroma and autopsy samples. However, in Meniere’s disease specimens, AQP6-IR was significantly increased and diffusely redistributed throughout the supporting cell cytoplasm. Na+K+ATPase, NKCC1, and α-syntrophin were expressed within sensory epithelia and were unaltered in Meniere’s disease specimens. Expression of AQP1, AQP4, or AQP6 mRNA did not differ in vestibular endorgans from patients with Meniere’s disease. Changes in AQP4 (decreased) and AQP6 (increased) expression in Meniere’s disease specimens suggest that the supporting cell might be a cellular target

    The radicalization of democracy: conflict, social movements and terrorism

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    The idea of democracy is being championed across the world, with some fifty new countries embracing this type of political system between 1974 and 2011 (Freedom House, 2016). Simultaneously, however, dissatisfaction has grown due to the perceived incapacity of democracy to deal with collective problems, hence the necessity to reconfigure it and redraw some of its principles. This paper links the analysis of the recent evolution of democratic systems with the trajectory of socio-political conflicts and the changing features of contemporary terrorism. It examines, therefore, two intertwined phenomena, namely the radicalization of democracy and the radicalization of the other. It concludes by stressing that encouraging dissent and heeding contentious claims made by social movements may be one way of mitigating both types of radicalization. Embedded in the tradition of critical criminology, this paper attempts to demonstrate that only by outflanking conventional categories of analysis can the criminological community aspire to grasp such thorny contemporary phenomena

    Immunogenicity and Protective Capacity of a Virosomal Respiratory Syncytial Virus Vaccine Adjuvanted with Monophosphoryl Lipid A in Mice

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    Respiratory Syncytial Virus (RSV) is a major cause of viral brochiolitis in infants and young children and is also a significant problem in elderly and immuno-compromised adults. To date there is no efficacious and safe RSV vaccine, partially because of the outcome of a clinical trial in the 1960s with a formalin-inactivated RSV vaccine (FI-RSV). This vaccine caused enhanced respiratory disease upon exposure to the live virus, leading to increased morbidity and the death of two children. Subsequent analyses of this incident showed that FI-RSV induces a Th2-skewed immune response together with poorly neutralizing antibodies. As a new approach, we used reconstituted RSV viral envelopes, i.e. virosomes, with incorporated monophosphoryl lipid A (MPLA) adjuvant to enhance immunogenicity and to skew the immune response towards a Th1 phenotype. Incorporation of MPLA stimulated the overall immunogenicity of the virosomes compared to non-adjuvanted virosomes in mice. Intramuscular administration of the vaccine led to the induction of RSV-specific IgG2a levels similar to those induced by inoculation of the animals with live RSV. These antibodies were able to neutralize RSV in vitro. Furthermore, MPLA-adjuvanted RSV virosomes induced high amounts of IFNγ and low amounts of IL5 in both spleens and lungs of immunized and subsequently challenged animals, compared to levels of these cytokines in animals vaccinated with FI-RSV, indicating a Th1-skewed response. Mice vaccinated with RSV-MPLA virosomes were protected from live RSV challenge, clearing the inoculated virus without showing signs of lung pathology. Taken together, these data demonstrate that RSV-MPLA virosomes represent a safe and efficacious vaccine candidate which warrants further evaluation

    Allergic inflammation does not impact chemical-induced carcinogenesis in the lungs of mice

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    <p>Abstract</p> <p>Background</p> <p>Although the relationship between allergic inflammation and lung carcinogenesis is not clearly defined, several reports suggest an increased incidence of lung cancer in patients with asthma. We aimed at determining the functional impact of allergic inflammation on chemical carcinogenesis in the lungs of mice.</p> <p>Methods</p> <p>Balb/c mice received single-dose urethane (1 g/kg at day 0) and two-stage ovalbumin during tumor initiation (sensitization: days -14 and 0; challenge: daily at days 6-12), tumor progression (sensitization: days 70 and 84; challenge: daily at days 90-96), or chronically (sensitization: days -14 and 0; challenge: daily at days 6-12 and thrice weekly thereafter). In addition, interleukin (IL)-5 deficient and wild-type C57BL/6 mice received ten weekly urethane injections. All mice were sacrificed after four months. Primary end-points were number, size, and histology of lung tumors. Secondary end-points were inflammatory cells and mediators in the airspace compartment.</p> <p>Results</p> <p>Ovalbumin provoked acute allergic inflammation and chronic remodeling of murine airways, evident by airspace eosinophilia, IL-5 up-regulation, and airspace enlargement. Urethane resulted in formation of atypical alveolar hyperplasias, adenomas, and adenocarcinomas in mouse lungs. Ovalbumin-induced allergic inflammation during tumor initiation, progression, or continuously did not impact the number, size, or histologic distribution of urethane-induced pulmonary neoplastic lesions. In addition, genetic deficiency in IL-5 had no effect on urethane-induced lung tumorigenesis.</p> <p>Conclusions</p> <p>Allergic inflammation does not impact chemical-induced carcinogenesis of the airways. These findings suggest that not all types of airway inflammation influence lung carcinogenesis and cast doubt on the idea of a mechanistic link between asthma and lung cancer.</p

    Anamnestic risk factor questionnaire as reliable diagnostic instrument for osteoporosis (reduced bone morphogenic density)

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    <p>Abstract</p> <p>Background</p> <p>Osteoporosis is a major health problem worldwide, and is included in the WHO list of the top 10 major diseases. However, it is often undiagnosed until the first fracture occurs, due to inadequate patient education and lack of insurance coverage for screening tests. Anamnestic risk factors like positive family anamnesis or early menopause are assumed to correlate with reduced BMD.</p> <p>Methods</p> <p>In our study of 78 patients with metaphyseal long bone fractures, we searched for a correlation between anamnestic risk factors, bone specific laboratory values, and the bone morphogenic density (BMD). Each indicator was examined as a possible diagnostic instrument for osteoporosis. The secondary aim of this study was to demonstrate the high prevalence of osteoporosis in patients with metaphyseal fractures.</p> <p>Results</p> <p>76.9% of our fracture patients had decreased bone density and 43.6% showed manifest osteoporosis in DXA (densitometry) measurements. Our questionnaire, identifying anamnestic risk factors, correlated highly significantly (p = 0.01) with reduced BMD, whereas seven bone-specific laboratory values (p = 0.046) correlated significantly.</p> <p>Conclusions</p> <p>Anamnestic risk factors correlate with pathological BMD. The medical questionnaire used in this study would therefore function as a cost-effective primary diagnostic instrument for identification of osteoporosis patients.</p

    Close association of water channel AQP1 with amyloid-β deposition in Alzheimer disease brains

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    Aquaporin-1 (AQP1), a membrane water channel protein, is expressed exclusively in the choroid plexus epithelium in the central nervous system under physiological conditions. However, AQP1 expression is enhanced in reactive astrocytes, accumulating in brain lesions of Creutzfeldt-Jakob disease and multiple sclerosis, suggesting a role of AQP1-expressing astrocytes in brain water homeostasis under pathological conditions. To clarify a pathological implication of AQP1 in Alzheimer disease (AD), we investigated the possible relationship between amyloid-beta (Aβ) deposition and astrocytic AQP1 expression in the motor cortex and hippocampus of 11 AD patients and 16 age-matched other neurological disease cases. In all cases, AQP1 was expressed exclusively in a subpopulation of multipolar fibrillary astrocytes. The great majority of AQP1-expressing astrocytes were located either on the top of or in close proximity to Aβ plaques in AD brains but not in non-AD cases, whereas those independent of Aβ deposition were found predominantly in non-AD brains. By Western blot, cultured human astrocytes constitutively expressed AQP1, and the levels of AQP1 protein expression were not affected by exposure to Aβ1-42 peptide, but were elevated by hypertonic sodium chloride. By immunoprecipitation, the C-terminal fragment-beta (CTFβ) of amyloid precursor protein interacted with the N-terminal half of AQP1 spanning the transmembrane helices H1, H2 and H3. These observations suggest the possible association of astrocytic AQP1 with Aβ deposition in AD brains
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