A dynamic petri net model for iterative and interactive distributed multimedia presentation

Object Composition Petri Nets (OCPN), Priority Petri Nets (P-Net), Dynamic OCPN (DOCPN) and Enhanced P-Nets (EP-Net) have extended the original Petri Net to achieve the modeling of media synchronization and asynchronous user interactions during multimedia playback. Dynamic Petri Net (DPN) has been conceptualized to tackle existing problems in these two areas of modeling distributed multimedia systems. DPN features dynamic modeling elements which allows iteration and hence is able to reduce graph sizes of synchronous playback models while allowing greater details to be shown. DPN also introduces asynchronous event handling techniques that are powerful and effective. DPN was used in the design and modeling of a multimedia orchestration tool which is a typical representation of an application that works in a distributed multimedia system

Nasopharyngeal cancer mimicking otitic barotrauma in a resource-challenged center: a case report

<p>Abstract</p> <p>Introduction</p> <p>Nasopharyngeal cancer commonly manifests with cervical lymphadenopathy, recurrent epistaxis and progressive nasal obstruction. Neuro-ophthalmic and otologic manifestations can also occur. Isolated otologic presentations of nasopharyngeal cancer are rare and the diagnosis of nasopharyngeal cancer may not be foremost in the list of differentials.</p> <p>Case presentation</p> <p>We present the case of a 29-year-old Nigerian woman with bilateral conductive hearing loss and tinnitus after air travel. There were no other symptoms. The persistence of the symptoms after adequate treatment for otitic barotrauma necessitated re-evaluation, which led to a diagnosis of nasopharyngeal cancer.</p> <p>Conclusion</p> <p>Isolated otologic manifestations of nasopharyngeal cancer are rare in regions with low incidence of the disease. There is a need for it to be considered as a possible differential in patients presenting with bilateral serous otitis media.</p

Membrane plasmalogen composition and cellular cholesterol regulation: a structure activity study

<p>Abstract</p> <p>Background</p> <p>Disrupted cholesterol regulation leading to increased circulating and membrane cholesterol levels is implicated in many age-related chronic diseases such as cardiovascular disease (CVD), Alzheimer's disease (AD), and cancer. <it>In vitro </it>and <it>ex vivo </it>cellular plasmalogen deficiency models have been shown to exhibit impaired intra- and extra-cellular processing of cholesterol. Furthermore, depleted brain plasmalogens have been implicated in AD and serum plasmalogen deficiencies have been linked to AD, CVD, and cancer.</p> <p>Results</p> <p>Using plasmalogen deficient (NRel-4) and plasmalogen sufficient (HEK293) cells we investigated the effect of species-dependent plasmalogen restoration/augmentation on membrane cholesterol processing. The results of these studies indicate that the esterification of cholesterol is dependent upon the amount of polyunsaturated fatty acid (PUFA)-containing ethanolamine plasmalogen (PlsEtn) present in the membrane. We further elucidate that the concentration-dependent increase in esterified cholesterol observed with PUFA-PlsEtn was due to a concentration-dependent increase in sterol-O-acyltransferase-1 (SOAT1) levels, an observation not reproduced by 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibition.</p> <p>Conclusion</p> <p>The present study describes a novel mechanism of cholesterol regulation that is consistent with clinical and epidemiological studies of cholesterol, aging and disease. Specifically, the present study describes how selective membrane PUFA-PlsEtn enhancement can be achieved using 1-alkyl-2-PUFA glycerols and through this action reduce levels of total and free cholesterol in cells.</p

Lifting defects for nonstable K_0-theory of exchange rings and C*-algebras

The assignment (nonstable K_0-theory), that to a ring R associates the monoid V(R) of Murray-von Neumann equivalence classes of idempotent infinite matrices with only finitely nonzero entries over R, extends naturally to a functor. We prove the following lifting properties of that functor: (1) There is no functor F, from simplicial monoids with order-unit with normalized positive homomorphisms to exchange rings, such that VF is equivalent to the identity. (2) There is no functor F, from simplicial monoids with order-unit with normalized positive embeddings to C*-algebras of real rank 0 (resp., von Neumann regular rings), such that VF is equivalent to the identity. (3) There is a {0,1}^3-indexed commutative diagram D of simplicial monoids that can be lifted, with respect to the functor V, by exchange rings and by C*-algebras of real rank 1, but not by semiprimitive exchange rings, thus neither by regular rings nor by C*-algebras of real rank 0. By using categorical tools from an earlier paper (larders, lifters, CLL), we deduce that there exists a unital exchange ring of cardinality aleph three (resp., an aleph three-separable unital C*-algebra of real rank 1) R, with stable rank 1 and index of nilpotence 2, such that V(R) is the positive cone of a dimension group and V(R) is not isomorphic to V(B) for any ring B which is either a C*-algebra of real rank 0 or a regular ring.Comment: 34 pages. Algebras and Representation Theory, to appea

Biomimetic hollow mesoporous hydroxyapatite microsphere with controlled morphology, entrapment efficiency and degradability for cancer therapy.

published_or_final_versio

A new vicious cycle involving glutamate excitotoxicity, oxidative stress and mitochondrial dynamics

Glutamate excitotoxicity leads to fragmented mitochondria in neurodegenerative diseases, mediated by nitric oxide and S-nitrosylation of dynamin-related protein 1, a mitochondrial outer membrane fission protein. Optic atrophy gene 1 (OPA1) is an inner membrane protein important for mitochondrial fusion. Autosomal dominant optic atrophy (ADOA), caused by mutations in OPA1, is a neurodegenerative disease affecting mainly retinal ganglion cells (RGCs). Here, we showed that OPA1 deficiency in an ADOA model influences N-methyl-D-aspartate (NMDA) receptor expression, which is involved in glutamate excitotoxicity and oxidative stress. Opa1enu/+ mice show a slow progressive loss of RGCs, activation of astroglia and microglia, and pronounced mitochondrial fission in optic nerve heads as found by electron tomography. Expression of NMDA receptors (NR1, 2A, and 2B) in the retina of Opa1enu/+ mice was significantly increased as determined by western blot and immunohistochemistry. Superoxide dismutase 2 (SOD2) expression was significantly decreased, the apoptotic pathway was activated as Bax was increased, and phosphorylated Bad and BcL-xL were decreased. Our results conclusively demonstrate that not only glutamate excitotoxicity and/or oxidative stress alters mitochondrial fission/fusion, but that an imbalance in mitochondrial fission/fusion in turn leads to NMDA receptor upregulation and oxidative stress. Therefore, we propose a new vicious cycle involved in neurodegeneration that includes glutamate excitotoxicity, oxidative stress, and mitochondrial dynamics

Narcissism and prosocial behavior

There are many motivations for prosocial behavior, some more altruistic and some more egoistic. We posit that more narcissistic people may perform prosocial acts strategically, for example, to improve their reputations or to receive something in return

Revisiting Date and Party Hubs: Novel Approaches to Role Assignment in Protein Interaction Networks

The idea of 'date' and 'party' hubs has been influential in the study of protein-protein interaction networks. Date hubs display low co-expression with their partners, whilst party hubs have high co-expression. It was proposed that party hubs are local coordinators whereas date hubs are global connectors. Here we show that the reported importance of date hubs to network connectivity can in fact be attributed to a tiny subset of them. Crucially, these few, extremely central, hubs do not display particularly low expression correlation, undermining the idea of a link between this quantity and hub function. The date/party distinction was originally motivated by an approximately bimodal distribution of hub co-expression; we show that this feature is not always robust to methodological changes. Additionally, topological properties of hubs do not in general correlate with co-expression. Thus, we suggest that a date/party dichotomy is not meaningful and it might be more useful to conceive of roles for protein-protein interactions rather than individual proteins. We find significant correlations between interaction centrality and the functional similarity of the interacting proteins.Comment: 27 pages, 5 main figures, 4 supplementary figure

Reversal of Tetracycline Resistance by Cepharanthine, Cinchonidine, Ellagic Acid and Propyl Gallate in a Multi-drug Resistant Escherichia coli

Bacterial resistance to antibiotics is an increasing threat to global healthcare systems. We therefore sought compounds with potential to reverse antibiotic resistance in a clinically relevant multi-drug resistant isolate of Escherichia coli (NCTC 13400). 200 natural compounds with a history of either safe oral use in man, or as a component of a traditional herb or medicine, were screened. Four compounds; ellagic acid, propyl gallate, cinchonidine and cepharanthine, lowered the minimum inhibitory concentrations (MICs) of tetracycline, chloramphenicol and tobramycin by up to fourfold, and when combined up to eightfold. These compounds had no impact on the MICs of ampicillin, erythromycin or trimethoprim. Mechanistic studies revealed that while cepharanthine potently suppressed efflux of the marker Nile red from bacterial cells, the other hit compounds slowed cellular accumulation of this marker, and/or slowed bacterial growth in the absence of antibiotic. Although cepharanthine showed some toxicity in a cultured HEK-293 mammalian cell-line model, the other hit compounds exhibited no toxicity at concentrations where they are active against E. coli NCTC 13400. The results suggest that phytochemicals with capacity to reverse antibiotic resistance may be more common in traditional medicines than previously appreciated, and may offer useful scaffolds for the development of antibiotic-sensitising drugs

Reduced levels of hydroxylated, polyunsaturated ultra long-chain fatty acids in the serum of colorectal cancer patients: implications for early screening and detection

<p>Abstract</p> <p>Background</p> <p>There are currently no accurate serum markers for detecting early risk of colorectal cancer (CRC). We therefore developed a non-targeted metabolomics technology to analyse the serum of pre-treatment CRC patients in order to discover putative metabolic markers associated with CRC. Using tandem-mass spectrometry (MS/MS) high throughput MS technology we evaluated the utility of selected markers and this technology for discriminating between CRC and healthy subjects.</p> <p>Methods</p> <p>Biomarker discovery was performed using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). Comprehensive metabolic profiles of CRC patients and controls from three independent populations from different continents (USA and Japan; total <it>n </it>= 222) were obtained and the best inter-study biomarkers determined. The structural characterization of these and related markers was performed using liquid chromatography (LC) MS/MS and nuclear magnetic resonance technologies. Clinical utility evaluations were performed using a targeted high-throughput triple-quadrupole multiple reaction monitoring (TQ-MRM) method for three biomarkers in two further independent populations from the USA and Japan (total <it>n </it>= 220).</p> <p>Results</p> <p>Comprehensive metabolomic analyses revealed significantly reduced levels of 28-36 carbon-containing hydroxylated polyunsaturated ultra long-chain fatty-acids in all three independent cohorts of CRC patient samples relative to controls. Structure elucidation studies on the C28 molecules revealed two families harbouring specifically two or three hydroxyl substitutions and varying degrees of unsaturation. The TQ-MRM method successfully validated the FTICR-MS results in two further independent studies. In total, biomarkers in five independent populations across two continental regions were evaluated (three populations by FTICR-MS and two by TQ-MRM). The resultant receiver-operator characteristic curve AUCs ranged from 0.85 to 0.98 (average = 0.91 ± 0.04).</p> <p>Conclusions</p> <p>A novel comprehensive metabolomics technology was used to identify a systemic metabolic dysregulation comprising previously unknown hydroxylated polyunsaturated ultra-long chain fatty acid metabolites in CRC patients. These metabolites are easily measurable in serum and a decrease in their concentration appears to be highly sensitive and specific for the presence of CRC, regardless of ethnic or geographic background. The measurement of these metabolites may represent an additional tool for the early detection and screening of CRC.</p