522 research outputs found

    A Study of Software Development Models for Small Organisations

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    Software Development is a complex and often difficult process requiring the synthesis of many disciplines, like modelling and design to code generation, project management, testing, deployment, change management and beyond. Software development organizations follow some process while developing a software product. A key component of any software development process is the lifecycle model on which the process is based

    A Two-Study Comparison of Clinical and MRI Markers of Transition from Mild Cognitive Impairment to Alzheimer's Disease

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    A published predictor model in a single-site cohort study (questionable dementia, QD) that contained episodic verbal memory (SRT total recall), informant report of function (FAQ), and MRI measures was tested using logistic regression and ROC analyses with comparable measures in a second multisite cohort study (Alzheimer's Disease Neuroimaging Initiative, ADNI). There were 126 patients in QD and 282 patients in ADNI with MCI followed for 3 years. Within each sample, the differences in AUCs between the statistical models were very similar. Adding hippocampal and entorhinal cortex volumes to the model containing AVLT/SRT, FAQ, age and MMSE increased the area under the curve (AUC) in ADNI but not QD, with sensitivity increasing by 2% in ADNI and 2% in QD for a fixed specificity of 80%. Conversely, adding episodic verbal memory (SRT/AVLT) and FAQ to the model containing age, Mini Mental State Exam (MMSE), hippocampal and entorhinal cortex volumes increased the AUC in ADNI and QD, with sensitivity increasing by 17% in ADNI and 10% in QD for 80% specificity. The predictor models showed similar differences from each other in both studies, supporting independent validation. MRI hippocampal and entorhinal cortex volumes showed limited added predictive utility to memory and function measures

    Understanding depletion forces beyond entropy

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    The effective interaction energy of a colloidal sphere in a suspension containing small amounts of non-ionic polymers and a flat glass surface has been measured and calculated using total internal reflection microscopy (TIRM) and a novel approach within density functional theory (DFT), respectively. Quantitative agreement between experiment and theory demonstrates that the resulting repulsive part of the depletion forces cannot be interpreted entirely in terms of entropic arguments but that particularly at small distances (\lesssim 100 nm) attractive dispersion forces have to be taken into account

    Pleurocidin-family cationic antimicrobial peptides are cytolytic for breast carcinoma cells and prevent growth of tumor xenografts

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    Introduction: Cationic antimicrobial peptides (CAPs) defend against microbial pathogens; however, certain CAPs also exhibit anticancer activity. The purpose of this investigation was to determine the effect of the pleurocidin-family CAPs, NRC-03 and NRC-07, on breast cancer cells. Methods: MTT (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) and acid phosphatase cell-viability assays were used to assess NRC-03- and NRC-07-mediated killing of breast carcinoma cells. Erythrocyte lysis was determined with hemolysis assay. NRC-03 and NRC-07 binding to breast cancer cells and normal fibroblasts was assessed with fluorescence microscopy by using biotinylated-NRC-03 and -NRC-07. Lactate dehydrogenase-release assays and scanning electron microscopy were used to evaluate the effect of NRC-03 and NRC-07 on the cell membrane. Flow-cytometric analysis of 3,3'-dihexyloxacarbocyanine iodide- and dihydroethidium-stained breast cancer cells was used to evaluate the effects of NRC-03 and NRC-07 on mitochondrial membrane integrity and reactive oxygen species (ROS) production, respectively. Tumoricidal activity of NRC-03 and NRC-07 was evaluated in NOD SCID mice bearing breast cancer xenografts. Results: NRC-03 and NRC-07 killed breast cancer cells, including drug-resistant variants, and human mammary epithelial cells but showed little or no lysis of human dermal fibroblasts, umbilical vein endothelial cells, or erythrocytes. Sublethal doses of NRC-03 and, to a lesser extent, NRC-07 significantly reduced the median effective concentration (EC 50) of cisplatin for breast cancer cells. NRC-03 and NRC-07 bound to breast cancer cells but not fibroblasts, suggesting that killing required peptide binding to target cells. NRC-03- and NRC-07-mediated killing of breast cancer cells correlated with expression of several different anionic cell-surface molecules, suggesting that NRC-03 and NRC-07 bind to a variety of negatively-charged cell-surface molecules. NRC-03 and NRC-07 also caused significant and irreversible cell-membrane damage in breast cancer cells but not in fibroblasts. NRC-03- and NRC-07-mediated cell death involved, but did not require, mitochondrial membrane damage and ROS production. Importantly, intratumoral administration of NRC-03 and NRC-07 killed breast cancer cells grown as xenografts in NOD SCID mice. Conclusions: These findings warrant the development of stable and targeted forms of NRC-03 and/or NRC-07 that might be used alone or in combination with conventional chemotherapeutic drugs for the treatment of breast cancer.Peer reviewed: YesNRC publication: Ye

    The Effect of Isovolemic Hemodilution with Oxycyte®, a Perfluorocarbon Emulsion, on Cerebral Blood Flow in Rats

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    BACKGROUND: Cerebral blood flow (CBF) is auto-regulated to meet the brain's metabolic requirements. Oxycyte is a perfluorocarbon emulsion that acts as a highly effective oxygen carrier compared to blood. The aim of this study is to determine the effects of Oxycyte on regional CBF (rCBF), by evaluating the effects of stepwise isovolemic hemodilution with Oxycyte on CBF. METHODOLOGY: Male rats were intubated and ventilated with 100% O(2) under isoflurane anesthesia. The regional (striatum) CBF (rCBF) was measured with a laser doppler flowmeter (LDF). Stepwise isovolemic hemodilution was performed by withdrawing 4ml of blood and substituting the same volume of 5% albumin or 2 ml Oxycyte plus 2 ml albumin at 20-minute intervals until the hematocrit (Hct) values reached 5%. PRINCIPAL FINDINGS: In the albumin-treated group, rCBF progressively increased to approximately twice its baseline level (208+/-30%) when Hct levels were less than 10%. In the Oxycyte-treated group on the other hand, rCBF increased by significantly smaller increments, and this group's mean rCBF was only slightly higher than baseline (118+/-18%) when Hct levels were less than 10%. Similarly, in the albumin-treated group, rCBF started to increase when hemodilution with albumin caused the CaO(2) to decrease below 17.5 ml/dl. Thereafter, the increase in rCBF was accompanied by a nearly proportional decrease in the CaO(2) level. In the Oxycyte-treated group, the increase in rCBF was significantly smaller than in the albumin-treated group when the CaO(2) level dropped below 10 ml/dl (142+/-20% vs. 186+/-26%), and rCBF returned to almost baseline levels (106+/-15) when the CaO(2) level was below 7 ml/dl. CONCLUSIONS/SIGNIFICANCE: Hemodilution with Oxycyte was accompanied with higher CaO(2) and PO(2) than control group treated with albumin alone. This effect may be partially responsible for maintaining relatively constant CBF and not allowing the elevated blood flow that was observed with albumin

    Polymer Induced Bundling of F-actin and the Depletion Force

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    The inert polymer polyethylene glycol (PEG) induces a "bundling" phenomenon in F-actin solutions when its concentration exceeds a critical onset value C_o. Over a limited range of PEG molecular weight and ionic strength, C_o can be expressed as a function of these two variables. The process is reversible, but hysteresis is also observed in the dissolution of the bundles, with ionic strength having a large influence. Additional actin filaments are able to join previously formed bundles. Little, if any, polymer is associated with the bundle structure. Continuum estimates of the Asakura-Oosawa depletion force, Coulomb repulsion, and van der Waals potential are combined for a partial explanation of the bundling effect and hysteresis. Conjectures are presented concerning the apparent limit in bundle size

    ‘Populism’ in Guyana and Newfoundland

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    SUMMARY Populist development, as an alternative to large?scale capitalist development, is sometimes interpreted as a form of ‘transition to socialism’, or even as socialism itself. This article examines two areas, Newfoundland and Guyana, where populist strategies have been so presented and concludes that this interpretation is difficult to sustain. RESUMEN ‘Populismo’ en Guyana y Newfoundland El desarrollo populista, como alternativa al desarrollo capitalista en gran escala, se interpreta a veces como una forma de ‘transición al socialismo’ o incluso como socialismo propiamente tal. Este artículo examina dos áreas, Newfoundland y Guyana, donde las estrategias populistas han sido presentadas de esa forma y concluye que esta interpretación es difícil de sostener. SOMMAIRE ‘Populisme’ en Guyane et Terre Neuve Le développement populiste, en alternative au développement capitaliste à grande échelle est parfois interprété comme une forme de ‘transition au socialisme’ ou même comme du socialisme. Cet article examine deux régions, Terre Neuve et Guyane, ou les stratégies populistes ont été appliquées et conclut en estimant que cette interprétation est difficile à soutenir

    An exploratory study of factors that affect the performance and usage of rapid diagnostic tests for malaria in the Limpopo Province, South Africa

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    <p>Abstract</p> <p>Background</p> <p>Malaria rapid diagnostic tests (RDTs) are relatively simple to perform and provide results quickly for making treatment decisions. However, the accuracy and application of RDT results depends on several factors such as quality of the RDT, storage, transport and end user performance. A cross sectional survey to explore factors that affect the performance and use of RDTs was conducted in the primary care facilities in South Africa.</p> <p>Methods</p> <p>This study was conducted in three malaria risk sub-districts of the Limpopo Province, in South Africa. Twenty nurses were randomly selected from 17 primary health care facilities, three nurses from hospitals serving the study area and 10 other key informants, representing the managers of the malaria control programmes, routine and research laboratories, were interviewed, using semi-structured questionnaires.</p> <p>Results</p> <p>There was a high degree of efficiency in ordering and distribution of RDTs, however only 13/20 (65%) of the health facilities had appropriate air-conditioning and monitoring of room temperatures. Sixty percent (12/20) of the nurses did not receive any external training on conducting and interpreting RDT. Fifty percent of nurses (10/20) reported RDT stock-outs. Only 3/20 nurses mentioned that they periodically checked quality of RDT. Fifteen percent of nurses reported giving antimalarial drugs even if the RDT was negative.</p> <p>Conclusion</p> <p>Storage, quality assurance, end user training and use of RDT results for clinical decision making in primary care facilities in South Africa need to be improved. Further studies of the factors influencing the quality control of RDTs, their performance of RDTs and the ways to improve their use of RDTs are needed.</p
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