Analytical and experimental study of two concentric cylinders coupled by a fluid gap

From a structural point of view a liquid coolant type nuclear reactor consists of a heavy steel vessel containing the core and related mechanical components and filled with a hot fluid. This vessel is protected from the severe environment of the core by a shielding structure, the thermal liner, which is usually a relatively thin steel cylinder concentric with the reactor vessel and separated from it by a gap filled with the coolant fluid. This arrangement leads to a potential vibration problem if the fundamental frequency, or one of the higher natural vibration frequencies, of this liner system is close to the frequency of some vibration source present in the reactor vessel. The shell rigidly clamped at its base and free at the top was investigated since it is a better description of the conditions encountered in typical reactor designs

The effect of stressed cell-derived exosomes on metastatic activity of ovarian and breast cancer cell lines in vitro

Metastasis is one of the main causes of cancer related death worldwide; hence elucidation of this mechanism, at least in part, will support development of effective therapies to improve the morbidity and mortality of people with cancer. Cells continually expel a large number and variety of extracellular vesicles. Of these secreted vesicles, exosomes have been studied extensively over the past decade. Exosomes are between 30–100 nm in diameter and contain protein and nucleic acids. They have only very recently become appreciated as communication mediators that transport signals between cells. It was hypothesised that exosomes secreted by more metastatic cells may have the ability to increase the motility of less metastatic cells, and vice versa. The motile capacity of nine ovarian cancer cell lines was established using the scratch wound healing assay. Following this, exosome swapping experiments were performed between more and less metastatic cells. It was shown that exosomes were unable to influence the motility of recipient cells, irrespective of the metastatic phenotype of their cells of origin. It was also hypothesised that exosomes derived from stressed cells increase the invasive capacity of recipient cells. Exosomes were extracted from heat shocked or cisplatin treated cells and were introduced to naïve cells. The invasive capacity of recipient cells was tested following administration of stressed cellderived exosomes. It was discovered that cell invasiveness increased following uptake of either heat shock or cisplatin exosomes. Additionally, both heat shock and cisplatin exosomes were found to be statistically significantly smaller in diameter than those extracted from control cells, when measured using transmission electron microscopy. This has implications for patients with cancer because tumour cells that resist, but become stressed during administration of cisplatin therapy, could be expelling exosomes that increase the invasiveness of neighbouring cancer cells, and the cells of the surrounding healthy stroma

Characterization of a Reductively-Activated Elimination Pathway Relevant to the Biological Chemistry of the Kinamycins and Lomaiviticins

The lomaiviticins (1 and 2) and kinamycins (3–5) are bacterial metabolites with potent antimicrobial and antiproliferative activities. Herein we establish that 1–5 are capable of generating electrophilic acylfulvene intermediates (6) under mildly reducing conditions. These acylfulvenes 6 are formed by a multistep process comprising two-electron reduction and loss of dinitrogen to form an ortho-quinone methide, followed by elimination. Based on these studies, the structure of the product formed from 1 in DNA-cleavage assays is proposed (26). We also show that the bis(hydroxynaphthoquinone) substructures of the lomaiviticins activate the metabolites toward reduction. Finally, based on COMPARE and time-dependent cell response profiling analyses, we show that kinamycin C (4) and the monomeric lomaiviticin aglycon (24) operate by a mechanism of action that is distinct from simple diazofluorenes, such as 23

From the Guest Editors: Nursing Home Litigation: An Overview

This article provides an overview of the most common fact patterns involved in the litigation of neglect or abuse of the elderly. The common fact patterns include: choking and feeding tube, wandering, falls and related injuries, physical and chemical restraints, scalding, burns, malnutrition and dehydration, pressure sores, medication errors, and sexual abuse

Proteomic Investigation of Murine Neuronal α7-Nicotinic Acetylcholine Receptor Interacting Proteins

The α7-nicotinic acetylcholine receptor (α7-nAChR) is a ligand-gated ion channel that is expressed widely in vertebrates and is the principal high-affinity α-bungarotoxin (α-bgtx) binding protein in the mammalian CNS. α7-nAChRs associate with proteins that can modulate its properties. The α7-nAChR interactome is the summation of proteins interacting or associating with α7-nAChRs in a protein complex. To identify an α7-nAChR interactome in neural tissue, we isolated α-bgtx-affinity protein complexes from wild-type and α7-nAChR knockout (α7 KO) mouse whole brain tissue homogenates using α-bgtx-affinity beads. Affinity precipitated proteins were trypsinized and analyzed with an Orbitrap Fusion mass spectrometer. Proteins isolated with the α7-nAChR specific ligand, α-bgtx, were determined to be α7-nAChR associated proteins. The α7-nAChR subunit and 120 additional proteins were identified. Additionally, 369 proteins were identified as binding to α-bgtx in the absence of α7-nAChR expression, thereby identifying nonspecific proteins for α7-nAChR investigations using α-bgtx enrichment. These results expand on our previous investigations of α7-nAChR interacting proteins using α-bgtx-affinity bead isolation by controlling for differences between α7-nAChR and α-bgtx-specific proteins, developing an improved protein isolation methodology, and incorporating the latest technology in mass spectrometry. The α7-nAChR interactome identified in this study includes proteins associated with the expression, localization, function, or modulation of α7-nAChRs, and it provides a foundation for future studies to elucidate how these interactions contribute to human disease

Fracture control methods for space vehicles. Volume 3: Space shuttle configurations

Engineering drawings are presented which represent the culmination of research efforts towards a space shuttle configuration with adequate fracture control properties

Management of dyslipidaemia in an HIV-positive cohort

Background: Dyslipidaemia, secondary to both HIV and the use of antiretroviral therapy (ART) is well recognised, with HIV replication and immune status also thought to contribute to the risk. Traditionally the HIV physician has looked after HIV with primary care physicians (GP) managing non-HIV-related medical issues. However with the ageing population and the effectiveness of ART the HIV physician is diversifying to focus management strategies on preventative measures also. Method: 127 subjects were recruited. All subjects were HIV-positive males without any traditional cardiovascular disease symptoms or history. Details of patients demographics, family history, statin therapy, and primary care physician contact were collected. Baseline parameters were recorded and fasting bloods taken. Results: 127 asymptomatic HIV-positive males were recruited. 74/127 (58.3%) met the EACS criteria for statin prescription. 33/74 (44.6%) were on a statin. There was no significant difference between the class of antiretroviral prescribed, (NNRTI v PI) and lipid abnormalities (p=0.628). Hypertension and increased waist:hip ratio significantly increased the chances of the patient being hyperlipidaemic. Patients were more likely to be prescribed a statin if they were older, had hypertension, an increased waist circumference, increased Framingham risk, increased brain natriuretic peptide (BNP), or were diagnosed HIV-positive for longer (p<0.05). Pravastatin (21/33 [63.6%]), was most commonly prescribed statin. 24.2% received their statin prescription from their HIV physician, with 75.8% receiving their prescription from their GP. 5/21 (23.8%) on pravastatin met the target verses 7/7 (100%) on atorvastatin verses 2/2 (100%) on simvastatin versus 1/3 (33.3%) on rosuvastatin (p=0.02). Meeting lipid targets was less successful in the protease inhibitor group (1/9) 11.1% versus 11/21 (52.4%) in the NNRTI group (p=0.16). Conclusion: The majority met criteria for lipid management but less than half of those were prescribed it. Of those, most received treatment from their GP. Nearly half of those on statins did not meet lipid targets. HIV physicians were most likely to prescribe pravastatin and those on pravastatin were the least likely to achieve lipid targets when compared to the other statins. HIV physicians need to diversify their knowledge base and have clearly defined management strategies for the management of dyslipidaemia

Detained and committed youth: Examining differences in achievement, mental health needs, and special education status

Currently, there is limited research about the relationship between academic, mental health needs, and special education status among populations of incarcerated youth. Additionally, little is known about differences between special education and general education students, or about differences between detained and committed populations. This article reports the results of an investigation of the academic achievement, mental health history, and special education status of 555 detained and incarcerated boys in one mid-Atlantic state. Descriptive data and results from a logistic regression analysis are reported. We found that mean standard scores of participants on standardized achievement tests were one standard deviation below the population mean. We also found high rates of participants with disabilities, and high rates of participants reporting prior therapy and prior use of psychotropic medication. In addition, we found that student academic and mental health characteristics obtained through an intake screening protocol were predictive of special education status, but not of placement in detention or commitment settings. Finally, we found that African American students had a significantly higher risk of being committed than Caucasian students. Implications for future research and practice are discussed