MiRNAs as novel adipokines : obesity-related circulating MiRNAs influence chemosensitivity in cancer patients

Adipose tissue is an endocrine organ, capable of regulating distant physiological processes in other tissues via the release of adipokines into the bloodstream. Recently, circulating adipose-derived microRNAs (miRNAs) have been proposed as a novel class of adipokine, due to their capacity to regulate gene expression in tissues other than fat. Circulating levels of adipokines are known to be altered in obese individuals compared with typical weight individuals and are linked to poorer health outcomes. For example, obese individuals are known to be more prone to the development of some cancers, and less likely to achieve event-free survival following chemotherapy. The purpose of this review was twofold; first to identify circulating miRNAs which are reproducibly altered in obesity, and secondly to identify mechanisms by which these obesity-linked miRNAs might influence the sensitivity of tumors to treatment. We identified 8 candidate circulating miRNAs with altered levels in obese individuals (6 increased, 2 decreased). A second literature review was then performed to investigate if these candidates might have a role in mediating resistance to cancer treatment. All of the circulating miRNAs identified were capable of mediating responses to cancer treatment at the cellular level, and so this review provides novel insights which can be used by future studies which aim to improve obese patient outcomes

Genetic Regulation of Mucoidy in Pseudomonas aeruginosa

Cystic fibrosis is a genetic disorder that results from mutations in the CF transmembrane conductance regulator gene. These mutations cause a disruption in the chloride transport in mucosal tissues causing the accumulation of dehydrated mucus, and a decrease in the mucocilliary removal of environmental pathogens within the lungs. Additionally, the accumulation of dehydrated mucus within the lungs provides a hospitable environment for various bacteria, including the Gram-negative opportunistic pathogen Pseudomonas aeruginosa. P. aeruginosa uses the overproduction of a surface polysaccharide called alginate to form a biofilm to evade the host’s immunological defenses. The overproduction of alginate, often referred to as mucoidy, is a virulence factor that is responsible for chronic P. aeruginosa infections, as well as an increased resistance to antibiotics and phagocytosis by the host defense cells. Chronic P. aeruginosa infections are the leading cause of morbidity and mortality in CF patients, and the detection of mucoid isolates is a proven predictor of a decline in the patient’s health. The transition from the non-mucoid phenotype, found in environmental isolates, to the mucoid phenotype found within the CF lung is typically due to “loss-of-function” mutations in the transmembrane anti-sigma factor MucA. However, P. aeruginosa can overproduce alginate independent of mutations in mucA, through the regulated proteolysis of MucA. A series of proteases, beginning with AlgW, can degrade MucA, and release the alternative sigma factor AlgU to drive transcription of the alginate biosynthetic operon. It is generally accepted that the regulated proteolysis of MucA is a mechanism used by early colonizing strains prior to the selection for MucA mutations. Therefore, understanding this mechanism employed by those early colonizing strains may prove beneficial in preventing the establishment of chronic P. aeruginosa respiratory infection. In this dissertation, I identify and characterize two novel regulators of alginate overproduction in P. aeruginosa strains possessing a wildtype MucA. Using the model strain PAO579, I determined that mutations that result in the truncation of the type-IV pilin precursor protein, PilA, can induce alginate overproduction through activation of the AlgW resulting in an increased rate of proteolysis of MucA. Additionally, I identify that expression of the genetic locus PA1494, referred to as mucoid inhibitor A (muiA), can suppress mucoidy in P. aeruginosa strains with a wild-type MucA. Collectively, these findings provide needed insight into the regulation of mucoidy in those early colonizing strains, as well as identifies potential therapeutic targets for the prevention of chronic P. aeruginosa infections in the CF lung

Predicting the onset of rafting of c 0 precipitates by channel deformation in a Ni superalloy

The growth or shrinkage, normal to 001, of the interfaces between the γ matrix and cuboidal γ' precipitates is examined for a Ni-base superalloy, by considering the force acting on the interfaces. The force is produced by the precipitate coherency misfit and the stress produced by plastic deformation in channels of the γ matrix. A simple expression, which directly addresses the origin of the surface force, is given. The plastic deformation within the initially active γ matrix channels exerts the force to cause rafting. The subsequent activation of other types of channels also promotes the rafting in the same direction as the first active channels, when the plastic strain of the former channels increases. These issues are also discussed in terms of analysis based on those dislocations caused by the precipitate misfit and those produced by the plastic deformation

HLA-B27 Positivity: associated health implications

HLA-B27 positivity makes the onset of autoimmune diseases such as uveitis, ankylosing spondylitis and Crohn's disease more likely to occur. Ankylosing spondylitis and Crohn's disease are two types of HLA-B27 positive diseases that demonstrate a direct association with uveitis. Although the possession of HLA-B27 positivity is not mandatory for autoimmune diseases such as uveitis to occur, HLA-B27 positivity not only makes it more likely but may modify the clinical picture in which a patient presents. In relation to assessment and diagnosis it is imperative that the medical history of patients is thoroughly examined to ensure pathological sequelae are appropriately treated. Nurses play an important role in assessing patients that have uveitis and should suspect ankylosing spondylitis or Crohn's disease may be present

Zirconia toughened SiC whisker reinforced alumina composites small business innovation research

The objective of this phase 1 project was to develop a ceramic composite with superior fracture toughness and high strength, based on combining two toughness inducing materials: zirconia for transformation toughening and SiC whiskers for reinforcement, in a controlled microstructure alumina matrix. The controlled matrix microstructure is obtained by controlling the nucleation frequency of the alumina gel with seeds (submicron alpha-alumina). The results demonstrate the technical feasibility of producing superior binary composites (Al2O3-ZrO2) and tertiary composites (Al2O3-ZrO2-SiC). Thirty-two composites were prepared, consolidated, and fracture toughness tested. Statistical analysis of the results showed that: (1) the SiC type is the key statistically significant factor for increased toughness; (2) sol-gel processing with a-alumina seed had a statistically significant effect on increasing toughness of the binary and tertiary composites compared to the corresponding mixed powder processing; and (3) ZrO2 content within the range investigated had a minor effect. Binary composites with an average critical fracture toughness of 6.6MPam sup 1/2, were obtained. Tertiary composites with critical fracture toughness in the range of 9.3 to 10.1 MPam sup 1/2 were obtained. Results indicate that these composites are superior to zirconia toughened alumina and SiC whisker reinforced alumina ceramic composites produced by conventional techniques with similar composition from published data

Study of the stress intensity factors in the bulk of the material with synchrotron diffraction

Artículo de Proceedings de Congreso Internacional Fatigue2017In this work we present the results of a hybrid experimental and analytical approach for estimating the stress intensity factor. It uses the elastic strains within the bulk obtained by synchrotron X-ray diffraction data. The stress intensity factor is calculated using a multi-point overdeterministic method where the number of experimental data points is higher than the number of unknowns describing the elastic field surrounding the crack-tip. The tool is tested on X-ray strain measurements collected on a bainitic steel. In contrast to surface techniques the approach provides insights into the crack tip mechanics deep within the sample.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. The authors are grateful to the ESRF for ID15 beamtime awarded under MA-1483. Financial support of Universidad de Malaga through Plan Propio, Junta de Andalucía through Proyectos de Excelencia grant reference TEP-3244, Campus de Excelencia Internacional del Mar (CEIMAR) and Ministerio de Economia y Competitividad through grant reference MAT2016-76951-C2-2-P is also acknowledged. PJW acknowledges an ERC advanced grant

Structure-related transport properties of A-site ordered perovskite Sr3ErMn4-xGaxO10.5-d

We report x-ray diffraction, resistivity, thermopower, and magnetization of Sr3ErMn4-xGaxO10.5-d, in which A-site ordered tetragonal phase appears above x=1, and reveal that the system exhibits typical properties seen in the antiferromagnetic insulator with Mn3+. We succeed in preparing both A-site ordered and disordered phases for x=1 in different preparation conditions, and observe a significant decrease of the resistivity in the disordered phase. We discuss possible origins of the decrease focusing on the dimensionality and the disordered effect.Comment: 4 pages, 6 figure

Piezomorphic materials

The development of stress-induced morphing materials which are described as piezomorphic materials is reported. The development of a piezomorphic material is achieved by introducing spatial dependency into the compliance matrix describing the elastic response of a material capable of undergoing large strain deformation. In other words, it is necessary to produce an elastically gradient material. This is achieved through modification of the microstructure of the compliant material to display gradient topology. Examples of polymeric (polyurethane) foam and microporous polymer (expanded polytetrafluoroethylene) piezomorphic materials are presented here. These materials open up new morphing applications where dramatic shape changes can be triggered by mechanical stress

Propfan Test Assessment (PTA)

The objectives of the Propfan Test Assessment (PTA) Program were to validate in flight the structural integrity of large-scale propfan blades and to measure noise characteristics of the propfan in both near and far fields. All program objectives were met or exceeded, on schedule and under budget. A Gulfstream Aerospace Corporation GII aircraft was modified to provide a testbed for the 2.74m (9 ft) diameter Hamilton Standard SR-7 propfan which was driven by a 4475 kw (600 shp) turboshaft engine mounted on the left-hand wing of the aircraft. Flight research tests were performed for 20 combinations of speed and altitude within a flight envelope that extended to Mach numbers of 0.85 and altitudes of 12,192m (40,000 ft). Propfan blade stress, near-field noise on aircraft surfaces, and cabin noise were recorded. Primary variables were propfan power and tip speed, and the nacelle tilt angle. Extensive low altitude far-field noise tests were made to measure flyover and sideline noise and the lateral attenuation of noise. In coopertion with the FAA, tests were also made of flyover noise for the aircraft at 6100m (20,000 ft) and 10,668m (35,000 ft). A final series of tests were flown to evaluate an advanced cabin wall noise treatment that was produced under a separate program by NASA-Langley Research Center