Analysis of microRNAs in Exosomes of Breast Cancer Patients in Search of Molecular Prognostic Factors in Brain Metastases

Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.     

Air-supported greenhouses

Air-supported structures can provide a suitable artificial environment for encouraging plant growth. How this can be achieved with a low rate of energy expenditure is described. The structural behaviour of air-supported structures is outlined, and the factors affecting the selection of cover materials, inflation systems and other auxiliary equipment discussed. Ventilation rates through air-supported greenhouses are examined, and the structures rated according to the requirements of their inflation systems. Methods of heating or cooling the environemnet within the greenhouse, and controls for internal humidity and carbon-dioxide concentrations, are discussed. It is concluded that air-supported structures can be utilised effectively as greenhouses.     

Evaluating the scope for energy-efficiency improvements in the public sector: Benchmarking NHSScotland's smaller health buildings

The National Health Service in Scotland (NHSScotland) has, in recent years, done much to reduce energy consumption in its major healthcare buildings (hospitals). On average, a reduction of 2% per year has been achieved since 2000, based on hospital buildings. However, there had been little or no attention paid to smaller premises such as health centres, clinics, dentists, etc. Such smaller healthcare buildings in Scotland constitute 29% of the total treated floor area of all NHSScotland buildings and, therefore, may contribute a similar percentage of carbon and other emissions to the environment. By concentrating on a sample of local health centres in Scotland, this paper outlines the creation of an energy benchmark target, which is part of a wider research project to investigate the environmental impacts of small healthcare buildings in Scotland and the scope for improvements. It was found that energy consumption varied widely between different centres but this variation could not be linked to building style, floor area or volume. Overall, it was found that a benchmark of 0.2 GJ/m³ would be challenging, but realistic.     

Emergence of New Mechanical Functionality in Materials via Size Reduction

Julia R. Greer received her S.B. in Chemical Engineering from the Massachusetts Institute of Technology (1997) and a Ph.D. in Materials Science from Stanford University, where she worked on the nanoscale plasticity of gold with W. D. Nix (2005). She also worked at Intel Corporation in Mask Operations (2000–03) and was a post‐doctoral fellow at the Palo Alto Research Center (2005–07), where she worked on organic flexible electronics with R. A. Street. Greer is a recipient of TR‐35, Technology Review's Top Young Innovator award (2008), a NSF CAREER Award (2007), a Gold Materials Research Society Graduate Student Award (2004), and an American Association of University Women Fellowship (2003). Julia joined Caltech's Materials Science department in 2007 where she is developing innovative experimental techniques to assess mechanical properties of nanometer‐sized materials. One such approach involves the fabrication of nanopillars with different initial microstructures and diameters between 25 nm and 1 µm by using focused ion beam and electron‐beam lithography microfabrication. The mechanical response of these pillars is subsequently measured in a custom‐built in situ mechanical deformation instrument, SEMentor, comprising a scanning electron microscope and a nanoindenter. Read our interview with Prof. Greer on MaterialsViews.com

     

Running from Stress: Neurobiological Mechanisms of Exercise-Induced Stress Resilience

Chronic stress, even stress of a moderate intensity related to daily life, is widely acknowledged to be a predisposing or precipitating factor in neuropsychiatric diseases. There is a clear relationship between disturbances induced by stressful stimuli, especially long-lasting stimuli, and cognitive deficits in rodent models of affective disorders. Regular physical activity has a positive effect on the central nervous system (CNS) functions, contributes to an improvement in mood and of cognitive abilities (including memory and learning), and is correlated with an increase in the expression of the neurotrophic factors and markers of synaptic plasticity as well as a reduction in the inflammatory factors. Studies published so far show that the energy challenge caused by physical exercise can affect the CNS by improving cellular bioenergetics, stimulating the processes responsible for the removal of damaged organelles and molecules, and attenuating inflammation processes. Regular physical activity brings another important benefit: increased stress robustness. The evidence from animal studies is that a sedentary lifestyle is associated with stress vulnerability, whereas a physically active lifestyle is associated with stress resilience. Here, we have performed a comprehensive PubMed Search Strategy for accomplishing an exhaustive literature review. In this review, we discuss the findings from experimental studies on the molecular and neurobiological mechanisms underlying the impact of exercise on brain resilience. A thorough understanding of the mechanisms underlying the neuroprotective potential of preconditioning exercise and of the role of exercise in stress resilience, among other things, may open further options for prevention and therapy in the treatment of CNS diseases.     

ScanBist: a multifrequency scan-based BIST method

The authors present ScanBist, a low-overhead, scan-based built-in self-test method, along with its performance in several designs. A novel clock synchronization scheme allows at-speed testing of circuits. This design allows the testing of circuits operating at more than one frequency while retaining the combinational character of the circuit to be analyzed. We can therefore apply scan patterns that will exercise the circuit under test at the system speed, potentially providing a better coverage of delay faults when compared to other self-test methods. Modifications to an existing transition fault simulator account for cases where inputs originating from scan registers clocked at different frequencies drive a gate. We claim to detect transition faults only if the transition originates from the inputs driven by the highest frequency clock. ScanBist is useful at all levels of system packaging assuming that a standard TAP provides the control and boundary scan isolates the circuit from primary inputs and outputs during BIST mode     

Fabrication, microstructure, and mechanical properties of tin nanostructures

Vertically aligned, cylindrical tin nanopillars have been fabricated via an electron beam lithography and electroplating method. Characterization by a non-destructive synchrotron X-ray microdiffraction (μSXRD) technique revealed that the tin nanostructures are body-centered tetragonal and are likely single-crystalline, or consist of a few large grains. The mechanical properties of tin nanopillars with average diameters of 920 nm, 560 nm, and 350 nm were studied by uniaxial compression in a nanoindenter outfitted with a flat punch diamond tip. The results of compression tests reveal strain rate sensitivity for nanoscale tin deformation, which matches closely to the previously reported bulk tin values. However, unlike bulk, tin nanopillars exhibit size-dependent flow stresses where smaller diameter specimens exhibit greater attained strengths. The observed size-dependence matches closely to that previously reported for single-crystalline face centered cubic metals at the nanoscale. μSXRD data was used to compare the dislocation density between as-fabricated and deformed tin nanopillars. Results of this comparison suggest that there is no measurable accumulation of dislocations within deformed tin nanopillars.     

The influence of end mill helix angle on high performance milling process

The results of experimental research on the influence of the helix angle on high performance milling of AlZn5.5MgCu alloy are presented. End mills with a wavy shape of a cutting edge, dedicated to rough high performance machining, were used. The helix angle was changed in the range of 20° to 50° with a step of 5°. During the milling tests, three cutting force components were measured. After each test cutting, chips were collected and analyzed. A recording of the chip evacuation process using a high-speed camera was also conducted. The influence of the helix angle on cutting force components was determined and the mathematical models of the forces were calculated. The significance of coefficients in the obtained equations was analyzed as well. The recorded images of the chip evacuation were analyzed. The displacement and the angle of the chip evacuation were determined. Based on the analysis of the selected images the impact of the helix angle on the direction and evacuation velocity of chips was determined. The size and shape of the obtained chips was also analyzed.