A Preliminary Report on the Role of Lipoxin A4 in Reinstating the Blood-Brain Barrier Integrity in a Rodent Model of Acute Inflammation with Impaired Cerebrovasculature

Background: The blood-brain barrier (BBB) is responsible for maintaining brain homeostasis and ultimately proper neuronal function. Disruption of the BBB, leading to increased BBB permeability, has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and traumatic brain injury (TBI). Lipoxins (LXs) are a class of arachidonate-derived eicosanoids, which are a class of specialized pro-resolving lipid mediators (SPMs). SPMs are known to inhibit immune response through inhibition of cellular infiltration, downregulation of pro-inflammatory mediators and upregulation of anti-inflammatory mediators. Hence, LXs are recognized as “breaking signals” in the inflammatory process. One form of LXs, Lipoxin A4 (LXA4), has been found to decreased production of proinflammatory mediators, inhibit neutrophils chemotaxis and infiltration to the site of injury, and promote the phagocytic clearance of debris by macrophages. Therefore, LXA4 serves a critical role in resolution of inflammatory process by regulating the activation of monocytes and modulating the generation of reactive oxygen species (ROS). Hypothesis: LXA4 treatment reinstates the BBB integrity in a rodent model of acute BBB breakdown and inflammation. Methods: Nine-month-old female Sprague Dawley rats were given an intravenous (IV) injection of 15 mg/kg lipopolysaccharide (LPS) through the tail for inducing acute inflammation and BBB breach. After three hours, the rats were injected with 9 µg/kg LXA4 or Saline (Vehicle control). Four treatment groups were thus developed: LPS only, LPS/LXA4, LXA4 only, and Saline only. Animals were euthanized at 24 hours of LPS treatment and brain samples were processed for paraffin-embedded sections and immunohistochemistry. Sections comprising of hippocampus and cortical regions were selected for detection of impaired BBB as demonstrated by the extravasation of immunoglobulin G (IgG) and IBA1 (microgliosis marker). The area of the cerebral cortex and number of cortical blood vessels presenting with IgG extravasation were estimated and compared between treatment groups. Similarly, IBA1 immunoreactivity was quantified using Color Deconvolution V9 tool of Aperio ImageScope (Leica BIOSYSTEMS). Results: LXA4 treatment following LPS injection demonstrated decrease in the extent of IgG leak compared to LPS only group. Likewise, we observed significant decrease in microgliosis in LPS-LXA4 group compared to LPS only. Conclusion: These preliminary results demonstrate potential beneficial effects of LXA4 in reinstating BBB integrity and reducing neuroinflammation in rat model of acute BBB breach and inflammation

The role of exports in manufacturing pollution in sub–Saharan Africa and South Asia: towards a better trade-environment governance

Based on the gaps and challenges identified through case studies, the report proposes recommendations for Kenya, the United Republic of Tanzania, Bangladesh, and Pakistan along with the main three areas of research: (i) Environmental Law and Public Governance, (ii) Private Sector Governance, and (iii) Life Cycle Assessment. Even though at different stages, the four countries are building diversified economies by developing their industrial sectors. As exports play a significant role in their economic growth, those countries gain from more sustainable manufacturing practices

An experimental investigation into resonance dry grinding of hardened steel and nickel alloys with element of MQL

Current policies on environmental issues put extra pressures on manufacturing processes to be resource efficient and eco-friendly. However, in grinding processes, large amounts of cutting fluids are used. These fluids are not environmental friendly thus require proper management before disposal with associated cost. Hence, this work sets to explore low-frequency vibration in grinding in order to improve coolant application in conventional grinding at the first stage with the aim to introduce this into high efficiency deep grinding (HEDG) at latter stage. An attempt is made to grind nickel alloys with minimum quantity lubricant (MQL) as oppose to flood cooling. To achieve this with minimum alterations to the machine tool, a piezo-driven workpiece holder was developed for surface grinding. This simple innovative workpiece holder allowed oscillating during actual grinding process. However, this paper presents the results of low-frequency oscillatory grinding in dry and near-dry conditions. The response of the machine tool spindle unit is presented alongside with the workpiece holder response. In this investigation, hardened steels and nickel alloys were ground with vibration assistance. The grinding forces are illustrated together with the surface finish. The wheel performance is given in terms of grinding ratio

A line-balancing strategy for designing flexible assembly systems

We present a rough-cut analysis tool that quickly determines a few potential cost-effective designs at the initial design stage of flexible assembly systems (FASs) prior to a detailed analysis such as simulation. It uses quantitative methods for selecting and configuring the components of an FAS suitable for medium to high volumes of several similar products. The system is organized as a series of assembly stations linked with an automated material-handling system moving parts in a unidirectional flow. Each station consists of a single machine or of identical parallel machines. The methods exploit the ability of flexible hardware to switch almost instantaneously from product to product. Our approach is particularly suitable where the product mix is expected to be stable, since we combine the hardware-configuration phase with the task-allocation phase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45513/1/10696_2004_Article_BF00167513.pd

Identification of a biomarker panel for improvement of prostate cancer diagnosis by volatile metabolic profiling of urine

Background: The lack of sensitive and specific biomarkers for the early detection of prostate cancer (PCa) is a major hurdle to improve patient management. Methods: A metabolomics approach based on GC-MS was used to investigate the performance of volatile organic compounds (VOCs) in general and, more specifically, volatile carbonyl compounds (VCCs) present in urine as potential markers for PCa detection. Results: Results showed that PCa patients (n = 40) can be differentiated from cancer-free subjects (n = 42) based on their urinary volatile profile in both VOCs and VCCs models, unveiling significant differences in the levels of several metabolites. The models constructed were further validated using an external validation set (n = 18 PCa and n = 18 controls) to evaluate sensitivity, specificity and accuracy of the urinary volatile profile to discriminate PCa from controls. The VOCs model disclosed 78% sensitivity, 94% specificity and 86% accuracy, whereas the VCCs model achieved the same sensitivity, a specificity of 100% and an accuracy of 89%. Our findings unveil a panel of 6 volatile compounds significantly altered in PCa patients' urine samples that was able to identify PCa, with a sensitivity of 89%, specificity of 83%, and accuracy of 86%. Conclusions: It is disclosed a biomarker panel with potential to be used as a non-invasive diagnostic tool for PCa.info:eu-repo/semantics/publishedVersio

A New Interface for Conceptual Design Based on Object Reconstruction from a Single Freehand Sketch

are troublesome for curvature-based classification, and (b) it has a short execution time that is not dependent on the length of the stroke or the number of sample points acquired (assuming coordinates have been summed while drawing the stroke). The procedure can therefore be used to provide continuous feedback of the interpreted entity during drawing, in real time. However, in spite of this ability, it is evident that geometrical-based classification is inherently limited and a more general, context-sensitive approach must be pursued. A new endpoint clustering scheme has also been presented based on adaptive tolerances at different parts of the sketch. The proposed formulation provides a framework for implementing various criteria for determining local thresholds, such as detail sensitive criteria, dynamic criteria, or other application specific criteria. Again, clustering can be improved using a contextsensitive approach. Acknowledgments This research has been supported in part by the Fund for 4 Pavlidis, T., and Van Wyk, C. J., 1985, "An Automatic Beautifler for Drawings and Illustrations," SIGGRAPH 85, Vol. 19, No. 3, pp. 225-234. 5 Bengi, F., and Ozguc, B., 1990, "Architectural Sketch Recognition," Architectural Science Review, Vol. 33, pp. 3-16. 6 Eggli, L., BrUderlin, B. P., and Elber, G. Introduction Improperly designed engineering products may fail in fatigue causing losses in revenue and personal injury or death. Currently, these failures are avoided by either using expensive design techniques involving extensive modeling and testing or by over designing the part. The expense of testing and modification of the initial design is reduced if the design criterion gives a good initial approximation. Several design approaches have been developed to address the problem of fatigue damage of ductile metals loaded with positive mean and alternating stresses. The Bagci, Gerber, Nichihara, modified Goodman, Quadratic, and Soderberg lines are a few of the techniques that have been proposed to address the problem. This paper presents the modified Findley line for designing parts which experience positive mean stress fatigue loading. The modified Findley line is based on the assumption that the critical shear decreases with an increase in the normal stress acting on the same plane, and is simple and less conservative than the modified Goodman line. The Modified Findley Line Flavenot and Skalli (1984) stated "the mechanism corresponding to the initiation of fatigue cracks is most often the shearing of crystallographic planes. It appears logical then to have a criterion relating the normal stress to alternating shear stress which might be local shear stress in most favorable oriented plane." This assumption was used before by Stanfield (1935), who suggested that both the shear and normal stresses on the fatigue plane should be considered in a fatigue failure criterion and proposed the relation (1) where TN and ON are the shear and normal stresses components on the critical plane; /and k are materials constants. Stulen and Cummings (1954), and Findley et al. (195 6) used similar forms as fatigue criteria to address the problem of absolutely reversing fatigue. Findley (1959) used the linear relationship between shear stress and normal stress on a critical plane to include the effect of mean stress on the fatigue of metals under combined loading. Journal of Mechanical Design MARCH 1997, Vol. 119/135 Copyright © 1997 by ASME where a^^" and <7" are the maximum and alternating fatigue stresses; / and k are experimental constants. Since these constants may vary with the design parameters, including materials, the actual design must be tested to determine the values of / and k. To experimentally find the values of these constants, the life of the part is determined, and at this point the values of / and k are of only academic interest. Thus, if the fatigue criterion presented in Eq. It should be noted that the negative root of Eq. Upon the application of condition (b), Eq. (4) becomes /=A:5",. Equations Substituting Eqs. 5" -[-S" + 4SI + 4(5", -5")(S", -a") ], (10) 2(5",-5") which is called the modified Findley line. Comparison With Actual Experimental Data The modified Findley, Gerber, and modified Goodman lines were compared with the experimentally developed fatigue data found in the literature. Typical data showing the fatigue points of both ferrous and non-ferrous ductile materials are shown in As shown in these figures and comparison done by Wang (1995), the modified Findley line falls between the modified Goodman line and Gerber parabola, which is supported by Conclusion The modified Findley line is based on the assumption that the critical shear decreases with an increase in the normal stress acting on the same plane, then by using ultimate strength and endurance limit as parameters to obtain a good initial approximation. Limited fatigue data is available in the open literature, and more comparison should be made before the modified Findley line is universally adopted. However, form the references found, it appears that the modified Findley line is a strong candidate for .fatigue criterion for parts made of non-ferrous ductile materials, and is conservative for ferrous parts. For a design engineer, the modified Findley line is simple and easy to use, and represents a very promising approach for leading to reasonable starting designs involving positive mean stress fatigue. Reference