Modulation of inflammatory pathway by inflammatory inhibitor JSH-23 mitigates diabetic retinopathy.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM). Its pathology is consisted of the breakdown of the blood-retinal barrier (BRB), particularly the inner blood-retinal barrier (iBRB). The exact mechanism that leads to the iBRB impairment and the development of DR has not been elucidated yet. However, chronic inflammation that is hallmark of the type I DM has recently become a key focus in DR study. Hyperglycemia causes dysregulation of nuclear factor-kappa B (NF-kB); and its constant activation increases the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and intercellular adhesion molecule-1 (ICAM-1) in the retina and vitreous of DR patients and animal models. This increase in inflammatory mediators leads to the degradation of junctional molecules, occludin, connexin-43, death of retinal cells via pyroptosis, and thus disruption of the iBRB. Derailment of the iBRB induces fluid accumulation into the retina of DR patients, which eventually progresses into vision impairment. The purpose of this study is to investigate whether chronic inflammation in DM induces disruption of iBRB; and whether inhibition of the expression and activity of NF-kB by Methyl-N1-(3-phenyl propyl) benzene-1, 2-diamine (JSH-23) would mitigate this iBRB disruption. Methods: Type 1 diabetic mouse model (Akita) on a C57BL/6J background along with non-diabetic littermate were used in the experiments. All mice were 22-24 weeks of age at the start of the experiments. The experimental and the control animals were treated for four weeks on alternate days with JSH-23 @5mg/Kg body weight. The intraocular pressure (IOP), blood pressure, blood glucose, and body weights of all animals were measured before and after treatment. Fluorescence angiography (FA), optical coherence tomography (OCT), and dark-adapted electroretinogram were performed before and after the treatment. Also, intraperitoneal glucose tolerance test (GTT) were performed in the animals before and after the treatment. Then, the retinas and plasma were collected. Western blotting and real-time polymerase chain reaction were performed to analyze protein expression and the mRNA levels of NF-kB p65, iNOS, COX-2, ICAM-1, occludin, connexin-43, NLRP3, caspase-1, and IL-1b. Additionally, plasma insulin levels were also analyzed via ELISA kit. Results: The body weight of Akita mice was significantly lower than the C57BL/6J mice. The treatment with JSH-23 did not have any effect on body weight. The blood glucose of Akita mice was significantly higher than the blood glucose of non-diabetic littermate control mice. The treatment substantially decreased blood glucose in Akita mice. Also, the plasma insulin level for the Akita mice was significantly lower compared to non-diabetic littermate control mice. The intraperitoneal GTT showed that the Akita mice were unable to lower their blood glucose levels. The total and phosphorylated protein expression levels of NF-kB p65 were significantly decreased after treatment with JSH-23 in Akita mice, and the gene expression of NF-kB p65 also reduced. The protein and gene expression levels of iNOS, COX-2, and ICAM-1 were reduced after treatment in Akita mice, and the treatment significantly lowered the expression of pyroptosis marker NLRP3. The gene expression of other proteins in the pyroptosis pathway were also reduced, including caspase-1 and IL-1b. On the other hand, the protein and gene expression levels of junctional molecules occludin, connexin-43 were significantly increased in Akita mice after treatment with JSH-23. The blood pressure of the animals was normal and the treatment did not have any effect on the blood pressure. FA depicted an increase in retinal capillary permeability in Akita mice, and the treatment significantly reduced that permeability. The OCT showed retinal layers thickening in the retina of Akita mice, and treatment increased the retinal layers thickness. Electroretinogram (ERG) showed an increase in the amplitude of the A-wave and the B-wave in Akita mice. Conclusions: The results showed that inhibitor (JSH-23) improved visual function by decreasing the retinal vascular permeability, IOP, and the retinal inflammation in Akita mice

Shedding Light with Trees

This multidisciplinary capstone project focuses on education of the benefits of trees to incentivize the planting of trees at stakeholder homes or businesses. The approach of taking individual action to address a large-scale issue is also highlighted as a qualitative aspect of the capstone. The goal of the project is to understand the benefits of trees, plant more trees and to utilize the approach taken to address other large-scale issues in the future. Global warming is a complex worldwide problem. The scope of the issue can be paralyzing, stymieing individual action. Tainter (2000, p 6) discusses our general aversion to complexity and states the reason behind sayings like “Keeping it simple” is universally understood. This capstone proceeds in that vein. The planting of trees at a stakeholder’s home or business provides a means to take a simple step to address a global issue on a manageable individual scale. Providing factual substantiated information about the environmental, health, and financial benefits of trees will serve as incentive to participate in the tree planting campaign

«I Do Not Understand the United States» Exploring why the gun issue is still so controversial, and why it is so difficult to enforce meaningful legislation in the wake of recent mass shootings

Master´s thesis in English (EN501

Fluid Milk or Cream for Iowa Creameries?

Iowa\u27s milk marketing machinery is being overhauled. It appears that more of Iowa\u27s milk can profitably enter fluid milk channels- because of changes in demand for dairy products, because of the rapid technical developments in processing and distributing milk and because of the development of substitutes for skimmilk in livestock feeding

Improving on-time delivery at Aker Solutions : a case study of the Spare Parts division

Masteroppgave i industriell økonomi og teknologiledelse IND 590 Universitetet i Agder 2014The purpose of this thesis is to present possible solutions to how Aker Solutions’ Spare Parts division can improve their on-time delivery. This thesis is a case study that focuses mainly on the supply chain of the Spare Parts division and not the entire organization. Spare Parts’ main task is to provide spare parts to customers. The process of providing the spare parts can involve both internal and external factors. The internal processes include the Procurement division if the items aren’t on stock, and warehouse for picking and packing. The external processes include the suppliers that provide Aker Solutions with the products they are selling to their customers. An increasing competition in the oil and gas industry has led to a stronger focus on achieving a competitive advantage over its competitors. For the Spare Parts division, competitive advantage can be obtained when increasing the on-time delivery and the reliability of the delivery dates given to the customer. Since the effects of having downtime in the drilling activity is much more cost heavy, than paying for an overpriced spare part, a factor such as price is not the most important. The important element is to have the spare parts delivered in a reliable and effective manner. Considering that Aker Solutions’ competition also provides most of the same products/services to the same prices, the focus has to be elsewhere than cost when you want to achieve a competitive advantage. The theory of the thesis focuses on competitive advantage, process improvement- and supplier performance. Insight in a typical process map and how it can be improved has been given, with the use of the tool process mapping. The process map theory has been strengthened with the lean philosophy. The supplier performance theory is mainly based on an article from Tom Davis, a technology manager at Hewlett-Packard. The article describes the uncertainties in a supply chain network. Furthermore, researchers input on how to improve supplier performance, as well as Kraljic´s matrix on how to categorize and work with your suppliers is also described. Method The thesis is focused around a case study of Aker Solutions’ Spare Parts division, a study that includes both qualitative and quantitative method. To strengthen reliability and validity of the collected data, interviews, a workshop and a survey have been used. Data has been collected from the ERP-system SAP, with the purpose of obtaining insight regarding suppliers, orders and customers. Results The results of the thesis involves two areas: supplier performance and process improvement. Supplier performance laid ground for a priority list of the 10 worst suppliers. The list contains comments, suggested focus and action for these 10 suppliers. These results come from an analysis of a specific selection of suppliers in the Spare Parts division that has room for improvement, with regards to raw-data analysis, Kraljic’s matrix analysis and survey results. The approach regarding process improvement led to an improved process map for Spare Parts. The process map was improved through several steps, starting with Spare Parts current process map. The idea was to make the map as accessible as possible, have the map reflect upon the processes as they really are, and to have all involved divisions on the same map. Since the total process of providing customers with spare parts also includes other divisions, it is important to have the map include those processes as well

What Is Bulk Milk Handling?

The bulk-tank cooling system offers so many advatages so many advantages is quality and efficiency that its eventual adoption for market milk appears certain. However, the problem of the small producer still remains unsolved