Bioengineered growth factor delivery molecules for vascularisation and wound healing

Chronic wounds, such as those exhibited by diabetic ulcers are a global health issue affecting approximately 3.75 million people worldwide. Chronic wounds are slower to heal, or fail to heal, due to decreased vascularisation among other factors. Growth factors are key signalling molecules which promote wound healing, however, they experience rapid degradation by proteolytic enzymes present in the chronic wound environment. Proteoglycans (PGs) are the natural binding, protective and signalling partners for many growth factors. However, the yield of PGs from natural sources is limited due to their low abundance in tissues and cell cultures. Recombinant DNA technology and metabolic engineering offer alternative PG production methods to increase the yield of PGs and to alter the structure of their glycosaminoglycan (GAG) chains. Serglycin is an intracellular PG, which has eight GAG attachment sites. Unlike other PGs, serglycin can be decorated with heparin, heparan sulphate (HS), chondroitin sulphate (CS) and/or dermatan sulphate (DS). Through these various GAG chains, serglycin present in intracellular granules can bind and release cytokines, chemokines and growth factors, which are ideal properties for growth factor delivery and signalling applications. Thus, this thesis examined the influence of various culture microenvironments on the yield and GAG structure of recombinant serglycin produced by both adherent and suspension mammalian cells. In addition, this thesis explored the ability of recombinant serglycin to support angiogenic growth factor binding and signalling. Adherent human embryonic kidney cells expressing recombinant serglycin (HEK-SGN) cultured in shaker flasks and continuously stirred tank reactors (CSTR) produced more protein decorated with GAGs compared to culture flasks. The cells cultured in CSTR produced more HS/heparin and CS/DS chains compared to the other culture flasks. HEK-SGN cells maintained in medium containing 25 mM glucose achieved the highest yields of protein (1.5 mg/L) and GAGs (1.9 mg/L). The cells maintained in medium containing 5.5 mM glucose produced less GAG chains compared to when these cells were grown in medium containing 25 mM glucose, however, heparin was produced. Suspension HEK-293 cells expressing recombinant serglycin (HEK-S-SGN) were established in this thesis. The presence of serum in the culture medium promoted the suspension cells to adhere during culture. HEK-S-SGN cells maintained in serum free medium produced a 4.6-fold higher yield of protein decorated with HS/heparin compared to the cells maintained in serum containing medium. Recombinant serglycin supported fibroblast growth factor 2 (FGF2) binding in vitro via its HS/heparin chains, while vascular endothelial growth factor 165 (VEGF165) binding was mediated via HS/heparin and CS/DS chains as well as the protein core of serglycin. In addition, recombinant serglycin potentiated FGF2 signalling via its GAG chains and FGF receptor 1c in vitro. Furthermore, recombinant serglycin supported angiogenesis in vivo by potentiating FGF2 and VEGF165 through its HS/heparin chains in the chicken chorioallantoic membrane assay. Thus, this thesis demonstrated that the culture conditions influenced the protein yield and type of GAG chains that decorated recombinant serglycin. In addition, recombinant serglycin was found to support angiogenesis via binding and signalling angiogenic growth factors via its GAG chains. These results suggest the potential of incorporating recombinant serglycin into tissue engineering or regenerative medicine strategies for growth factor-mediated tissue repair applications

Inter-Organizational Information Systems Visibility in Buyer-Supplier Relationships: Buyer and Supplier Perspectives

Many researchers have called for the need to improve the understanding of the concept and working of supply chain visibility. The facilitating role of inter-organizational information systems (IOIS) in achieving SC visibility has received inadequate research attention. This paper is to elaborate on the novel concept of IOIS visibility and to look into the antecedents and consequences of IOIS visibility. Further, investigating SC cooperation from the perspectives of both partners is important, especially when channel partners depend on each other and there can be asymmetries in IOIS visibility. This study attempts to accommodate both partners’ perspectives in IOIS visibility. The data that this study requires were collected from 51 matched pairs of intermediate producers of telecommunication equipment components and their immediate suppliers. The results show that IOIS visibility from the supplier’s perspectives is an important predictor of supply chain performance. In turn, IOIS visibility is significantly influenced by supply chain partner’s internal IS integration and inter-organizational IT infrastructure compatibility. The impact of asymmetries in IOIS visibility on supply chain performance is also investigated

Effect of the characteristics of nylon microparticles on Mode-I interlaminar fracture toughness of carbon-fibre/epoxy composites

Interleaving a laminated composite with thermoplastic particles is known as an effective method to improve the interlaminar fracture toughness. In this work, to provide useful insight into what particle characteristics are the most critical to the toughening effect, the interlaminar fracture behaviours of carbon fibre/epoxy composites interleaved with different types of nylon 6 and 12 particles were investigated in the same range of particle areal weights. The results showed the particle size affects the toughness only when the particle–matrix interfacial bonding is well established, which is related to the curing temperature relative to the melting temperature of the particle. High interfacial bonding strength allowed the particles to be plastically deformed while bridging the crack, and smaller particles were more effective due to the increased density of particle bridging. It was also found that both the particle size and shape affect thickening of the interlayer, which can cause a knockdown of in-plane laminate properties due to the reduced fibre volume fraction.</p

COMBUSTION CHARACTERISTICS AND EMISSION OF HAZARDOUS AIR POLLUTANTS IN COMMERCIAL FLUIDIZED BED COMBUSTORS FOR SEWAGE SLUDGE

Since the disposal of sewage sludge in ocean has been prohibited recently according to London Dumping Convention, technological need for treating sewage sludge safely and efficiently are getting increased in Korea. FBC (Fluidized Bed Combustor) technology has been selected and utilized as one of the alternatives because of combustible content in sludge, on-going process development to maintain the best combustion efficiency, and good heat recovery for energy utilization. In this paper, the process and combustion characteristics of commercially operating FBC incineration plants with the capacity ranging from 50 – 150 tons of sludge per day were investigated by comparing emission data from 4 different plants. Concentrations of hazardous gaseous pollutants (HAPs) such as fine particulate matter, heavy metals, and dioxin from sludge combustion before and after air pollution control devices were measured and analyzed at commercial operating conditions of one typical incinerator. Most of emission data at stack showed under the environmental regulatory limits. Mercury and some heavy metals emission have been reduced significantly as co-beneficial effect since the air pollution control configuration was well arranged and installed to control the regulatory gases such as NOx, SO2, particulates, and dioxin. Sludge, especially generated from industrial plants, contained measurable amounts of acidic materials and heavy metals including Hg. Therefore, such metal emission should receive an attention by monitoring them and further mass balance study for better understanding their fates in the process must proceed in future

Selective uptake of epidermal growth factor-conjugated gold nanoparticle (EGF-GNP) facilitates non-thermal plasma (NTP)-mediated cell death

Non-thermal atmospheric pressure plasma (NTP) has been shown to induce cell death in various mammalian cancer cells. Accumulated evidence also shows that NTP could be clinically used in cancer therapy. However, the current NTP-based applications lack target specificity. Here, a novel method in NTP-mediated cancer therapeutics was described with enhanced target specificity by treating EGF (epidermal growth factor)-conjugated GNP (gold nanoparticle). The treatment with EGF-conjugated GNP complex, followed by NTP irradiation showed selective apoptosis of cells having receptor-mediated endocytosis. NTP triggered gamma-H2AX elevation which is a typical response elicited by DNA damage. These results suggest that EGF-conjugated GNP functions as an important adjuvant which gives target specificity in applications of conventional plasma therapy.111Ysciescopu

Improved Correction of Atmospheric Pressure Data Obtained by Smartphones through Machine Learning

A correction method using machine learning aims to improve the conventional linear regression (LR) based method for correction of atmospheric pressure data obtained by smartphones. The method proposed in this study conducts clustering and regression analysis with time domain classification. Data obtained in Gyeonggi-do, one of the most populous provinces in South Korea surrounding Seoul with the size of 10,000 km2, from July 2014 through December 2014, using smartphones were classified with respect to time of day (daytime or nighttime) as well as day of the week (weekday or weekend) and the user’s mobility, prior to the expectation-maximization (EM) clustering. Subsequently, the results were analyzed for comparison by applying machine learning methods such as multilayer perceptron (MLP) and support vector regression (SVR). The results showed a mean absolute error (MAE) 26% lower on average when regression analysis was performed through EM clustering compared to that obtained without EM clustering. For machine learning methods, the MAE for SVR was around 31% lower for LR and about 19% lower for MLP. It is concluded that pressure data from smartphones are as good as the ones from national automatic weather station (AWS) network

Fibrinogen gamma-A chain precursor in CSF: a candidate biomarker for Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Cerebrospinal fluid (CSF) may be valuable for exploring protein markers for the diagnosis of Alzheimer's disease (AD). The prospect of early detection and treatment, to slow progression, holds hope for aging populations with increased average lifespan. The aim of the present study was to investigate candidate CSF biological markers in patients with mild cognitive impairment (MCI) and AD and compare them with age-matched normal control subjects.</p> <p>Methods</p> <p>We applied proteomics approaches to analyze CSF samples derived from 27 patients with AD, 3 subjects with MCI and 30 controls. The AD group was subdivided into three groups by clinical severity according to clinical dementia rating (CDR), a well known clinical scale for dementia.</p> <p>Results</p> <p>We demonstrated an elevated level of fibrinogen gamma-A chain precursor protein in CSF from patients with mild cognitive impairment and AD compared to the age-matched normal subjects. Moreover, its expression was more prominent in the AD group than in the MCI and correlated with disease severity and progression. In contrast, fibrinogen gamma-A chain precursor protein was detected very low in the age-matched normal group.</p> <p>Conclusion</p> <p>These findings suggest that the CSF level of fibrinogen gamma-A chain precursor may be a candidate biomarker for AD.</p

Anti-CV2/CRMP5 Paraneoplastic Chorea Effectively Managed with Intravenous Amantadine

Background: Paraneoplastic chorea is typically a subacute progressive hyperkinetic movement disorder. The mainstay of treatment is managing the underlying neoplasm. However, the clinical course may be variable, and effective symptomatic management can precede the start of cancer treatment. Case report: A 63-year-old man presented with insidious onset, slowly progressive generalized chorea for 1 year, later diagnosed as anti-CV2/CRMP5 autoantibody positive paraneoplastic chorea. His chorea was markedly improved with intravenous amantadine. Discussion: In patients with anti-CV2/CRMP5 autoantibody-related chorea, sequential follow-up of brain magnetic resonance imaging reveals progression from active inflammation to atrophy. Our report highlights the efficacy of intravenous amantadine in paraneoplastic chorea

17β-estradiol reduces inflammation and modulates antioxidant enzymes in colonic epithelial cells

Background/Aims: Estrogen is known to have protective effect in colorectal cancer development. The aims of this study are to investigate whether estradiol treatment reduces inflammation in CCD841CoN, a female human colonic epithelial cell line and to uncover underlying mechanisms of estradiol effects. Methods: 17 beta-Estradiol (E2) effect was measured by Western blot after inducing inflammation of CCD841CoN by tumor necrosis factor alpha (TNF-alpha). Expression levels of estrogen receptor alpha (ER alpha) and beta (ER beta), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-kappa B), heme oxygenase-1 (HO-1), and NAD(P)H-quinone oxidoreductase-1 (NQO-1) were also evaluated. Results: E2 treatment induced expression of ERO but did not increase that of ER alpha. E2 treatment for 48 hours significantly elevated the expression of anti-oxidant enzymes, HO-1 and NQO-1. TNF-alpha treatment significantly increased the level of activated NF-kappa B (p < 0.05), and this increase was significantly suppressed by treatment of to nM of E2 (p < 0.05). E2 treatment ameliorated TNF-alpha-induced COX-2 expression and decrease of HO-1 expression. 4-(2-phenyl-5,7-bis(trifluoromethyl) pyrazolo(1,5-a)pyrimidin-3-yl)phenol (PHTPP), antagonist of ER beta, removed the inhibitory effect of E2 in the TNF-alpha-induced COX-2 expression (p = 0.05). Conclusions: Estrogen seems to inhibit inflammation in female human colonic epithelial cell lines, through down-regulation of NF-kappa B and COX-2 expression and induction of anti-oxidant enzymes such as HO-1 and NQO-1.