Mitigating uncertainty in logistics outsourcing with ERP systems

Outsourcing is a common strategy for companies looking for cost savings and improvements in performance. This has been especially prevalent in logistics, where warehousing and transporting are typical targets for outsourcing. However, while the benefits from logistics outsourcing are clear on paper, there are several cases companies fail to reach these benefits. The most commonly cited reasons for this are poor information flow between the company and the third party logistics partner, and a lack of integration between the two partners. Uncertainty stems from lack of information, and it can cripple the whole outsourcing operation. This is where enterprise resource planning (ERP) systems step in, as they can have a significant role in improving the flow of information, and integration, which consequently mitigates uncertainty. The purpose of the study is to examine if ERP systems have an effect on a company's decision to outsource logistics operations. Along the rapid advancements in technology during the past decades, ERP systems have also evolved. Therefore, empirical research on the subject needs constant revision as it can quickly become outdated due to ERP systems having more advanced capabilities every year. The research was conducted using a qualitative single-case study of a Finnish manufacturing firm that had outsourced warehousing and transportation operations in the Swedish market. The empirical data was gathered with use of semi-structured interviews with three employees from the case company that were closely related to the outsourcing operation. The theoretical framework that was used to analyze the empirical data was based on Transaction Cost Economics theory. The results of the study were align with the theoretical framework, in that the ERP system of the case company was seen as an enabler for their logistics outsourcing operation. However, the full theoretical benefits from ERP systems concerning extended enterprise functionality and flexibility were not attained due to the case company having an older version of their ERP system. This emphasizes the importance of having up-to-date technology if you want to overcome the shortcomings of ERP systems in outsourcing situations.

Biomedical Event Extraction with Machine Learning

Biomedical natural language processing (BioNLP) is a subfield of natural language processing, an area of computational linguistics concerned with developing programs that work with natural language: written texts and speech. Biomedical relation extraction concerns the detection of semantic relations such as protein-protein interactions (PPI) from scientific texts. The aim is to enhance information retrieval by detecting relations between concepts, not just individual concepts as with a keyword search. In recent years, events have been proposed as a more detailed alternative for simple pairwise PPI relations. Events provide a systematic, structural representation for annotating the content of natural language texts. Events are characterized by annotated trigger words, directed and typed arguments and the ability to nest other events. For example, the sentence “Protein A causes protein B to bind protein C” can be annotated with the nested event structure CAUSE(A, BIND(B, C)). Converted to such formal representations, the information of natural language texts can be used by computational applications. Biomedical event annotations were introduced by the BioInfer and GENIA corpora, and event extraction was popularized by the BioNLP'09 Shared Task on Event Extraction. In this thesis we present a method for automated event extraction, implemented as the Turku Event Extraction System (TEES). A unified graph format is defined for representing event annotations and the problem of extracting complex event structures is decomposed into a number of independent classification tasks. These classification tasks are solved using SVM and RLS classifiers, utilizing rich feature representations built from full dependency parsing. Building on earlier work on pairwise relation extraction and using a generalized graph representation, the resulting TEES system is capable of detecting binary relations as well as complex event structures. We show that this event extraction system has good performance, reaching the first place in the BioNLP'09 Shared Task on Event Extraction. Subsequently, TEES has achieved several first ranks in the BioNLP'11 and BioNLP'13 Shared Tasks, as well as shown competitive performance in the binary relation Drug-Drug Interaction Extraction 2011 and 2013 shared tasks. The Turku Event Extraction System is published as a freely available open-source project, documenting the research in detail as well as making the method available for practical applications. In particular, in this thesis we describe the application of the event extraction method to PubMed-scale text mining, showing how the developed approach not only shows good performance, but is generalizable and applicable to large-scale real-world text mining projects. Finally, we discuss related literature, summarize the contributions of the work and present some thoughts on future directions for biomedical event extraction. This thesis includes and builds on six original research publications. The first of these introduces the analysis of dependency parses that leads to development of TEES. The entries in the three BioNLP Shared Tasks, as well as in the DDIExtraction 2011 task are covered in four publications, and the sixth one demonstrates the application of the system to PubMed-scale text mining.

Value-based Reference Marketing in a Small Process Industry Software and Service Company

This master’s thesis was done for a small company, Vipetec Oy, which offers specialized technological services for companies mainly in forest industry. The study was initiated partly because the company wants to expand its customer base to a new industry. There were two goals connected to each other. First was to find out how much and what kind of value current customers have realized from ATA Process Event Library, one of the products that the company offers. Second was to determine the best way to present this value and its implications for future value potential to both current and potential customers. ATA helps to make grade and product changes, starting after machine downtime, and recovery from production break faster for customers. All three events sometimes occur in production line. The faster operation results to savings in time and material. In addition to ATA Vipetec also offers other services related to development of automation and optimization of controls. Theoretical part concentrates on the concept of value, how it can be delivered to customers, and what kind of risk customer faces in industrial purchasing. Also the function of reference marketing towards customers is discussed. In the empirical part the realized value for existing customers is evaluated based on both numerical data and interviews. There’s also a brief case study about one customer. After that the value-based reference marketing for a target industry is examined through interviews of these potential customers. Finally answers to the research questions are stated and compared also to the theoretical knowledge about the subject. Results show that those customers’ machines which use the full service concept of ATA usually are able to save more time and material than the machines which use only some features of the product. Interviews indicated that sales arguments which focus on improved competitive status are not as effective as current arguments which focus on numerical improvements. In the case of potential customers in the new industry, current sales arguments likely work best for those whose irregular production situations are caused mainly by fault situations. When the actions of Vipetec were compared to ten key elements of creating customer references, it was seen that many of them the company has either already included in its strategy or has good chances to include them with the help of the results of this study.

The neural processes generating visual phenomenal consciousness: ERP and neuronavigated brain stimulation studies

One of the greatest conundrums to the contemporary science is the relation between consciousness and brain activity, and one of the specifi c questions is how neural activity can generate vivid subjective experiences. Studies focusing on visual consciousness have become essential in solving the empirical questions of consciousness. Th e main aim of this thesis is to clarify the relation between visual consciousness and the neural and electrophysiological processes of the brain. By applying electroencephalography and functional magnetic resonance image-guided transcranial magnetic stimulation (TMS), we investigated the links between conscious perception and attention, the temporal evolution of visual consciousness during stimulus processing, the causal roles of primary visual cortex (V1), visual area 2 (V2) and lateral occipital cortex (LO) in the generation of visual consciousness and also the methodological issues concerning the accuracy of targeting TMS to V1. Th e results showed that the fi rst eff ects of visual consciousness on electrophysiological responses (about 140 ms aft er the stimulus-onset) appeared earlier than the eff ects of selective attention, and also in the unattended condition, suggesting that visual consciousness and selective attention are two independent phenomena which have distinct underlying neural mechanisms. In addition, while it is well known that V1 is necessary for visual awareness, the results of the present thesis suggest that also the abutting visual area V2 is a prerequisite for conscious perception. In our studies, the activation in V2 was necessary for the conscious perception of change in contrast for a shorter period of time than in the case of more detailed conscious perception. We also found that TMS in LO suppressed the conscious perception of object shape when TMS was delivered in two distinct time windows, the latter corresponding with the timing of the ERPs related to the conscious perception of coherent object shape. Th e result supports the view that LO is crucial in conscious perception of object coherency and is likely to be directly involved in the generation of visual consciousness. Furthermore, we found that visual sensations, or phosphenes, elicited by the TMS of V1 were brighter than identically induced phosphenes arising from V2. Th ese fi ndings demonstrate that V1 contributes more to the generation of the sensation of brightness than does V2. Th e results also suggest that top-down activation from V2 to V1 is probably associated with phosphene generation. The results of the methodological study imply that when a commonly used landmark (2 cm above the inion) is used in targeting TMS to V1, the TMS-induced electric fi eld is likely to be highest in dorsal V2. When V1 was targeted according to the individual retinotopic data, the electric fi eld was highest in V1 only in half of the participants. Th is result suggests that if the objective is to study the role of V1 with TMS methodology, at least functional maps of V1 and V2 should be applied with computational model of the TMS-induced electric fi eld in V1 and V2. Finally, the results of this thesis imply that diff erent features of attention contribute diff erently to visual consciousness, and thus, the theoretical model which is built up of the relationship between visual consciousness and attention should acknowledge these diff erences. Future studies should also explore the possibility that visual consciousness consists of several processing stages, each of which have their distinct underlying neural mechanisms.

Potential for Greenhouse Gas Emission Reductions by Using Biomethane as a Road Transportation Fuel

The aim of this thesis is to study whether the use of biomethane as a transportation fuel is reasonable from climate change perspective. In order to identify potentials and challenges for the reduction of greenhouse gas (GHG) emissions, this dissertation focuses on GHG emission comparisons, on feasibility studies and on the effects of various calculation methodologies. The GHG emissions calculations are carried out by using life cycle assessment (LCA) methodologies. The aim of these LCA studies is to figure out the key parameters affecting the GHG emission saving potential of biomethane production and use and to give recommendations related to methodological choices. The feasibility studies are also carried out from the life cycle perspective by dividing the biomethane production chain for various operators along the life cycle of biomethane in order to recognize economic bottlenecks. Biomethane use in the transportation sector leads to GHG emission reductions compared to fossil transportation fuels in most cases. In addition, electricity and heat production from landfill gas, biogas or biomethane leads to GHG reductions as well. Electricity production for electric vehicles is also a potential route to direct biogas or biomethane energy to transportation sector. However, various factors along the life cycle of biomethane affect the GHG reduction potentials. Furthermore, the methodological selections have significant effects on the results. From economic perspective, there are factors related to different operators along the life cycle of biomethane, which are not encouraging biomethane use in the transportation sector. To minimize the greenhouse gas emissions from the life cycle of biomethane, waste feedstock should be preferred. In addition, energy consumption, methane leakages, digestate utilization and the current use of feedstock or biogas are also key factors. To increase the use of biomethane in the transportation sector, political steering is needed to improve the feasibility for the operators. From methodological perspective, it is important to recognize the aim of the life cycle assessment study. The life cycle assessment studies can be divided into two categories: 1.) To produce average GHG information of biomethane to evaluate the acceptability of biomethane use compared to fossil transportation fuels. 2.) To produce GHG information of biomethane related to actual decision-making situations. This helps to figure out the actual GHG emission changes in cases when feedstock, biogas or biomethane are already in other use. For example directing biogas from electricity production to transportation use does not necessarily lead to additional GHG emission reductions. The use of biomethane seems to have a lot of potential for the reduction of greenhouse gas emissions as a transportation fuel. However, there are various aspects related to production processes, to the current use of feedstock or biogas and to the feasibility that have to be taken into account.

Metsäteollisuuden puunhankinnan ohjaus: Hankintalähteen kannattavuus ja siihen vaikuttavat tekijät

Tutkielmassa rakennettiin laskentamalli metsäteollisuuden puunhankinnan hankintalähteen kannattavuuden määrittämiseksi ja selittämiseksi. Tutkimuksessa noudatettiin konstruktiivisen tapaustutkimuksen tutkimusotetta. Tutkimuksen kohdeorganisaationa oli kansainvälisesti toimivan metsäteollisuusyrityksen Suomen puunhankintaorganisaatio. Kannattavuusmalli määrittelee hankintalähteen kannattavuuden sekä käsitteellisellä että laskentamenettelyn tasolla. Kannattavuusmallin katesuure on porttikate, joka rakennettiin taloudellisen lisäarvon teoriaan nojaten kohdeorganisaation tarpeiden ja sen laskenta-asiantuntijoiden näkemysten perusteella. Kannattavuusmallin rakenne ja osat kuvattiin seikkaperäisesti. Kannattavuusmallin käyttämän liiketoimintadatan poiminta ja laskentasuureiden raportointi testattiin. Mallin tarvitsemat laskentatiedot on saatavissa kohdeorganisaation kehitteillä olevasta toiminnanohjausjärjestelmästä. Laskentamallin hyödyntämismahdollisuudet arvioitiin. Hankintalähteen kannattavuutta mittaavalla porttikatteella voidaan ohjata puunhankintaorganisaatiota sen tavoitteiden saavuttamisessa. Malli ilmaisee porttikatteeseen vaikuttavien tekijöiden vaikutuksen kannattavuuteen, minkä avulla voidaan tehdä parempia päätöksiä hankintalähteiden hyödyntämisessä. Aiemmista tutkimuksista poiketen malli huomioi hankintalähteen suoritteen arvon tärkeimmille asiakastehtaille perustuen todellisiin liiketapahtumiin. Kannattavuusmallia voidaan hyödyntää laajalti metsäteollisuusyritysten tavaralajimenetelmään perustuvassa puunhankinnassa. Kannattavuusmallin rakentaminen rohkaisee puunhankinnan johtoa ja laskentahenkilöitä hedelmällisen yhteistyöhön.

Abnormal proliferative response of the carotid artery of spontaneously hypertensive rats after angioplasty may be related to the depolarized state of its smooth muscle cells

Hypertension is one of the major precursors of atherosclerotic vascular disease, and vascular smooth muscle abnormal cell replication is a key feature of plaque formation. The present study was conducted to examine the relationship between hypertension and smooth muscle cell proliferation after balloon injury and to correlate neointima formation with resting membrane potential of uninjured smooth muscle cells, since it has been suggested that altered vascular function in hypertension may be related to the resetting of the resting membrane potential in spontaneously hypertensive rats (SHR). Neointima formation was induced by balloon injury to the carotid arteries of SHR and renovascular hypertensive rats (1K-1C), as well as in their normotensive controls, i.e., Wistar Kyoto (WKY) and normal Wistar (NWR) rats. After 14 days the animals were killed and the carotid arteries were submitted to histomorphometric and immunohistochemical analyses. Resting membrane potential measurements showed that uninjured carotid arteries from SHR smooth muscle cells were significantly depolarized (-46.5 ± 1.9 mV) compared to NWR (-69 ± 1.4 mV), NWR 1K-1C (-60.8 ± 1.6 mV), WKY (-67.1 ± 3.2 mV) and WKY 1K-1C (-56.9 ± 1.2 mV). The SHR arteries responded to balloon injury with an enhanced neointima formation (neo/media = 3.97 ± 0.86) when compared to arteries of all the other groups (NWR 0.93 ± 0.65, NWR 1K-1C 1.24 ± 0.45, WKY 1.22 ± 0.32, WKY 1K-1C 1.15 ± 0.74). Our results indicate that the increased fibroproliferative response observed in SHR is not related to the hypertensive state but could be associated with the resetting of the carotid smooth muscle cell resting membrane potential to a more depolarized state.

Evaluating land-use related environmental impacts of biomass value chains for decision-support : Comparison and testing of methodologies proposed for environmental life cycle assessment

Life cycle assessment (LCA) is one of the most established quantitative tools for environmental impact assessment of products. To be able to provide support to environmentally-aware decision makers on environmental impacts of biomass value-chains, the scope of LCA methodology needs to be augmented to cover landuse related environmental impacts. This dissertation focuses on analysing and discussing potential impact assessment methods, conceptual models and environmental indicators that have been proposed to be implemented into the LCA framework for impacts of land use. The applicability of proposed indicators and impact assessment frameworks is tested from practitioners' perspective, especially focusing on forest biomass value chains. The impacts of land use on biodiversity, resource depletion, climate change and other ecosystem services is analysed and discussed and the interplay in between value choices in LCA modelling and the decision-making situations to be supported is critically discussed. It was found out that land use impact indicators are necessary in LCA in highlighting differences in impacts from distinct land use classes. However, many open questions remain on certainty of highlighting actual impacts of land use, especially regarding impacts of managed forest land use on biodiversity and ecosystem services such as water regulation and purification. The climate impact of energy use of boreal stemwood was found to be higher in the short term and lower in the long-term in comparison with fossil fuels that emit identical amount of CO2 in combustion, due to changes implied to forest C stocks. The climate impacts of energy use of boreal stemwood were found to be higher than the previous estimates suggest on forest residues and stumps. The product lifetime was found to have much higher influence on the climate impacts of woodbased value chains than the origin of stemwood either from thinnings or final fellings. Climate neutrality seems to be likely only in the case when almost all the carbon of harvested wood is stored in long-lived wooden products. In the current form, the land use impacts cannot be modelled with a high degree of certainty nor communicated with adequate level of clarity to decision makers. The academia needs to keep on improving the modelling framework, and more importantly, clearly communicate to decision-makers the limited certainty on whether land-use intensive activities can help in meeting the strict mitigation targets we are globally facing.

Curcumin induces human HT-29 colon adenocarcinoma cell apoptosis by activating p53 and regulating apoptosis-related protein expression

Curcumin, a major yellow pigment and active component of turmeric, has multiple anti-cancer properties. However, its molecular targets and mechanisms of action on human colon adenocarcinoma cells are unknown. In the present study, we examined the effects of curcumin on the proliferation of human colon adenocarcinoma HT-29 cells by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method and confirmed the curcumin-induced apoptosis by morphology and DNA ladder formation. At the same time, p53, phospho-p53 (Ser15), and other apoptosis-related proteins such as Bax, Bcl-2, Bcl-xL, pro-caspase-3, and pro-caspase-9 were determined by Western blot analysis. The colon adenocarcinoma cells were treated with curcumin (0-75 µM) for 0-24 h. We observed that p53 was highly expressed in HT-29 cells and curcumin could up-regulate the serine phosphorylation of p53 in a time- and concentration-dependent manner. An increase in expression of the pro-apoptotic factor Bax and a decrease in expression of the anti-apoptotic factor Bcl-2 were also observed in a time-dependent manner after exposure of 50 µM curcumin, while the expression of the anti-apoptotic factor Bcl-xL was unchanged. Curcumin could also down-regulate the expression of pro-caspase-3 and pro-caspase-9 in a time-dependent manner. These data suggest a possible underlying molecular mechanism whereby curcumin could induce the apoptosis signaling pathway in human HT-29 colon adenocarcinoma cells by p53 activation and by the regulation of apoptosis-related proteins. This property of curcumin suggests that it could have a possible therapeutic potential in colon adenocarcinoma patients.

Transient outward potassium current and Ca2+ homeostasis in the heart: beyond the action potential

Normal central nervous system development relies on accurate intrinsic cellular programs as well as on extrinsic informative cues provided by extracellular molecules. Migration of neuronal progenitors from defined proliferative zones to their final location is a key event during embryonic and postnatal development. Extracellular matrix components play important roles in these processes, and interactions between neurons and extracellular matrix are fundamental for the normal development of the central nervous system. Guidance cues are provided by extracellular factors that orient neuronal migration. During cerebellar development, the extracellular matrix molecules laminin and fibronectin give support to neuronal precursor migration, while other molecules such as reelin, tenascin, and netrin orient their migration. Reelin and tenascin are extracellular matrix components that attract or repel neuronal precursors and axons during development through interaction with membrane receptors, and netrin associates with laminin and heparan sulfate proteoglycans, and binds to the extracellular matrix receptor integrins present on the neuronal surface. Altogether, the dynamic changes in the composition and distribution of extracellular matrix components provide external cues that direct neurons leaving their birthplaces to reach their correct final location. Understanding the molecular mechanisms that orient neurons to reach precisely their final location during development is fundamental to understand how neuronal misplacement leads to neurological diseases and eventually to find ways to treat them.

An examination of factors influencing ERP key-user satisfaction: A qualitative case study

Several companies are trying to improve their operation efficiency by implementing an enterprise resource planning (ERP) system that makes it possible to control the resources of the company in real time. However, the success of the implementation project is not a foregone conclusion; a significant part of these projects end in a failure, one way or another. Therefore it is important to investigate ERP system implementation more closely in order to increase understanding about factors influencing ERP system success and to improve the probability of a successful ERP implementation project. Consequently, this study was initiated because a manufacturing case company wanted to review the success of their ERP implementation project. To be exact, the case company hoped to gain both information about the success of the project and insight for future implementation improvement. This study investigated ERP success specifically by examining factors that influence ERP key-user satisfaction. User satisfaction is one of the most commonly applied indicators of information system success. The research data was mainly collected by conducting theme interviews. The subjects of the interviews were six key-users of the newly implemented ERP system. The interviewees were closely involved in the implementation project. Furthermore, they act as representative users that utilize the new system in everyday business processes. The collected data was analyzed by thematizing. Both data collection and analysis were guided by a theoretical frame of reference. This frame was based on previous research on the subject. The results of the study aligned with the theoretical framework to large extent. The four principal factors influencing key-user satisfaction were change management, contractor service, key-user’s system knowledge and characteristics of the ERP product itself. One of the most significant contributions of the research is that it confirmed the existence of a connection between change management and ERP key-user satisfaction. Furthermore, it discovered two new sub-factors influencing contractor service related key-user satisfaction. In addition, the research findings indicated that in order to improve the current level of key-user satisfaction, the case company should pay special attention to system functionality improvement and enhancement of the key-users’ knowledge. During similar implementation projects in the future, it would be important to assure the success of change management and contractor service related processes.

Fuzzy real option analysis in patent related decision making and patent valuation

The shift towards a knowledge-based economy has inevitably prompted the evolution of patent exploitation. Nowadays, patent is more than just a prevention tool for a company to block its competitors from developing rival technologies, but lies at the very heart of its strategy for value creation and is therefore strategically exploited for economic pro t and competitive advantage. Along with the evolution of patent exploitation, the demand for reliable and systematic patent valuation has also reached an unprecedented level. However, most of the quantitative approaches in use to assess patent could arguably fall into four categories and they are based solely on the conventional discounted cash flow analysis, whose usability and reliability in the context of patent valuation are greatly limited by five practical issues: the market illiquidity, the poor data availability, discriminatory cash-flow estimations, and its incapability to account for changing risk and managerial flexibility. This dissertation attempts to overcome these impeding barriers by rationalizing the use of two techniques, namely fuzzy set theory (aiming at the first three issues) and real option analysis (aiming at the last two). It commences with an investigation into the nature of the uncertainties inherent in patent cash flow estimation and claims that two levels of uncertainties must be properly accounted for. Further investigation reveals that both levels of uncertainties fall under the categorization of subjective uncertainty, which differs from objective uncertainty originating from inherent randomness in that uncertainties labelled as subjective are highly related to the behavioural aspects of decision making and are usually witnessed whenever human judgement, evaluation or reasoning is crucial to the system under consideration and there exists a lack of complete knowledge on its variables. Having clarified their nature, the application of fuzzy set theory in modelling patent-related uncertain quantities is effortlessly justified. The application of real option analysis to patent valuation is prompted by the fact that both patent application process and the subsequent patent exploitation (or commercialization) are subject to a wide range of decisions at multiple successive stages. In other words, both patent applicants and patentees are faced with a large variety of courses of action as to how their patent applications and granted patents can be managed. Since they have the right to run their projects actively, this flexibility has value and thus must be properly accounted for. Accordingly, an explicit identification of the types of managerial flexibility inherent in patent-related decision making problems and in patent valuation, and a discussion on how they could be interpreted in terms of real options are provided in this dissertation. Additionally, the use of the proposed techniques in practical applications is demonstrated by three fuzzy real option analysis based models. In particular, the pay-of method and the extended fuzzy Black-Scholes model are employed to investigate the profitability of a patent application project for a new process for the preparation of a gypsum-fibre composite and to justify the subsequent patent commercialization decision, respectively; a fuzzy binomial model is designed to reveal the economic potential of a patent licensing opportunity.

The cytotoxicity of methacryloxylethyl cetyl ammonium chloride, a cationic antibacterial monomer, is related to oxidative stress and the intrinsic mitochondrial apoptotic pathway

Antibacterial monomers incorporated in dentin bonding systems may have toxic effects on the pulp. Thus, the cytotoxicity of antibacterial monomers and its underlying mechanisms must be elucidated to improve the safety of antibacterial monomer application. The influence of an antibacterial monomer, methacryloxylethyl cetyl ammonium chloride (DMAE-CB), on the vitality of L929 mouse fibroblasts was tested using MTT assay. Cell cycle progression was studied using flow cytometry. Production of intracellular reactive oxygen species (ROS) after DMAE-CB treatment was measured using 2,7-dichlorodihydrofluorescein diacetate staining and flow cytometry analysis. Loss of mitochondrial membrane potential, disturbance of Bcl-2 and Bax expression, as well as release of cytochrome C were also measured using flow cytometry analysis or Western blot to explore the possible involvement of the mitochondrial-related apoptotic pathway. DMAE-CB elicited cell death in a dose-dependent manner and more than 50% of cells were killed after treatment with 30 µM of the monomer. Both necrosis and apoptosis were observed. DMAE-CB also induced G1- and G2-phase arrest. Increased levels of intracellular ROS were observed after 1 h and this overproduction was further enhanced by 6-h treatment with the monomer. DMAE-CB may cause apoptosis by disturbing the expression of Bcl-2 and Bax, reducing the mitochondrial potential and inducing release of cytochrome C. Taken together, these findings suggest that the toxicity of the antibacterial monomer DMAE-CB is associated with ROS production, mitochondrial dysfunction, cell cycle disturbance, and cell apoptosis/necrosis.

Circulating levels of inflammation-associated miR-155 and endothelial-enriched miR-126 in patients with end-stage renal disease

Circulating microRNAs (miRNAs) may represent a potential noninvasive molecular biomarker for various pathological conditions. Moreover, the detection of circulating miRNAs can provide important novel disease-related information. In particular, inflammation-associated miR-155 and endothelial-enriched miR-126 are reported to be associated with vascular homeostasis. Vascular damage is a common event described in end-stage renal disease (ESRD). We hypothesized that miR-155 and miR-126 may be detectable in the circulation and serve as potential biomarkers for risk stratification. In this study, we assessed miR-155 and miR-126 in the plasma of 30 ESRD patients and 20 healthy controls using real-time quantification RT-PCR. The circulating levels of miR-155 and miR-126 were significantly reduced in patients with ESRD compared to healthy controls. However, there was no significant difference of circulating miR-155 and miR-126 levels between prehemodialysis and posthemodialysis patients. Furthermore, both circulating miR-126 and miR-155 correlated positively with estimated glomerular filtration rate (miR-126: r = 0.383, P = 0.037; miR-155: r = 0.494, P = 0.006) and hemoglobin (miR-126: r = 0.515, P = 0.004; miR-155: r = 0.598, P < 0.001) and correlated inversely with phosphate level (miR-126: r = -0.675, P < 0.001; miR-155: r = -0.399, P = 0.029). Pearson’s correlation was used to compare circulating levels of miRNAs with clinical parameters. These results suggested that circulating miR-155 and miR-126 might be involved in the development of ESRD. Further studies are needed to demonstrate the role of circulating miR-155 and miR-126 as candidate biomarkers for risk estimation.

ERKs and mitochondria-related pathways are essential for glycyrrhizic acid-mediated neuroprotection against glutamate-induced toxicity in differentiated PC12 cells

The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.