Studies of the role of nf-κb in controlling osteoclast differentiation and bone loss

Increased osteoclast (OC) bone resorption and/or decreased osteoblast (OB) bone formation contribute to bone loss in osteoporosis and rheumatoid arthritis (RA). Findings of the basic and translational research presented in this thesis demonstrate a number of mechanisms by which cytokine-induced NF-κB activation controls bone resorption and formation: 1) Tumour necrosis factor-α (TNF) expands pool of OC precursors (OCPs) by promoting their proliferation through stimulation of the expression of macrophage colony stimulating factor (M-CSF) receptor, c-Fms, and switching M-CSF-induced resident (M2) to inflammatory (M1) macrophages with enhanced OC forming potential and increased production of inflammatory factors through induction of NF-κB RelB; 2) Similar to RANKL, TNF sequentially activates transcriptional factors NF-κB p50 and p52 followed by c-Fos and then NFATc1 to induce OC differentiation. However, TNF alone induces very limited OC differentiation. In contrast, it pre-activates OCPs to express cFos which cooperates with interleukin-1 (IL-1) produced by these OCPs in an autocrine mechanism by interacting with bone matrix to mediate the OC terminal differentiation and bone resorption from these pre-activated OCPs. 3) TNF-induced OC formation is independent of RANKL but it also induces NF-κB2 p100 to limit OC formation and bone resorption, and thus p100 deletion accelerates joint destruction and systemic bone loss in TNF-induced RA; 4) TNF receptor associated factor-3 (TRAF3) limits OC differentiation by negatively regulating non-canonical NF-κB activation and RANKL induces TRAF3 ubiquitination and lysosomal degradation to promote OC differentiation. Importantly, a lysosomal inhibitor that inhibits TRAF3 degradation prevents ovariectomy-induced bone loss; 5) RelB and Notch NICD bind RUNX2 to inhibit OB differentiation and RelB:p52 dimer association with NICD inhibit OB differentiation by enhancing the binding of RBPjκ to Hes1. These findings suggest that non-canonical NF- κB signaling could be targets to develop new therapies for RA or osteoporosis. For example 1) Agents that degrade TNF-induced RelB could block M1 macrophage differentiation to inhibit inflammation and joint destruction for the therapy of RA; 2)Agents that prevent p100 processing or TRAF3 degradation could inhibit bone resorption and also stimulate bone formation simultaneously for the therapy of osteoporosis.

Partner selection for reverse logistics centres in green supply chains: a fuzzy artificial immune optimization approach

The design of reverse logistics networks has now emerged as a major issue for manufacturers, not only in developed countries where legislation and societal pressures are strong, but also in developing countries where the adoption of reverse logistics practices may offer a competitive advantage. This paper presents a new model for partner selection for reverse logistic centres in green supply chains. The model offers three advantages. Firstly, it enables economic, environment, and social factors to be considered simultaneously. Secondly, by integrating fuzzy set theory and artificial immune optimization technology, it enables both quantitative and qualitative criteria to be considered simultaneously throughout the whole decision-making process. Thirdly, it extends the flat criteria structure for partner selection evaluation for reverse logistics centres to the more suitable hierarchy structure. The applicability of the model is demonstrated by means of an empirical application based on data from a Chinese electronic equipment and instruments manufacturing company.

Modulare Logistiksysteme in der Prozessindustrie unter Einbeziehung von Industrie 4.0

Zur Gewährleistung einer kundenindividuellen, flexiblen Produktion, welche auch kleine Losegrößen kostengünstig produzieren kann, werden zukünftig Fabriken der Prozessindustrie nicht nur modular sondern darüber hinaus mobil sein. Zur Erreichung dieses Zieles werden neben Produktionselemente, auch sämtliche Logistikkomponenten in Containern zu Modulen zusammengefasst. Hierfür ist es notwendig Lager, aber auch komplexe Verpackungsmaschinen, zu konzipieren welche sich zusammen mit Produktionsmodulen, nach dem Plug-and-Produce-Prinzip, zu kompletten Produktionslinien verknüpfen lassen. Die Steuerung und Organisation erfolgt nach den Gedanken von Industrie 4.0.

Factors and mechanisms controlling soil organic carbon turnover in subsoils of agricultural sites

Two-third of the terrestrial C is stored in soils, and more than 50% of soil organic C (SOC) is stored in subsoils from 30 – 100 cm. Hence, subsoil is important as a source or sink for CO2 in the global carbon cycle. Especially the stable organic carbon (OC) is stored in subsoil, as several studies have shown that subsoil OC is of a higher average age than topsoil OC. However, there is still a lack of knowledge regarding the mechanisms of C sequestration and C turnover in subsoil. Three main factors are discussed, which possibly reduce carbon turnover rates in subsoil: Resource limitation, changes in the microbial community, and changes in gas conditions. The experiments conducted in this study, which aimed to elucidate the importance of the mentioned factors, focused on two neighbouring arable sites, with depth profiles differing in SOC stocks: One Colluvic Cambisol (Cam) with high SOC contents (8-12 g kg-1) throughout the profile and one Haplic Luvisol (Luv) with low SOC contents (3-4 g kg-1) below 30 cm depth. The first experiment was designed to gain more knowledge regarding the microbial community and its influence on carbon sequestration in subsoil. Soil samples were taken at four different depths on the two sites. Microbial biomass C (MBC) was determined to identify depth gradients in relation to the natural C availability. Bacterial and fungal residues as well as ergosterol were determined to quantify changes in the in the microbial community composition. Multi-substrate-induced-respiration (MSIR) was used to identify shifts in functional diversity of the microbial community. The MSIR revealed that substrate use in subsoil differed significantly from that in topsoil and also differed highly between the two subsoils, indicating a strong influence of resource limitations on microbial substrate use. Amino sugar analysis and the ratio of ergosterol to microbial biomass C showed that fungal dominance decreased with depth. The results clearly demonstrated that microbial parameters changed with depth according to substrate availability. The second experiment was an incubation experiment using subsoil gas conditions with and without the addition of C4 plant residues. Soil samples were taken from topsoil and subsoil of the two sites. SOC losses during the incubation, were not influenced by the subsoil gas conditions. Plant-derived C losses were generally stronger in the Cam (7.5 mg g-1), especially at subsoil gas conditions, than in the Luv (7.0 mg g-1). Subsoil gas conditions had no general effects on microbial measures with and without plant residue addition. However, the contribution of plant-derived MBC to total MBC was significantly reduced at subsoil gas conditions. This lead to the conclusion that subsoil gas conditions alter the metabolism of microorganisms but not the degradation of added plant residues is general. The third experiment was a field experiment carried out for two years. Mesh bags containing original soil material and maize root residues (C4 plant) were buried at three different depths at the two sites. The recovery of the soilbags took place 12, 18, and 24 months after burial. We determined the effects of these treatments on SOC, density fractions, and MBC. The mean residence time for maize-derived C was similar at all depths and both sites (403 d). MBC increased to a similar extent (2.5 fold) from the initial value to maximum value. This increase relied largely on the added maize root residues. However, there were clear differences visible in terms of the substrate use efficiency, which decreased with depth and was lower in the Luv than in the Cam. Hence freshly added plant material is highly accessible to microorganisms in subsoil and therefore equally degraded at both sites and depths, but its metabolic use was determined by the legacy of soil properties. These findings provide strong evidence that resource availability from autochthonous SOM as well as from added plant residues have a strong influence on the microbial community and its use of different substrates. However, under all of the applied conditions there was no evidence that complex substrates, i.e. plant residues, were less degraded in subsoil than in topsoil.

Influence of Forecasting, Planning and Controlling on the performance of Small and Medium Enterprises

Production Planning and Control (PPC) systems have grown and changed because of the developments in planning tools and models as well as the use of computers and information systems in this area. Though so much is available in research journals, practice of PPC is lagging behind and does not use much from published research. The practices of PPC in SMEs lag behind because of many reasons, which need to be explored. This research work deals with the effect of identified variables such as forecasting, planning and control methods adopted, demographics of the key person, standardization practices followed, effect of training, learning and IT usage on firm performance. A model and framework has been developed based on literature. Empirical testing of the model has been done after collecting data using a questionnaire schedule administered among the selected respondents from Small and Medium Enterprises (SMEs) in India. Final data included 382 responses. Hypotheses linking SME performance with the use of forecasting, planning and controlling were formed and tested. Exploratory factor analysis was used for data reduction and for identifying the factor structure. High and low performing firms were classified using a Logistic Regression model. A confirmatory factor analysis was used to study the structural relationship between firm performance and dependent variables.

Coordination in humanitarian logistics through clusters

Purpose – In the field of humanitarianism, cluster thinking has been suggested as a solution to the lack of coordinated disaster response. Clusters for diverse functions, including sheltering, logistics and water and sanitation, can be viewed as an effort to achieve functional coordination. The purpose of this paper is to contribute to a greater understanding of the potential of cluster concepts using supply chain coordination and inter‐cluster coordination. The focus is on the conceptual level rather than on specific means of coordination. Design/methodology/approach – The cluster concept in humanitarian relief, along with some key empirical issues, is based on a case study. The concept is then compared to the literature on clusters and coordination in order to develop a theoretical framework with propositions on the tradeoffs between different types of coordination. Findings – The results provide important reflections on one of the major trends in contemporary development of humanitarian logistics. This paper shows that there is a tradeoff between different types of coordination, with horizontal coordination inside cluster drawing attention away from important issues of the supply chain as well as the need to coordinate among the clusters. Research limitations/implications – There is a need for more in‐depth case studies of experiences with clusters in various operations. Various perspectives should be taken into account, including the field, responding agencies, beneficiaries, donors, military and commercial service providers, both during and between disasters. Practical implications – The paper presents the tradeoffs between different types of coordination, in which basic aims such as standardisation through functional coordination, must be balanced with cross‐functional and vertical coordination in order to more successfully serve the users' composite needs. Originality/value – The focus on possible trade‐offs between different types of coordination is an important complement to the literature, which often assumes simultaneous high degrees of horizontal and vertical coordination.

Theory development in humanitarian logistics : A framework and three cases

Purpose: There is a need for theory development within the field of humanitarian logistics to understand logistics needs in different stages of a crisis and how to meet these. This paper aims to discuss three dimensions identified in logistics and organization theories and how they relate to three different cases of humanitarian logistics operations - the regional concept of the International Federation of Red Cross Red Crescent Societies, the development and working of the United Nations Joint Logistics Centre and coordination challenges of military logistics in UN mandated peacekeeping operations. The purpose is to build a framework to be used in further studies. Design/methodology/approach: A framework for the study of humanitarian logistics along three dimensions is developed, followed by a discussion of the chosen cases in relation to these dimensions. The framework will be used as basis for the case studies to be undertaken for the purpose of understanding and identification of new questions and needs for other or revised concepts from theory. Findings: The paper shows the relevance of a wide literature to the issues pertinent to humanitarian logistics. There is considerable promise in extant literature on logistics, SCM and coordination, but this needs to be confronted with the particular issues seen in the humanitarian logistics setting to achieve further theory development. Originality/value: The major contribution of the paper lies in its breadth of theoretical perspectives presented and combined in a preliminary theoretical framework. This is applied more specifically in the three case studies described in the paper.

Designing gainsharing model variations with logistics service company

This thesis studies, in collaboration with a Finnish logistics service company, gainsharing and the development of a gainsharing models in a logistics outsourcing context. The purpose of the study is to create various gainsharing model variations for the use of a service provider and its customers in order to develop and enhance the customer’s processes and operations, create savings and improve the collaboration between the companies. The study concentrates on offering gainsharing model alternatives for companies operating in internal logistics outsourcing context. Additionally, the prerequisites for the gainsharing arrangement are introduced. In the beginning of the study an extensive literature review is conducted. There are three main themes explored which are the collaboration in an outsourcing context, key account management and gainsharing philosophy. The customer expectations and experiences are gathered by interviewing case company’s employees and its key customers. In order to design the gainsharing model prototypes, customers and other experts’ knowledge and experiences are utilized. The result of this thesis is five gainsharing model variations that are based on the empirical and theoretical data. In addition, the instructions related to each created model are given to the case company, but are not available in this paper

Controlling Nanostructures for in-situ TEM Characterization

Low dimensional nanostructures, such as nanotubes and 2D sheets, have unique and promising material properties both from a fundamental science and an application standpoint. Theoretical modelling and calculations predict previously unobserved phenomena that experimental scientists often struggle to reproduce because of the difficulty in controlling and characterizing the small structures under real-world constraints. The goal of this dissertation is to controlling these structures so that nanostructures can be characterized in-situ in transmission electron microscopes (TEM) allowing for direct observation of the actual physical responses of the materials to different stimuli. Of most interest to this work are the thermal and electrical properties of carbon nanotubes, boron nitride nanotubes, and graphene. The first topic of the dissertation is using surfactants for aqueous processing to fabricate, store, and deposit the nanostructures. More specifically, thorough characterization of a new surfactant, ammonium laurate (AL), is provided and shows that this new surfactant outperforms the standard surfactant for these materials, sodium dodecyl sulfate (SDS), in almost all tested metrics. New experimental set-ups have been developed by combining specialized in-situ TEM holders with innovative device fabrication. For example, electrical characterization of graphene was performed by using an STM-TEM holder and depositing graphene from aqueous solutions onto lithographically patterned, electron transparent silicon nitride membranes. These experiments produce exciting information about the interaction between graphene and metal probes and the substrate that it rests on. Then, by adding indium to the backside of the membrane and employing the electron thermal microscopy (EThM) technique, the same type of graphene samples could be characterized for thermal transport with high spatial resolution. It is found that reduced graphene oxide sheets deposited onto a silicon nitride membrane and displaying high levels of wrinkling have higher than expected electrical and thermal conduction properties. We are clearly able to visualize the ability of graphene to spread heat away from an electronic hot spot and into the substrate.

Analysis of the role of the transcription factor C/EBPβ in controlling uterine functions during early pregnancy

Embryo implantation into the endometrium is a complex biological process involving the integration of steroid hormone signaling, endometrial tissue remodeling and maternal- fetal communications. A successful pregnancy is the outcome of the timely integration of these events during the early stages of implantation. The involvement of ovarian steroid hormones, estrogen (E) and progesterone (P), acting through their cognate receptors, is essential for uterine functions during pregnancy. The molecular mechanisms that control the process of implantation are undergoing active exploration. Through our recent efforts, we identified the transcription factor, CCAAT Enhancer Binding Protein Beta (C/EBPb) as a prominent target of estrogen and progesterone signaling in the uterus. The development of a C/EBPb-null mouse model, which is infertile, presented us with an opportunity to analyze the role of this molecule in uterine function. We discovered that C/EBPb functions in two distinct manners: (i) by acting as a mediator of E-induced proliferation of the uterine epithelium and (ii) by controlling uterine stromal cell differentiation, a process known as decidualization, during pregnancy. My studies have delineated important mechanisms by which E regulates C/EBPb expression to induce DNA replication and prevent apoptosis of uterine epithelial cells during E-induced epithelial growth. In subsequent studies, I analyzed the role of C/EBPb in decidualization and uncovered a unique mechanism by which C/EBPb regulates the synthesis of a unique laminin-containing extracellular matrix (ECM) that supports stromal cell differentiation and embryo invasion. In order to better define the role of laminin in implantation, we developed a laminin gamma 1-conditional knockout mouse model. This is currently an area of ongoing investigation. The information gained from our analysis of C/EBPb function in the uterus provides new insights into the mechanisms of steroid hormone action during early pregnancy. Ultimately, our findings may aid in the understanding of dysregulation of hormone-controlled pathways that underlie early pregnancy loss and infertility in women.

Generation of a business plan for a logistics service provider

The purpose of this Master’s Thesis was to study the suitability of transportation of liquid wastes to the portfolio of the case company. After the preliminary study the waste types were narrowed down to waste oil and oily waste from ports. The thesis was executed by generating a business plan. The qualitative research of this Master’s Thesis was executed as a case study by collecting information from multiple sources. The business plan was carried out by first familiarizing oneself with literature related to business planning which was then used as a base for the interview of the customer and interviews of the personnel of the case company. Additionally, internet sources and informal conversational interviews with the personnel of the case company were used and these interviews took place during the preliminary study and this thesis. The results of this thesis describe the requirements for the case company that must be met to be able to start operations. Import of waste oil fits perfectly to the portfolio of the case company and it doesn’t require any big investments. Success of the import of waste oil is affected by price of crude oil, exchange rate of ruble and legislation among others. Transportation of oily waste from ports, in turn, is not a core competence of the case company so more actions are required to start operating such as subcontracting with a waste management company.

Development of Imatra`s logistics hub as a part of Nordic region

This thesis is dedicated to enhancement and development of Imatra`s logistics potential in order to increase its key parameters and improve the efficiency of the region. To find out the most promising logistics projects was proposed a tool “integral-matrix analysis” which enables to make the priority among the list of proposed projects. Description and functionality of the tool are explained in detail. As a result of analysis, the list of priority projects for the development of the region is presented. Project with the greatest potential is implemented in the thesis work. In conclusion, recommendations for the further development of economic potential of the region are given. The thesis is basically focused on literature review, overlook of secondary and primary data (including the results of the interviews, which were carried out among companies that represent the logistics market). Primary data was collected in interviews with the representatives of the companies, who regularly use logistics services. Total effects that make various Russian regions and companies on the Finnish logistics is summed up and discussed.