Thymocyte migration: an affair of multiple cellular interactions?

Cell migration is a crucial event in the general process of thymocyte differentiation. The cellular interactions involved in the control of this migration are beginning to be defined. At least chemokines and extracellular matrix proteins appear to be part of the game. Cells of the thymic microenvironment produce these two groups of molecules, whereas developing thymocytes express the corresponding receptors. Moreover, although chemokines and extracellular matrix can drive thymocyte migration per se, a combined role for these molecules appears to contribute to the resulting migration patterns of thymocytes in their various stages of differentiation. The dynamics of chemokine and extracellular matrix production and degradation is not yet well understood. However, matrix metalloproteinases are likely to play a role in the breakdown of intrathymic extracellular matrix contents. Thus, the physiological migration of thymocytes should be envisioned as a resulting vector of multiple, simultaneous and/or sequential stimuli involving chemokines, adhesive and de-adhesive extracellular matrix proteins, as well as matrix metalloproteinases. Accordingly, it is conceivable that any pathological change in any of these loops may result in the alteration of normal thymocyte migration. This seems to be the case in murine infection by the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas' disease. A better knowledge of the physiological mechanisms governing thymocyte migration will provide new clues for designing therapeutic strategies targeting developing T cells.

A Template for Cloud Technology Deployment in an Energy Trading Environment

Nykyaikaiset pilvipalvelut tarjoavat suurille yrityksille mahdollisuuden tehostaa laskennallista tietojenkäsittelyä. Pilvipalveluiden käyttöönotto tuo mukanaan kuitenkin esimerkiksi useita tietoturvakysymyksiä, joiden vuoksi käyttöönoton tulee olla tarkasti suunniteltua. Tämä tutkimus esittelee kirjallisuuskatsaukseen perustuvan, asteittaisen suunnitelman pilvipalveluiden käyttöönotolle energialiiketoimintaympäristössä. Kohdeyrityksen sisäiset haastattelut ja katsaus nykyisiin energiateollisuuden pilviratkaisuihin muodostavat kokonaiskuvan käyttöönoton haasteista ja mahdollisuuksista. Tutkimuksen päätavoitteena on esittää ratkaisut tyypillisiin pilvipalvelun käyttöönotossa esiintyviin ongelmiin käyttöönottomallin avulla. Tutkimuksessa rakennettu käyttöönottomalli testattiin esimerkkitapauksen avulla ja malli todettiin toimivaksi. Ulkoisten palveluiden herättämien tietoturvakysymysten takia käyttöönoton ensimmäiset osiot, kuten lopputuotteen määrittely ja huolellinen suunnittelu, ovat koko käyttöönottoprosessin ydin. Lisäksi pilvipalveluiden käyttöönotto vaatii nykyiseltä käyttöympäristöltä uusia teknisiä ja hallinnollisia taitoja. Tutkimuksen tulokset osoittavat pilvipalveluiden monipuolisen hyödyn erityisesti laskentatehon tarpeen vaihdellessa. Käyttöönottomallin rinnalle luotu kustannusvertailu tukee kirjallisuuskatsauksessa esille tuotuja hyötyjä ja tarjoaa kohdeyritykselle perusteen tutkimuksen eteenpäin viemiselle.

Multicellular spheroids of bone marrow stromal cells: a three-dimensional in vitro culture system for the study of hematopoietic cell migration

Cell fate decisions are governed by a complex interplay between cell-autonomous signals and stimuli from the surrounding tissue. In vivo cells are connected to their neighbors and to the extracellular matrix forming a complex three-dimensional (3-D) microenvironment that is not reproduced in conventional in vitro systems. A large body of evidence indicates that mechanical tension applied to the cytoskeleton controls cell proliferation, differentiation and migration, suggesting that 3-D in vitro culture systems that mimic the in vivo situation would reveal biological subtleties. In hematopoietic tissues, the microenvironment plays a crucial role in stem and progenitor cell survival, differentiation, proliferation, and migration. In adults, hematopoiesis takes place inside the bone marrow cavity where hematopoietic cells are intimately associated with a specialized three 3-D scaffold of stromal cell surfaces and extracellular matrix that comprise specific niches. The relationship between hematopoietic cells and their niches is highly dynamic. Under steady-state conditions, hematopoietic cells migrate within the marrow cavity and circulate in the bloodstream. The mechanisms underlying hematopoietic stem/progenitor cell homing and mobilization have been studied in animal models, since conventional two-dimensional (2-D) bone marrow cell cultures do not reproduce the complex 3-D environment. In this review, we will highlight some of the mechanisms controlling hematopoietic cell migration and 3-D culture systems.

Alternagin-C, a disintegrin-like protein from the venom of Bothrops alternatus, modulates alpha2ß1 integrin-mediated cell adhesion, migration and proliferation

The alpha2ß1 integrin is a major collagen receptor that plays an essential role in the adhesion of normal and tumor cells to the extracellular matrix. Alternagin-C (ALT-C), a disintegrin-like protein purified from the venom of the Brazilian snake Bothrops alternatus, competitively interacts with the alpha2ß1 integrin, thereby inhibiting collagen binding. When immobilized in plate wells, ALT-C supports the adhesion of fibroblasts as well as of human vein endothelial cells (HUVEC) and does not detach cells previously bound to collagen I. ALT-C is a strong inducer of HUVEC proliferation in vitro. Gene expression analysis was done using an Affimetrix HU-95A probe array with probe sets of ~10,000 human genes. In human fibroblasts growing on collagen-coated plates, ALT-C up-regulates the expression of several growth factors including vascular endothelial growth factor, as well as some cell cycle control genes. Up-regulation of the vascular endothelial growth factor gene and other growth factors could explain the positive effect on HUVEC proliferation. ALT-C also strongly activates protein kinase B phosphorylation, a signaling event involved in endothelial cell survival and angiogenesis. In human neutrophils, ALT-C has a potent chemotactic effect modulated by the intracellular signaling cascade characteristic of integrin-activated pathways. Thus, ALT-C acts as a survival factor, promoting adhesion, migration and endothelial cell proliferation after binding to alpha2ß1 integrin on the cell surface. The biological activities of ALT-C may be helpful as a therapeutic strategy in tissue regeneration as well as in the design of new therapeutic agents targeting alpha2ß1 integrin.

The extracellular matrix provides directional cues for neuronal migration during cerebellar development

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.

Dexamethasone blocks the migration of the human neuroblastoma cell line SK-N-SH

Glucocorticoids (Gc) influence the differentiation of neural crest-derived cells such as those composing sympathoadrenal tumors like pheochromocytomas, as well as neuroblastomas and gangliomas. In order to obtain further information on the effects of Gc on cells evolving from the neural crest, we have used the human neuroblastoma cell line SK-N-SH to analyze: 1) the presence and the binding characteristics of Gc receptors in these cells, 2) the effect of dexamethasone (Dex) on the migration of SK-N-SH cells, and 3) the effect of Dex on the organization of the cytoskeleton of SK-N-SH cells. We show that: 1) receptors that bind [³H]-Dex with high affinity and high capacity (Kd of 9.6 nM, Bmax of 47 fmol/mg cytosolic protein, corresponding to 28,303 sites/cell) are present in cytosolic preparations of SK-N-SH cells, and 2) treatment with Dex (in the range of 10 nM to 1 µM) has an inhibitory effect (from 100% to 74 and 43%, respectively) on the chemotaxis of SK-N-SH cells elicited by fetal bovine serum. This inhibition is completely reversed by the Gc receptor antagonist RU486 (1 µM), and 3) as demonstrated by fluorescent phalloidin-actin detection, the effect of Dex (100 nM) on SK-N-SH cell migration is accompanied by modifications of the cytoskeleton organization that appear with stress fibers. These modifications did not take place in the presence of 1 µM RU486. The present data demonstrate for the first time that Dex affects the migration of neuroblastoma cells as well as their cytoskeleton organization by interacting with specific receptors. These findings provide new insights on the mechanism(s) of action of Gc on cells originating in the neural crest.

Relationship of macrophage migration inhibitory factor levels in PBMCs, lesional skin and serum with disease severity and activity in vitiligo vulgaris

Melanocyte loss in vitiligo vulgaris is believed to be an autoimmune process. Macrophage migration inhibitory factor (MIF) is involved in many autoimmune skin diseases. We determined the possible role of MIF in the pathogenesis of vitiligo vulgaris, and describe the relationship between MIF expressions and disease severity and activity. Serum MIF concentrations and mRNA levels in PBMCs were measured in 44 vitiligo vulgaris patients and 32 normal controls, using ELISA and real-time RT-PCR. Skin biopsies from 15 patients and 6 controls were analyzed by real-time RT-PCR. Values are reported as median (25th-75th percentile). Serum MIF concentrations were significantly increased in patients [35.81 (10.98-43.66) ng/mL] compared to controls [7.69 (6.01-9.03) ng/mL]. MIF mRNA levels were significantly higher in PBMCs from patients [7.17 (3.59-8.87)] than controls [1.67 (1.23-2.42)]. There was also a significant difference in MIF mRNA levels in PBMCs between progressive and stable patients [7.86 (5.85-9.13)vs 4.33 (2.23-8.39)] and in serum MIF concentrations [40.47 (27.71-46.79) vs 26.80 (10.55-36.07) ng/mL]. In addition, the vitiligo area severity index scores of patients correlated positively with changes of both serum MIF concentrations (r = 0.488) and MIF mRNA levels in PBMCs (r = 0.426). MIF mRNA levels were significantly higher in lesional than in normal skin [2.43 (2.13-7.59)vs 1.18 (0.94-1.83)] and in patients in the progressive stage than in the stable stage [7.52 (2.43-8.84)vs 2.13 (1.98-2.64)]. These correlations suggest that MIF participates in the pathogenesis of vitiligo vulgaris and may be useful as an index of disease severity and activity.

Involvement of Src tyrosine kinase and protein kinase C in the expression of macrophage migration inhibitory factor induced by H2O2 in HL-1 mouse cardiac muscle cells

Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, plays an important role in the pathogenesis of atrial fibrillation; however, the upstream regulation of MIF in atrial myocytes remains unclear. In the present study, we investigated whether and how MIF is regulated in response to the renin-angiotensin system and oxidative stress in atrium myocytes (HL-1 cells). MIF protein and mRNA levels in HL-1 cells were assayed using immunofluorescence, real-time PCR, and Western blot. The result indicated that MIF was expressed in the cytoplasm of HL-1 cells. Hydrogen peroxide (H2O2), but not angiotensin II, stimulated MIF expression in HL-1 cells. H2O2-induced MIF protein and gene levels increased in a dose-dependent manner and were completely abolished in the presence of catalase. H2O2-induced MIF production was completely inhibited by tyrosine kinase inhibitors genistein and PP1, as well as by protein kinase C (PKC) inhibitor GF109203X, suggesting that redox-sensitive MIF production is mediated through tyrosine kinase and PKC-dependent mechanisms in HL-1 cells. These results suggest that MIF is upregulated by HL-1 cells in response to redox stress, probably by the activation of Src and PKC.

RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

Implementing Green IT approach for transferring Big Data over Parallel Data Link

The whole research of the current Master Thesis project is related to Big Data transfer over Parallel Data Link and my main objective is to assist the Saint-Petersburg National Research University ITMO research team to accomplish this project and apply Green IT methods for the data transfer system. The goal of the team is to transfer Big Data by using parallel data links with SDN Openflow approach. My task as a team member was to compare existing data transfer applications in case to verify which results the highest data transfer speed in which occasions and explain the reasons. In the context of this thesis work a comparison between 5 different utilities was done, which including Fast Data Transfer (FDT), BBCP, BBFTP, GridFTP, and FTS3. A number of scripts where developed which consist of creating random binary data to be incompressible to have fair comparison between utilities, execute the Utilities with specified parameters, create log files, results, system parameters, and plot graphs to compare the results. Transferring such an enormous variety of data can take a long time, and hence, the necessity appears to reduce the energy consumption to make them greener. In the context of Green IT approach, our team used Cloud Computing infrastructure called OpenStack. It’s more efficient to allocated specific amount of hardware resources to test different scenarios rather than using the whole resources from our testbed. Testing our implementation with OpenStack infrastructure results that the virtual channel does not consist of any traffic and we can achieve the highest possible throughput. After receiving the final results we are in place to identify which utilities produce faster data transfer in different scenarios with specific TCP parameters and we can use them in real network data links.

Inclusion or Exclusion? Trade union strategies and Labor migration

Inclusion or Exclusion? Trade Union Strategies and Labor Migration This research identified and analyzed immigration-related strategies of the Finnish Construction Trade Union (FCTU) and the Service Union United (SUU); e.g. how the unions react to labor immigration, whether unions seek to include migrants in the unions, and what is migrants’ position in the unions. The two unions were chosen as the focus of the research because the workforce in the sectors they represent is migrant-dense. The study also analyzed the experiences that migrants who work in these sectors have with trade unions. The Estonian labor market situation –including the role of Estonian trade unions– was also examined as it has a considerable impact on the operating environment of the FCTU. The results of the study indicate that immigration is a contradictory issue for both unions. On the one hand, they strive to include migrants as trade union members and to defend migrants’ labor rights. On the other hand, they, together with their umbrella organization the Central Organisation of Finnish Trade Unions (SAK), seek to prevent labor immigration from outside the EU and EEA countries. They actively defend current labor immigration restrictions by drawing atten- tion to high unemployment figures and to the breaches of working conditions migrants encounter. In contrast, the employer organizations promote a more liberal state policy on labor immigration because they see it as a boost for business. Both the unions and the employer organizations ground their arguments on national interest. However, the position of the trade union movement is not uniform: unions belonging to the Confederation of Unions for Professionals and Managerial Staff in Finland (Akava) embrace more liberal labor immigration stances than the SAK. A key trade union strategy is to try to guarantee that migrants’ working condi- tions do not differ from those of the natives. The FCTU and the SUU inform migrants about Finnish collective agreements and trade union membership in the most common migrant languages. This is important for the unions because it is not in their interest that migrants’ working conditions are undercut. The interviewed migrants said that natives had more negotiating power with employers, which is often negatively portrayed in migrants’ working conditions. Migrants perceive that trade unions have an important role in protecting their working conditions. However, they stressed that migrants’ knowledge of unions is often very limited. The number of migrants in both two unions studied here is increasing. Espe- cially in the SUU, a considerable proportion of the new members are migrants. The FCTU is in a more challenging situation than the SUU because migrant construc- tion workers often work only for short periods in Finland and are consequently not interested in becoming union members. The unions’ strategies partly differ: the FCTU was the first Finnish trade union to establish a trade union branch/lo- cal for migrant members. The goal is to facilitate migrants’ inclusion in the union and to highlight the specific problems they face. The SUU, for its part, insists that such a special strategy would exclude migrants within the union organization. Despite the unions’ strategies, migrants are still underrepresented as union members and officials, which some of the interviewed migrants saw as a problem. Immigrants’ perception of trade unions was pragmatic: they had joined unions when membership yielded concrete benefits. In spite of the unions’ strategies, migrants –and temporary migrants– encoun- ter specific problems in terms of working conditions. Both unions demand more state intervention to protect migrants’ labor rights because overseeing working conditions consumes union resources. However, without the unions’ intervention, these problems would be more common than is currently the case. For instance, some of the interviewed migrants had received trade union assistance in claim- ing unpaid wages. The study demonstrated with the help of building on Walter Korpi’s power resources theory, that immigration is a power resource issue for the unions: suc- cessful immigration-related strategies strengthen unions –and vice versa. The research also showed how the unions’ operating environments constrain and enable their immigration-related strategies. This study has illuminated a previously ignored dimension: the immigrant- inclusive strategies of the Finnish trade unions. The research material consists of 78 qualitative interviews, observation in trade union events, and trade unions’ and employer organizations’ public state- ments.

Cloud computing contribution to manufacturing industry

Manufacturing industry has been always facing challenge to improve the production efficiency, product quality, innovation ability and struggling to adopt cost-effective manufacturing system. In recent years cloud computing is emerging as one of the major enablers for the manufacturing industry. Combining the emerged cloud computing and other advanced manufacturing technologies such as Internet of Things, service-oriented architecture (SOA), networked manufacturing (NM) and manufacturing grid (MGrid), with existing manufacturing models and enterprise information technologies, a new paradigm called cloud manufacturing is proposed by the recent literature. This study presents concepts and ideas of cloud computing and cloud manufacturing. The concept, architecture, core enabling technologies, and typical characteristics of cloud manufacturing are discussed, as well as the difference and relationship between cloud computing and cloud manufacturing. The research is based on mixed qualitative and quantitative methods, and a case study. The case is a prototype of cloud manufacturing solution, which is software platform cooperated by ATR Soft Oy and SW Company China office. This study tries to understand the practical impacts and challenges that are derived from cloud manufacturing. The main conclusion of this study is that cloud manufacturing is an approach to achieve the transformation from traditional production-oriented manufacturing to next generation service-oriented manufacturing. Many manufacturing enterprises are already using a form of cloud computing in their existing network infrastructure to increase flexibility of its supply chain, reduce resources consumption, the study finds out the shift from cloud computing to cloud manufacturing is feasible. Meanwhile, the study points out the related theory, methodology and application of cloud manufacturing system are far from maturity, it is still an open field where many new technologies need to be studied.

What is the current state of cloud service research and its promise for the future? A systematic literature review

The information technology (IT) industry has recently witnessed the proliferation of cloud services, which have allowed IT service providers to deliver on-demand resources to customers over the Internet. This frees both service providers and consumers from traditional IT-related burdens such as capital and operating expenses and allows them to respond rapidly to new opportunities in the market. Due to the popularity and growth of cloud services, numerous researchers have conducted studies on various aspects of cloud services, both positive and negative. However, none of those studies have connected all relevant information to provide a holistic picture of the current state of cloud service research. This study aims to investigate that current situation and propose the most promising future directions. In order to determine achieve these goals, a systematic literature review was conducted on studies with a primary focus on cloud services. Based on carefully crafted inclusion criteria, 52 articles from highly credible online sources were selected for the review. To define the main focus of the review and facilitate the analysis of literature, a conceptual framework with five main factors was proposed. The selected articles were organized under the factors of the proposed framework and then synthesized using a narrative technique. The results of this systematic review indicate that the impacts of cloud services on enterprises were the factor best covered by contemporary research. Researchers were able to present valuable findings about how cloud services impact various aspects of enterprises such as governance, performance, and security. By contrast, the role of service provider sub-contractors in the cloud service market remains largely uninvestigated, as do cloud-based enterprise software and cloud-based office systems for consumers. Moreover, the results also show that researchers should pay more attention to the integration of cloud services into legacy IT systems to facilitate the adoption of cloud services by enterprise users. After the literature synthesis, the present study proposed several promising directions for cloud service research by outlining research questions for the underexplored areas of cloud services, in order to facilitate the development of cloud service markets in the future.

Pilvipalveluilla joustavuutta ja kustannustehokkuutta Stora Enso Metsän tietojärjestelmiin

Tämän diplomityön tavoitteena oli selvittää hyödyttääkö Stora Enso Metsää tietojärjestelmien siirto perinteisistä konesalipalveluista pilvipalveluihin. Stora Enso Metsällä on paljon erilaisia suunnitteluun liittyviä eräajoja. Joitakin niistä ajetaan vain muutamia kertoja vuodessa kuten tehtaiden puuntarve, toisia muutaman kerran kuussa kuten kuljetusten malliajot tai muutaman kerran viikossa ajettava korjuun suunnittelu. Niissä tapauksissa palvelimet voidaan käynnistää erikseen ja käyttää niitä vain silloin, kun niitä oikeasti tarvitaan. Työn lopputuloksena havaittiin, että pilvipalveluiden käyttöönotto tuo kustannussäästöjä ja palveluiden hallintaan joustavuutta. Itsepalveluna toteutettuna palvelimia voidaan hallinnoida joustavasti kustannusten säästämiseksi. Pilvipalveluilla voidaan nopeuttaa projektien läpimenoa ja kohdentaa käyttökatkot tarkemmin koska siihen ei välttämättä tarvita toimittajan työtä lainkaan. Loppujen lopuksi asiakkaan on erittäin vaikea tietää kuinka paljon kustannuksia on jaettu eri tavalla eri palvelujen välillä.