Chemokine receptor trio: CXCR3, CXCR4 and CXCR7 crosstalk via CXCL11 and CXCL12.

Although chemokines are well established to function in immunity and endothelial cell activation and proliferation, a rapidly growing literature suggests that CXC Chemokine receptors CXCR3, CXCR4 and CXCR7 are critical in the development and progression of solid tumors. The effect of these chemokine receptors in tumorigenesis is mediated via interactions with shared ligands I-TAC (CXCL11) and SDF-1 (CXCL12). Over the last decade, CXCR4 has been extensively reported to be overexpressed in most human solid tumors and has earned considerable attention toward elucidating its role in cancer metastasis. To enrich the existing armamentarium of anti-cancerous agents, many inhibitors of CXCL12-CXCR4 axis have emerged as additional or alternative agents for neo-adjuvant treatments and even many of them are in preclinical and clinical stages of their development. However, the discovery of CXCR7 as another receptor for CXCL12 with rather high binding affinity and recent reports about its involvement in cancer progression, has questioned the potential of "selective blockade" of CXCR4 as cancer chemotherapeutics. Interestingly, CXCR7 can also bind another chemokine CXCL11, which is an established ligand for CXCR3. Recent reports have documented that CXCR3 and their ligands are overexpressed in different solid tumors and regulate tumor growth and metastasis. Therefore, it is important to consider the interactions and crosstalk between these three chemokine receptors and their ligand mediated signaling cascades for the development of effective anti-cancer therapies. Emerging evidence also indicates that these receptors are differentially expressed in tumor endothelial cells as well as in cancer stem cells, suggesting their direct role in regulating tumor angiogenesis and metastasis. In this review, we will focus on the signals mediated by this receptor trio via their shared ligands and their role in tumor growth and progression.

Osteolytic metastasis detected by F18-FDG PET in a patient with lung carcinoma

We present a 53-year-old man with a vocal cord paralysis observed as a primary manifestation of lung carcinoma. Tc-99m MDP whole body bone scan were performed and resulted a normal scintiscan. The bone scan does not revealed suspicious foci of uptake. The possibility of bone metastasis was taken into consideration. A whole body F18-FDG-PET scan showed intense uptake in the left upper lung corresponding to the primary tumor. A bronchial biopsy confirmed infiltration by small cell lung carcinoma (SCLC). SCLC is composed of poorly differentiated, rapidly growing cells with disease usually occurring centrally rather than peripherally. It metastasizes early. The whole-body F18-FDG-PET scan clearly demonstrated a focus of increased uptake in the second lumbar vertebral body suspicious for osteolytic metastasis. A lytic bone metastasis was confirmed by MRI. The patient then received therapy and underwent follow up abdominal CT. The scan showed blastic changes in the L2 vertebra suggesting response to treatment.

Quantitative integration of high-resolution hydrogeophysical data through Monte-Carlo-type conditional simulations

Geophysical techniques can help to bridge the inherent gap with regard to spatial resolution and the range of coverage that plagues classical hydrological methods. This has lead to the emergence of the new and rapidly growing field of hydrogeophysics. Given the differing sensitivities of various geophysical techniques to hydrologically relevant parameters and their inherent trade-off between resolution and range the fundamental usefulness of multi-method hydrogeophysical surveys for reducing uncertainties in data analysis and interpretation is widely accepted. A major challenge arising from such endeavors is the quantitative integration of the resulting vast and diverse database in order to obtain a unified model of the probed subsurface region that is internally consistent with all available data. To address this problem, we have developed a strategy towards hydrogeophysical data integration based on Monte-Carlo-type conditional stochastic simulation that we consider to be particularly suitable for local-scale studies characterized by high-resolution and high-quality datasets. Monte-Carlo-based optimization techniques are flexible and versatile, allow for accounting for a wide variety of data and constraints of differing resolution and hardness and thus have the potential of providing, in a geostatistical sense, highly detailed and realistic models of the pertinent target parameter distributions. Compared to more conventional approaches of this kind, our approach provides significant advancements in the way that the larger-scale deterministic information resolved by the hydrogeophysical data can be accounted for, which represents an inherently problematic, and as of yet unresolved, aspect of Monte-Carlo-type conditional simulation techniques. We present the results of applying our algorithm to the integration of porosity log and tomographic crosshole georadar data to generate stochastic realizations of the local-scale porosity structure. Our procedure is first tested on pertinent synthetic data and then applied to corresponding field data collected at the Boise Hydrogeophysical Research Site near Boise, Idaho, USA.

GuavaH: a compendium of host genomic data in HIV biology and disease.

BACKGROUND: There is an ever-increasing volume of data on host genes that are modulated during HIV infection, influence disease susceptibility or carry genetic variants that impact HIV infection. We created GuavaH (Genomic Utility for Association and Viral Analyses in HIV, http://www.GuavaH.org), a public resource that supports multipurpose analysis of genome-wide genetic variation and gene expression profile across multiple phenotypes relevant to HIV biology. FINDINGS: We included original data from 8 genome and transcriptome studies addressing viral and host responses in and ex vivo. These studies cover phenotypes such as HIV acquisition, plasma viral load, disease progression, viral replication cycle, latency and viral-host genome interaction. This represents genome-wide association data from more than 4,000 individuals, exome sequencing data from 392 individuals, in vivo transcriptome microarray data from 127 patients/conditions, and 60 sets of RNA-seq data. Additionally, GuavaH allows visualization of protein variation in ~8,000 individuals from the general population. The publicly available GuavaH framework supports queries on (i) unique single nucleotide polymorphism across different HIV related phenotypes, (ii) gene structure and variation, (iii) in vivo gene expression in the setting of human infection (CD4+ T cells), and (iv) in vitro gene expression data in models of permissive infection, latency and reactivation. CONCLUSIONS: The complexity of the analysis of host genetic influences on HIV biology and pathogenesis calls for comprehensive motors of research on curated data. The tool developed here allows queries and supports validation of the rapidly growing body of host genomic information pertinent to HIV research.

Ulkomaiset valmistajat Venäjän henkilöautomarkkinoilla

Tämä NORDIn julkaisusarjan raportti 41 keskittyy ulkomaisten automerkkien nopeasti kasvavaan valmistukseen Venäjällä. Julkaisussa arvioidaan Venäjällä toimivien ulkomaisten autonvalmistajien toimintaedellytyksiä. Tutkimuksessa selvitetään miksi ulkomaiset autonvalmistajat ovat laajentaneet toimintaansa Venäjälle

Robots and robotic systems for the electronics and telecommunication industry

Tämä diplomityö tutkii elektroniikka- ja telekommunikaatioteollisuutta sekä siihen läheisesti liittyviä robotteja ja robottijärjestelmiä. Tavoitteena on määrittää E&T-teollisuuden prosesseihin soveltuvien robottien testausmenetelmä. Tavoitteena on myös selvittää kahden ABB:n robotin soveltuvuutta E&T-teollisuuden tarpeisiin. Muutamia systemaattisia valmistusjärjestelmien suunnitteluun soveltuvia menetelmiä ja apuvälineitä on myös käsitelty. Alussa työ keskittyy elektroniikka- ja telekommunikaatioteollisuuden nykytilan tutkimiseen sekä siellä vallitsevien ja ennustettujen trendien kartoitukseen. Kohdat “Collaborative manufacturing” ja E&T-teollisuuden valmistusjärjestelmille asettamat vaatimukset käydään yksityiskohtaisesti läpi. Tutkimuksen pääkohteina ovat robotit, erityisesti ABB:n IRB 140 ja IRB 340 sekä robottien testausmenetelmän määrittäminen. Työssä käydään läpi IRB 340:llä suoritetut testit, jotka tehtiin sekä konenäköjärjestelmää apuna käyttäen että ilman. Myös TTKK:lla suoritetut robottitestit on käyty läpi. Robottien testituloksia on analysoitu ja vertailtu muihin robotteihin. Testausmenetelmät perustuvat ISO 9283 standardiin. Viimeinen osa työstä esittelee robottijärjestelmien systemaattiseen suunnitteluun soveltuvia menetelmiä ja apuvälineitä. Esillä ovat mm. Modular function deployment (MFD) ja The system design method (SDM).

Oliopohjaisen sähköisen kaupankäynnin järjestelmän suunnittelu ja mallinnus

Sähköinen kaupankäynti (electronic commerce, EC) on jatkuvasti ja nopeasti kasvava liiketoiminnan muoto. Suurten yritysten välistä sähköistä kaupankäyntiä, EDI:ä, on harjoitettu jo noin kaksikymmentä vuotta, mutta aivan viime vuosina sähköisen kaupankäynnin suosio on kokenut räjähdysmäisen kasvun sen siirryttyä yhä kevyemmille markkinoille, pienyritysten ja jopa yksityisten kuluttajien käytettäväksi. Perinteisen EDI:n järjestelmät ovat kuitenkin suuria, raskaita ja ne kykenevät huonosti tarjoamaan nykyaikaisen sähköisen kaupankäynnin vaatimia toimintoja. Tässä on tarkoituksena esittää malli uudelle, tehokkaammalle järjestelmälle. Tavoitteena on luotettava, helposti ylläpidettävä ja suorituskyvyltään sekä ominaisuuksiltaan skaalautuva järjestelmä. Koko järjestelmä toteutetaan käyttäen oliokeskeisiä menetelmiä. Järjestelmän perustana käytetään yleistä hajautettua komponentti-arkkitehtuuria. Työn tuloksena esitetään periaatteeltaan toteuttamiskelpoinen malli nykyaikaisesta sähköisen kaupankäynnin järjestelmästä. Malli mahdollistaa tehokkaan toiminnallisuuden hajauttamisen ja tehokkaan, hyvin määritellyn liitynnän eri sovellusjärjestelmien kanssa. Tämä toteutetaan rakentamalla koko järjestelmä CORBA-arkkitehtuurin ympärille.

Capital Controls with International Reserve Accumulation: Can this Be Optimal ?

Motivated by the Chinese experience, we analyze a semi-open economy where the central bank has access to international capital markets, but the private sector has not. This enables the central bank to choose an interest rate different from the international rate. We examine the optimal policy of the central bank by modelling it as a Ramsey planner who can choose the level of domestic public debt and of international reserves. The central bank can improve savings opportunities of credit-constrained consumers modelled as in Woodford (1990). We find that in a steady state it is optimal for the central bank to replicate the open economy, i.e., to issue debt financed by the accumulation of reserves so that the domestic interest rate equals the foreign rate. When the economy is in transition, however, a rapidly growing economy has a higher welfare without capital mobility and the optimal interest rate differs from the international rate. We argue that the domestic interest rate should be temporarily above the international rate. We also find that capital controls can still help reach the first best when the planner has more fiscal instruments.

Treatment of Prosthetic Joint Infections

Prosthetic joint replacement is one of the most successful surgical procedures of the last century and the number of implanted artificial joints is rapidly growing. While the result of the procedure is generally positive, infections may occur leading to patient suffering, surgeon's frustration and important costs to the health system. Infection after prosthetic joint replacement is thus a feared complication as healing rates can be low, functional result poor and satisfaction of the patient abysmal. However, if a patient-adapted treatment of infected total joints is used, an overall success rate of above 90 % can be obtained. The patient-adapted treatment concept is based on five strong pillars: teamwork, understanding biofilm, proper diagnostics, proper definition and classification and patient-tailored treatment.

Emotions in International Politics. Beyond Mainstream International Relations

In recent years, social scientists have increasingly recognized the interconnectedness of thought on emotions. Nowhere is the role of passions more evident than international politics, where pride, anger, guilt, fear, empathy, and other feelings are routinely on display. But in the absence of an overarching theory of emotions, how can we understand their role at the international level? Emotions in International Politics fills the need for theoretical tools in the new and rapidly growing subfield of international relations. Eminent scholars from a range of disciplines consider how emotions can be investigated from an international perspective involving collective players, drawing evidence from such emotionally fraught events as the Rwandan genocide, World War II, the 9/11 attacks, and the Iranian nuclear standoff. The path-breaking research collected in Emotions in International Politics will be a valuable theoretical guide to understanding conflict and cooperation in international relations.

Voimakkaasti kasvavan projektiyrityksen talousohjaus

Työn tarkoituksena oli tutkia kasvun vaikutuksia yrityksen talous-ohjaukseen. Yrityksen kasvun mandollisuuksia ja kasvuvaiheita tutkimalla pyrittiin löytämään ne keskeiset osa-alueet, joiden seuranta on tärkeää yrityksen kasvukyvykkyyden ja kasvun hallinnan kannalta nimenomaan talousohjauksen näkökulmasta. Tutkimus on toteutettu yhden tapauksen kvalitatiivisena tutkimuksena, jota on täydennetty myös kvantitatiivisin menetelmin. Tutkimusaineistoa kerättiin usealla eri metodilla. Tutkimustulokset osoittivat, että talousohjauksen rooli on erittäin tärkeä voimakkaasti kasvavassa yrityksessä. Talousohjauksen ensisijainen tehtävä kasvuyrityksessä on tukea johtoa muutostilanteessa luomalla yhtenäiset toimintatavat ja seurantajärjestelmät. Myös kannattavuuden ja rahoituksen seuranta on kasvuyritykselle tärkeää.

Transforming Maritime Safety Culture. Evaluation of the impacts of the ISM Code on maritime safety culture in Finland

The purpose of the METKU Project (Development of Maritime Safety Culture) is to study how the ISM Code has influenced the safety culture in the maritime industry. This literature review is written as a part of the Work Package 2 which is conducted by the University of Turku, Centre for Maritime Studies. The maritime traffic is rapidly growing in the Baltic Sea which leads to a growing risk of maritime accidents. Particularly in the Gulf of Finland, the high volume of traffic causes a high risk of maritime accidents. The growing risks give us good reasons for implementing the research project concerning maritime safety and the effectiveness of the safety measures, such as the safety management systems. In order to reduce maritime safety risks, the safety management systems should be further developed. The METKU Project has been launched to examine the improvements which can be done to the safety management systems. Human errors are considered as the most important reason for maritime accidents. The international safety management code (the ISM Code) has been established to cut down the occurrence of human errors by creating a safety-oriented organizational culture for the maritime industry. The ISM Code requires that a company should provide safe practices in ship operation and a safe working environment and establish safeguards against all identified risk. The fundamental idea of the ISM Code is that companies should continuously improve safety. The commitment of the top management is essential for implementing a safety-oriented culture in a company. The ISM Code has brought a significant contribution to the progress of maritime safety in recent years. Shipping companies and ships’ crews are more environmentally friendly and more safety-oriented than 12 years ago. This has been showed by several studies which have been analysed for this literature research. Nevertheless, the direct effect and influence of the ISM Code on maritime safety could not be isolated very well. No quantitative measurement (statistics/hard data) could be found in order to present the impacts of the ISM Code on maritime safety. In this study it has been discovered that safety culture has emerged and it is developing in the maritime industry. Even though the roots of the safety culture have been established there are still serious barriers to the breakthrough of the safety management. These barriers could be envisaged as cultural factors preventing the safety process. Even though the ISM Code has been effective over a decade, the old-established behaviour which is based on the old day’s maritime culture still occurs. In the next phase of this research project, these cultural factors shall be analysed in regard to the present safety culture of the maritime industry in Finland.

Research of wood fuel market in North-West of Russia

The main purposes of this study are analyzing of forest sector of North-West and research of potentials of wood fuel market in this region. Research is focused on definition of the most perspective areas for export of wood fuel: logging residues, industrial wood processing residues, pellets and briquettes. Russian wood energy industry is very young in comparison with European countries. Nowadays there are no support and serious attention from the government to this sector. Hence almost all wood fuel market is oriented to the Western Europe. Export of wood fuel is dominated over the internal consumption. Pellet production in North –West is rapidly growing. Despite internal market has been developed the lion's share of pellets goes to export. Part of industrial wood processing residues is used by producers for their own goals, part goes to the export and rest of them is not used at all. Logging residues as raw materials for fuel have great potentials; most of them are left in a forest. Special techniques for their processing are too expensive for Russian entrepreneur. Some parts of North –West, which are situated close to the border with European countries, are potential for export. Political, economical and logistical challenges are complicated facilities for foreign customer to purchase wood fuel in remote parts of North-West. However some decisions for solving this problem exist and Russian manufactures are still interested in export of their products.

Semicarbazonas e tiossemicarbazonas: o amplo perfil farmacológico e usos clínicos

This article shows that thiosemicarbazones, semicarbazones and their metal complexes can exhibit target selectivity along with a wide pharmacological profile. Complexes of thiosemicarbazones with cytotoxic or antitumoral activity are presented, some of which show activity against cisplatinum-resistant cells. The inhibition mechanism of the enzyme ribonucleoside diphosphate reductase (RDR), involved in DNA syntheses, by alpha(N)-heterocyclic thiosemicarbazones is discussed. The encouraging results of clinical trials with the RDR inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone ("Triapine") against rapidly growing tumors are outlined. Examples are also given of thiosemicarbazones with antiviral and antimicrobial activity. The possible applications of semicarbazones as anticonvulsants with low toxicity and good therapeutic index are presented.

Osteolytic metastasis detected in a patient with lung carcinoma by F18-FDG PET

We present a 53-year-old man with a vocal cord paralysis observed as a primary manifestation of lung carcinoma. Tc-99m MDP whole body bone scan was performed and resulted in a normal scintiscan. The bone scan did not reveal any suspicious foci of uptake. The possibility of bone metastasis was taken into consideration. A whole body F18-FDG-PET scan showed intense uptake in the left upper lung corresponding to the primary tumor. A bronchial biopsy confirmed infiltration by small cell lung carcinoma (SCLC). SCLC is composed of poorly differentiated, rapidly growing cells with diseases usually occurring centrally rather than peripherally. It metastasizes early. The whole-body F18-FDG-PET scan clearly demonstrated a focus of increased uptake in the second lumbar vertebral body suspicious for osteolytic metastasis. A lytic bone metastasis was confirmed by MRI. The patient then received therapy and underwent follow up abdominal CT. The scan showed blastic changes in the L2 vertebra suggesting response to treatment.