Business Negotiations Between Americans and Russians

In the past decade, Russia has emerged as an important player in the global economy. In the Goldman Sachs “Dreaming with the BRICs” Report, Jim O’Neil contends that “over the next 50 years, Brazil, Russia, India and China – the BRICs economies – could become a much larger force in the world economy.” By 2050, Russia’s “GDP per capita is by far the highest in the group, and comparable to the G6. Russia’s economy overtakes Italy in 2018; France in 2024; UK in 2027 and Germany in 2028.” In line with this, foreign direct investment into Russia has skyrocketed (Exhibit 1). As more and more foreign companies are starting to look at Russia, it is becoming important to understand how to negotiate with its inhabitants. In this paper, we determine if business negotiations between Russians and Americans are different from business negotiations between Americans and Americans by employing both qualitative and quantitative methods. While there is a risk of stereotyping, we hope to shed some light on the intricacies of negotiations in order to help prepare Western business professionals interested in this fast-growing market

Voimaa kuin pienessä kylässä : tarvekartoitus ruukkikylään perustettavalle yhteiskunnalliselle yritykselle

Opinnäytetyön tarkoituksena oli kartoittaa toimintamahdollisuuksia perustettavalle yhteiskunnalliselle yritykselle Fiskarsin ruukin alueella. Tavoitteena oli tehdä tutkimus, joka voisi toimia yrityksen toiminnan ohjenuorana perustamisvaiheessa tarjoten vastauksia kysymyksiin, kuten ”mitä” ja ”kenelle”. Opinnäytetyö toteutettiin kvalitatiivisen tutkimuksen menetelmin käyttäen menetelmätriangulaatiota tutkimuksen tulosten luotettavuuden vahvistamiseksi. Työ alkoi esiselvityksellä ja varsinaisessa tutkimusvaiheessa käytettiin menetelminä Opera-ryhmätyöskentelymetodia, ryhmäkeskustelua ja osallistuvaa havainnointia. Tulokset osoittivat, että ruukissa on paljon mikroyrityksiä, joiden resurssit eivät riitä liiketoiminnan kaikkien osa-alueiden ylläpitoon. Useiden yritysten toiminta on kausiluontoista ja se asettaa rajoitteita tasapainoiselle yritystoiminnalle. Selkeimmin aineistosta nousi esiin huoli viestinnästä niin ruukin alueella yleisesti kuin yrityksissäkin sekä kokonaisuuksien koordinoinnin puute. Tulosten pohjalta osoittautui todennäköiseksi, että ruukkiin tarvittaisiin toimija, joka näkisi yrittäjien tarpeet ja osaisi törmäyttää yrityksiä ja asioita toisiinsa. Tämän onnistuessa yrittäjät voisivat yhteistyötä tekemällä saada enemmän ja vaikuttavampia tuloksia samoilla taloudellisilla panostuksilla. Tulokset ja niistä tehdyt johtopäätökset antavat aiheen yritystoiminnan aloittamiselle. Opinnäytetyön jatkotoimenpiteenä perustettiin yhteiskunnallinen yritys ”X”, joka tarjoaa viestinnän ja markkinoinnin palveluita. Yritys keskittyy yhteisluomisen menetelmin kehittämään ruukin yritysten liiketoimintaa suuntaan, joka mahdollistaa uusia yhteistyömahdollisuuksia ja synergiaetuja pienyrittäjille. Yritystoiminnan tärkeimpinä tavoitteina on yhteistyön ja hyvinvoinnin lisääminen uusia työtapoja kehittämällä. Opinnäytetyössä kerrotaan pääpiirteittäin yrityksen palvelutarjoomasta ja liiketoiminnan tulevaisuudesta.The purpose of this thesis is to identify opportunities for operational criteria for social enterprise in Fiskars Village area. The aim was to carry out a study, which could serve as a guideline for undertaking the action-start-up phase, providing answers to questions such as what and to whom. The thesis has been implemented by using three different methods of qualitative research to strengthen the reliability of the results. The work began with a preliminary survey and in the main research phase there was used Opera –workshop method, group discussions and participant observation. The results showed that in Fiskars village there is is a lot of micro-enterprises that do not have enough resources to maintain the business in all areas. A number of the businesses are seasonal and it sets limitations for balanced business operations. The material showed notably that there is a need for improving communication both between the actors in Fiskars Village and in the companies. Based on the results there is a clear need for an actor who could coordinate the operations in Fiskars and enable co-operation between the entrepreneurs so that they could get more results with the same investments. The results and the conclusions drawn from the thesis give reason for further action which is starting a business. The social enterprise "X" was founded during the thesis project. The company offers communications and marketing services but focuses mainly on developing the Fiskars villages businesses by offering co-design workshops and finding new methods that help the companies to see their customers’ needs better and focus on the right things in the operations. The main aim is to increase wellbeing by enabling synergy between the small-businesses, and by working together find new and better ways of doing things. The thesis contains a description of the social enterprise “X”s service offering as well the future of the business development

Transcriptional inhibition of type I collagen gene expression in scleroderma fibroblasts by the antineoplastic drug ecteinascidin 743.

We previously showed that COL1A1 expression is up-regulated at the transcriptional level in systemic sclerosis (SSc) fibroblasts and that the CCAAT-binding factor (CBF) is involved in this increased expression. Ecteinascidin 743 (ET-743) is a chemotherapeutic agent that binds with sequence specificity to the minor groove of DNA and inhibits CBF-mediated transcriptional activation of numerous genes. Therefore, we examined the effects of ET-743 on the increased COL1A1 expression in SSc fibroblasts. The drug caused a potent and dose-dependent inhibition of type I collagen biosynthesis, which reached 70-90% at 700 pM without affecting cell viability. The same drug concentration caused 60-80% reduction in COL1A1 mRNA levels. The stability of the corresponding transcripts was not affected. In vitro nuclear transcription assays demonstrated a 54% down-regulation of COL1A1 transcription. Transient transfections with COL1A1 promoter constructs containing the specific CBF binding sequence into SSc cells previously treated with 700 pM ET-743 failed to show an effect on COL1A1 promoter activity. Furthermore, ET-743 did not affect the binding of CBF or Sp1 transcription factors to their cognate COL1A1 elements. However, treatment with 700 pM ET-743 of stably transfected NIH 3T3 cells expressing a human type II procollagen gene under the control of the human COL1A1 promoter caused a greater than 50% reduction in the production of type II procollagen and a similar decrease in the corresponding type II procollagen transcripts. These results indicate that ET-743 is a potent inhibitor of COL1A1 transcription. However, this effect cannot be explained by a direct effect on CBF binding to the COL1A1 promoter. Although the exact mechanisms responsible for the transcriptional inhibition of COL1A1 by ET-743 are not apparent, our observations suggest that the drug may be an effective agent to decrease collagen overproduction in SSc and other fibrotic diseases

Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to altered dysbindin-1 gene expression

DTNBP1 (dystrobrevin binding protein 1) remains one of the top candidate genes in schizophrenia. Reduced expression of this gene and the protein it encodes, dysbindin-1, has been reported in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia cases. It has not been established, however, if all dysbindin-1 isoforms are reduced in the DLPFC or if the reduction is associated with reduced DTNBP1 gene expression. Using Western blotting of whole-tissue lysates of the DLPFC with antibodies differentially sensitive to the three major isoforms of this protein (dysbindin-1A, -1B, and -1C), we found no significant differences between our schizophrenia cases and matched controls in dysbindin-1A or -1B, but did find a mean 46% reduction in dysbindin-1C in 71% of 28 case-control pairs (p = 0.022). This occurred in the absence of the one DTNBP1 risk haplotype for schizophrenia reported in the US and without alteration in levels of dysbindin-1C transcripts. Conversely, the absence of changes in the dysbindin-1A and -1B isoforms was accompanied by increased levels of their transcripts. We thus found no correspondence between alterations in dysbindin-1 gene and protein expression, the latter of which might be due to posttranslational modifications such as ubiquitination. Reduced DLPFC dysbindin-1C in schizophrenia probably occurs in PSDs, where we find dysbindin-1C to be heavily concentrated in the human brain. Given known postsynaptic effects of dysbindin-1 reductions in the rodent homolog of the prefrontal cortex, these findings suggest that reduced dysbindin-1C in the DLPFC may contribute to cognitive deficits of schizophrenia by promoting NMDA receptor hypofunction

Effect of oxidative stress on protein tyrosine phosphatase 1B in scleroderma dermal fibroblasts

Objective Platelet‐derived growth factor (PDGF) and its receptor, PDGFR, promote fibrosis in systemic sclerosis (SSc; scleroderma) dermal fibroblasts, and such cells in scleroderma skin lesions produce excessive reactive oxygen species (ROS). PDGFR is phosphorylated upon PDGF stimulation, and is dephosphorylated by protein tyrosine phosphatases (PTPs), including PTP1B. This study was undertaken to determine whether the thiol‐sensitive PTP1B is affected by ROS in SSc dermal fibroblasts, thereby enhancing the phosphorylation of PDGFR and synthesis of type I collagen. This study also sought to investigate the effect of a thiol antioxidant, N ‐acetylcysteine (NAC), in SSc. Methods Fibroblasts were isolated from the skin of patients with diffuse SSc and normal healthy donors for cell culture experiments and immunofluorescence analyses. A phosphate release assay was used to determine the activity of PTP1B. Results Levels of ROS and type I collagen were significantly higher and amounts of free thiol were significantly lower in SSc fibroblasts compared to normal fibroblasts. After stimulation with PDGF, not only were PDGFR and ERK‐1/2 phosphorylated to a greater extent, but also the ability to produce PTP1B was hampered in SSc fibroblasts. The activity of PTP1B was significantly inactivated in SSc fibroblasts as a result of cysteine oxidation by the raised levels of ROS, which was confirmed by the oxidation of multiple PTPs, including PTP1B, in SSc fibroblasts. Decreased expression of PTP1B in normal fibroblasts led to increased expression of type I collagen. Treatment of the cells with NAC restored the activity of PTP1B, improved the profile of PDGFR phosphorylation, decreased the numbers of tyrosine‐phosphorylated proteins and levels of type I collagen, and scavenged ROS in SSc fibroblasts. Conclusion This study describes a new mechanism by which ROS may promote a profibrotic phenotype in SSc fibroblasts through the oxidative inactivation of PTP1B, leading to pronounced activation of PDGFR. The study also presents a novel molecular mechanism by which NAC may act on ROS and PTP1B to provide therapeutic benefit in SSc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91336/1/34336_ftp.pd

Synaptic Dysbindin-1 Reductions in Schizophrenia Occur in an Isoform-Specific Manner Indicating Their Subsynaptic Location

Background: An increasing number of studies report associations between variation in DTNBP1, a top candidate gene in schizophrenia, and both the clinical symptoms of the disorder and its cognitive deficits. DTNBP1 encodes dysbindin-1, reduced levels of which have been found in synaptic fields of schizophrenia cases. This study determined whether such synaptic reductions are isoform-specific. Methodology/Principal Findings: Using Western blotting of tissue fractions, we first determined the synaptic localization of the three major dysbindin-1 isoforms (A, B, and C). All three were concentrated in synaptosomes of multiple brain areas, including auditory association cortices in the posterior half of the superior temporal gyrus (pSTG) and the hippocampal formation (HF). Tests on the subsynaptic tissue fractions revealed that each isoform is predominantly, if not exclusively, associated with synaptic vesicles (dysbindin-1B) or with postsynaptic densities (dysbindin-1A and -1C). Using Western blotting on pSTG (n = 15) and HF (n = 15) synaptosomal fractions from schizophrenia cases and their matched controls, we discovered that synaptic dysbindin-1 is reduced in an isoform-specific manner in schizophrenia without changes in levels of synaptophysin or PSD-95. In pSTG, about 92% of the schizophrenia cases displayed synaptic dysbindin-1A reductions averaging 48% (p = 0.0007) without alterations in other dysbindin-1 isoforms. In the HF, by contrast, schizophrenia cases displayed normal levels of synaptic dysbindin-1A, but 67% showed synaptic reductions in dysbindin-1B averaging 33% (p = 0.0256), while 80% showed synaptic reductions in dysbindin-1C averaging 35% (p = 0.0171). Conclusions/Significance: Given the distinctive subsynaptic localization of dysbindin-1A, -1B, and -1C across brain regions, the observed pSTG reductions in dysbindin-1A are postsynaptic and may promote dendritic spine loss with consequent disruption of auditory information processing, while the noted HF reductions in dysbindin-1B and -1C are both presynaptic and postsynaptic and could promote deficits in spatial working memory

PDE-4 inhibition rescues aberrant synaptic plasticity in Drosophila and mouse models of fragile X syndrome.

Fragile X syndrome (FXS) is the leading cause of both intellectual disability and autism resulting from a single gene mutation. Previously, we characterized cognitive impairments and brain structural defects in a Drosophila model of FXS and demonstrated that these impairments were rescued by treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium. A well-documented biochemical defect observed in fly and mouse FXS models and FXS patients is low cAMP levels. cAMP levels can be regulated by mGluR signaling. Herein, we demonstrate PDE-4 inhibition as a therapeutic strategy to ameliorate memory impairments and brain structural defects in the Drosophila model of fragile X. Furthermore, we examine the effects of PDE-4 inhibition by pharmacologic treatment in the fragile X mouse model. We demonstrate that acute inhibition of PDE-4 by pharmacologic treatment in hippocampal slices rescues the enhanced mGluR-dependent LTD phenotype observed in FXS mice. Additionally, we find that chronic treatment of FXS model mice, in adulthood, also restores the level of mGluR-dependent LTD to that observed in wild-type animals. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of FXS is an important advance, in that this identifies and validates PDE-4 inhibition as potential therapeutic intervention for the treatment of individuals afflicted with FXS