Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination.

Inherited mutations in human PALB2 are associated with a predisposition to breast and pancreatic cancers. PALB2's tumor-suppressing effect is thought to be based on its ability to facilitate BRCA2's function in homologous recombination. However, the biochemical properties of PALB2 are unknown. Here we show that human PALB2 binds DNA, preferentially D-loop structures, and directly interacts with the RAD51 recombinase to stimulate strand invasion, a vital step of homologous recombination. This stimulation occurs through reinforcing biochemical mechanisms, as PALB2 alleviates inhibition by RPA and stabilizes the RAD51 filament. Moreover, PALB2 can function synergistically with a BRCA2 chimera (termed piccolo, or piBRCA2) to further promote strand invasion. Finally, we show that PALB2-deficient cells are sensitive to PARP inhibitors. Our studies provide the first biochemical insights into PALB2's function with piBRCA2 as a mediator of homologous recombination in DNA double-strand break repair.

Potential for enterprise cooperation between Southeast Finland and Northwest Russia

Tutkimus käsittelee Kaakkois-Suomen ja Luoteis-Venäjän yritysten nykyistä yhteistyötä ja arvioi sen tulevaisuuden mahdollisuuksia. Raportissa käydään läpi useita toimialoja, jotka ovat tärkeitä paikalliselle elinkeinoelämälle tai joissa Venäjän merkitys on korostunut. Tutkimukset kattamat alat ovat metsäteollisuus, elintarviketeollisuus, metalliteollisuus, tieto- ja viestintäteollisuus, logistiikka, matkailusekä energia ja ympäristö. Kaakkois-Suomen ja Luoteis-Venäjän väliset kauppa- ja taloussuhteet ovat perinteisesti olleet vilkkaat maantieteellisestä läheisyydestä johtuen. Pääpaino kanssakäymisessä on ollut kaupalla, mutta Neuvostoliiton hajottua yritysten välille on kehittynyt myös muita yhteistoiminnan muotoja kutenyhteistuotantoa ja alihankintaa. Kaakkois-Suomen yritysten näkökulmasta Venäjänedullinen kustannustaso houkuttelee siirtämään tuotannollisia toimintoja rajan taakse. Tuotannollisen yhteistoiminnan aloittamista ja menestyksellistä toteuttamista hankaloittaa kuitenkin yritysympäristön kehittymättömyys Venäjällä ja usein myös osapuolten näkemyserot toiminnan tavoitteista ja liiketoimintakäytännöistä. Raportin ensimmäisessä osassa arvioidaan yhteistyöpotentiaalia valituilla toimialoilla analysoimalla alojen nykytilaa Kaakkois-Suomessa ja Luoteis- Venäjällä. Nykytilakartoituksen avulla selvitetään yhteistyön motiiveja suomalaisten yritysten kannalta ja sen tuottamaa mahdollista kilpailuetua. Toisessa osassa kuvataan Luoteis-Venäjän muodollista liiketoimintaympäristöä, mukaan lukien lainsäädäntö, hallinto ja liiketoiminnan tukiorganisaatiot. Kolmannessa osassa esitetään suomalais-venäläistä yritysyhteistyötä koskevia kokemuksia ja odotuksia, verrataan eri osapuolten näkemyksiä keskenään ja kuvataan yhteistyön yleisimpiä rajoitteita ja ongelmia. Tutkimustulosten valossa vaikuttaa siltä, että Luoteis-Venäjällä tuotannosta saatu kustannushyöty on pienenemässä palkkojen ja energiakustannusten noustessa. Luoteis-Venäjän merkitys markkina-alueena on vastaavasti kasvussa. Tavaroiden viennin lisäksi talouskasvu ja paikalliset investoinnit esimerkiksilogistiikka- ja energiainfrastruktuuriin tarjoavat mahdollisuuksia suomalaisille palveluiden ja teknologian viejille. Toisaalta monikansallisten yritysten etabloituminen Luoteis-Venäjälle (esim. Ford ja IKEA) luovat kysyntää paikallisille alihankkijoille. Suomalaisyritykset voisivat ottaa siitä osansa investoimalla paikalliseen tuotantoon. Palvelualoilla, kuten logistiikkasektorilla ja matkailussa Luoteis-Venäjän merkitys Kaakkois-Suomen kilpailijana on kasvussa paikallisen infrastruktuurin kehittyessä. Näillä aloilla tulisikin keskittyä ei ainoastaan Suomen kilpailukyvyn ylläpitoon vaan myös liiketoimintayhteistyön kehittämiseen venäläisten toimijoiden kanssa.

Let's share perspectives! Mentalistic skills involved in cooperation = ¿A tu Izquierda o a la Mía? Habilidades Mentalistas Implicadas en la Cooperación

Previous research has found a link between theory of mind and cooperation. The aim of this study is to deepen into this relationship, to identify which theory of mind skills are more related to the cooperative capacity on a referential communication task. A total of 50 children from first and fifth grade completed a battery of theory of mind tasks, and also a cooperative task where children worked in pairs to build block models. Each pair was composed by a builder and a guide, who gave instructions to his partner about how to build a replica of the model. The results show a significant relationship between the theory of mind skills and cooperation. Specifically, we found that the second-order false-belief task was the variable most related to cooperation after controlling the effect of age. In addition, we observed that the mentalist skills were more important for cooperation in the builders than in the guides. Finally, we discuss the findings of this study and make suggestions for the future

Diagnostic and Prognostic Impact of pc-ASPECTS Applied to Perfusion CT in the Basilar Artery International Cooperation Study.

BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-APECTS) applied to CT angiography source images (CTA-SI) predicts the functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic and prognostic impact of pc-ASPECTS applied to perfusion CT (CTP) in the BASICS registry population. METHODS: We applied pc-ASPECTS to CTA-SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA-SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal. RESULTS: CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93%; 95% confidence interval [CI], 76%-99%), compared with 78% (58%-91%) for CTA-SI and CBF, and 46% (27%-67%) for CBV (P < .001). All 3 patients with a CBV pc-ASPECTS < 8 compared to 6/23 patients with a CBV pc-ASPECTS ≥ 8 had died at 1 month (RR 3.8; 95% CI, 1.9-7.6). CONCLUSION: CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps. CBV pc-ASPECTS < 8 may indicate patients with high case fatality.

The Swiss reform of the allocation of tasks : The conventions-programs as a new partnership model for vertical cooperation ?

This research examines the impacts of the Swiss reform of the allocation of tasks which was accepted in 2004 and implemented in 2008 to "re-assign" the responsibilities between the federal government and the cantons. The public tasks were redistributed, according to the leading and fundamental principle of subsidiarity. Seven tasks came under exclusive federal responsibility; ten came under the control of the cantons; and twenty-two "common tasks" were allocated to both the Confederation and the cantons. For these common tasks it wasn't possible to separate the management and the implementation. In order to deal with nineteen of them, the reform introduced the conventions-programs (CPs), which are public law contracts signed by the Confederation with each canton. These CPs are generally valid for periods of four years (2008-11, 2012-15 and 2016-19, respectively). The third period is currently being prepared. By using the principal-agent theory I examine how contracts can improve political relations between a principal (Confederation) and an agent (canton). I also provide a first qualitative analysis by examining the impacts of these contracts on the vertical cooperation and on the implication of different actors by focusing my study on five CPs - protection of cultural heritage and conservation of historic monuments, encouragement of the integration of foreigners, economic development, protection against noise and protection of the nature and landscape - applied in five cantons, which represents twenty-five cases studies.

Cooperation versus competition effects on information sharing and use in group decision making

Information processing in groups has long been seen as a cooperative process. In contrast with this assumption, group members were rarely found to behave cooperatively: They withhold unshared information and stick to initial incorrect decisions. In the present article, we examined how group members' cooperative and competitivemotives impact on group information processing and propose that information sharing and use in groups could be seen as strategic behavior. We reviewed the latest developments in the literature investigating different forms of strategic information processing and their underlying mechanisms. This review suggests that explicit cooperative goals are needed for effective group decision-making.

Privatization, cooperation and costs of solid waste services in small towns

This paper analyzes the cost implications of privatization and cooperation in the provision of solid waste services for a sample of small municipalities. In conducting this empirical analysis, a survey is first designed and administered to municipalities in the Spanish region of Aragon, and then an estimation of the determinants of service costs is undertaken, considering the possible endogeneity of delivery choices. Our findings indicate that cooperation is more effective than privatization in saving costs. Both production forms can enable small municipalities to cut costs by exploiting scale economies. However, the fact that inter-municipal cooperation involves lower transaction costs and is less likely to be affected by competition problems would seem to account for the fact that it is a more effective way of reducing costs.

Co-opetition: Coexistence of cooperation and competition in public sector – A case study in one city’s public companies

Business actions do not take place in isolation. Complementary competencies and capabilities are the most important resources in the exponential knowledge growth. These resources are partially accessed via business partners. A company needs partners and the capability to cooperate, but also the awareness of the competitive tension, when operating in the market with multiple actors. The co-opetition research studies the occurrence and the forms of simultaneous cooperation and competition between companies or their units. Public sector’s governmental and municipal organs have been transformed into companies over the past years. Despite of their non-profit nature, public sector and public companies are adopting business doctrines from private sector towards efficient business operations. This case study aims to show, how co-opetition concept can be observed within public sector companies and in their operations with others, how public companies cooperate but also compete with others and why this happens. This thesis also explicates advantages and disadvantages of the co-opetition phenomenon.

Pleiotropy and the low cost of individual traits promote cooperation.

The evolution of cooperation is thought to be promoted by pleiotropy, whereby cooperative traits are coregulated with traits that are important for personal fitness. However, this hypothesis faces a key challenge: what happens if mutation targets a cooperative trait specifically rather than the pleiotropic regulator? Here, we explore this question with the bacterium Pseudomonas aeruginosa, which cooperatively digests complex proteins using elastase. We empirically measure and theoretically model the fate of two mutants-one missing the whole regulatory circuit behind elastase production and the other with only the elastase gene mutated-relative to the wild-type (WT). We first show that, when elastase is needed, neither of the mutants can grow if the WT is absent. And, consistent with previous findings, we show that regulatory gene mutants can grow faster than the WT when there are no pleiotropic costs. However, we find that mutants only lacking elastase production do not outcompete the WT, because the individual cooperative trait has a low cost. We argue that the intrinsic architecture of molecular networks makes pleiotropy an effective way to stabilize cooperative evolution. Although individual cooperative traits experience loss-of-function mutations, these mutations may result in weak benefits, and need not undermine the protection from pleiotropy.

Cooperation in R&D, firm size and type of partnership: Evidence for the Spanish automotive industry

This paper aims to analyse cooperation in R&D in the automobile industry in Spain. It first examines to what extent firms cooperate with external actors in the field of technological innovation, and if so, with what type of cooperation partner, paying special attention to the differentiation according to the size of the firms. Second, it aims to study how the firm’s size may affect not only the decision of cooperating but also with which type of partner, while controlling for other determinants that have been considered in the literature as main drivers of collaborative activities in R&D. We use data provided by the Technological Innovation Panel in the 2006-2008 period for firms in the automotive sector. We estimate a bivariate probit model that takes into account the two types of cooperation mostly present in the automotive industry, vertical and institutional, explicitly considering the interdependencies that may arise in the simultaneous choice of both.