On fair cost facility location games with non-singleton players

In the fair cost facility location game, players control terminals and must open and connect each terminal to a facility, while paying connection costs and equally sharing the opening costs associated with the facilities it connects to. In most of the literature, it is assumed that each player control a single terminal. We explore a more general version of the game where each player may control multiple terminals. We prove that this game does not always possess pure Nash equilibria, and deciding whether an instance has equilibria is NP-Hard, even in metric instances. Furthermore, we present results regarding the efficiency of equilibria, showing that the price of stability of this game is equal to the price of anarchy, in both uncapacitated and capacitated settings

On the effectiveness of connection tolls in fair cost facility location games

We investigate the effectiveness of tolls to reduce the inefficiency of Nash equilibria in the classical fair cost facility location game. In this game, every terminal corresponds to a selfish player who wants to connect to some facility at minimum cost. The cost of a player is determined by the connection cost to the chosen facility plus an equal share of its opening cost. We are interested in the problem of imposing tolls on the connections to induce a socially optimal Nash equilibrium such that the total amount of tolls is minimized. It turns out that this problem is challenging to solve even for simple special cases. We provide polynomial-time algorithms for (i) instances with two facilities, and (ii) instances with a constant number of facilities arranged as a star. Our algorithm for (ii) exploits a relation between our tolling problem and a novel bipartite matching problem without crossings, which we prove to be NP-hard

Potential contribution of beneficial microbes to face the COVID-19 pandemic

The year 2020 will be remembered by a never before seen, at least by our generation, global pandemic of COVID-19. While a desperate search for effective vaccines or drug therapies is on the run, nutritional strategies to promote immunity against SARS-CoV-2, are being discussed. Certain fermented foods and probiotics may deliver viable microbes with the potential to promote gut immunity. Prebiotics, on their side, may enhance gut immunity by selectively stimulating certain resident microbes in the gut. Different levels of evidence support the use of fermented foods, probiotics and prebiotics to promote gut and lungs immunity. Without being a promise of efficacy against COVID-19, incorporating them into the diet may help to low down gut inflammation and to enhance mucosal immunity, to possibly better face the infection by contributing to diminishing the severity or the duration of infection episodes.Fil: Antunes, Adriane E.C.. Universidade Estadual de Campinas; BrasilFil: Vinderola, Celso Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Xavier-Santos, Douglas. Universidade Estadual de Campinas; BrasilFil: Sivieri, Katia. Universidade Estadual Paulista Julio de Mesquita Filho; Brasi

Structural Basis for the Inhibition of Host Protein Ubiquitination by Shigella Effector Kinase OspG

SummaryShigella invasion of its human host is assisted by T3SS-delivered effector proteins. The OspG effector kinase binds ubiquitin and ubiquitin-loaded E2-conjugating enzymes, including UbcH5b and UbcH7, and attenuates the host innate immune NF-kB signaling. We present the structure of OspG bound to the UbcH7∼Ub conjugate. OspG has a minimal kinase fold lacking the activation loop of regulatory kinases. UbcH7∼Ub binds OspG at sites remote from the kinase active site, yet increases its kinase activity. The ubiquitin is positioned in the “open” conformation with respect to UbcH7 using its I44 patch to interact with the C terminus of OspG. UbcH7 binds to OspG using two conserved loops essential for E3 ligase recruitment. The interaction of the UbcH7∼Ub with OspG is remarkably similar to the interaction of an E2∼Ub with a HECT E3 ligase. OspG interferes with the interaction of UbcH7 with the E3 parkin and inhibits the activity of the E3

Effects of dietary curcumin in growth performance, oxidative status and gut morphometry and function of gilthead seabream postlarvae

An imbalance in the production and detoxification of reactive oxygen species and other oxidants can disrupt a l l types of cellular compounds, and lead to a state of oxidative stress. Preventing this state is essential to improve growth and health in animal production. Therefore, the aim of this work was to assess i f the dieta r y supple-mentation of curcumin cou l d improve the antioxidant status and intestine structu r e and functionalit y of gilthead seabream postlarvae, with the global objective of improving fish growth performance and robustness. Two experimental diets supplemented with different doses of curcumin (LOW and HIGH diets), and a commercial diet were fed to quadruplicate groups of postlarvae, for 20 days. At the end of the feeding trial fish fed the supple-mented diets significantly improved their antioxidant status compared to CTRL fed fish. LOW and HIGH fed fish presented lower protein oxidative damage (P 0.05). In conclusion, dieta r y curcumin supplementation was able to enhance gilthead seabream postlarvae robustness through a modulation of the oxidative status, increasing total antioxidant capacity and decreasing protein oxidative damage. This data pro-vide evidence that curcumin can be a suitable feed additive to promote heath status and robustness of fish at early stages of development, therefore contributing for the development and sustainabilit y of marine fish hatchery production.info:eu-repo/semantics/publishedVersio

Diagnostic criteria and long-term outcomes in AIH-PBC variant syndrome under combination therapy

Background &amp; Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria. Methods: Eighty-three patients with a clinical suspicion of AIH-PBC who were treated with combination therapy were included. Histology was re-evaluated. Characteristics and long-term outcomes were retrospectively compared to patients with AIH and PBC. Results: Seventeen (24%) patients treated with combination therapy fulfilled the Paris criteria. Fifty-two patients (70%) fulfilled the Zhang criteria. Patients who met Paris and Zhang criteria more often had inflammation and fibrosis on histology compared to patients only meeting the Zhang criteria. Ten-year liver transplant (LT)-free survival was 87.3% (95% CI 78.9–95.7%) in patients with AIH-PBC. This did not differ in patients in or outside the Paris or Zhang criteria (p = 0.46 and p = 0.40, respectively) or from AIH (p = 0.086). LT-free survival was significantly lower in patients with PBC and severe hepatic inflammation – not receiving immunosuppression – compared to those with AIH-PBC (65%; 95% CI 52.2–77.8% vs. 87%; 95% CI 83.2–90.8%; hazard ratio 0.52; p = 0.043). Conclusions: In this study, patients with AIH-PBC outside Paris or Zhang criteria were frequently labeled as having AIH-PBC and were successfully treated with combination therapy with similar outcomes. LT-free survival was worse in patients with PBC and hepatic inflammation than in those treated as having AIH-PBC. More patients may benefit from combination therapy. Impact and implications: This study demonstrated that patients with AIH-PBC variant syndrome treated with combined therapy consisting of immunosuppressants and ursodeoxycholic acid often do not fulfill the Paris criteria. They do however have comparable response to therapy and long-term outcomes as patients who do fulfill the diagnostic criteria. Additionally, patients with PBC and additional signs of hepatic inflammation have poorer long-term outcomes compared to patients treated as having AIH-PBC. These results implicate that a larger group of patients with features of both AIH and PBC may benefit from combined treatment. With our results, we call for improved consensus among experts in the field on the diagnosis and management of AIH-PBC variant syndrome.</p

Diagnostic criteria and long-term outcomes in AIH-PBC variant syndrome under combination therapy

Background &amp; Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria. Methods: Eighty-three patients with a clinical suspicion of AIH-PBC who were treated with combination therapy were included. Histology was re-evaluated. Characteristics and long-term outcomes were retrospectively compared to patients with AIH and PBC. Results: Seventeen (24%) patients treated with combination therapy fulfilled the Paris criteria. Fifty-two patients (70%) fulfilled the Zhang criteria. Patients who met Paris and Zhang criteria more often had inflammation and fibrosis on histology compared to patients only meeting the Zhang criteria. Ten-year liver transplant (LT)-free survival was 87.3% (95% CI 78.9–95.7%) in patients with AIH-PBC. This did not differ in patients in or outside the Paris or Zhang criteria (p = 0.46 and p = 0.40, respectively) or from AIH (p = 0.086). LT-free survival was significantly lower in patients with PBC and severe hepatic inflammation – not receiving immunosuppression – compared to those with AIH-PBC (65%; 95% CI 52.2–77.8% vs. 87%; 95% CI 83.2–90.8%; hazard ratio 0.52; p = 0.043). Conclusions: In this study, patients with AIH-PBC outside Paris or Zhang criteria were frequently labeled as having AIH-PBC and were successfully treated with combination therapy with similar outcomes. LT-free survival was worse in patients with PBC and hepatic inflammation than in those treated as having AIH-PBC. More patients may benefit from combination therapy. Impact and implications: This study demonstrated that patients with AIH-PBC variant syndrome treated with combined therapy consisting of immunosuppressants and ursodeoxycholic acid often do not fulfill the Paris criteria. They do however have comparable response to therapy and long-term outcomes as patients who do fulfill the diagnostic criteria. Additionally, patients with PBC and additional signs of hepatic inflammation have poorer long-term outcomes compared to patients treated as having AIH-PBC. These results implicate that a larger group of patients with features of both AIH and PBC may benefit from combined treatment. With our results, we call for improved consensus among experts in the field on the diagnosis and management of AIH-PBC variant syndrome.</p