80 research outputs found

    Driven Spin Systems as Quantum Thermodynamic Machines: Fundamental Limits

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    We show that coupled two level systems like qubits studied in quantum information can be used as a thermodynamic machine. At least three qubits or spins are necessary and arranged in a chain. The system is interfaced between two split baths and the working spin in the middle is externally driven. The machine performs Carnot-type cycles and is able to work as heat pump or engine depending on the temperature difference of the baths ΔT\Delta T and the energy differences in the spin system ΔE\Delta E. It can be shown that the efficiency is a function of ΔT\Delta T and ΔE\Delta E.Comment: 9 pages, 11 figures, accepted for publication in Phys. Rev.

    Global and local relaxation of a spin-chain under exact Schroedinger and master-equation dynamics

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    We solve the Schroedinger equation for an interacting spin-chain locally coupled to a quantum environment with a specific degeneracy structure. The reduced dynamics of the whole spin-chain as well as of single spins is analyzed. We show, that the total spin-chain relaxes to a thermal equilibrium state independently of the internal interaction strength. In contrast, the asymptotic states of each individual spin are thermal for weak but non-thermal for stronger spin-spin coupling. The transition between both scenarios is found for couplings of the order of 0.1×ΔE0.1 \times \Delta E, with ΔE\Delta E denoting the Zeeman-splitting. We compare these results with a master equation treatment; when time averaged, both approaches lead to the same asymptotic state and finally with analytical results.Comment: RevTeX, 8 pages, 14 figures, added DOI and forgotten reference

    Visibility in Information Spaces and in Geographic Environments. Post-Proceedings of the KI'11 Workshop (October 4th, 2011, TU Berlin, Germany)

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    In the post-proceedings of the Workshop "Visibility in Information Spaces and in Geographic Environments" a selection of research papers is presented where the topic of visibility is addressed in different contexts. Visibility governs information selection in geographic environments as well as in information spaces and in cognition. The users of social media navigate in information spaces and at the same time, as embodied agents, they move in geographic environments. Both activities follow a similar type of information economy in which decisions by individuals or groups require a highly selective filtering to avoid information overload. In this context, visibility refers to the fact that in social processes some actors, topics or places are more salient than others. Formal notions of visibility include the centrality measures from social network analysis or the plethora of web page ranking methods. Recently, comparable approaches have been proposed to analyse activities in geographic environments: Place Rank, for instance, describes the social visibility of urban places based on the temporal sequence of tourist visit patterns. The workshop aimed to bring together researchers from AI, Geographic Information Science, Cognitive Science, and other disciplines who are interested in understanding how the different forms of visibility in information spaces and geographic environments relate to one another and how the results from basic research can be used to improve spatial search engines, geo-recommender systems or location-based social networks

    Social construction, evolution and cultural universals

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    This paper discusses the connection between social constructionism and universals in the generation of mind. It proposes a new concept of Cultural Construction, distinct from social construction, and suggests that the latter succumbs to a Paradox of Sociality in which a socially constructed mind is non-social. Cultural construction avoids this paradox, and is best explained by an approach that roots learning in flexible evolutionary dispositions to possess culture. It also offers a novel perspective on traditional and more recent social constructionist accounts of psychological universals (e.g. omniculture) and has different implications for the prospects of reducing conflict in inter-cultural encounters

    Profiling of Flavonol Derivatives for the Development of Antitrypanosomatidic Drugs

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    Flavonoids represent a potential source of new antitrypanosomatidic leads. Starting from a library of natural products, we combined target-based screening on pteridine reductase 1 with phenotypic screening on Trypanosoma brucei for hit identification. Flavonols were identified as hits, and a library of 16 derivatives was synthesized. Twelve compounds showed EC50 values against T. brucei below 10 \u3bcM. Four X-ray crystal structures and docking studies explained the observed structure-activity relationships. Compound 2 (3,6-dihydroxy-2-(3-hydroxyphenyl)-4H-chromen-4-one) was selected for pharmacokinetic studies. Encapsulation of compound 2 in PLGA nanoparticles or cyclodextrins resulted in lower in vitro toxicity when compared to the free compound. Combination studies with methotrexate revealed that compound 13 (3-hydroxy-6-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one) has the highest synergistic effect at concentration of 1.3 \u3bcM, 11.7-fold dose reduction index and no toxicity toward host cells. Our results provide the basis for further chemical modifications aimed at identifying novel antitrypanosomatidic agents showing higher potency toward PTR1 and increased metabolic stability

    Genetic Determinants of Cardiovascular Events among Women with Migraine: A Genome-Wide Association Study

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    Migraine is associated with an increased risk for cardiovascular disease (CVD). Both migraine and CVD are highly heritable. However, the genetic liability for CVD among migraineurs is unclear.We performed a genome-wide association study for incident CVD events during 12 years of follow-up among 5,122 migraineurs participating in the population-based Women's Genome Health Study. Migraine was self-reported and CVD events were confirmed after medical records review. We calculated odds ratios (OR) and 95% confidence intervals (CI) and considered a genome-wide p-value <5×10(-8) as significant.Among the 5,122 women with migraine 164 incident CVD events occurred during follow-up. No SNP was associated with major CVD, ischemic stroke, myocardial infarction, or CVD death at the genome-wide level; however, five SNPs showed association with p<5×10(-6). Among migraineurs with aura rs7698623 in MEPE (OR = 6.37; 95% CI 3.15-12.90; p = 2.7×10(-7)) and rs4975709 in IRX4 (OR = 5.06; 95% CI 2.66-9.62; p = 7.7×10(-7)) appeared to be associated with ischemic stroke, rs2143678 located close to MDF1 with major CVD (OR = 3.05; 95% CI 1.98-4.69; p = 4.3×10(-7)), and the intergenic rs1406961 with CVD death (OR = 12.33; 95% CI 4.62-32.87; p = 5.2×10(-7)). Further, rs1047964 in BACE1 appeared to be associated with CVD death among women with any migraine (OR = 4.67; 95% CI 2.53-8.62; p = 8.0×10(-7)).Our results provide some suggestion for an association of five SNPs with CVD events among women with migraine; none of the results was genome-wide significant. Four associations appeared among migraineurs with aura, two of those with ischemic stroke. Although our population is among the largest with migraine and incident CVD information, these results must be treated with caution, given the limited number of CVD events among women with migraine and the low minor allele frequencies for three of the SNPs. Our results await independent replication and should be considered hypothesis generating for future research

    Physiological Correlates of Volunteering

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    We review research on physiological correlates of volunteering, a neglected but promising research field. Some of these correlates seem to be causal factors influencing volunteering. Volunteers tend to have better physical health, both self-reported and expert-assessed, better mental health, and perform better on cognitive tasks. Research thus far has rarely examined neurological, neurochemical, hormonal, and genetic correlates of volunteering to any significant extent, especially controlling for other factors as potential confounds. Evolutionary theory and behavioral genetic research suggest the importance of such physiological factors in humans. Basically, many aspects of social relationships and social activities have effects on health (e.g., Newman and Roberts 2013; Uchino 2004), as the widely used biopsychosocial (BPS) model suggests (Institute of Medicine 2001). Studies of formal volunteering (FV), charitable giving, and altruistic behavior suggest that physiological characteristics are related to volunteering, including specific genes (such as oxytocin receptor [OXTR] genes, Arginine vasopressin receptor [AVPR] genes, dopamine D4 receptor [DRD4] genes, and 5-HTTLPR). We recommend that future research on physiological factors be extended to non-Western populations, focusing specifically on volunteering, and differentiating between different forms and types of volunteering and civic participation

    Path dependence and the stabilization of strategic premises: how the funeral industry buries itself

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    Several studies have shown that path-dependent organizations may pathologically reproduce their paths even in times of crisis. The unchallenged retention of underlying strategic premises seems to play a key role in this selfdestructive process. Whereas the previous literature largely assumes that organizational crises provide sufficient impetus for updating strategic premises, recent empirical studies have highlighted that path-dependent organizations may find this highly difficult. In the present study, I explore how path-dependent organizations stabilize strategic premises even in times of crisis. Drawing on a case study of the funeral industry, I theoretically distill four mechanisms that stabilize strategic premises in path-dependent organizations despite the fierce pressures of organizational crises. While these mechanisms constitute either reflexive modes of processing feedback or generative modes of producing market outcomes, they all inhibit a disconfirmation and, thus, an update of strategic premises. Furthermore, the study presents indicative evidence of how this unchallenged retention of strategic premises leads to the pathological reproduction of the path

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
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