The Physical Basis for Long-lived Electronic Coherence in Photosynthetic Light Harvesting Systems

The physical basis for observed long-lived electronic coherence in photosynthetic light-harvesting systems is identified using an analytically soluble model. Three physical features are found to be responsible for their long coherence lifetimes: i) the small energy gap between excitonic states, ii) the small ratio of the energy gap to the coupling between excitonic states, and iii) the fact that the molecular characteristics place the system in an effective low temperature regime, even at ambient conditions. Using this approach, we obtain decoherence times for a dimer model with FMO parameters of $\approx$ 160 fs at 77 K and $\approx$ 80 fs at 277 K. As such, significant oscillations are found to persist for 600 fs and 300 fs, respectively, in accord with the experiment and with previous computations. Similar good agreement is found for PC645 at room temperature, with oscillations persisting for 400 fs. The analytic expressions obtained provide direct insight into the parameter dependence of the decoherence time scales.Comment: 5 figures; J. Phys. Chem. Lett. (2011

HIV gp120 in the lungs of antiretroviral therapy–treated Individuals impairs alveolar macrophage responses to pneumococci

Rationale People living with HIV (PLWH) are at significantly increased risk of invasive pneumococcal disease, despite long-term antiretroviral therapy (ART). The mechanism explaining this observation remains undefined. Objectives We hypothesized apoptosis-associated microbicidal mechanisms, required to clear intracellular pneumococci that survive initial phagolysosomal killing, are perturbed. Methods Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) from healthy donors or HIV-1-seropositive donors on long-term ART with undetectable plasma viral load. Monocyte-derived macrophages (MDM) were obtained from healthy donors and infected with HIV-1BaL or treated with gp120. Macrophages were challenged with opsonized serotype 2 Streptococcus pneumoniae and assessed for apoptosis, bactericidal activity, protein expression and mitochondrial reactive oxygen species (mROS). AM phenotyping, ultra-sensitive HIV-1 RNA quantification and gp120 measurement were also performed in BAL. Measurements and Main Results HIV-1BaL infection impaired apoptosis, induction of mROS and pneumococcal killing by MDM. Apoptosis-associated pneumococcal killing was also reduced in AM from ART treated HIV-1-seropositive donors. BAL fluid from these individuals demonstrated persistent lung CD8+ T-cell lymphocytosis, and gp120 or HIV-1 RNA was also detected. Despite this, transcriptional activity in AM freshly isolated from PLWH was broadly similar to healthy volunteers. Instead, gp120 phenocopied the defect in pneumococcal killing in healthy MDM through post-translational modification of Mcl-1, preventing apoptosis induction, caspase activation and increased mROS generation. Moreover gp120 also inhibited mROS dependent pneumococcal killing in MDM. Conclusions. Despite ART, HIV-1, via gp120, drives persisting innate immune defects in AM microbicidal mechanisms, enhancing susceptibility to pneumococcal disease

How journal rankings can suppress interdisciplinary research. A comparison between Innovation Studies and Business & Management

This study provides quantitative evidence on how the use of journal rankings can disadvantage interdisciplinary research in research evaluations. Using publication and citation data, it compares the degree of interdisciplinarity and the research performance of a number of Innovation Studies units with that of leading Business & Management schools in the UK. On the basis of various mappings and metrics, this study shows that: (i) Innovation Studies units are consistently more interdisciplinary in their research than Business & Management schools; (ii) the top journals in the Association of Business Schools' rankings span a less diverse set of disciplines than lower-ranked journals; (iii) this results in a more favourable assessment of the performance of Business & Management schools, which are more disciplinary-focused. This citation-based analysis challenges the journal ranking-based assessment. In short, the investigation illustrates how ostensibly 'excellence-based' journal rankings exhibit a systematic bias in favour of mono-disciplinary research. The paper concludes with a discussion of implications of these phenomena, in particular how the bias is likely to affect negatively the evaluation and associated financial resourcing of interdisciplinary research organisations, and may result in researchers becoming more compliant with disciplinary authority over time.Comment: 41 pages, 10 figure

Computational Methodologies and Physical Insights into Electronic Energy Transfer in Photosynthetic Light-Harvesting Complexes

We examine computational techniques and methodologies currently in use to explore electronic excitation energy transfer in the context of light-harvesting complexes in photosynthetic antenna systems, and comment on some new insights into the underlying physics. Advantages and pitfalls of these methodologies are discussed, as are some physical insights into the photosynthetic dynamics. By combining results from molecular modelling of the complexes (structural description) with an effective non-equilibrium statistical description (time evolution), we identify some general features, regardless of the particular distribution in the protein scaffold, that are central to light-harvesting dynamics and, that could ultimately be related to the high efficiency of the overall process. Based on these general common features, some possible new directions in the field are discussed.Comment: Invited Perspective Article for Phys. Chem. Chem. Phy

Impaired Mitochondrial Microbicidal Responses in Chronic Obstructive Pulmonary Disease Macrophages

RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by impaired clearance of pulmonary bacteria. OBJECTIVES: The effect of COPD on alveolar macrophage (AM) microbicidal responses was investigated. METHODS: Alveolar macrophages (AMs) were obtained from bronchoalveolar lavage from healthy donors or COPD patients and challenged with opsonized serotype 14 Streptococcus pneumoniae. Cells were assessed for apoptosis, bactericidal activity and mitochondrial reactive oxygen species (mROS) production. A transgenic mouse line, in which the CD68 promoter ensures macrophage specific expression of human Mcl-1 (CD68.hMcl-1), was used to model the molecular aspects of COPD. MEASUREMENTS AND MAIN RESULTS: COPD AM had elevated levels of Mcl-1, an anti-apoptotic Bcl-2 family member, with selective reduction of delayed intracellular bacterial killing. CD68.hMcl-1 AM phenocopied the microbicidal defect since transgenic mice demonstrated impaired clearance of pulmonary bacteria and increased neutrophilic inflammation. Murine bone marrow-derived macrophages (BMDM) and human monocyte-derived macrophages (MDM) generated mitochondrial reactive oxygen species (mROS) in response to pneumococci, which co-localized with bacteria and phagolysosomes to enhance bacterial killing. The Mcl-1 transgene increased oxygen consumption rates and mROS expression in mock-infected BMDM but reduced caspase-dependent mROS production after pneumococcal challenge. COPD AM also increased basal mROS expression, but failed to increase production after pneumococcal challenge, in keeping with reduced intracellular bacterial killing. The defect in COPD AM intracellular killing was associated with a reduced ratio of mROS /superoxide dismutase 2. CONCLUSIONS: Upregulation of Mcl-1 and chronic adaption to oxidative stress alters mitochondrial metabolism and microbicidal function, reducing the delayed phase of intracellular bacterial clearance in COPD

Scaffolding development and the human condition

This paper addresses the concept of semiotic scaffolding by considering it in light of questions arising from the contemporary challenge to the humanities. This challenge comes from a mixture of scientistic demands, opportunism on the part of Western governments in thrall to neo-liberalism, along with crass economic utilitarianism. In this paper we attempt to outline what a theory of semiotic scaffolding may offer to an understanding of the humanities’ contemporary role, as well as what the humanities might offer to the elucidation of semiotic scaffolding. We argue that traditional humanist positions adopted in defence of the humanities fail to articulate the enhancement of humanity that semiotic scaffolding represents. At the same time, we note that the concept of scaffolding is sometimes in danger of taking on a functionalist perspective which understanding the humanities modus operandi is likely to dispel. Putting forward these arguments, we draw on the work of Peirce, Cassirer and Sebeok in elucidating the structural and ‘future-orientated’ benefits of the scaffolding process as it suffuses the humanities

In the Shadow of Celebrity? World-Class University Policies and Public Value in Higher Education

The growing popularity of the concept of world-class universities raises the question of whether investing in such universities is a worthwhile use of public resources. Does concentrating public resources on the most excellent universities improve the overall quality of a higher education system, especially if definitions of excellence and world-class are made by external ranking organizations? This paper addresses that question by developing a framework for weighing up trade-offs between institutional and system performance, focusing on the potential system-wide improvements which world-class university programmes (WCUPs) may bring. Because WCUPs are in a relatively early stage of their development, systemic effects are not yet clear. We therefore analyse the ex ante reasons that policy makers have for adopting WCUPs to see if they at least seek to create these systemic benefit