Quantum probing beyond pure dephasing

Quantum probing is the art of exploiting simple quantum systems interacting with a complex environment to extract precise information about some environmental parameters, e.g. the temperature of the environment or its spectral density. Here we analyze the performance of a single-qubit probe in characterizing Ohmic bosonic environments at thermal equilibrium. In particular, we analyze the effects of tuning the interaction Hamiltonian between the probe and the environment, going beyond the traditional paradigm of pure dephasing. In the weak-coupling and short-time regime, we address the dynamics of the probe analytically, whereas numerical simulations are employed in the strong coupling and long-time regime. We then evaluate the quantum Fisher information for the estimation of the cutoff frequency and the temperature of the environment. Our results provide clear evidence that pure dephasing is not optimal, unless we focus attention to short times. In particular, we found several working regimes where the presence of a transverse interaction improves the maximum attainable precision, i.e. it increases the quantum Fisher information. We also explore the role of the initial state of the probe and of the probe characteristic frequency in determining the estimation precision, thus providing quantitative guidelines to design optimized detection to characterize bosonic environments at the quantum level.Comment: 11 pages, 4 figures, accepted versio

Human Immunodeficiency Virus Type 1 Nef protein modulates the lipid composition of virions and host cell membrane microdomains

BACKGROUND: The Nef protein of Human Immunodeficiency Viruses optimizes viral spread in the infected host by manipulating cellular transport and signal transduction machineries. Nef also boosts the infectivity of HIV particles by an unknown mechanism. Recent studies suggested a correlation between the association of Nef with lipid raft microdomains and its positive effects on virion infectivity. Furthermore, the lipidome analysis of HIV-1 particles revealed a marked enrichment of classical raft lipids and thus identified HIV-1 virions as an example for naturally occurring membrane microdomains. Since Nef modulates the protein composition and function of membrane microdomains we tested here if Nef also has the propensity to alter microdomain lipid composition. RESULTS: Quantitative mass spectrometric lipidome analysis of highly purified HIV-1 particles revealed that the presence of Nef during virus production from T lymphocytes enforced their raft character via a significant reduction of polyunsaturated phosphatidylcholine species and a specific enrichment of sphingomyelin. In contrast, Nef did not significantly affect virion levels of phosphoglycerolipids or cholesterol. The observed alterations in virion lipid composition were insufficient to mediate Nef's effect on particle infectivity and Nef augmented virion infectivity independently of whether virus entry was targeted to or excluded from membrane microdomains. However, altered lipid compositions similar to those observed in virions were also detected in detergent-resistant membrane preparations of virus producing cells. CONCLUSION: Nef alters not only the proteome but also the lipid composition of host cell microdomains. This novel activity represents a previously unrecognized mechanism by which Nef could manipulate HIV-1 target cells to facilitate virus propagation in vivo

Soil respiratory quotient determined via barometric process separation combined with nitrogen-15 labeling

The barometric process separation (BaPS) and ¹⁵N dilution techniques were used to determine gross nitrification rates on the same soil cores from an old grassland soil. The BaPS-technique separates the O₂ consumption into that from nitrification and that from soil organic matter (SOM) respiration. The most sensitive parameter for the calculations via the BaPS technique is the respiratory quotient (RQ = ∆CO₂/∆O₂) for SOM turnover (RQSOM). Combining both methods (BaPS–¹⁵N ) allowed the determination of the RQSOM. The RQ value determined in such a way is adjusted for the influence of nitrification and denitrification, which are both characterized by totally different RQ values. The results for the grassland soil showed that 6 to 10% of O₂ was consumed by nitrification when incubated at 20°C and 0.49 g H₂O g⁻¹ soil. A set of BaPS measurements with the same soil at various temperature and moisture contents showed that up to 49% of the total O₂ consumption was due to nitrification. The calculated RQSOM values via the BaPS–¹⁵N technique presented here are more closely associated with the overall SOM turnover than the usual net RQ reported in the literature. Furthermore, the RQSOM value provides an overall indication of the decomposability and chemical characteristics of the respired organic material. Hence, it has the potential to serve as a single state index for SOM quality and therefore be a useful index for SOM turnover models based on substrate quality

Metabolite Damage and Damage Control in a Minimal Genome

Analysis of the genes retained in the minimized Mycoplasma JCVI-Syn3A genome established that systems that repair or preempt metabolite damage are essential to life. Several genes known to have such functions were identified and experimentally validated, including 5-formyltetrahydrofolate cycloligase, coenzyme A (CoA) disulfide reductase, and certain hydrolases. Furthermore, we discovered that an enigmatic YqeK hydrolase domain fused to NadD has a novel proofreading function in NAD synthesis and could double as a MutT-like sanitizing enzyme for the nucleotide pool. Finally, we combined metabolomics and cheminformatics approaches to extend the core metabolic map of JCVI-Syn3A to include promiscuous enzymatic reactions and spontaneous side reactions. This extension revealed that several key metabolite damage control systems remain to be identified in JCVI-Syn3A, such as that for methylglyoxal. IMPORTANCE Metabolite damage and repair mechanisms are being increasingly recognized. We present here compelling genetic and biochemical evidence for the universal importance of these mechanisms by demonstrating that stripping a genome down to its barest essentials leaves metabolite damage control systems in place. Furthermore, our metabolomic and cheminformatic results point to the existence of a network of metabolite damage and damage control reactions that extends far beyond the corners of it that have been characterized so far. In sum, there can be little room left to doubt that metabolite damage and the systems that counter it are mainstream metabolic processes that cannot be separated from life itself

Beyond the project: building a strategic theory of change to address dementia care, treatment and support gaps across seven middle-income countries

Evidence from middle-income countries indicates high and increasing prevalence of dementia and need for services. However, there has been little investment in care, treatment or support for people living with dementia and their carers. The Strengthening Responses to Dementia in Developing Countries (STRiDE) project aims to build both research capacity and evidence on dementia care and services in Brazil, Indonesia, India, Jamaica, Kenya, Mexico and South Africa. This article presents the Theory of Change (ToC) approach we used to co-design our research project and to develop a strategic direction for dementia care, treatment and support, with stakeholders. ToC makes explicit the process underlying how a programme will achieve its impact. We developed ToCs in each country and across the STRiDE project with researchers, practitioners, people living with dementia, carers and policymakers at different levels of government. This involved (1) an initial ToC workshop with all project partners (43 participants); (2) ToC workshops in each STRiDE country (22–49 participants in each); (3) comparison between country-specific and overall project ToCs; (4) review of ToCs in light of WHO dementia guidelines and action plan and (5) a final review. Our experiences suggest ToC is an effective way to generate a shared vision for dementia care, treatment and support among diverse stakeholders. However, the project contribution should be clearly delineated and use additional strategies to ensure appropriate participation from people living with dementia and their carers in the ToC process

Immediate Outcome Indicators in Perioperative Care: A Controlled Intervention Study on Quality Improvement in Hospitals in Tanzania.

Outcome assessment is the standard for evaluating the quality of health services worldwide. In this study, outcome has been divided into immediate and final outcome. Aim was to compare an intervention hospital with a Continuous Quality Improvement approach to a control group using benchmark assessments of immediate outcome indicators in surgical care. Results were compared to final outcome indicators. Surgical care quality in six hospitals in Tanzania was assessed from 2006-2011, using the Hospital Performance Assessment Tool. Independent observers assessed structural, process and outcome quality using checklists based on evidence-based guidelines. The number of surgical key procedures over the benchmark of 80% was compared between the intervention hospital and the control group. Results were compared to Case Fatality Rates. In the intervention hospital, in 2006, two of nine key procedures reached the benchmark, one in 2009, and four in 2011. In the control group, one of nine key procedures reached the benchmark in 2006, one in 2009, and none in 2011. Case Fatality Rate for all in-patients in the intervention hospital was 5.5% (n = 12,530) in 2006, 3.5% (n = 21,114) in 2009 and 4.6% (n = 18,840) in 2011. In the control group it was 3.1% (n = 17,827) in 2006, 4.2% (n = 13,632) in 2009 and 3.8% (n = 17,059) in 2011. Results demonstrated that quality assurance improved performance levels in both groups. After the introduction of Continuous Quality Improvement, performance levels improved further in the intervention hospital while quality in the district hospital did not. Immediate outcome indicators appeared to be a better steering tool for quality improvement compared to final outcome indicators. Immediate outcome indicators revealed a need for improvement in pre- and postoperative care. Quality assurance programs based on immediate outcome indicators can be effective if embedded in Continuous Quality Improvement. Nevertheless, final outcome indicators cannot be neglected

Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects

International audienceInterference with immune cell proliferation represents a successful treatment strategy in T cell-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis (MS). One prominent example is pharmacological inhibition of dihydroorotate dehydrogenase (DHODH), which mediates de novo pyrimidine synthesis in actively proliferating T and B lymphocytes. Within the TERIDYNAMIC clinical study, we observed that the DHODH inhibitor teriflunomide caused selective changes in T cell subset composition and T cell receptor repertoire diversity in patients with relapsing-remitting MS (RRMS). In a preclinical antigen-specific setup, DHODH inhibition preferentially suppressed the proliferation of high-affinity T cells. Mechanistically, DHODH inhibition interferes with oxidative phosphorylation (OXPHOS) and aerobic glycolysis in activated T cells via functional inhibition of complex III of the respiratory chain. The affinity-dependent effects of DHODH inhibition were closely linked to differences in T cell metabolism. High-affinity T cells preferentially use OXPHOS during early activation, which explains their increased susceptibility toward DHODH inhibition. In a mouse model of MS, DHODH inhibitory treatment resulted in preferential inhibition of high-affinity autoreactive T cell clones. Compared to T cells from healthy controls, T cells from patients with RRMS exhibited increased OXPHOS and glycolysis, which were reduced with teriflunomide treatment. Together, these data point to a mechanism of action where DHODH inhibition corrects metabolic disturbances in T cells, which primarily affects profoundly metabolically active high-affinity T cell clones. Hence, DHODH inhibition may promote recovery of an altered T cell receptor repertoire in autoimmunity

Exploring European Writing Cultures : Country Reports on Genres, Writing Practices and Languages Used in European Higher Education

At European universities, writing is a traditional way of learning, assessment, and independent study, but it is handled in an implicit, tradition-based way that has only recently been contrasted with and supported by a more explicit writing ped-agogy. Still, little systematic knowledge is available about the pedagogical ap-proaches to writing, writing practices, and genres across Europe and much of it is codified in the national languages without correlation to internationally accept-ed terminology and theories. This book explores the writing cultures of Europe, nation by nation, and reports the idiosyncrasies for each respective country. The reports are based on a 17-item topic list used by the authors to collect data be-fore synthesizing the results. Next to writing practices and genres, a high level of emphasis was placed on the structure of educational systems, the languages in use, and the kind of support provided for student writers. Note: This research project has been conducted within the framework of COST Action IS0703 “European Research Network on Learning to Write Effectively”, funded by the European Union. We are also thankful to Christiane Donahue, Eliza Kitis, Charles Bazerman, Helmut Gruber, and David Russell for their cooperation and support in this project.Wissenschaftliches Schreiben an europäischen Hochschulen ist eine herkömmliche Form des Lernens, Prüfens und autonomen Studierens, auch wenn es in einer impliziten, eher auf Tradition denn auf bewusster Didaktik beruhenden Weise eingesetzt wird. Wenig auf systematische Weise erhobenes vergleichendes Wissen gibt es bislang über Schreibpraktiken, Genres und schreibdidaktische Ansätze in Europa und das, was an Wissen existiert ist oft in den nationalen Sprachen verfasst, die nicht mit internationalen Terminologien und Theorien der Schreibwissenschaft verbunden sind. Der vorliegende Band untersucht Schreibkulturen in Europa Land für Land und berichtet was jeweils hervorsticht. Die Berichte basieren auf einer 17-Item Themenliste, nach der die Autorenteams Daten über ihr jeweiliges Land sammelten, bevor sie es zu einem Bericht synthetisierten. Neben Schreibpraktiken und Genres werden dabei die Struktur des jeweiligen Bildungssystems, die verwendeten Sprachen und die besondere Schreibdidaktik hervorgehoben. Anmerkung: Das Projekt wurde im Rahmen der COST Aktion IS0703 “European Research Network on Learning to Write Effectively” durchgeführt, das von der EU finanziert wird. Wir bedanken uns bei Christiane Donahue, Eliza Kitis, Charles Bazerman, Helmut Gruber und David Russell für ihre Unterstützung und Mitwirkung in diesem Projekt.At European universities, writing is a traditional way of learning, assessment, and independent study, but it is handled in an implicit, tradition-based way that has only recently been contrasted with and supported by a more explicit writing ped-agogy. Still, little systematic knowledge is available about the pedagogical ap-proaches to writing, writing practices, and genres across Europe and much of it is codified in the national languages without correlation to internationally accept-ed terminology and theories. This book explores the writing cultures of Europe, nation by nation, and reports the idiosyncrasies for each respective country. The reports are based on a 17-item topic list used by the authors to collect data be-fore synthesizing the results. Next to writing practices and genres, a high level of emphasis was placed on the structure of educational systems, the languages in use, and the kind of support provided for student writers. Note: This research project has been conducted within the framework of COST Action IS0703 “European Research Network on Learning to Write Effectively”, funded by the European Union. We are also thankful to Christiane Donahue, Eliza Kitis, Charles Bazerman, Helmut Gruber, and David Russell for their cooperation and support in this project

Stratification of candidate genes for Parkinson’s disease using weighted protein interaction network analysis

Genome wide association studies (GWAS) have helped identify large numbers of genetic loci that significantly associate with increased risk of developing diseases. However, translating genetic knowledge into understanding of the molecular mechanisms underpinning disease (i.e. disease-specific impacted biological processes) has to date proved to be a major challenge. This is primarily due to difficulties in confidently defining candidate genes at GWAS-risk loci. The goal of this study was to better characterize candidate genes within GWAS loci using a protein interactome based approach and with Parkinson's disease (PD) data as a test case.We applied a recently developed Weighted Protein-Protein Interaction Network Analysis (WPPINA) pipeline as a means to define impacted biological processes, risk pathways and therein key functional players. We used previously established Mendelian forms of PD to identify seed proteins, and to construct a protein network for genetic Parkinson's and carried out functional enrichment analyses. We isolated PD-specific processes indicating 'mitochondria stressors mediated cell death', 'immune response and signaling', and 'waste disposal' mediated through 'autophagy'. Merging the resulting protein network with data from Parkinson's GWAS we confirmed 10 candidate genes previously selected by pure proximity and were able to nominate 17 novel candidate genes for sporadic PD.With this study, we were able to better characterize the underlying genetic and functional architecture of idiopathic PD, thus validating WPPINA as a robust pipeline for the in silico genetic and functional dissection of complex disorders