Efficiency at optimal work from finite reservoirs: a probabilistic perspective

We revisit the classic thermodynamic problem of maximum work extraction from two arbitrary sized hot and cold reservoirs, modelled as perfect gases. Assuming ignorance about the extent to which the process has advanced, which implies an ignorance about the final temperatures, we quantify the prior information about the process and assign a prior distribution to the unknown temperature(s). This requires that we also take into account the temperature values which are regarded to be unphysical in the standard theory, as they lead to a contradiction with the physical laws. Instead in our formulation, such values appear to be consistent with the given prior information and hence are included in the inference. We derive estimates of the efficiency at optimal work from the expected values of the final temperatures, and show that these values match with the exact expressions in the limit when any one of the reservoirs is very large compared to the other. For other relative sizes of the reservoirs, we suggest a weighting procedure over the estimates from two valid inference procedures, that generalizes the procedure suggested earlier in [J. Phys. A: Math. Theor. {\bf 46}, 365002 (2013)]. Thus a mean estimate for efficiency is obtained which agrees with the optimal performance to a high accuracy.Comment: 14 pages, 6 figure

A systematic review and quality assessment of case reports of adverse events for borage (Borago officinalis), coltsfoot (Tussilago farfara) and comfrey (Symphytum officinale).

Symphytum officinale (comfrey), Tussilago farfara (coltsfoot) and Borago officinalis (borage) have long histories of therapeutic use, but their safety has been questioned due to the presence of unsaturated pyrrolizidine alkaloids (PAs). The evidence base underlying these concerns relies in part on case reports. This systematic review assesses these case reports for their reliability to inform this debate.MethodStudy selection was restricted to case reports describing possible pyrrolizidine alkaloid related harm and ingestion of comfrey, coltsfoot or borage. An extensive search of academic databases was conducted. Papers meeting the criteria were critically appraised.ResultsThe search resulted in 11 appropriate case reports, none of which involved borage. Nine reports were assessed for causality and indicated some degree of association between the material ingested and the adverse event. Lack of unequivocal identification of the species ingested compromised attribution and was a significant source of uncertainty. Three levels of identity confusions were found; misidentification or substitution at the level of the whole herb; omission of appropriate botanical identification and attribution of a specific PA to either comfrey or coltsfoot when it is a constituent found in other plants of established toxicity.ConclusionThese cases are an unreliable body of evidence on which to draw conclusions about the safety of the oral consumption of Symphytum officinale and Tussilago farfara. Toxicological studies based on oral ingestion of phytochemically-complex preparations of these herbs may be the most accurate methodology for assessing clinical risk

The nature and prevalence of psychological problems in New Zealand primary healthcare: a report on Mental Health and General Practice Investigation ( MaGPIe)

Aims This paper describes the methods used in a study of the prevalence and types of common mental disorders among patients attending New Zealand general practices, and reports some key findings from the first phase of the study. The study also aimed to determine the degree of associated disability and other factors influencing recognition, management, course and outcome of these disorders, and subsequent papers will address these issues. Methods General practitioners (GPs) were selected randomly. In the first phase of the study, all adult attenders at each practice on selected days were administered a short questionnaire, the General Health Questionnaire (GHQ-12), which screens for psychological symptoms. The GP recorded the reasons for each consultation, and was interviewed at the end of each day about selected patients to determine their opinion about the type of psychological problems experienced. Selected patients were then visited in their own homes and an extensive interview conducted, which included the Composite International Diagnostic Interview (CIDI) to determine mental health status, the World Health Organization’s Disability Assessment Schedule (WHODAS) to determine disability, and a detailed exploration of use of health services. In the second phase of the study, patients were contacted by telephone at three, six, nine and 12 months, and both patients and GPs were re-interviewed at 12 months. Results The study achieved a very high response rate among the GPs (90%). Nearly all eligible patients (93%) completed the GHQ screening, and their response rate was 70% for the first-phase interview. GPs thought that 54% of female and 46% of male patients had experienced some level of psychological problems in the past year. GHQ screening also found that more than half of those attending their general practitioner experienced some psychological symptoms at initial screening, and the CIDI interview found that more than one in three had a diagnosable mental disorder during the past 12 months. The most common mental disorders were depressive, anxiety and substance use disorders. These disorders were more common among younger than older general practice attenders, and comorbidity was high. Conclusions Mental health problems are very common among general practice attenders. Contrary to the prevailing view that general practitioners seldom identify psychological problems in their patients, they identified about half their patients as having some type of psychological problems in the past year, although they considered that these were moderate or severe in about only one in ten patients. Further work from this large New Zealand study will focus on the nature of the relationship between disorder and disability, and on the recognition, management and outcome of psychological problems

The dynamics of a strongly driven two component Bose-Einstein Condensate

We consider a two component Bose-Einstein condensate in two spatially localized modes of a double well potential, with periodic modulation of the tunnel coupling between the two modes. We treat the driven quantum field using a two mode expansion and define the quantum dynamics in terms of the Floquet Operator for the time periodic Hamiltonian of the system. It has been shown that the corresponding semiclassical mean-field dynamics can exhibit regions of regular and chaotic motion. We show here that the quantum dynamics can exhibit dynamical tunneling between regions of regular motion, centered on fixed points (resonances) of the semiclassical dynamics

Deletion of the protein tyrosine phosphatase PTPN22 for adoptive T cell therapy facilitates CTL effector function but promotes T cell exhaustion

Background Adoptive cell therapy (ACT) is a promising strategy for treating cancer, yet it faces several challenges such as lack of long term protection due to T cell exhaustion induced by chronic TCR stimulation in the tumor microenvironment. One benefit of ACT, however, is that it allows for cellular manipulations, such as deletion of the phosphotyrosine phosphatase non-receptor type 22 (PTPN22), which improves CD8+ T cell anti-tumor efficacy in ACT. We tested whether Ptpn22KO cytolytic T cells (CTL) were also more effective than Ptpn22WT CTL in controlling tumors in scenarios that favor T cell exhaustion. Methods Tumor control by Ptpn22WT and Ptpn22KO CTL was assessed following adoptive transfer of low numbers of CTL to mice with subcutaneously implanted MC38 tumors. Tumor infiltrating lymphocytes were isolated for analysis of effector functions. An in vitro assay was established to compare CTL function in response to acute and chronic re-stimulation with antigen-pulsed tumor cells. The expression of effector and exhaustion-associated proteins by Ptpn22WT and Ptpn22KO T cells was followed over time in vitro and in vivo using the ID8 tumor model. Finally, the effect of PD-1 and TIM-3 blockade on Ptpn22KO CTL tumor control was assessed using monoclonal antibodies and CRISPR/Cas9-mediated knockout. Results Despite having improved effector function at the time of transfer, Ptpn22KO CTL became more exhausted than Ptpn22WT CTL, characterized by more rapid loss of effector functions, and earlier and higher expression of inhibitory receptors (IRs), particularly the terminal exhaustion marker TIM-3. TIM-3 expression, under the control of the transcription factor NFIL3, was induced by IL-2 signaling which was enhanced in Ptpn22KO cells. Anti-tumor responses of Ptpn22KO CTL were improved following PD-1 blockade in vivo, yet knockout or antibody-mediated blockade of TIM-3 did not improve but further impaired tumor control, indicating TIM-3 signaling itself did not drive the diminished function seen in Ptpn22KO CTL. Conclusions This study questions whether TIM-3 plays a role as an IR and highlights that genetic manipulation of T cells for ACT needs to balance short term augmented effector function against the risk of T cell exhaustion in order to achieve longer term protection. What is already known on this topic • T cell exhaustion in the tumor microenvironment is a major factor limiting the potential success of adoptive cell therapy (ACT) in the treatment of solid tumors. • Deletion of the phosphatase PTPN22 in CD8+ T cells improves their response to tumors, but it is not known whether this influences development of exhaustion. What this study adds • Under conditions which promote exhaustion, CTL lacking PTPN22 exhaust more rapidly than WT cells, despite displaying enhanced effector function in their initial response to antigen. • Ptpn22KO CTL express high levels of the inhibitory receptor TIM-3, but TIM-3 signaling does not directly contribute to Ptpn22KO CTL dysfunction. • Ptpn22KO T cells are more responsive to IL-2 through JAK-STAT signaling, which induces TIM-3 expression via the transcription factor NFIL3. How this study might affect research, practice or policy • Strategies aimed at augmenting T cell effector function for ACT should balance improved responses against an increased risk of T cell exhaustion

Kaitiakitanga - Active guardianship, responsibilities and relationships with the world: Towards a bio-cultural future In early childhood education

The world is a vast family, and humans are children of the earth and sky, and cousins to all living things. Such unity means that nature is the ultimate teacher about life (Royal 2010, p. 9). For Māori (indigenous peoples of Aotearoa New Zealand) the term kaitiakitanga (pronounced, kye-tee-ah-key-tar-ngah) is often used to refer to the active guardianship and management of natural organisms and their environments. Mātauranga Māori or Māori knowledge positions humans within nature and focuses on ways in which cultural understandings and intergenerational connections between people and their biophysical contexts assist in the retention and protection of biodiversity and ecologically sustainable ecosystems. This entry critically reflects notions of kaitiakitanga and bio-cultural connectivity as important and meaningful contributors for young children and their relationships with and for the world

A Plasmid-Transposon Hybrid Mutagenesis System Effective in a Broad Range of Enterobacteria.

Random transposon mutagenesis is a powerful technique used to generate libraries of genetic insertions in many different bacterial strains. Here we develop a system facilitating random transposon mutagenesis in a range of different Gram-negative bacterial strains, including Pectobacterium atrosepticum, Citrobacter rodentium, Serratia sp. ATCC39006, Serratia plymuthica, Dickeya dadantii, and many more. Transposon mutagenesis was optimized in each of these strains and three studies are presented to show the efficacy of this system. Firstly, the important agricultural pathogen D. dadantii was mutagenized. Two mutants that showed reduced protease production and one mutant producing the previously cryptic pigment, indigoidine, were identified and characterized. Secondly, the enterobacterium, Serratia sp. ATCC39006 was mutagenized and mutants incapable of producing gas vesicles, proteinaceous intracellular organelles, were identified. One of these contained a β-galactosidase transcriptional fusion within the gene gvpA1, essential for gas vesicle production. Finally, the system was used to mutate the biosynthetic gene clusters of the antifungal, anti-oomycete and anticancer polyketide, oocydin A, in the plant-associated enterobacterium, Dickeya solani MK10. The mutagenesis system was developed to allow easy identification of transposon insertion sites by sequencing, after facile generation of a replicon encompassing the transposon and adjacent DNA, post-excision. Furthermore, the system can also create transcriptional fusions with either β-galactosidase or β-glucuronidase as reporters, and exploits a variety of drug resistance markers so that multiple selectable fusions can be generated in a single strain. This system of various transposons has wide utility and can be combined in many different ways.The authors would like to acknowledge several funding sources. D. Smith was supported by a PhD studentship from the BBSRC. Work in the MW lab is supported by the BBSRC (grants BB/G015171/1 and BB/M019411/1). K. Roberts was funded by an MRC studentship. R. Monson and the Salmond lab were supported by grants from the BBSRC (Grant No Provisional BB/K001833/1). M.A. Matilla was supported by the EU Marie-Curie Intra-European Fellowship for Career Development (FP7-PEOPLE-2011-IEF), grant number 298003. B. Richardson was supported by a Harry Smith vacation studentship from the SGM, UK. The authors would also like to thank Ray Chai for careful reading and comments on this manuscript. Alison Drew provided technical support. Work with plant pathogens was carried out under DEFRA licence No. 50864/197900/1.This is the final version of the article. It was first available from Frontiers via http://dx.doi.org/10.3389/fmicb.2015.0144

Population Monte Carlo algorithms

We give a cross-disciplinary survey on ``population'' Monte Carlo algorithms. In these algorithms, a set of ``walkers'' or ``particles'' is used as a representation of a high-dimensional vector. The computation is carried out by a random walk and split/deletion of these objects. The algorithms are developed in various fields in physics and statistical sciences and called by lots of different terms -- ``quantum Monte Carlo'', ``transfer-matrix Monte Carlo'', ``Monte Carlo filter (particle filter)'',``sequential Monte Carlo'' and ``PERM'' etc. Here we discuss them in a coherent framework. We also touch on related algorithms -- genetic algorithms and annealed importance sampling.Comment: Title is changed (Population-based Monte Carlo -> Population Monte Carlo). A number of small but important corrections and additions. References are also added. Original Version is read at 2000 Workshop on Information-Based Induction Sciences (July 17-18, 2000, Syuzenji, Shizuoka, Japan). No figure