On complexified analytic Hamiltonian flows and geodesics on the space of Kahler metrics

In the case of a compact real analytic symplectic manifold M we describe an approach to the complexification of Hamiltonian flows [Se, Do1, Th1] and corresponding geodesics on the space of Kahler metrics. In this approach, motivated by recent work on quantization, the complexified Hamiltonian flows act, through the Grobner theory of Lie series, on the sheaf of complex valued real analytic functions, changing the sheaves of holomorphic functions. This defines an action on the space of (equivalent) complex structures on M and also a direct action on M. This description is related to the approach of [BLU] where one has an action on a complexification M_C of M followed by projection to M. Our approach allows for the study of some Hamiltonian functions which are not real analytic. It also leads naturally to the consideration of continuous degenerations of diffeomorphisms and of Kahler structures of M. Hence, one can link continuously (geometric quantization) real, and more general non-Kahler, polarizations with Kahler polarizations. This corresponds to the extension of the geodesics to the boundary of the space of Kahler metrics. Three illustrative examples are considered. We find an explicit formula for the complex time evolution of the Kahler potential under the flow. For integral symplectic forms, this formula corresponds to the complexification of the prequantization of Hamiltonian symplectomorphisms. We verify that certain families of Kahler structures, which have been studied in geometric quantization, are geodesic families.Comment: final versio

Geometric quantization, complex structures and the coherent state transform

It is shown that the heat operator in the Hall coherent state transform for a compact Lie group $K$ is related with a Hermitian connection associated to a natural one-parameter family of complex structures on $T^*K$. The unitary parallel transport of this connection establishes the equivalence of (geometric) quantizations of $T^*K$ for different choices of complex structures within the given family. In particular, these results establish a link between coherent state transforms for Lie groups and results of Hitchin and Axelrod, Della Pietra and Witten.Comment: to appear in Journal of Functional Analysi

On the BKS pairing for Kahler quantizations of the cotangent bundle of a Lie group

A natural one-parameter family of K\"ahler quantizations of the cotangent bundle $T^*K$ of a compact Lie group $K$, taking into account the half-form correction, was studied in \cite{FMMN}. In the present paper, it is shown that the associated Blattner-Kostant-Sternberg (BKS) pairing map is unitary and coincides with the parallel transport of the quantum connection introduced in our previous work, from the point of view of \cite{AdPW}. The BKS pairing map is a composition of (unitary) coherent state transforms of $K$, introduced in \cite{Ha1}. Continuity of the Hermitian structure on the quantum bundle, in the limit when one of the K\"ahler polarizations degenerates to the vertical real polarization, leads to the unitarity of the corresponding BKS pairing map. This is in agreement with the unitarity up to scaling (with respect to a rescaled inner product) of this pairing map, established by Hall.Comment: final version, to appear in Journ. Funct. Ana

Block copolymer-based magnetic mixed matrix membranes-effect of magnetic field on protein permeation and membrane fouling

In this study, we report the impact of the magnetic field on protein permeability through magnetic-responsive, block copolymer, nanocomposite membranes with hydrophilic and hydrophobic characters. The hydrophilic nanocomposite membranes were composed of spherical polymeric nanoparticles (NPs) synthesized through polymerization-induced self-assembly (PISA) with iron oxide NPs coated with quaternized poly(2-dimethylamino)ethyl methacrylate. The hydrophobic nanocomposite membranes were prepared via nonsolvent-induced phase separation (NIPS) containing poly (methacrylic acid) and meso-2, 3-dimercaptosuccinic acid-coated superparamagnetic nanoparticles (SPNPs). The permeation experiments were carried out using bovine serum albumin (BSA) as the model solute, in the absence of the magnetic field and under permanent and cyclic magnetic field conditions OFF/ON (strategy 1) and ON/OFF (strategy 2). It was observed that the magnetic field led to a lower reduction in the permeate fluxes of magnetic-responsive membranes during BSA permeation, regardless of the magnetic field strategy used, than that obtained in the absence of the magnetic field. Nevertheless, a comparative analysis of the effect caused by the two cyclic magnetic field strategies showed that strategy 2 allowed for a lower reduction of the original permeate fluxes during BSA permeation and higher protein sieving coefficients. Overall, these novel magneto-responsive block copolymer nanocomposite membranes proved to be competent in mitigating biofouling phenomena in bioseparation processes

Adoption of the ADA/EASD guidelines in 10 Eastern and Southern European countries: Physician survey and good clinical practice recommendations from an international expert panel

Aims: Evidence from cardiovascular outcomes trials (CVOTs) of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors was reflected in the most recent guidelines from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). The aim of the present study was to assess the adoption of the ADA/EASD guidelines in a convenience sample of physicians from Eastern and Southern Europe, the barriers to the implementation of these guidelines and the measures needed to facilitate their implementation. Methods: Attendees at two international diabetes conferences could volunteer to respond to a fully anonymous survey. Responses were analysed descriptively and a panel of experts from around the region was consulted to interpret the survey results. Results: Responses (n = 96) from 10 countries were analysed. Most participants (63.4%) considered the ADA/EASD guidelines fundamental to their practice. All respondents saw the value of the CVOT-based ADA/EASD recommendations and 77-80% generally implemented them. Measures suggested to improve adherence to the ADA/EASD guidelines included aligning reimbursement policy with the guidelines (54.4%), publishing guidelines in a simple and concise form (42.4%) and translating guidelines into local languages (33.3%). Conclusions: Aligning reimbursement with recent evidence and providing short summaries of the ADA/EASD guidelines in local languages could facilitate physician adherence.(c) 2020 The Author. Published by Elsevier B.V. This is an open access article under the CC BY NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Proteomic profile of KSR1-regulated signalling in response to genotoxic agents in breast cancer

Kinase suppressor of Ras 1 (KSR1) has been implicated in tumorigenesis in multiple cancers, including skin, pancreatic and lung carcinomas. However, our recent study revealed a role of KSR1 as a tumour suppressor in breast cancer, the expression of which is potentially correlated with chemotherapy response. Here, we aimed to further elucidate the KSR1-regulated signalling in response to genotoxic agents in breast cancer. Stable isotope labelling by amino acids in cell culture (SILAC) coupled to high-resolution mass spectrometry (MS) was implemented to globally characterise cellular protein levels induced by KSR1 in the presence of doxorubicin or etoposide. The acquired proteomic signature was compared and GO-STRING analysis was subsequently performed to illustrate the activated functional signalling networks. Furthermore, the clinical associations of KSR1 with identified targets and their relevance in chemotherapy response were examined in breast cancer patients. We reveal a comprehensive repertoire of thousands of proteins identified in each dataset and compare the unique proteomic profiles as well as functional connections modulated by KSR1 after doxorubicin (Doxo-KSR1) or etoposide (Etop-KSR1) stimulus. From the up-regulated top hits, several proteins, including STAT1, ISG15 and TAP1 are also found to be positively associated with KSR1 expression in patient samples. Moreover, high KSR1 expression, as well as high abundance of these proteins, is correlated with better survival in breast cancer patients who underwent chemotherapy. In aggregate, our data exemplify a broad functional network conferred by KSR1 with genotoxic agents and highlight its implication in predicting chemotherapy response in breast cancer

Selectively targeting the kinome-conserved lysine of PI3K (delta) as a general approach to covalent kinase inhibition

Selective covalent inhibition of kinases by targeting poorly conserved cysteines has proven highly fruitful to date in the development of chemical probes and approved drugs. However, this approach is limited to ~200 kinases possessing such a cysteine near the ATP-binding pocket. Herein, we report a novel approach to achieve selective, irreversible kinase inhibition, by targeting the conserved catalytic lysine residue. We have illustrated our approach by developing selective, covalent PI3Kδ inhibitors that exhibit nanomolar potency in cellular assays, and a duration of action >48 h in CD4+ T cells. Despite conservation of the lysine residue throughout the kinome, the lead compound shows high levels of selectivity over a selection of lipid and protein kinases in biochemical assays, as well as covalent binding to very few off-target proteins in live-cell proteomic studies. We anticipate this approach could offer an alternative general strategy, to targeting non-conserved cysteines, for the development of selective covalent kinase inhibitors

Ambient Particulate Air Pollution and Daily Mortality in 652 Cities.

BACKGROUND: The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias. METHODS: We evaluated the associations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 μm or less (PM10) and fine PM with an aerodynamic diameter of 2.5 μm or less (PM2.5) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions. Daily data on mortality and air pollution were collected from 652 cities in 24 countries or regions. We used overdispersed generalized additive models with random-effects meta-analysis to investigate the associations. Two-pollutant models were fitted to test the robustness of the associations. Concentration-response curves from each city were pooled to allow global estimates to be derived. RESULTS: On average, an increase of 10 μg per cubic meter in the 2-day moving average of PM10 concentration, which represents the average over the current and previous day, was associated with increases of 0.44% (95% confidence interval [CI], 0.39 to 0.50) in daily all-cause mortality, 0.36% (95% CI, 0.30 to 0.43) in daily cardiovascular mortality, and 0.47% (95% CI, 0.35 to 0.58) in daily respiratory mortality. The corresponding increases in daily mortality for the same change in PM2.5 concentration were 0.68% (95% CI, 0.59 to 0.77), 0.55% (95% CI, 0.45 to 0.66), and 0.74% (95% CI, 0.53 to 0.95). These associations remained significant after adjustment for gaseous pollutants. Associations were stronger in locations with lower annual mean PM concentrations and higher annual mean temperatures. The pooled concentration-response curves showed a consistent increase in daily mortality with increasing PM concentration, with steeper slopes at lower PM concentrations. CONCLUSIONS: Our data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.)

Current Wildland Fire Patterns and Challenges in Europe : A Synthesis of National Perspectives

Changes in climate, land use, and land management impact the occurrence and severity of wildland fires in many parts of the world. This is particularly evident in Europe, where ongoing changes in land use have strongly modified fire patterns over the last decades. Although satellite data by the European Forest Fire Information System provide large-scale wildland fire statistics across European countries, there is still a crucial need to collect and summarize in-depth local analysis and understanding of the wildland fire condition and associated challenges across Europe. This article aims to provide a general overview of the current wildland fire patterns and challenges as perceived by national representatives, supplemented by national fire statistics (2009-2018) across Europe. For each of the 31 countries included, we present a perspective authored by scientists or practitioners from each respective country, representing a wide range of disciplines and cultural backgrounds. The authors were selected from members of the COST Action "Fire and the Earth System: Science & Society" funded by the European Commission with the aim to share knowledge and improve communication about wildland fire. Where relevant, a brief overview of key studies, particular wildland fire challenges a country is facing, and an overview of notable recent fire events are also presented. Key perceived challenges included (1) the lack of consistent and detailed records for wildland fire events, within and across countries, (2) an increase in wildland fires that pose a risk to properties and human life due to high population densities and sprawl into forested regions, and (3) the view that, irrespective of changes in management, climate change is likely to increase the frequency and impact of wildland fires in the coming decades. Addressing challenge (1) will not only be valuable in advancing national and pan-European wildland fire management strategies, but also in evaluating perceptions (2) and (3) against more robust quantitative evidence.Peer reviewe

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease