A Bayesian Approach to Inverse Quantum Statistics

A nonparametric Bayesian approach is developed to determine quantum potentials from empirical data for quantum systems at finite temperature. The approach combines the likelihood model of quantum mechanics with a priori information over potentials implemented in form of stochastic processes. Its specific advantages are the possibilities to deal with heterogeneous data and to express a priori information explicitly, i.e., directly in terms of the potential of interest. A numerical solution in maximum a posteriori approximation was feasible for one--dimensional problems. Using correct a priori information turned out to be essential.Comment: 4 pages, 6 figures, revte

Моделирование структуры топливно-энергетического баланса региона в условиях применения концепции устойчивого развития для достижения стратегических показателей регионального развития

Purpose: is to study the possibilities of applying the concept of sustainable development in the fuel and energy complex of the region to achieve strategic development goals, modeling the structure of the fuel and energy balance based on the principles of sustainable regional development.Methods: the study is based on the application of the principles of sustainable development to the planning of new urban spaces, which allowed us to consider the possibilities of their implementation in the fuel and energy balance model.Results: the study of the possibilities of applying the concept of sustainable development and their impact on the fuel and energy balance is based on the example of Primorsky Krai. The essence of the fuel and energy balance as a tool for the implementation of strategic goals of the national economy is studied. The implementation of the regional development strategy and its role in the formation of the fuel and energy balance of the region are evaluated. Key initiatives for the development of the region, including the construction of new urban spaces, have been identified. Based on the data on the planned population, the need for electric and thermal energy is determined. A scenario analysis of the fuel and energy balance and risk assessment of the implementation of the developed scenarios have been carried out. The authors propose to supplement the fuel and energy balance model with indicators of the usage of secondary energy sources for the production of electric and heat energy. It is revealed that modeling the structure of consumption and production of energy sources paying attention to long-term strategies and trends in energy development contributes to forecasting the achievement of planned indicators.Сonclusions and Relevance: the expansion of the fuel and energy balance model paying attention to secondary energy sources, will allow for more accurate forecasts of the need for primary energy sources, monitor and analyze trends in the implementation of initiatives for the use of secondary energy sources, determine the economy of primary fuel and energy sources in kind, which will contribute to the implementation of the principles of sustainable development of the region's economy.Цель работы – моделирование структуры топливно-энергетического баланса региона на основе изучения возможностей применения концепции устойчивого развития в топливно-энергетическом комплексе для достижения стратегических целей развития региона.Метод или методология проведения работы. Исследование основано на применении принципов устойчивого развития к планированию новых городских пространств, что позволило рассмотреть возможности их внедрения в модель топливно-энергетического баланса региона.Результаты работы. Исследование возможностей применения концепции устойчивого развития и их влияние на топливно-энергетический баланс исследовано на примере Приморского края: рассмотрено значение топливно-энергетического баланса как инструмента реализации стратегических целей национальной экономики, оценена реализация стратегии развития региона и ее роль в формировании топливно-энергетического баланса, определены ключевые инициативы развития региона, в том числе строительство новых городских пространств, на основе данных о планируемой численности населения определена потребность в электрической и тепловой энергии, проведен сценарный анализ топливно-энергетического баланса и оценка рисков реализации разработанных сценариев. Авторами предложено дополнить модель топливно-энергетического баланса показателями, которые позволят учесть использование вторичных энергетических ресурсов для производства электрической и тепловой энергии. Выявлено, что моделирование структуры потребления и производства энергетических ресурсов с учетом долгосрочных стратегий программ развития и тенденций развития энергетики способствует прогнозированию достижения плановых показателей.Выводы. Расширение модели топливно-энергетического баланса с учетом вторичных энергетических ресурсов позволит осуществлять более точные прогнозы потребности в первичных энергетических ресурсах, отслеживать и анализировать тенденции по реализации инициатив использования вторичных энергетических ресурсов, определять экономию первичных топливно-энергетических ресурсов в натуральном выражении. Использование вторичных энергетических ресурсов для производства электрической и тепловой энергии будет способствовать реализации принципов устойчивого развития экономики региона

Quantum Bayes rule

We state a quantum version of Bayes's rule for statistical inference and give a simple general derivation within the framework of generalized measurements. The rule can be applied to measurements on N copies of a system if the initial state of the N copies is exchangeable. As an illustration, we apply the rule to N qubits. Finally, we show that quantum state estimates derived via the principle of maximum entropy are fundamentally different from those obtained via the quantum Bayes rule.Comment: REVTEX, 9 page

Late local recurrence of dermatofibrosarcoma protuberans in the skin of female breast

Dermatofibrosarcoma protuberans (DFSP) of the breast is exceptionally obscure and late local recurrence of this entity on this site is even more uncommon. We describe such a case in a 48-year-old woman, who at the age of 35 had a DFSP excised from her right breast. Thirteen years later, she developed an ovoid mass in her right breast over the postsurgical scar area. Wide local excision of the tumor with generous tissue margin was performed and microscopic and immunohistochemical findings established the diagnosis of recurrent DFSP. No further treatment was administered and she remains well 18 months later, without tumor recurrence. We report an exceptionally rare case of local recurrence of DFSP in the female breast and discuss in detail the diagnostic and therapeutic implications of this pathology

Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial

Background: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19. Methods: A phase I first-in-human dose-ranging trial of a saRNA COVID-19 vaccine candidate LNP-nCoVsaRNA, was conducted at Imperial Clinical Research Facility, and participating centres in London, UK, between 19th June to 28th October 2020. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at six different dose levels, 0.1-10.0μg, given four weeks apart. An open-label dose escalation was followed by a dose evaluation. Solicited adverse events (AEs) were collected for one week from enrolment, with follow-up at regular intervals (1-8 weeks). The binding and neutralisation capacity of anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, immunoblot, SARS-CoV-2 pseudoneutralisation and wild type neutralisation assays. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). Findings: 192 healthy individuals with no history or serological evidence of COVID-19, aged 18-45 years were enrolled. The vaccine was well tolerated with no serious adverse events related to vaccination. Seroconversion at week six whether measured by ELISA or immunoblot was related to dose (both p<0.001), ranging from 8% (3/39; 0.1μg) to 61% (14/23; 10.0μg) in ELISA and 46% (18/39; 0.3μg) to 87% (20/23; 5.0μg and 10.0μg) in a post-hoc immunoblot assay. Geometric mean (GM) anti-S IgG concentrations ranged from 74 (95% CI, 45-119) at 0.1μg to 1023 (468-2236) ng/mL at 5.0μg (p<0.001) and was not higher at 10.0μg. Neutralisation of SARS-CoV-2 by participant sera was measurable in 15% (6/39; 0.1μg) to 48% (11/23; 5.0μg) depending on dose level received. Interpretation: Encapsulated saRNA is safe for clinical development, is immunogenic at low dose levels but failed to induce 100% seroconversion. Modifications to optimise humoral responses are required to realise its potential as an effective vaccine against SARS-CoV-2. Funding: This study was co-funded by grants and gifts from the Medical Research Council UKRI (MC_PC_19076), and the National Institute Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust, Pierre Andurand, Restore the Earth

Coilin Phosphomutants Disrupt Cajal Body Formation, Reduce Cell Proliferation and Produce a Distinct Coilin Degradation Product

Coilin is a nuclear phosphoprotein that accumulates in Cajal bodies (CBs). CBs participate in ribonucleoprotein and telomerase biogenesis, and are often found in cells with high transcriptional demands such as neuronal and cancer cells, but can also be observed less frequently in other cell types such as fibroblasts. Many proteins enriched within the CB are phosphorylated, but it is not clear what role this modification has on the activity of these proteins in the CB. Coilin is considered to be the CB marker protein and is essential for proper CB formation and composition in mammalian cells. In order to characterize the role of coilin phosphorylation on CB formation, we evaluated various coilin phosphomutants using transient expression. Additionally, we generated inducible coilin phosphomutant cell lines that, when used in combination with endogenous coilin knockdown, allow for the expression of the phosphomutants at physiological levels. Transient expression of all coilin phosphomutants except the phosphonull mutant (OFF) significantly reduces proliferation. Interestingly, a stable cell line induced to express the coilin S489D phosphomutant displays nucleolar accumulation of the mutant and generates a N-terminal degradation product; neither of which is observed upon transient expression. A N-terminal degradation product and nucleolar localization are also observed in a stable cell line induced to express a coilin phosphonull mutant (OFF). The nucleolar localization of the S489D and OFF coilin mutants observed in the stable cell lines is decreased when endogenous coilin is reduced. Furthermore, all the phosphomutant cells lines show a significant reduction in CB formation when compared to wild-type after endogenous coilin knockdown. Cell proliferation studies on these lines reveal that only wild-type coilin and the OFF mutant are sufficient to rescue the reduction in proliferation associated with endogenous coilin depletion. These results emphasize the role of coilin phosphorylation in the formation and activity of CBs

A Generalized Framework for Quantifying the Dynamics of EEG Event-Related Desynchronization

Brains were built by evolution to react swiftly to environmental challenges. Thus, sensory stimuli must be processed ad hoc, i.e., independent—to a large extent—from the momentary brain state incidentally prevailing during stimulus occurrence. Accordingly, computational neuroscience strives to model the robust processing of stimuli in the presence of dynamical cortical states. A pivotal feature of ongoing brain activity is the regional predominance of EEG eigenrhythms, such as the occipital alpha or the pericentral mu rhythm, both peaking spectrally at 10 Hz. Here, we establish a novel generalized concept to measure event-related desynchronization (ERD), which allows one to model neural oscillatory dynamics also in the presence of dynamical cortical states. Specifically, we demonstrate that a somatosensory stimulus causes a stereotypic sequence of first an ERD and then an ensuing amplitude overshoot (event-related synchronization), which at a dynamical cortical state becomes evident only if the natural relaxation dynamics of unperturbed EEG rhythms is utilized as reference dynamics. Moreover, this computational approach also encompasses the more general notion of a “conditional ERD,” through which candidate explanatory variables can be scrutinized with regard to their possible impact on a particular oscillatory dynamics under study. Thus, the generalized ERD represents a powerful novel analysis tool for extending our understanding of inter-trial variability of evoked responses and therefore the robust processing of environmental stimuli

High-Resolution Functional Mapping of the Venezuelan Equine Encephalitis Virus Genome by Insertional Mutagenesis and Massively Parallel Sequencing

We have developed a high-resolution genomic mapping technique that combines transposon-mediated insertional mutagenesis with either capillary electrophoresis or massively parallel sequencing to identify functionally important regions of the Venezuelan equine encephalitis virus (VEEV) genome. We initially used a capillary electrophoresis method to gain insight into the role of the VEEV nonstructural protein 3 (nsP3) in viral replication. We identified several regions in nsP3 that are intolerant to small (15 bp) insertions, and thus are presumably functionally important. We also identified nine separate regions in nsP3 that will tolerate small insertions at low temperatures (30°C), but not at higher temperatures (37°C, and 40°C). Because we found this method to be extremely effective at identifying temperature sensitive (ts) mutations, but limited by capillary electrophoresis capacity, we replaced the capillary electrophoresis with massively parallel sequencing and used the improved method to generate a functional map of the entire VEEV genome. We identified several hundred potential ts mutations throughout the genome and we validated several of the mutations in nsP2, nsP3, E3, E2, E1 and capsid using single-cycle growth curve experiments with virus generated through reverse genetics. We further demonstrated that two of the nsP3 ts mutants were attenuated for virulence in mice but could elicit protective immunity against challenge with wild-type VEEV. The recombinant ts mutants will be valuable tools for further studies of VEEV replication and virulence. Moreover, the method that we developed is applicable for generating such tools for any virus with a robust reverse genetics system

DEB025 (Alisporivir) Inhibits Hepatitis C Virus Replication by Preventing a Cyclophilin A Induced Cis-Trans Isomerisation in Domain II of NS5A

DEB025/Debio 025 (Alisporivir) is a cyclophilin (Cyp)-binding molecule with potent anti-hepatitis C virus (HCV) activity both in vitro and in vivo. It is currently being evaluated in phase II clinical trials. DEB025 binds to CypA, a peptidyl-prolyl cis-trans isomerase which is a crucial cofactor for HCV replication. Here we report that it was very difficult to select resistant replicons (genotype 1b) to DEB025, requiring an average of 20 weeks (four independent experiments), compared to the typically <2 weeks with protease or polymerase inhibitors. This indicates a high genetic barrier to resistance for DEB025. Mutation D320E in NS5A was the only mutation consistently selected in the replicon genome. This mutation alone conferred a low-level (3.9-fold) resistance. Replacing the NS5A gene (but not the NS5B gene) from the wild type (WT) genome with the corresponding sequence from the DEB025res replicon resulted in transfer of resistance. Cross-resistance with cyclosporine A (CsA) was observed, whereas NS3 protease and NS5B polymerase inhibitors retained WT-activity against DEB025res replicons. Unlike WT, DEB025res replicon replicated efficiently in CypA knock down cells. However, DEB025 disrupted the interaction between CypA and NS5A regardless of whether the NS5A protein was derived from WT or DEB025res replicon. NMR titration experiments with peptides derived from the WT or the DEB025res domain II of NS5A corroborated this observation in a quantitative manner. Interestingly, comparative NMR studies on two 20-mer NS5A peptides that contain D320 or E320 revealed a shift in population between the major and minor conformers. These data suggest that D320E conferred low-level resistance to DEB025 probably by reducing the need for CypA-dependent isomerisation of NS5A. Prolonged DEB025 treatment and multiple genotypic changes may be necessary to generate significant resistance to DEB025, underlying the high barrier to resistance