Propositional Encoding of Constraints over Tree-Shaped Data

We present a functional programming language for specifying constraints over tree-shaped data. The language allows for Haskell-like algebraic data types and pattern matching. Our constraint compiler CO4 translates these programs into satisfiability problems in propositional logic. We present an application from the area of automated analysis of (non-)termination of rewrite systems

Meningococcal genetic variation mechanisms viewed through comparative analysis of Serogroup C strain FAM18

Copyright @ 2007 Public Library of ScienceThe bacterium Neisseria meningitidis is commonly found harmlessly colonising the mucosal surfaces of the human nasopharynx. Occasionally strains can invade host tissues causing septicaemia and meningitis, making the bacterium a major cause of morbidity and mortality in both the developed and developing world. The species is known to be diverse in many ways, as a product of its natural transformability and of a range of recombination and mutation-based systems. Previous work on pathogenic Neisseria has identified several mechanisms for the generation of diversity of surface structures, including phase variation based on slippage-like mechanisms and sequence conversion of expressed genes using information from silent loci. Comparison of the genome sequences of two N. meningitidis strains, serogroup B MC58 and serogroup A Z2491, suggested further mechanisms of variation, including C-terminal exchange in specific genes and enhanced localised recombination and variation related to repeat arrays. We have sequenced the genome of N. meningitidis strain FAM18, a representative of the ST-11/ET-37 complex, providing the first genome sequence for the disease-causing serogroup C meningococci; it has 1,976 predicted genes, of which 60 do not have orthologues in the previously sequenced serogroup A or B strains. Through genome comparison with Z2491 and MC58 we have further characterised specific mechanisms of genetic variation in N. meningitidis, describing specialised loci for generation of cell surface protein variants and measuring the association between noncoding repeat arrays and sequence variation in flanking genes. Here we provide a detailed view of novel genetic diversification mechanisms in N. meningitidis. Our analysis provides evidence for the hypothesis that the noncoding repeat arrays in neisserial genomes (neisserial intergenic mosaic elements) provide a crucial mechanism for the generation of surface antigen variants. Such variation will have an impact on the interaction with the host tissues, and understanding these mechanisms is important to aid our understanding of the intimate and complex relationship between the human nasopharynx and the meningococcus.This work was supported by the Wellcome Trust through the Beowulf Genomics Initiative

Characterizing long COVID in an international cohort: 7 months of symptoms and their impact

Background: A significant number of patients with COVID-19 experience prolonged symptoms, known as Long COVID. Few systematic studies have investigated this population, particularly in outpatient settings. Hence, relatively little is known about symptom makeup and severity, expected clinical course, impact on daily functioning, and return to baseline health. // Methods: We conducted an online survey of people with suspected and confirmed COVID-19, distributed via COVID-19 support groups (e.g. Body Politic, Long COVID Support Group, Long Haul COVID Fighters) and social media (e.g. Twitter, Facebook). Data were collected from September 6, 2020 to November 25, 2020. We analyzed responses from 3762 participants with confirmed (diagnostic/antibody positive; 1020) or suspected (diagnostic/antibody negative or untested; 2742) COVID-19, from 56 countries, with illness lasting over 28 days and onset prior to June 2020. We estimated the prevalence of 203 symptoms in 10 organ systems and traced 66 symptoms over seven months. We measured the impact on life, work, and return to baseline health. // Findings: For the majority of respondents (>91%), the time to recovery exceeded 35 weeks. During their illness, participants experienced an average of 55.9+/- 25.5 (mean+/-STD) symptoms, across an average of 9.1 organ systems. The most frequent symptoms after month 6 were fatigue, post-exertional malaise, and cognitive dysfunction. Symptoms varied in their prevalence over time, and we identified three symptom clusters, each with a characteristic temporal profile. 85.9% of participants (95% CI, 84.8% to 87.0%) experienced relapses, primarily triggered by exercise, physical or mental activity, and stress. 86.7% (85.6% to 92.5%) of unrecovered respondents were experiencing fatigue at the time of survey, compared to 44.7% (38.5% to 50.5%) of recovered respondents. 1700 respondents (45.2%) required a reduced work schedule compared to pre-illness, and an additional 839 (22.3%) were not working at the time of survey due to illness. Cognitive dysfunction or memory issues were common across all age groups (~88%). Except for loss of smell and taste, the prevalence and trajectory of all symptoms were similar between groups with confirmed and suspected COVID-19. // Interpretation: Patients with Long COVID report prolonged, multisystem involvement and significant disability. By seven months, many patients have not yet recovered (mainly from systemic and neurological/cognitive symptoms), have not returned to previous levels of work, and continue to experience significant symptom burden

Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact

Objective: To characterize the symptom profile and time course in patients with Long COVID, along with the impact on daily life, work, and return to baseline health. / Design: International web-based survey of suspected and confirmed COVID-19 cases with illness lasting over 28 days and onset prior to June 2020. / Setting: Survey distribution via online COVID-19 support groups and social media. / Participants: 3,762 respondents from 56 countries completed the survey. 1166 (33.7%) were 40-49 years old, 937 (27.1%) were 50-59 years old, and 905 (26.1%) were 30-39 years old. 2961 (78.9%) were women, 718 (19.1%) were men, and 63 (1.7%) were nonbinary. 8.4% reported being hospitalized. 27% reported receiving a laboratory-confirmed diagnosis of COVID-19. 96% reported symptoms beyond 90 days. / Results: Prevalence of 205 symptoms in 10 organ systems was estimated in this cohort, with 66 symptoms traced over seven months. Respondents experienced symptoms in an average of 9.08 (95% confidence interval 9.04 to 9.13) organ systems. The most frequent symptoms reported after month 6 were: fatigue (77.7%, 74.9% to 80.3%), post-exertional malaise (72.2%, 69.3% to 75.0%), and cognitive dysfunction (55.4%, 52.4% to 58.8%). These three symptoms were also the three most commonly reported overall. In those who recovered in less than 90 days, the average number of symptoms peaked at week 2 (11.4, 9.4 to 13.6), and in those who did not recover in 90 days, the average number of symptoms peaked at month 2 (17.2, 16.5 to 17.8). Respondents with symptoms over 6 months experienced an average of 13.8 (12.7 to 14.9) symptoms in month 7. 85.9% (84.8% to 87.0%) experienced relapses, with exercise, physical or mental activity, and stress as the main triggers. 86.7% (85.6% to 92.5%) of unrecovered respondents were experiencing fatigue at the time of survey, compared to 44.7% (38.5% to 50.5%) of recovered respondents. 45.2% (42.9% to 47.2%) reported requiring a reduced work schedule compared to pre-illness and 22.3% (20.5% to 24.3%) were not working at the time of survey due to their health conditions. / Conclusions: Patients with Long COVID report prolonged multisystem involvement and significant disability. Most had not returned to previous levels of work by 6 months. Many patients are not recovered by 7 months, and continue to experience significant symptom burden

Comment mesurer les progrès de la lecture?

New observations of Neptune’s clouds in the near infrared were acquired in October 2013 with SINFONI on ESO’s Very Large Telescope (VLT) in Chile. SINFONI is an Integral Field Unit spectrometer returning a 64 × 64 pixel image with 2048 wavelengths. Image cubes in the J-band (1.09 – 1.41 μm) and H-band (1.43 – 1.87 μm) were obtained at spatial resolutions of 0.1″and 0.025″per pixel, while SINFONI’s adaptive optics provided an effective resolution of approximately 0.1″. Image cubes were obtained at the start and end of three successive nights to monitor the temporal development of discrete clouds both at short timescales (i.e. during a single night) as well as over the longer period of the three-day observing run. These observations were compared with similar H-band observations obtained in September 2009 with the NIFS Integral Field Unit spectrometer on the Gemini-North telescope in Hawaii, previously reported by Irwin et al., Icarus 216, 141-158, 2011, and previously unreported Gemini/NIFS observations at lower spatial resolution made in 2011. We find both similarities and differences between these observations, spaced over four years. The same overall cloud structure is seen with high, bright clouds visible at mid-latitudes (30 – 40°N,S), with slightly lower clouds observed at lower latitudes, together with small discrete clouds seen circling the pole at a latitude of approximately 60°S. However, while discrete clouds were visible at this latitude at both the main cloud deck level (at 2–3 bars) and in the upper troposphere (100–500mb) in 2009, no distinct deep (2–3 bar), discrete circumpolar clouds were visible in 2013, although some deep clouds were seen at the southern edge of the main cloud belt at 30–40°S, which have not been observed before. The nature of the deep sub-polar discrete clouds observed in 2009 is intriguing. While it is possible that in 2013 these deeper clouds were masked by faster moving, overlying features, we consider that it is unlikely that this should have happened in 2013, but not in 2009 when the upper-cloud activity was generally similar. Meanwhile, the deep clouds seen at the southern edge of the main cloud belt at 30 – 40°S in 2013, should also have been detectable in 2009, but were not seen. Hence, these observations may have detected a real temporal variation in the occurrence of Neptune’s deep clouds, pointing to underlying variability in the convective activity at the pressure of the main cloud deck at 2–3 bars near Neptune’s south pole and also in the main observable cloud belt at 30 – 40°S.</p

An investigation of supervector regression for forensic voice comparison on small data

International audienceThe present paper deals with an observer design for a nonlinear lateral vehicle model. The nonlinear model is represented by an exact Takagi-Sugeno (TS) model via the sector nonlinearity transformation. A proportional multiple integral observer (PMIO) based on the TS model is designed to estimate simultaneously the state vector and the unknown input (road curvature). The convergence conditions of the estimation error are expressed under LMI formulation using the Lyapunov theory which guaranties bounded error. Simulations are carried out and experimental results are provided to illustrate the proposed observer

Delivery of sTRAIL variants by MSCs in combination with cytotoxic drug treatment leads to p53-independent enhanced antitumor effects

Mesenchymal stem cells (MSCs) are able to infiltrate tumor tissues and thereby effectively deliver gene therapeutic payloads. Here, we engineered murine MSCs (mMSCs) to express a secreted form of the TNF-related apoptosis-inducing ligand (TRAIL), which is a potent inducer of apoptosis in tumor cells, and tested these MSCs, termed MSC.sTRAIL, in combination with conventional chemotherapeutic drug treatment in colon cancer models. When we pretreated human colorectal cancer HCT116 cells with low doses of 5-fluorouracil (5-FU) and added MSC.sTRAIL, we found significantly increased apoptosis as compared with single-agent treatment. Moreover, HCT116 xenografts, which were cotreated with 5-FU and systemically delivered MSC.sTRAIL, went into remission. Noteworthy, this effect was protein 53 (p53) independent and was mediated by TRAIL-receptor 2 (TRAIL-R2) upregulation, demonstrating the applicability of this approach in p53-defective tumors. Consequently, when we generated MSCs that secreted TRAIL-R2-specific variants of soluble TRAIL (sTRAIL), we found that such engineered MSCs, labeled MSC.sTRAIL DR5, had enhanced antitumor activity in combination with 5-FU when compared with MSC.sTRAIL. In contrast, TRAIL-resistant pancreatic carcinoma PancTu1 cells responded better to MSC.sTRAIL DR4 when the antiapoptotic protein XIAP (X-linked inhibitor of apoptosis protein) was silenced concomitantly. Taken together, our results demonstrate that TRAIL-receptor selective variants can potentially enhance the therapeutic efficacy of MSC-delivered TRAIL as part of individualized and tumor-specific combination treatments. © 2013 Macmillan Publishers Limited All rights reserved

Sporormiella as a tool for detecting the presence of large herbivores in the Neotropics

The reliability of using the abundance of Sporormiella spores as a proxy for the presence and abundance of megaherbivores was tested in southern Brazil. Mud-water interface samples from nine lakes, in which cattle-use was categorized as high, medium, or low, were assayed for Sporormiella representation. The sampling design allowed an analysis of both the influence of the number of animals using the shoreline and the distance of the sampling site from the nearest shoreline. Sporormiella was found to be a reliable proxy for the presence of large livestock. The concentration and abundance of spores declined from the edge of the lake toward the center, with the strongest response being in sites with high livestock use. Consistent with prior studies in temperate regions, we find that Sporormiella spores are a useful proxy to study the extinction of Pleistocene megafauna or the arrival of European livestock in Neotropical landscapes

Dynamical tunneling in molecules: Quantum routes to energy flow

Dynamical tunneling, introduced in the molecular context, is more than two decades old and refers to phenomena that are classically forbidden but allowed by quantum mechanics. On the other hand the phenomenon of intramolecular vibrational energy redistribution (IVR) has occupied a central place in the field of chemical physics for a much longer period of time. Although the two phenomena seem to be unrelated several studies indicate that dynamical tunneling, in terms of its mechanism and timescales, can have important implications for IVR. Examples include the observation of local mode doublets, clustering of rotational energy levels, and extremely narrow vibrational features in high resolution molecular spectra. Both the phenomena are strongly influenced by the nature of the underlying classical phase space. This work reviews the current state of understanding of dynamical tunneling from the phase space perspective and the consequences for intramolecular vibrational energy flow in polyatomic molecules.Comment: 37 pages and 23 figures (low resolution); Int. Rev. Phys. Chem. (Review to appear in Oct. 2007