Miracle-dz/UniFAR-FTUs huggingface dataset:
Complex Ecological Dynamics and Eradicability of the Vector Borne Macroparasitic Disease, Lymphatic Filariasis

Background The current global efforts to control the morbidity and mortality caused by infectious diseases affecting developing countries—such as HIV/AIDS, polio, tuberculosis, malaria and the Neglected Tropical Diseases (NTDs)—have led to an increasing focus on the biological controllability or eradicability of disease transmission by management action. Here, we use an age-structured dynamical model of lymphatic filariasis transmission to show how a quantitative understanding of the dynamic processes underlying infection persistence and extinction is key to evaluating the eradicability of this macroparasitic disease. Methodology/Principal Findings We investigated the persistence and extinction dynamics of lymphatic filariasis by undertaking a numerical equilibrium analysis of a deterministic model of parasite transmission, based on varying values of the initial L3 larval density in the system. The results highlighted the likely occurrence of complex dynamics in parasite transmission with three major outcomes for the eradicability of filariasis. First, both vector biting and worm breakpoint thresholds are shown to be complex dynamic entities with values dependent on the nature and magnitude of vector-and host specific density-dependent processes and the degree of host infection aggregation prevailing in endemic communities. Second, these thresholds as well as the potential size of the attractor domains and hence system resilience are strongly dependent on peculiarities of infection dynamics in different vector species. Finally, the existence of multiple stable states indicates the presence of hysteresis nonlinearity in the filariasis system dynamics in which infection thresholds for infection invasion are lower but occur at higher biting rates than do the corresponding thresholds for parasite elimination. Conclusions/Significance The variable dynamic nature of thresholds and parasite system resilience reflecting both initial conditions and vector species-infection specificities, and the existence of hysteresis loop phenomenon, suggests that eradication of filariasis may require taking a more flexible and locally relevant approach to designing elimination programmes compared to the current command and control approach advocated by the global programme.
Decomposing phonological transformations in serial derivations

While most phonological transformations have been shown to be subsequential, there are tonal processes that do not belong to any subregular class, thereby making it difﬁcult to identify a tighter bound on the complexity of phonological processes than the regular languages. This paper argues that a tighter bound obtains from examining the way transformations are computed: when derived in serial, phonological processes can be decomposed into iterated subsequential maps.
Diversifying Carotenoid Biosynthetic Pathways by Directed Evolution

SUMMARY Microorganisms and plants synthesize a diverse array of natural products, many of which have proven indispensable to human health and well-being. Although many thousands of these have been characterized, the space of possible natural products—those that could be made biosynthetically—remains largely unexplored. For decades, this space has largely been the domain of chemists, who have synthesized scores of natural product analogs and have found many with improved or novel functions. New natural products have also been made in recombinant organisms, via engineered biosynthetic pathways. Recently, methods inspired by natural evolution have begun to be applied to the search for new natural products. These methods force pathways to evolve in convenient laboratory organisms, where the products of new pathways can be identified and characterized in high-throughput screening programs. Carotenoid biosynthetic pathways have served as a convenient experimental system with which to demonstrate these ideas. Researchers have mixed, matched, and mutated carotenoid biosynthetic enzymes and screened libraries of these “evolved” pathways for the emergence of new carotenoid products. This has led to dozens of new pathway products not previously known to be made by the assembled enzymes. These new products include whole families of carotenoids built from backbones not found in nature. This review details the strategies and specific methods that have been employed to generate new carotenoid biosynthetic pathways in the laboratory. The potential application of laboratory evolution to other biosynthetic pathways is also discussed.
Expression of intermediate filament-associated proteins paranemin and synemin in chicken development

The expression of two intermediate filament-associated proteins, paranemin (280,000 mol wt) and synemin (230,000 mol wt), was investigated with respect to the expression of two core intermediate filament proteins, desmin and vimentin, in various embryonic and adult chicken muscle and nonmuscle cells. All developing muscle cells, regardless of their type, simultaneously express desmin, vimentin, paranemin, and synemin. However, a difference is observed in the expression of paranemin in adult muscle. This protein is removed during differentiation of both fast and slow skeletal muscle, visceral smooth muscle, and the smooth muscle of muscular arteries, but remains in mature myocardial cells, cardiac conducting fibers, and the smooth muscle cells of elastic arteries. Some of these cells express vimentin, others desmin, and still others a mixture of the two. On the other hand, synemin is expressed in all the above types of adult muscle cells except myocardial cells. Adult myocardial cells also lack vimentin, and its presence is gradually reduced after hatching. Since in adult striated muscle all expressed intermediate filament proteins are found predominantly in association with the peripheries of myofibrillar Z discs, these results suggest that a change in the composition of skeletal and cardiac muscle Z discs occurs during chicken development and maturation. Erythrocytes that express synemin and vimentin do not express paranemin, while both embryonic and adult Schwann cells co- express paranemin and vimentin, but not synemin. Endothelial cells of muscular vessels express paranemin, while those of elastic vessels do not, and neither contains synemin. Paranemin and synemin are not expressed in neurons, epithelial, and most glial cells, suggesting that these two polypeptides are expressed only in conjunction with desmin or vimentin. These results suggest that the composition of intermediate filaments changes during chicken development, not only with respect to their core subunit proteins but also with respect to two associated polypeptides, particularly in muscle cells.
Cell Therapy: A Safe and Efficacious Therapeutic Treatment for Alzheimer’s Disease in APP+PS1 Mice

Previously, our lab was the first to report the use of antigen-sensitized dendritic cells as a vaccine against Alzheimer’s disease (AD). In preparation of this vaccine, we sensitized the isolated dendritic cells ex vivo with Aβ peptide, and administered these sensitized dendritic cells as a therapeutic agent. This form of cell therapy has had success in preventing and/or slowing the rate of cognitive decline when administered prior to the appearance of Aβ plaques in PDAPP mice, but has not been tested in 2×Tg models. Herein, we test the efficacy and safety of this vaccine in halting and reversing Alzheimer’s pathology in 9-month-old APP+PS1 mice. The results showed that administration of this vaccine elicits a long-lasting antibody titer, which correlated well with a reduction of Aβ burden upon histological analysis. Cognitive function in transgenic responders to the vaccine was rescued to levels similar to those found in non-transgenic mice, indicating that the vaccine is capable of providing therapeutic benefit in APP+PS1 mice when administered after the onset of AD pathology. The vaccine also shows indications of circumventing past safety problems observed in AD immunotherapy, as Th1 pro-inflammatory cytokines were not elevated after long-term vaccine administration. Moreover, microhemorrhaging and T-cell infiltration into the brain are not observed in any of the treated subjects. All in all, this vaccine has many advantages over contemporary vaccines against Alzheimer’s disease, and may lead to a viable treatment for the disease in the future.
Prodromal schizophrenia in primary care: a randomised sensitisation study.

BACKGROUND GPs are often the first point of contact for patients with prodromal schizophrenia. Early intervention, and therefore early detection, of schizophrenia is pivotal for the further disease course. However, recent studies have revealed that, due to its low prevalence in general practice and its insidious features, prodromal schizophrenia often remains unnoticed. AIM To test whether a repeated sensitisation method using clinical vignettes can improve diagnostic knowledge of GPs. DESIGN OF STUDY Postal survey using anonymous questionnaires. Repeated sensitisation model using clinical vignettes. SETTING GPs in three distinct regions in Switzerland covering a general population of 1.43 million. METHOD The study was conducted between September 2008 and October 2009. Questionnaires were sent to 1138 GPs at baseline, and at 6 and 12 months. After randomisation, 591 GPs were sensitised at 1, 3, and 5 months, while no sensitisation was carried out in the remaining 547 GPs. RESULTS The overall response rate was 66% (750 GPs). Sensitised GPs demonstrated a highly significant increase in diagnostic knowledge at 6 and at 12 months when compared to their own baseline knowledge scores and also to non-sensitised GPs (P<0.001). In particular, awareness of insidious features, such as functional decline and social withdrawal as signs of prodromal schizophrenia, accounted for this effect. CONCLUSION Theoretical knowledge of prodromal schizophrenia among GPs can successfully be increased by repeated sensitisation models using clinical vignettes.
Human Nutrition and Metabolism Dietary Supplementation with g-Linolenic Acid or Fish Oil Decreases T Lymphocyte Proliferation in Healthy Older Humans 1

Animal and human studies have shown that greatly increasing the amounts of flaxseed oil [rich in the (n-3) polyunsaturated fatty acid (PUFA) a-linolenic acid (ALNA)] or fish oil [FO; rich in the long chain (n-3) PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease mitogen-stimulated lymphocyte proliferation. The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, g-linolenic acid (GLA), arachidonic acid (ARA), DHA or FO on the proliferation of mitogen-stimulated human peripheral blood mononuclear cells (PBMC) and on the production of cytokines by those cells. The study was randomized, placebo-controlled, double-blinded and parallel. Healthy subjects ages 55–75 y consumed nine capsules/d for 12 wk; the capsules contained placebo oil (an 80:20 mix of palm and sunflower seed oils) or blends of placebo oil with oils rich in ALNA, GLA, ARA or DHA or FO. Subjects in these groups consumed 2 g of ALNA or 770 mg of GLA or 680 mg of ARA or 720 mg of DHA or 1 g of EPA plus DHA (720 mg of EPA 1 280 mg of DHA) daily from the capsules. Total fat intake from the capsules was 4 g/d. The fatty acid composition of PBMC phospholipids was significantly changed in the GLA, ARA, DHA and FO groups. Lymphocyte proliferation was not significantly affected by the placebo, ALNA, ARA or DHA treatments. GLA and FO caused a significant decrease (up to 65%) in lymphocyte proliferation. This decrease was partly reversed by 4 wk after stopping the supplementation. None of the treatments affected the production of interleukin-2 or interferon-g by PBMC and none of the treatments affected the number or proportion of T or B lymphocytes, helper or cytotoxic T lymphocytes or memory helper T lymphocytes in the circulation. We conclude that a moderate level GLA or EPA but not of other (n-6) or (n-3) PUFA can decrease lymphocyte proliferation but not production of interleukin-2 or interferon-g. J. Nutr. 131: 1918–1927, 2001.
More efficient PAC-learning of DNF with membership queries under the uniform distribution

An efficient algorithm exists for learning disjunctive normal form (DNF) expressions in the uniformdistribution PAC learning model with membership queries (J. Comput. System Sci. 55 (1997) 414), but in practice the algorithm can only be applied to small problems. We present several modifications to the algorithm that substantially improve its asymptotic efficiency. First, we show how to significantly improve the time and sample complexity of a key subprogram, resulting in similar improvements in the bounds on the overall DNF algorithm. We also apply known methods to convert the resulting algorithm to an attribute efficient algorithm. Furthermore, we develop a technique for lower bounding the sample size required for PAC learning with membership queries under a fixed distribution and apply this technique to produce a lower bound on the number of membership queries needed for the uniform-distribution DNF learning problem. Finally, we present a learning algorithm for DNF that is attribute efficient in its use of random bits.
Trace equivalence decision: negative tests and non-determinism

We consider security properties of cryptographic protocols that can be modeled using the notion of trace equivalence. The notion of equivalence is crucial when specifying privacy-type properties, like anonymity, vote-privacy, and unlinkability. In this paper, we give a calculus that is close to the applied pi calculus and that allows one to capture most existing protocols that rely on classical cryptographic primitives. First, we propose a symbolic semantics for our calculus relying on constraint systems to represent infinite sets of possible traces, and we reduce the decidability of trace equivalence to deciding a notion of symbolic equivalence between sets of constraint systems. Second, we develop an algorithm allowing us to decide whether two sets of constraint systems are in symbolic equivalence or not. Altogether, this yields the first decidability result of trace equivalence for a general class of processes that may involve else branches and/or private channels (for a bounded number of sessions).
Dengue Virus Pathogenesis: an Integrated View

SUMMARY Much remains to be learned about the pathogenesis of the different manifestations of dengue virus (DENV) infections in humans. They may range from subclinical infection to dengue fever, dengue hemorrhagic fever (DHF), and eventually dengue shock syndrome (DSS). As both cell tropism and tissue tropism of DENV are considered major determinants in the pathogenesis of dengue, there is a critical need for adequate tropism assays, animal models, and human autopsy data. More than 50 years of research on dengue has resulted in a host of literature, which strongly suggests that the pathogenesis of DHF and DSS involves viral virulence factors and detrimental host responses, collectively resulting in abnormal hemostasis and increased vascular permeability. Differential targeting of specific vascular beds is likely to trigger the localized vascular hyperpermeability underlying DSS. A personalized approach to the study of pathogenesis will elucidate the basis of individual risk for development of DHF and DSS as well as identify the genetic and environmental bases for differences in risk for development of severe disease.
Made-to-measure N-body systems

We describe an algorithm for constructing N-body realisations of equilibrium stellar systems. The algorithm complements existing orbit-based modelling techniques using linear programming or other optimization algorithms. The equilibria are constructed by integrating an N-body system while slowly adjusting the masses of the particles until the time-averaged density field and other observables converge to a prescribed value. The procedure can be arranged to maximise a linear combination of the entropy of the system and the $\chi^2$ statistic for the observables. The equilibria so produced may be useful as initial conditions for N-body simulations or for modelling observations of individual galaxies.
Higher differentiation among subspecies of the house mouse (Mus musculus) in genomic regions with low recombination

In the early stages of reproductive isolation, genomic regions of reduced recombination are expected to show greater levels of differentiation, either because gene flow between species is reduced in these regions or because the effects of selection at linked sites within species are enhanced in these regions. Here, we study the patterns of DNA sequence variation at 27 autosomal loci among populations of Mus musculus musculus, M. m. domesticus, and M. m. castaneus, three subspecies of house mice with collinear genomes. We found that some loci exhibit considerable shared variation among subspecies, while others exhibit fixed differences. We used an isolation‐with‐gene‐flow model to estimate divergence times and effective population sizes (Ne) and to disentangle ancestral variation from gene flow. Estimates of divergence time indicate that all three subspecies diverged from one another within a very short period of time approximately 350 000 years ago. Overall, Ne for each subspecies was associated with the degree of genetic differentiation: M. m. musculus had the smallest Ne and the greatest proportion of monophyletic gene genealogies, while M. m. castaneus had the largest Ne and the smallest proportion of monophyletic gene genealogies. M. m. domesticus and M. m. musculus were more differentiated from each other than either were from M. m. castaneus, consistent with greater reproductive isolation between M. m. domesticus and M. m. musculus. FST was significantly greater at loci experiencing low recombination rates compared to loci experiencing high recombination rates in comparisons between M. m. castaneus and M. m. musculus or M. m. domesticus. These results provide evidence that genomic regions with less recombination show greater differentiation, even in the absence of chromosomal rearrangements.
Comparative study of high-strength steel weld metals obtained by the SMAW and FCAW processes for offshore applications and mooring chains

A comparative study of the clad electrode and tubular wire processes was carried out, looking at the mechanical and micro-structural properties of weld metals of high-resistance steel, in the ‘as-welded’ and ‘stress-relief heat treatment’ (PWHT) conditions. The results show that the procedures adopted for welding with tubular wire and clad electrodes allow satisfactory levels of mechanical resistance to be obtained, with the exception of the value of percentage lengthening of the tubular wire, in the as-welded condition. The impact tests show that both the weld metals showed satisfactory impact resistance, in both the as-welded and PWHT conditions, observing that, for the tubular wire, the impact resistance is lower for the clad electrode in both conditions, lying close to the limit applied for the acceptance criterion of 50 J at 0°C in the PWHT condition. It was confirmed that the productivity achieved by the tubular wire process was approximately twice as high as that for the clad electrode process. As a result, the inherent advantage of the tubular wire process must be complemented with a consideration of all the mechanical properties obtained, orienting suitable selection of the welding process, in particular, for application in equipment that operates in fatigue conditions.
De Novo Mutation in the SCN5A Gene Associated With Early Onset of Sudden Infant Death

Background—Congenital long QT syndrome (LQTS), a cardiac ion channel disease, is an important cause of sudden cardiac death. Prolongation of the QT interval has recently been associated with sudden infant death syndrome, which is the leading cause of death among infants between 1 week and 1 year of age. Available data suggest that early onset of congenital LQTS may contribute to premature sudden cardiac death in otherwise healthy infants. Methods and Results—In an infant who died suddenly at the age of 9 weeks, we performed mutation screening in all known LQTS genes. In the surface ECG soon after birth, a prolonged QTc interval (600 ms1/2) and polymorphic ventricular tachyarrhythmias were documented. Mutational analysis identified a missense mutation (Ala1330Pro) in the cardiac sodium channel gene SCN5A, which was absent in both parents. Subsequent genetic testing confirmed paternity, thus suggesting a de novo origin. Voltage-clamp recordings of recombinant A1330P mutant channel expressed in HEK-293 cells showed a positive shift in voltage dependence of inactivation, a slowing of the time course of inactivation, and a faster recovery from inactivation. Conclusions—In this study, we report a de novo mutation in the sodium channel gene SCN5A, which is associated with sudden infant death. The altered functional characteristics of the mutant channel was different from previously reported LQTS3 mutants and caused a delay in final repolarization. Even in families without a history of LQTS, de novo mutations in cardiac ion channel genes may lead to sudden cardiac death in very young infants.