Team semantics is the mathematical basis of modern logics of dependence and independence. In contrast to classical Tarski semantics, a formula is evaluated not for a single assignment of values to the free variables, but on a set of such assignments, called a team. Team semantics is appropriate for a purely logical understanding of dependency notions, where only the presence or absence of data matters, but being based on sets, it does not take into account multiple occurrences of data values. It is therefore insufficient in scenarios where such multiplicities matter, in particular for reasoning about probabilities and statistical independencies. Therefore, an extension from teams to multiteams (i.e. multisets of assignments) has been proposed by several authors.
In this paper we aim at a systematic development of logics of dependence and independence based on multiteam semantics. We study atomic dependency properties of finite multiteams and discuss the appropriate meaning of logical operators to extend the atomic dependencies to full-fledged logics for reasoning about dependence properties in a multiteam setting. We explore properties and expressive power of a wide spectrum of different multiteam logics and compare them to second-order logic and to logics with team semantics. In many cases the results resemble what is known in team semantics, but there are also interesting differences. While in team semantics, the combination of inclusion and exclusion dependencies leads to a logic with the full power of both independence logic and existential second-order logic, independence properties of multiteams are not definable by any combination of properties that are downwards closed or union closed and thus are strictly more powerful than inclusion-exclusion logic. We also study the relationship of logics with multiteam semantics with existential second-order logic for a specific class of metafinite structures. It turns out that inclusion-exclusion logic can be characterised in a precise sense by the Presburger fragment of this logic, but for capturing independence, we need to go beyond it and add some form of multiplication. Finally, we also consider multiteams with weights in the reals and study the expressive power of formulae by means of topological properties.
Doxorubicin (Dox) is a wide-spectrum drug to treat different kinds of cancers. However, in clinical practice, Dox usually showed untargeted distributions to the other organs, which can cause serious side effects, such as cardiotoxity. Herein, the formulation of Dox into nanoparticles
is critical to enhance its distribution to tumors. Herein, we used polysaccharide, hyaluronic acid, to stabilize the Dox to form nano-precipitations (PD NPs) for the therapy of osteosarcoma. The PD NPs showed enhanced drug accumulation to tumor cells and realized better anticancer effects
than free drugs.
Electromyography (EMG) is a sophisticated electrodiagnostic-neurophysiological method, which serves to diagnose neuromuscular system diseases. It is based on the measurement of the electrical potentials created by the skeletal muscle activity. For this technique, surface electrodes and needle electrodes can be used, which read the action potential of a large number of motor units and read a small number of motor units, respectively. The wide-spectrum application of this method extends our diagnostic possibilities of the clinical examination in veterinary practice. Together with a clinical neurological examination and imaging methods, EMG forms a part of the diagnosis of nervous system diseases and it is a useful diagnostic technique for differentiating neuropathies, junctionopathies, and myopathies. The results of the neurophysiological examination inform us about the functional state of the peripheral and central nervous system; it can demonstrate subclinical diseases and monitor the dynamics of changes in the functional state of individual nervous systems over time. In this article, we review the electromyographic method and its use in veterinary practice.
The quantum quasi-docking procedure is used to compare the docking accuracies of two quantum-chemical semiempirical methods, namely, PM6-D3H4X and PM7. Quantum quasi-docking is an approximation to quantum docking. In quantum docking, it is necessary to search directly for the global minimum of the energy of the protein-ligand complex calculated by the quantum-chemical method. In quantum quasi-docking, firstly, we look for a wide spectrum of low-energy minima, calculated using the MMFF94 force field, and secondly, we recalculate the energies of all these minima using the quantum-chemical method, and among these recalculated energies we determine the lowest energy and the corresponding ligand position. Both PM6-D3H4X and PM7 are novel methods that describe well-dispersion interactions, hydrogen and halogen bonds. The PM6-D3H4X and PM7 methods are used with the COSMO implicit solvent model as it is implemented in the MOPAC program. The comparison is made for 25 high quality protein-ligand complexes. Firstly, the docking positioning accuracies have been compared, and we demonstrated that PM7+COSMO provides better positioning accuracy than PM6-D3H4X. Secondly, we found that PM7+COSMO demonstrates a much higher correlation between the calculated and measured protein–ligand binding enthalpies than PM6-D3H4X. For future quantum docking PM7+COSMO is preferable, but the COSMO model must be improved.
The oral cavity is inhabited by a wide spectrum of microbial species, and their colonization is mostly based on commensalism. These microbes are part of the normal oral flora, but there are also opportunistic species that can cause oral and systemic diseases. Although there is a strong exposure to various microorganisms, the oral mucosa reduces the colonization of microorganisms with high rotation and secretion of various types of cytokines and antimicrobial proteins such as defensins. In some circumstances, the imbalance between normal oral flora and pathogenic flora may lead to a change in the ratio of commensalism to parasitism. Healthy oral mucosa has many important functions. Thanks to its integrity, it is impermeable to most microorganisms and constitutes a mechanical barrier against their penetration into tissues. Our study aims to present the role and composition of the oral cavity microbiota as well as defense mechanisms within the oral mucosa which allow for maintaining a balance between such numerous species of microorganisms. We highlight the specific aspects of the oral mucosa protecting barrier and discuss up-to-date information on the immune cell system that ensures microbiota balance. This study presents the latest data on specific tissue stimuli in the regulation of the immune system with particular emphasis on the resistance of the gingival barrier. Despite advances in understanding the mechanisms regulating the balance on the microorganism/host axis, more research is still needed on how the combination of these diverse signals is involved in the regulation of immunity at the oral mucosa barrier.
Cyclic peptides have emerged as a promising class of organic compounds that possess polypeptide chains with a cyclic ring structure. There is a circular sequence of bonds in which the ring structure is formed via linkage between one end of the peptide bond and the other end with an amide bond or any other chemically stable bonds like ether, thioether, lactone, and disulfide. Generally, the cyclic peptides are isolated from natural resources like invertebrate animals, micro-organisms of marine habitats, and higher plants. These cyclic peptides possess unique structures with diverse pharmacological activities. Now a day, cyclic peptides possess superior therapeutic value due to several reasons such as greater resistance to enzymatic degradation (in vivo) and higher bio-availability. Some of these cyclic peptides are rich in leucine, proline while some have other amino acids as their major constituents. Numerous novel cyclic peptides isolated from natural sources are successfully developed as bioactive products. Recently, cyclic peptides derived from natural resources have attracted attention for exploring their numerous beneficial effects. Moreover, it is reported that natural cyclic peptides exhibit various therapeutic activities like an anthelmintic, ACE inhibitor, anti-tumor, microtubule inhibitor, anti-fungal, anti-malarial, and platelet aggregation inhibiting activity. In this review, various cyclic peptides are reported with structures and biological activities that are isolated from various natural sources. The natural cyclic peptides possess a wide spectrum of biological activities and can become a drug of the future for replacing the existing drugs which develop resistance
Magnetic cell separation has become a key methodology for the isolation of target cell populations from biological suspensions, covering a wide spectrum of applications from diagnosis and therapy in biomedicine to environmental applications or fundamental research in biology. There now exists a great variety of commercially available separation instruments and reagents, which has permitted rapid dissemination of the technology. However, there is still an increasing demand for new tools and protocols which provide improved selectivity, yield and sensitivity of the separation process while reducing cost and providing a faster response. This review aims to introduce basic principles of magnetic cell separation for the neophyte, while giving an overview of recent research in the field, from the development of new cell labeling strategies to the design of integrated microfluidic cell sorters and of point-of-care platforms combining cell selection, capture, and downstream detection. Finally, we focus on clinical, industrial and environmental applications where magnetic cell separation strategies are amongst the most promising techniques to address the challenges of isolating rare cells.
Many enteric viruses are found in pig farms around the world and can cause death of animals or important production losses for breeders. Among the wide spectrum of enteric viral species, porcine Sapelovirus (PSV), porcine Kobuvirus (PKoV) and porcine Astrovirus (PAstV) are frequently found in pig feces. In this study we investigated sixteen pig farms in Corsica, France, to evaluate the circulation of three enteric viruses (PKoV, PAstV-1 and PSV). In addition to the three viruses studied by RT–qPCR (908 pig feces samples), 26 stool samples were tested using the Next Generation Sequencing method (NGS). Our results showed viral RNA detection rates (i) of 62.0% [58.7–65.1] (n = 563/908) for PSV, (ii) of 44.8% [41.5–48.1] (n = 407/908) for PKoV and (iii) of 8.6% [6.8–10.6] (n = 78/908) for PAstV-1. Significant differences were observed for all three viruses according to age (P-value = 2.4e–13 for PAstV-1; 2.4e–12 for PKoV and 0.005 for PSV). The type of breeding was significantly associated with RNA detection only for PAstV-1 (P-value = 9.6e–6). Among the 26 samples tested with NGS method, consensus sequences corresponding to 10 different species of virus were detected. This study provides first insight on the presence of three common porcine enteric viruses in France. We also showed that they are frequently encountered in pigs born and bred in Corsica, which demonstrates endemic local circulation.
Objectives:The associations of long-term risks of the full spectrum of mental disorders with clinically reassuring but suboptimal score range 7–9 remain unclear. This study investigated these associations during up to 38 years of follow-up.Methods:In a nationwide cohort study of 2,213,822 singletons born in Denmark during 1978–2015, we used cox regression to estimate the hazard ratio (HR) of mental disorders with a 95% CI.Results:A total of 3,00,679 (13.6%) individuals were diagnosed with mental disorders. The associations between suboptimal Apgar score 7–9 and mental disorders differed by attained age. In childhood (≤ 18 years), declining Apgar scores were associated with increased risks of overall mental disorders with HRs (95% CI) of 1.13(1.11-1.15), 1.34 (1.27–1.41), and 1.48 (1.31–1.67) for Apgar scores of 7–9, 4–6, and 1–3, respectively, compared with a score of 10. A dose-response association was seen even within the score range from 9 to 7 (HR 1.11 [95% CI: 1.08–1.13], 1.14 [1.10–1.18], and 1.20 [1.14–1.27], respectively). Of note, individuals with scores of 7–9 had increased risks of organic disorders (HR: 1.27, 95% CI: 1.05–1.53), neurotic disorders (HR: 1.07, 95% CI: 1.03–1.11), and a wide range of neurodevelopmental disorders, such as intellectual disability (1.87, 1.76–1.98), childhood autism (1.13, 1.05–1.22) and attention deficit hyperactivity disorder (1.10, 1.06–1.15). In early adulthood (19–39 years), suboptimal Apgar scores 7–9 were not associated with the risks of overall and specific mental disorders.Conclusion:Infants born with clinically reassuring but suboptimal 5-min scores 7–9 are at increased risks of a wide spectrum of mental disorders in childhood.
The Epstein-Barr Virus (EBV) is involved in the etiology of multiple hematologic and epithelial human cancers. EBV+ tumors employ multiple immune escape mechanisms, including the recruitment of immunosuppressive regulatory T cells (Treg). Here, we show some EBV+ tumor cells express high levels of the chemokines CCL17 and CCL22 both in vitro and in vivo and that this expression mirrors the expression levels of expression of the EBV LMP1 gene in vitro. Patient samples from lymphoblastic (Hodgkin lymphoma) and epithelial (nasopharyngeal carcinoma; NPC) EBV+ tumors revealed CCL17 and CCL22 expression of both tumor cell-intrinsic and -extrinsic origin, depending on tumor type. NPCs grown as mouse xenografts likewise showed both mechanisms of chemokine production. Single cell RNA-sequencing revealed in vivo tumor cell-intrinsic CCL17 and CCL22 expression combined with expression from infiltrating classical resident and migratory dendritic cells in a CT26 colon cancer mouse tumor engineered to express LMP1. These data suggest that EBV-driven tumors employ dual mechanisms for CCL17 and CCL22 production. Importantly, both in vitro and in vivo Treg migration was effectively blocked by a novel, small molecule antagonist of CCR4, CCR4-351. Antagonism of the CCR4 receptor may thus be an effective means of activating the immune response against a wide spectrum of EBV+ tumors.