Positivity constraints on the low-energy constants of the chiral pion-nucleon Lagrangian

Positivity constraints on the pion-nucleon scattering amplitude are derived in this article with the help of general S-matrix arguments, such as analyticity, crossing symmetry and unitarity, in the upper part of Mandelstam triangle, R. Scanning inside the region R, the most stringent bounds on the chiral low energy constants of the pion-nucleon Lagrangian are determined. When just considering the central values of the fit results from covariant baryon chiral perturbation theory using extended-on-mass-shell scheme, it is found that these bounds are well respected numerically both at O(p^3) and O(p^4) level. Nevertheless, when taking the errors into account, only the O(p^4) bounds are obeyed in the full error interval, while the bounds on O(p^3) fits are slightly violated. If one disregards loop contributions, the bounds always fail in certain regions of R. Thus, at a given chiral order these terms are not numerically negligible and one needs to consider all possible contributions, i.e., both tree-level and loop diagrams. We have provided the constraints for special points in R where the bounds are nearly optimal in terms of just a few chiral couplings, which can be easily implemented and employed to constrain future analyses. Some issues about calculations with an explicit Delta(1232) resonance are also discussed.Comment: 15 pages, 13 eps figures, 2 table

Development Of Metal-Containing Nanoparticles For Chemical Analysis And Bioanalysis

Metal-containing nanoparticles (MCPs) have been applied in fields ranging from environmental monitoring to biomedicine. This breadth is due to the outstanding behavior of MCPs as catalysts and imaging agents, and the ease with which nanoparticle morphology, composition, and reactivity (such as agglomeration) can be controlled. The work described in this dissertation will have two fundamentally different foci that are both essential for further development of MCPs as tools for chemical and bioanalysis. The first focus is on particle-by-particle characterization MCPs and the second focus is on creation of new composite MCPs. A total of four projects are included in this dissertation as follows. The first project shows how to optimize a relatively new analysis method, single-particle inductively-coupled plasma mass spectrometry (spICP-MS), for the particle-by-particle characterization of MCPs. Bulk analysis methods such conventional ICP-MS produce an aggregate signal derived from many particles at once, whereas spICP-MS produces a discrete per-particle signal that is monitored over time to produce an ensemble of per-particle signals. Bulk analysis is very reliable for obtaining accurate average metal content per particle because the signal is inherently an average for many particles. However, all per-particle information is lost with bulk analysis methods. Conversely, spICP-MS provides a very rare window into the per-particle composition of MCPs; however, its method parameters such as particle concentration, ICP ionization efficiency, and dwell time must be carefully optimized for accurate per-particle analysis. This work demonstrates how to optimize spICP-MSfor large MCPs—a particularly challenging size range—by using standard samples of gold nanoparticles ranging from 30 nm to 150 nm. The second project uses properly optimized spICP-MS conditions to measure per-particle metal concentration of large-sized (\u3e 100 nm) silica nanoparticles prepared by the water-in-oil microemulsion method and doped with tris(2,2’-bipyridyl)ruthenium(II). This is a well-studied MCP model that provides numerous avenues for bulk analysis (e.g., absorption spectrophotometry) and comparison with spICP-MS findings. Despite excellent correspondence of all methods for average Ru content over a wide range in doping levels, the per-particle doping level provided by spICP-MS does not—remarkably—adhere to a simple Gaussian-like distribution but shows a highly unusual geometric distribution. This result means, contrary to common assumption, the per-particle concentration of metal-dopant in silica nanoparticles prepared by the water-in-oil microemulsion method varies significantly per particle. These findings demonstrate that spICP-MS provides an essential per-particle window into MCP composition that is entirely missing with conventional bulk analysis methods. They also show that spICP-MS screening should become a routine characterization for new MCPs. The third project shows how to prepare and apply a ratiometric and fluorescent MCP for the sensitive and selective in vitro imaging of copper ions (Cu2+). This MCP contains conjugated polymer dots prepared from polydioctylfluorene (PFO), doped with a silica nanoparticle (PFO@SiO2), and assembled with red emissive gold nanoclusters (AuNCs) at the PFO@SiO2 surface to form a sandwich nanostructure, PFO@SiO2@AuNCs. This nanostructure exhibits two fluorescence emission peaks associated with the PFO polymers (438 nm) and AuNCs (630 nm). When Cu2+ coordinates with carboxyl groups on the AuNCs, the AuNC emission decreases in contrast to the constant PFO emission. This behavior provides a highly sensitive and selective ratiometric signal that can be applied for in vitro imaging and determination of Cu2+ in biological samples. The fourth project develops a turn-off type fluorescence resonance energy transfer (FRET) method based on a MCP composite that is sensitive to cysteine. The composite consists of AuNCs conjugated with polyvinylcarbazole polymer nanoparticles (PVK PNs) that demonstrate a strong FRET between two distinct fluorescence emission peaks under excitation of 342 nm. The MCP composite is highly sensitive to cysteine concentration though a quenching process at 630 nm due to the decomposition of aurophilic bonds consisting of Au(I)-thiolate ligands under high pH value and the etching ability of cysteine toward gold atoms. The MCP composite shows potential for determination of other biomolecules

Generation of Oligodendrocyte Progenitor Cells From Mouse Bone Marrow Cells.

Oligodendrocyte progenitor cells (OPCs) are a subtype of glial cells responsible for myelin regeneration. Oligodendrocytes (OLGs) originate from OPCs and are the myelinating cells in the central nervous system (CNS). OLGs play an important role in the context of lesions in which myelin loss occurs. Even though many protocols for isolating OPCs have been published, their cellular yield remains a limit for clinical application. The protocol proposed here is novel and has practical value; in fact, OPCs can be generated from a source of autologous cells without gene manipulation. Our method represents a rapid, and high-efficiency differentiation protocol for generating mouse OLGs from bone marrow-derived cells using growth-factor defined media. With this protocol, it is possible to obtain mature OLGs in 7-8 weeks. Within 2-3 weeks from bone marrow (BM) isolation, after neurospheres formed, the cells differentiate into Nestin+ Sox2+ neural stem cells (NSCs), around 30 days. OPCs specific markers start to be expressed around day 38, followed by RIP+O4+ around day 42. CNPase+ mature OLGs are finally obtained around 7-8 weeks. Further, bone marrow-derived OPCs exhibited therapeutic effect in shiverer (Shi) mice, promoting myelin regeneration and reducing the tremor. Here, we propose a method by which OLGs can be generated starting from BM cells and have similar abilities to subventricular zone (SVZ)-derived cells. This protocol significantly decreases the timing and costs of the OLGs differentiation within 2 months of culture

Carnosol Modulates Th17 Cell Differentiation and Microglial Switch in Experimental Autoimmune Encephalomyelitis

Medicinal plants as a rich pool for developing novel small molecule therapeutic medicine have been used for thousands of years. Carnosol as a bioactive diterpene compound originated from Rosmarinus officinalis (Rosemary) and Salvia officinalis, herbs extensively applied in traditional medicine for the treatment of multiple autoimmune diseases (1). In this study, we investigated the therapeutic effects and molecule mechanism of carnosol in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Carnosol treatment significantly alleviated clinical development in the myelin oligodendrocyte glycoprotein (MOG35–55) peptide-induced EAE model, markedly decreased inflammatory cell infiltration into the central nervous system and reduced demyelination. Further, carnosol inhibited Th17 cell differentiation and signal transducer and activator of transcription 3 phosphorylation, and blocked transcription factor NF-κB nuclear translocation. In the passive-EAE model, carnosol treatment also significantly prevented Th17 cell pathogenicity. Moreover, carnosol exerted its therapeutic effects in the chronic stage of EAE, and, remarkably, switched the phenotypes of infiltrated macrophage/microglia. Taken together, our results show that carnosol has enormous potential for development as a therapeutic agent for autoimmune diseases such as MS

Understanding charge transport in organic field effect transistors

The organic electronics research field has advanced tremendously in the last decades, having already led to field-effect mobilities able to compete with their inorganic counterparts. However, many fundamental aspects of this field remain still unclear and need to be clarified before its final blossoming, which would probably come with the complete understanding of the charge transport mechanism in organic materials. It is well-known that the performance of organic semiconductors is governed not only by their molecular structures but also by their intermolecular assembly in the solid state. Therefore, analyzing organic materials from both a molecular and supramolecular point of view is highly desirable. For this end, Raman spectroscopy is a rapid, non invasive technique able to gather information on molecular and supramolecular levels, thus being greatly useful in the organic electronics research field. Analyzing buried interfaces, such as the semiconductor-dielectric interface in organic field effect transistors (OFETs) is fundamental, since the largest contribution to charge transport occurs within the first few nanometers of the semiconductor near the dielectric interface. Surface Enhanced Raman Spectroscopy (SERS) appears as an easy and straightforward technique to carry out this task and to provide useful information on molecular orientation at the device active layer. In this communication, some examples will be presented in which several spectroscopic techniques, conventional Raman and SERS, supported by DFT quantum chemical calculations have been used to shed light on the mechanism of charge transport in OFETs.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

miR-1258: a novel microRNA that controls TMPRSS4 expression is associated with malignant progression of papillary thyroid carcinoma

Background: MicroRNA-1258 (miR-1258) has been shown to play an anti-cancer role in a variety of cancers, but its relationship with papillary thyroid cancer (PTC) has not been reported. The emphasis of this research was to reveal the biological function of miR-1258 in PTC and its potential mechanisms. Material and methods: We measured miR-1258 expression in PTC cells and the transfection efficiency of miR-1258 mimic and miR-1258 inhibitor by quantitative real-time PCR (qRT-PCR) assay. Cell Counting Kit-8 assay (CCK8) and Transwell experiments were conducted to examine the influences of altering miR-1258 expression on the viability, migration, and invasion of PTC cells. Bioinformatics prediction and dual-luciferase experiment were performed to verify the target gene of miR-1258. Finally, we carried out a rescue assay to verify whether the regulation of miR-1258 on the biological behaviour of PTC cells needs to be achieved by regulating TMPRSS4. Results: The outcomes revealed that miR-1258 was lowly expressed in PTC cell lines and miR-1258 showed the lowest expression in KTC-1 and the highest expression in B-CPAP among all tested PTC cell lines. Overexpression of miR-1258 inhibited KTC-1 cell viability and ability to migrate and invade, whereas inhibition of miR-1258 in B-CPAP cells has the opposite effect. Furthermore, we affirmed that miR-1258 can directly target TMPRSS4, and miR-1258 can reduce the biological malignant behaviour of PTC cells via regulation of TMPRSS4. Conclusion: Taken together, our research raised the possibility that miR-1258 was an anti-oncogene, which exerts its anti-cancer function by targeting TMPRSS4. Hence, it may be possible to treat PTC by targeting the miR-1258/TMPRSS4 axis in the future.