Trigonometry of 'complex Hermitian' type homogeneous symmetric spaces

This paper contains a thorough study of the trigonometry of the homogeneous symmetric spaces in the Cayley-Klein-Dickson family of spaces of 'complex Hermitian' type and rank-one. The complex Hermitian elliptic CP^N and hyperbolic CH^N spaces, their analogues with indefinite Hermitian metric and some non-compact symmetric spaces associated to SL(N+1,R) are the generic members in this family. The method encapsulates trigonometry for this whole family of spaces into a single "basic trigonometric group equation", and has 'universality' and '(self)-duality' as its distinctive traits. All previously known results on the trigonometry of CP^N and CH^N follow as particular cases of our general equations. The physical Quantum Space of States of any quantum system belongs, as the complex Hermitian space member, to this parametrised family; hence its trigonometry appears as a rather particular case of the equations we obtain.Comment: 46 pages, LaTe

Análisis de las sobretasas arancelarias de materias primas utilizadas en la producción de muebles de madera y su efecto en la competitividad de los fabricantes de muebles en la provincia de Pichincha

En 2015, el Gobierno del Ecuador implementó la Resolución No. 011-2015 con la finalidad de salvaguardar el equilibrio de la balanza de pagos, afectando con esta medida a las materias primas utilizadas en la fabricación de muebles de madera. El objetivo de esta investigación es determinar el efecto de las sobretasas arancelarias de estas materias sobre la competitividad de las empresas fabricantes de muebles de madera en la Provincia de Pichincha. Las metodologías de investigación utilizadas son el método comparativo y el método analítico. Se obtuvo fuentes de información primaria con encuestas de percepción a productores de muebles de madera, y fuentes de información secundaria con información de importaciones, resoluciones, aranceles, páginas especializadas e informes oficinales de entidades estatales. Como resultado se encontró que las sobretasas arancelarias aplicadas a las materias primas están relacionadas en forma directa o indirecta con la disminución de la competitividad de los fabricantes de muebles de madera de la Provincia de Pichincha. Se concluye que, por un lado, las importaciones de muebles de madera han aumentado durante los últimos años, mientras que las materias primas utilizadas para su fabricación han disminuido; además la competitividad de los fabricantes de muebles se ha visto afectada por los precios altos de las materias primas importadas, provocando aumento en sus costos de producción y disminución de sus ventas por el incremento en los precios de sus productos.In 2015, the Government of Ecuador implemented Resolution No. 011-2015 in order to safeguard the balance of payments. This measure the raw materials used in the manufacture of wooden furniture. The objective of this investigation is to determine the effect of tariff surcharges of these matters on the competitiveness of wood furniture manufacturing companies in the Province of Pichincha. The research methodologies used are the comparative method and the analytical method. Primary information sources were obtained with perception surveys of wood furniture producers, and secondary information sources with information on imports, resolutions, tariffs, specialized pages and official reports of state entities. As a result, it was found that tariff surcharges applied to raw materials are directly or indirectly related to the decrease in competitiveness of wood furniture manufacturers in the Pichincha Province. It is concluded that, on the one hand, imports of wooden furniture have increased during the last years, while the raw materials used for their manufacture have decreased; In addition, the competitiveness of furniture manufacturers has been affected by the high prices of imported raw materials, causing an increase in their production costs and a decrease in their sales due to the increase in the prices of their products

Trigonometry of spacetimes: a new self-dual approach to a curvature/signature (in)dependent trigonometry

A new method to obtain trigonometry for the real spaces of constant curvature and metric of any (even degenerate) signature is presented. The method encapsulates trigonometry for all these spaces into a single basic trigonometric group equation. This brings to its logical end the idea of an absolute trigonometry, and provides equations which hold true for the nine two-dimensional spaces of constant curvature and any signature. This family of spaces includes both relativistic and non-relativistic homogeneous spacetimes; therefore a complete discussion of trigonometry in the six de Sitter, minkowskian, Newton--Hooke and galilean spacetimes follow as particular instances of the general approach. Any equation previously known for the three classical riemannian spaces also has a version for the remaining six spacetimes; in most cases these equations are new. Distinctive traits of the method are universality and self-duality: every equation is meaningful for the nine spaces at once, and displays explicitly invariance under a duality transformation relating the nine spaces. The derivation of the single basic trigonometric equation at group level, its translation to a set of equations (cosine, sine and dual cosine laws) and the natural apparition of angular and lateral excesses, area and coarea are explicitly discussed in detail. The exposition also aims to introduce the main ideas of this direct group theoretical way to trigonometry, and may well provide a path to systematically study trigonometry for any homogeneous symmetric space.Comment: 51 pages, LaTe

Characterization of Different Functionalized Lipidic Nanocapsules as Potential Drug Carriers

Lipid nanocapsules (LNC) based on a core-shell structure consisting of an oil-filled core with a surrounding polymer layer are known to be promising vehicles for the delivery of hydrophobic drugs in the new therapeutic strategies in anti-cancer treatments. The present work has been designed as basic research about different LNC systems. We have synthesized—and physico-chemically characterized—three different LNC systems in which the core was constituted by olive oil and the shell by different phospholipids (phosphatidyl-serine or lecithin) and other biocompatible molecules such as Pluronic® F68 or chitosan. It is notable that the olive-oil-phosphatidyl-serine LCN is a novel formulation presented in this work and was designed to generate an enriched carboxylic surface. This carboxylic layer is meant to link specific antibodies, which could facilitate the specific nanocapsule uptake by cancer cells. This is why nanoparticles with phosphatidyl-serine in their shell have also been used in this work to form immuno-nanocapsules containing a polyclonal IgG against a model antigen (C-reactive protein) covalently bounded by means of a simple and reproducible carbodiimide method. An immunological study was made to verify that these IgG-LNC complexes showed the expected specific immune response. Finally, a preliminary in vitro study was performed by culturing a breast-carcinoma cell line (MCF-7) with Nile-Red-loaded LNC. We found that these cancer cells take up the fluorescent Nile- Red molecule in a process dependent on the surface properties of the nanocarriers

Evaluación del grado de queratinización y el recuento de AgNORs en citología exfoliativa de mucosa oral normal de individuos fumadores y no fumadores

Objetivos. En individuos fumadores con mucosa oral clínicamente sana, se han observado cambios citológicos como una mayor queratinización, existiendo también reportes de un mayor grado de actividad nucleolar. En estos estudios, las células para frotis se han obtenido por medio de espátula de madera. Nuestro objetivo es evaluar la profundidad de muestras citológicas de mucosa oral obtenidas con cepillo para frotis (endobrush) y comparar el grado de queratinización y la actividad nucleolar en pacientes fumadores y no fumadores. Diseño del estudio. Se obtuvieron frotis de mucosa oral de borde de lengua clínicamente normal de 30 individuos fumadores y 30 no fumadores, utilizando espátula de madera y endobrush. Las muestras fueron teñidas con Papanicolaou y con la tinción AgNORs. Resultados. Con la espátula de madera se obtuvo un mayor porcentaje de células epiteliales superficiales anucleadas (P= 0.016) y con el endobrush se obtuvieron células más profundas (tipo intermedias) (P= 0.035). Los individuos fumadores presentaron un mayor porcentaje de células superficiales anucleadas con ambas técnicas, diferencia que fue estadísticamente significativa con la técnica endobrush (P=0.005). El promedio de AgNORs en las células nucleadas fue mayor en los individuos fumadores (3.83) que en los no fumadores (2.79) (P= 0.003). Conclusiones. El endobrush permite obtener células de estratos más profundos. Los individuos fumadores con mucosa clínicamente normal presentan un mayor porcentaje de células queratinizadas y una mayor actividad nucleolar, sugiriendo que el consumo de cigarrillo influye en la actividad celular de la mucosa del borde de lengua.Objetive.In smokers with clinically normal buccal mucosa, cytological changes such as increased keratinization, and higher nucleolar activity have been observed. In these studies the cells for cytological smears were obtained with a wooden spatula. Our objectives were to evaluate the depth of cytological smears of oral mucosa obtained with both a brush (endobrush) and a wooden spatula, and to compare the degree of keratinization and the nucleolar activity in smokers and non-smokers. Design. We obtained cytological smears of clinically normal lateral tongues of 30 smokers and 30 non-smokers using both a wooden spatula and endobrush. The samples were dyed with Papanicolaou and the AgNORs. Results. With the wooden spatula we found a greater percentage of enucleated superficial epithelial cells (P = 0.016) and deeper cells were obtained with an endobrush (intermediate cells) (P =0.035). The smokers showed a greater percentage of enucleated superficial cells with both techniques, however this difference was significantly greater with Endobrush (P=0.005). The average of AgNORs in the nucleated cells was greater in smokers (3.83) than in non-smokers (2.79) (P=0.003). Conclusion. The Endobrush allows the clinician to obtain deeper cells of buccal mucosa. Smokers with clinically normal mucosa show a greater percentage of keratinized cells and a greater nucleolar activity, suggesting that cigarette smoking influences the cellular activity of the mucosa of the lateral tongue

A nano-enabled cancer-specific ITCH RNAi chemotherapy booster for pancreatic cancer

UNLABELLED: Gemcitabine is currently the standard therapy for pancreatic cancer. However, growing concerns over gemcitabine resistance mean that new combinatory therapies are required to prevent loss of efficacy with prolonged treatment. Here, we suggest that this could be achieved through co-administration of RNA interference agents targeting the ubiquitin ligase ITCH. Stable anti-ITCH siRNA and shRNA dendriplexes with a desirable safety profile were prepared using generation 3 poly(propylenimine) dendrimers (DAB-Am16). The complexes were efficiently taken up by human pancreatic cancer cells and produced a 40-60% decrease in ITCH RNA and protein expression in vitro (si/shRNA) and in a xenograft model of pancreatic cancer (shRNA). When co-administered with gemcitabine (100 mg/kg/week) at a subtherapeutic dose, treatment with ITCH-shRNA (3x 50 mg/week) was able to fully suppress tumour growth for 17 days, suggesting that downregulation of ITCH mediated by DAB-Am16/shRNA sensitizes pancreatic cancer to gemcitabine in an efficient and specific manner. FROM THE CLINICAL EDITOR: Gemcitabine delivery to pancreatic cancer often results in the common problem of drug resistance. This team overcame the problem through co-administration of siRNA and shRNA dendriplexes targeting the ubiquitin ligase ITCH

Influence of the surface properties of nanocapsules on their interaction with intestinal barriers

Despite the convenience of the oral route for drug administration, the existence of different physiological barriers associated with the intestinal tract greatly lowers the bioavailability of many active compounds. We have previously suggested the potential polymeric nanocapsules, consisting of an oily core surrounded by a polymer shell, as oral drug delivery carriers. Here we present a systematic study of the influence of the surface properties of these nanocapsules on their interaction with the intestinal barriers. Two different surfactants, Pluronic®F68 (PF68) and F127 (PF127), and two polymeric shells, chitosan (CS) and polyarginine (PARG) were chosen for the formulation of the nanocapsules. We analyzed nine different combinations of these polymers and surfactants, and studied the effect of each specific combination on their colloidal stability, enzymatic degradation, and mucoadhesion/mucodiffusion. Our results indicate that both, the polymer shell and the surfactants located at the oil/water interface, influence the interaction of the nanocapsules with the intestinal barriers. More interestingly, according to our observations, the shell components of the nanosystems may have either synergic or disruptive effects on their capacity to overcome the intestinal barriersThe authors acknowledge financial support from the TRANS‐INT European Consortium −FP7, under grant agreement No. 281035 and the Xunta de Galicia (Competitive Reference Groups ‐FEDER Funds; Ref 2014/043). Irene Santalices acknowledges a predoctoral grant from the FPU program (No. FPU13/02015) from the Ministry of Education, Culture and Sports, MECD, Spain. The authors acknowledge Servier for providing Servier Medical Art (http://smart.servier.com/), being the small intestine, intestinal villi and laboratory material and equipment (https://creativecommons.org/licenses/by/3.0/) modified from the original work and used for the creation of the graphical abstract and Figure 1.S

A nano-enabled cancer-specific ITCH RNAi chemotherapy booster for pancreatic cancer

Gemcitabine is currently the standard therapy for pancreatic cancer. However, growing concerns over gemcitabine resistance mean that new combinatory therapies are required to prevent loss of efficacy with prolonged treatment. Here, we suggest that this could be achieved through co-administration of RNA interference agents targeting the ubiquitin ligase ITCH. Stable anti-ITCH siRNA and shRNA dendriplexes with a desirable safety profile were prepared using generation 3 poly(propylenimine) dendrimers (DAB-Am16). The complexes were efficiently taken up by human pancreatic cancer cells and produced a 40-60% decrease in ITCH RNA and protein expression in vitro (si/shRNA) and in a xenograft model of pancreatic cancer (shRNA). When co-administered with gemcitabine (100 mg/kg/week) at a subtherapeutic dose, treatment with ITCH-shRNA (3x 50 mg/week) was able to fully suppress tumour growth for 17 days, suggesting that downregulation of ITCH mediated by DABAm16/shRNA sensitizes pancreatic cancer to gemcitabine in an efficient and specific manner

Rational design of polyarginine nanocapsules intended to help peptides overcoming intestinal barriers

The aim of this work was to rationally design and characterize nanocapsules (NCs) composed of an oily core and a polyarginine (PARG) shell, intended for oral peptide delivery. The cationic polyaminoacid, PARG, and the oily core components were selected based on their penetration enhancing properties. Insulin was adopted as a model peptide to assess the performance of the NCs. After screening numerous formulation variables, including different oils and surfactants, we defined a composition consisting of oleic acid, sodium deoxycholate (SDC) and Span 80. This selected NCs composition, produced by the solvent displacement technique, exhibited the following key features: (i) an average size of 180 nm and a low polydispersity (0.1), (ii) a high insulin association efficacy (80–90% AE), (iii) a good colloidal stability upon incubation in simulated intestinal fluids (SIF, FaSSIF-V2, FeSSIF-V2), and (iv) the capacity to control the release of the associated insulin for > 4 h. Furthermore, using the Caco-2 model cell line, PARG nanocapsules were able to interact with the enterocytes, and reversibly modify the TEER of the monolayer. Both cell adhesion and membrane permeabilization could account for the pronounced transport of the NCs-associated insulin (3.54%). This improved interaction was also visualized by confocal fluorescent microscopy following oral administration of PARG nanocapsulesto mice. Finally, in vivo efficacy studies performed in normoglycemic rats showed a significant decrease in their plasma glucose levels after treatment. In conclusion, here we disclose key formulation elements for making possible the oral administration of peptidesThis work was supported by the European TRANS-INT Consortium, which received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement No. 281035. Z. Niu also would like to thank the Chinese Scholarship Council for his scholarshipS

Immunomodulatory effect of gut microbiota-derived bioactive peptides on human immune system from healthy controls and patients with inflammatory bowel disease

Bioactive peptides secreted by probiotic Bifidobacterium longum (peptide B7) and opportunistic pathogen Bacteroides fragilis (peptide B12) modulate the intestinal cytokine milieu in health. Here, we characterized their capacity to modulate both the mucosal cytokine production and the phenotype of circulating antigen presenting cells (APCs) in active inflammatory bowel disease (IBD). The IBD mucosa produced higher levels of pro-inflammatory cytokines referred to healthy controls (HCs). Peptides B7 and B12, however, did not ameliorate the mucosal cytokine milieu in IBD. Human circulating APCs (B-cells, monocytes, plasmacytoid dendritic cells (pDCs), and conventional dendritic cells (cDCs)) were characterized by flow cytometry in presence/absence of the peptides. Circulating B-cells, monocytes, and cDCs from IBD patients were more activated than those from HCs. Peptide B7, but not B12, decreased CCR2 expression on all APC subsets from HC, but not IBD patients. Moreover, both peptides tend to further increase their pro-inflammatory profile in IBD. In summary, IBD patients display mucosal and circulating APC pro-inflammatory properties. Peptide B7 immunomodulatory capacity elicited over circulating APCs from HC, but not IBD patients, suggests the presence of disrupted modulatory mechanisms for this peptide in IBD. Future studies should address the effect of bacteria-derived immunomodulatory peptides in non-inflamed (quiescent) IBD patientsThis work was supported by the Spanish Ministry of Economy (SAF2014-56642-JIN), the Spanish Ministry of Health (PIE13/00041), GETECCU (Grupo Español de Trabajo en Enfermedad Crohn y Colitis Ulcerosa), and the Community of Madrid (Consejería de Educación, Juventud y Deporte, Programa de Garantía Juvenil 2015 and 2016)