Cuantificación del crecimiento de pliegues con sedimentos sintectónicos asociados: aplicación al anticlinal de Santarén (orógeno cubano, cuenca de antepaís de las Bahamas)

The Santaren anticline, located offshore, is the outermost structure of the Cuban fold and thrust belt. The detailed study of the geometry of the syntectonic sediments associated with this anticline has allowed us to document its kinematic evolution. A number of reverse modelling geometrical techniques have been used to quantify fold gr owth (crestal structural relief, shortening, limb dip, interlimb angle and axial plane dip) during different stages. The values obtained for each of these parameters have been plotted versus time in order to s h ow their evolution through time. The conclusions achieved from all these plots are consistent and enable us to understand how fold amplification took place. Thus, the data obtained indicate that fold gr owth initiated during Middle Eocene, or before, and it continued until present day. Fold amplification took place at extremately slow rates from Middle Miocene to present day, and perhaps faster during deposition of older growth strata. In particular, data concerning rotation of the southern limb and interlimb angle tightening support this hypothesis. The data presented in this paper regarding the Santaren anticline evolution disagree with previous plate tectonic models that postulate the end of tectonic activity in this region during Middle Eocene

Water Manipulation through Curvature Energy on Humidity Microparticles

The electric field created in a curvature energy sensor on air microparticles is used to obtain a temperature-humidity map by stereoradially of the sensor design to detect and measure the temperature and humidity of certain local region of the environment space. Likewise,considering the curvature energy as the deviation of any field interaction,even the obstruction to its proper flow, is designed and created a humidityresistor sensor to the control and optimization of humidity in a space with different gradients of humidity, pressure and temperature in a radial detection and measuring. Then the sensing problem is a problem of free boundary conditions where is satisfied an energy functional of norm  ,to curvature functions  that satisfy in the temperature and humidity function  the change limit condition This carries to that the temperature-humidity sensor must be designed on a length gauge to measure the changes of humidity and temperature in the space

Cuantificación del crecimiento de pliegues con sedimentos sintectónicos asociados: aplicación al anticlinal de Santarén (orógeno cubano, cuenca de antepaís de las Bahamas)

El estudio detallado de la geometría de los sedimentos sintectónicos asociados al crecimiento del anticlinal de Santaren, localizado bajo el mar en la parte más externa de la faja plegada cubana, ha permitido documentar la evolución cinemática de dicho pliegue. Para ello se han utilizado una serie de técnicas geométricas de modelización inversa que permiten cuantificar el crecimiento del pliegue en función de: el relieve estructural de la cresta, el acortamiento, el buzamiento de los flancos, el ángulo entre flancos y el buzamiento del plano axial para diferentes estadios durante el depósito de los sedimentos sintectónicos. Para cada uno de los parámetros, los valores obtenidos se representan en una gráfica con respecto a la edad correspondiente, y de esta manera se conoce su evolución a través del tiempo. Las conclusiones que se obtienen a partir de las diferentes gr á ficas son coherentes entre sí y permiten vislumbrar datos importantes de la evolución del pliegue. Así, los resultados obtenidos indican que el anticlinal se inició en el Eoceno Medio, o anteriormente, y su crecimiento perduró hasta la actualidad. El anticlinal creció de forma extremadamente lenta a partir del Mioceno Medio y tal vez lo hizo de forma mas rápida durante el depósito de los sedimentos sintectónicos más antiguos. En particular, los datos sobre la rotación del flanco sur del anticlinal y sobre la variación del ángulo entre flancos parecen estar de acuerdo con esta última hipótesis. Estos nuevos datos sobre la evolución del anticlinal de Santaren contradicen modelos previos que postulan que la deformación en esta región culminó en el Eoceno Medio.The Santaren anticline, located offshore, is the outermost structure of the Cuban fold and thrust belt. The detailed study of the geometry of the syntectonic sediments associated with this anticline has allowed us to document its kinematic evolution. A number of reverse modelling geometrical techniques have been used to quantify fold gr owth (crestal structural relief, shortening, limb dip, interlimb angle and axial plane dip) during different stages. The values obtained for each of these parameters have been plotted versus time in order to s h ow their evolution through time. The conclusions achieved from all these plots are consistent and enable us to understand how fold amplification took place. Thus, the data obtained indicate that fold gr owth initiated during Middle Eocene, or before, and it continued until present day. Fold amplification took place at extremately slow rates from Middle Miocene to present day, and perhaps faster during deposition of older growth strata. In particular, data concerning rotation of the southern limb and interlimb angle tightening support this hypothesis. The data presented in this paper regarding the Santaren anticline evolution disagree with previous plate tectonic models that postulate the end of tectonic activity in this region during Middle Eocene

Shopping tourism: challenges, opportunities and development strategies for the destination Havana.

En los últimos años ha tomado mayor fuerza la relación entre el comercio y el turismo, y en consecuencia, se ha desarrollado aún más la modalidad de turismo de compras. La presente investigación tiene como objetivo identificar los retos y oportunidades del destino La Habana para el desarrollo de la modalidad de turismo de compras, a partir del estudio del mercado (demanda y competencia) y de la oferta del destino. Para dar cumplimiento a este objetivo, se llevó a cabo un benchmarking entre varios destinos de compras en América Latina y La Habana, y se aplicó la matriz de atractividad-competitividad-modalidad turística para varios segmentos de demanda. El estudio se dividió en varios momentos, primeramente, se realizó una conceptualización sobre la modalidad de turismo de compras; en un segundo momento se valoró la modalidad para su desarrollo en el destino La Habana, a partir del comercio de bienes, el benchmarking y la matriz; y se culminó la investigación con la determinación de retos, oportunidades y estrategias de desarrollo para la modalidad en este destino. Como base científica de la investigación se emplearon métodos empíricos, teóricos y estadísticos, tales como la entrevista, la observación no participativa, el análisis documental y el análisis comparativo.In recent years, the relationship between trade and tourism has grown stronger, and consequently, the modality of shopping tourism has developed even more. The present research aims to identify the challenges and opportunities of the Havana destination for the development of the shopping tourism modality, based on the study of the market (demand and competition) and the supply of the destination. To fulfill this objective, a benchmarking was carried out between various shopping destinations in Latin America and Havana, and the attractiveness-competitiveness-tourism modality matrix was applied for various demand segments. The study was divided into several moments, firstly, a conceptualization was carried out on the modality of shopping tourism; in a second moment, the modality for its development in the Havana destination was assessed, based on the trade of goods, benchmarking and the matrix; and the investigation was completed with the determination of challenges, opportunities and development strategies for the modality in this destination. As scientific basis for the research, empirical, theoretical and statistical methods were used, such as the interview, non-participatory observation, documentary analysis and comparative analysis

Fertilidad, desarrollo embrionario y prolificidad de conejas nulíparas alimentadas con piensos enriquecidos en ácidos grasos poliinsaturados n-3

One hundred and five nulliparous rabbit does were fed ad libitum one month before and during pregnancy with two isofibrous, isoenergetic and isoproteic diets supplemented with two different fat sources: 0.75% lard for control diet (C group: n=53) or 1.5% of a supplement (Optomega-50; Optivite International Ltd., España) containing a 50% of ether extract and 38% of n-3 polyunsaturated fatty acids (PUFA) for experimental diet (group P n-3; n=52). Fertility after artificial insemination and induction of ovulation with 20 μg of Gonadorelina (Inducel-GnRH, Ovejero) at 4.5 months of age was assessed. At parturition, pregnancy length and prolificacy (number and weight of born alive and number of stillborn) were observed. A total of 8 pregnant does from each experimental group were chosen at random to study embryo and placenta dimensions by means of ultrasonography at 8, 15 and 22 days of pregnancy. PUFA n-3 supplementation did not affect any productive results due the success on reproductive features of nulliparous does which are difficult to improve. Neither, any differences in ultrasonographic meausrements were obtained; nevertheless we have defined useful physiological parameters of rabbit embryo and placenta to future studies in this specie.Un total de 105 conejas nulíparas se alimentaron ad libitum un mes antes y durante su primera gestación con dos piensos isofibrosos, isoenergéticos e isoproteicos suplementados con dos fuentes de grasa diferentes: 0,75% de manteca para la dieta control (grupo C; n=53) ó 1,5% de un suplemento (Optomega-50; Optivite International Ltd., España) que contenía un 50% de extracto etéreo y 38% de ácidos grasos poli-insaturados (AG n-3) para la dieta experimental (grupo P; n=52). A los 4,5 meses de edad se determinó la fertilidad después de ser inseminadas artificialmente y tratadas con 20 μg de Gonadorelina (Inducel-GnRH, Ovejero) para inducirles la ovulación. Al parto se determinó la duración de la gestación, el número y peso de los gazapos nacidos vivos y muertos. Se escogieron 16 conejas al azar, 8 de cada grupo, y se realizaron ecografías a los 8, 15 y 22 días de gestación en las que se determinó las dimensiones del embrión y de los anejos fetales. La suplementación con AG n-3 no afectó a los resultados productivos determinados ya que se trata de parámetros que en nulíparas son difíciles de mejorar y suelen ser altos. Tampoco se observaron diferencias en las determinaciones ecográficas pero se han podido definir medidas fisiológicas de los fetos y anejos placentarios de gran utilidad para futuros estudios en esta especie

Development of Targeted Drug Delivery System To Improve Immunotherapy In Pancreatic Cancer

Introduction: About 95% of tumor arises from epithelial cell lining ducts known to be pancreatic ductal adenocarcinomas, with less than 5-7% survival rate. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). Immunotherapy has shown promising results in other cancers but limited response in pancreatic cancer due to desmoplasia and fibrotic tumor microenvironment. A recently identified mucin, MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas. Due to its high membrane expression, MUC13 may serve as an excellent target for PanCa treatment. Our recently published studies demonstrate a unique ability of our novel patented superparamagnetic iron oxide nanoparticles (SPIONS) of curcumin (Indian spice with high medicinal value) to inhibit desmoplasia and make the drug more bioavailable (1,2). Therefore, our objective is to conjugate SPION -curcumin with MUC13 antibody to directly target the pancreatic tumors and to improve immunotherapies by targeting tumor stroma. Methodology: Patented SPION1 particle was used for loading curcumin and later conjugated with MUC13 for directly targeting the pancreatic tumor. We characterized (size, zeta potential, charge and Dynamic light scattering), optimized and validated the uptake (Prussian blue staining and flow cytometer) of the formulation in invitro using ASPC1, HPAF, Panc 1, Panc M13 cell lines. Targeting efficiency of MNP-Anti-MUC13 particles in Panc-1-M13 and Panc-1 pancreatic cancer cells was done by immunofluorescence using flow cytometer and confocal microscopy. Cells treated with formulation were investigated for effect on PDAC cells and desmoplasia using Western blotting, qPCR, and immunofluorescence. Results: Our results demonstrate optimal particle size and zeta potential of SPION formulation. MUC13 conjugated SPIONS can efficiently internalize the PDAC cells and target immune checkpoint inhibitors, PDL-1 and CTLA4. MUC13-SPION formulation led to an enhanced uptake in MUC13 positive (MUC13+) PanCa cells as compared with MUC13 null (MUC13-) cells as demonstrated by immunofluorescence, Prussian blue staining and flow cytometry experiments. Interestingly, the formulation resulted in sustained delivery of CUR, enhanced inhibition of cell proliferation, migration and invasion in MUC13+ cells as compared with MUC13- cells, which suggests the targeting efficacy of the formulation. Additionally, the treatment of cells with the formulation inhibited the tumor spheroid formation and growth. The formulation softens up the tumors for therapies that can result in improved response to checkpoint immunotherapies. Conclusion: This study indicates high therapeutic significance of MUC13-SPIONS for achieving pancreatic tumor specific delivery of drugs. Therefore, the efficient MUC13 conjugated SPION-curcumin can potentiate checkpoint immunotherapies, inhibit tumor growth and its progression. This study has a potential to reduce morbidity and mortality caused by the disease and improve survival in patients

Novel therapy targeting Mutant-KRASG12D and Galectin-1 in Pancreatic Cancer

Introduction: Although, surgical resection and chemotherapy are the gold standard for treating Pancreatic Ductal Adenocarcinoma (PDAC), low patient survival rate remains the problem. The activating point mutation of the KRAS on codon-12 is present in 70–95% of PDAC cases and so far, no success has been achieved to inhibit KRAS. KRASG12D regulates cell proliferation, differentiation, apoptosis. Recent preliminary and published studies show high Galectin-1 (Gal-1) levels in both pancreatic cancer and stromal cells, which modulate tumor microenvironment and metastasis. Additionally, genetic deletion of gal1 inhibits metastasis and improves survival in KRAS mouse model of PDAC (1). Therefore, our objective is to develop a novel combination therapy for PDAC by targeting mutated KRASG12D point mutation and Gal1. This includes the delivery of KRASG12D inhibiting siRNA (siKRASG12D) using a superparamagnetic iron oxide nanoparticle (SPION) and a galectin inhibitor. Methods: ASPC1/Panc-1 (human), KPC (mouse) cells were used. Our patented SPION nano-formulation (2) has been used to deliver siKRASG12D and investigated in conjunction with Gal-1 for its anticancer efficacy. Particles were investigated for size, physico-chemical characterization (Dynamic light scattering), hemocompatibility (hemolysis assay) and the complexation of siKRAS (gel retardation assay). Cellular internalization and uptake of the particles were investigated using FAM labelled siRNA and Prussian blue assay. KRASG12D silencing was confirmed at both mRNA and protein levels. Anti-cancer efficacy of the formulation was determined using in vitro functional assays for cell viability (MTT), migration (Boyden chambers), invasion (Matrigel), clonogenicity, tumor spheroid formation, and in nude mice. Results: Our results demonstrate optimal particle size and zeta potential of SP-siKRAS formulation. SPsiKRAS efficiently internalized in PDAC cells and suppressed KRASG12D as well as its downstream targets, YAP and PDL-1. Combined targeting of siKRAS and Gal-1 inhibited cell proliferation. The formulation inhibited chemoresistance, cell proliferation, clonogenicity, migration, and invasion of pancreatic cancer cells. This resulted in activation of death related mechanisms, such as Bax, bcl-2, PARP cleavage in KRASG12D cells. Interestingly, the formulation was highly effective in inhibiting KRASG12D and growth of tumor spheroid in 3D cell models, which recapitulate the heterogeneity and pathophysiology of PDAC. This further provides a clinical validation demonstrating potential of SP-siKRAS particles to efficiently silence KRAS expression. SP-siKRAS also exhibited hemocompatibility, suggesting its potential of silencing KRAS without being toxic to the body. Additionally, the formulation was efficiently delivered in nude mice to exhibit KRasG12D silencing and inhibit tumor growth. Conclusion: This gene therapy targeting KRAS G12D mutation with a Gal-1 inhibition has a potential to modulate the oncogenic network and tumor microenvironment resulting in the repression of growth, metastasis, chemoresistance, and improvement in patient survival. This study will develop a novel sustainable therapeutic approach to target pancreatic cancer growth and improve patient survivability

Pancreatic and psoas abscesses as a late complication of intravesical administration of bacillus Calmette-Guerin for bladder cancer: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Bacillus Calmette-Guerin (BCG) is a live attenuated strain of <it>Mycobacterium bovis</it> that has been used to treat urothelial carcinoma since 1976, and has been reported to eradicate disease in more than 70% of patients with <it>in situ</it> and stage I disease. To the best of our knowledge, we report the first case of disseminated bacillus Calmette-Guerin infection causing multiple abscesses affecting the pancreatic head and right psoas muscle, diagnosed 5 years after intravesical treatment with bacillus Calmette-Guerin therapy for bladder cancer.</p> <p>Case presentation</p> <p>An 83-year-old Caucasian man was hospitalized with a 2-month history of back pain, anorexia, generalized weakness and a 47-pound weight loss. He had previously undergone two transurethral resections for high-grade transitional cell carcinoma of the bladder and had received 12 intravesical bacillus Calmette-Guerin instillations without any complications. He complained of abdominal pain in his right flank. A computed tomography scan of the abdomen showed multiple abscesses affecting the pancreatic head and right psoas muscle. Growth of <it>Mycobacterium bovis</it> was determined in cultures of the purulent material obtained by surgical drainage of the abscesses.</p> <p>Conclusions</p> <p>This case illustrates the fact that although intravesical administration of bacillus Calmette-Guerin is generally considered to be safe, it is not exempt from complications and these could appear immediately after treatment or as a delayed complication many years later.</p