br Results br Discussion The aim


The aim of this study was to examine the neural correlates of facial affect processing across this sensitive period of adolescent socioemotional development by using a highly ecologically valid stimulus set and paradigm (assessing implicit regulation of dynamic adolescent expressions) in a healthy sample of 10–23 year-old females. Consistent with prior studies that employed various emotion regulation paradigms (Lieberman et al., 2007; McRae et al., 2012; Ochsner et al., 2009; Pitskel et al., 2011; Silvers et al., 2015), our novel peer dynamic stimulus set reliably and robustly recruited key neural regions involved in the network of emotion reactivity (MOFC/vMPFC, bilateral amygdala) and regulation (bilateral dorsal and ventral LPFC). These data suggest that viewing peer faces (compared to labeling) was associated with heightened MOFC/vMPFC activity, while labeling peer faces (compared to viewing) was associated with heightened activity in bilateral ventral LPFC and bilateral dorsal LPFC as well as left amygdala. However, in our cross-sectional study spanning most of adolescence, none of our a priori regions of interest (MOFC/vMPFC, amygdala, dLPFC, and vLPFC) demonstrated the age-related trends in activity to dynamic peer faces that could be expected by extending imbalance models to the affective domain. These findings suggest that the field’s characterization of sensitive periods in socio-affective neurodevelopment may be highly influenced by the particular stimuli and paradigms used. In particular, when using stimuli and paradigms that may be more socially salient (peer faces) and ecologically valid (dynamic expressions and implicit regulation), the neurodevelopmental trends in emotional reactivity and regulation may vary from commonly assumed patterns derived from applying dual systems or imbalance models to the affective domain.


Current neurodevelopmental models posit that changes in amygdala and prefrontal function – or in their connectivity (Casey, 2015) – underlie changes in affective responding in childhood and adolescence (Casey et al., 2008; Ernst et al., 2006). Such models are bolstered by a rich body of animal work demonstrating developmental changes in prefrontal-amygdala dynamics (Bouwmeester et al., 2002a,b; McCallum et al., 2010; Pattwell et al., 2012), as well as extensive adult neuroimaging research linking the amygdala and prefrontal stearoyl-coa desaturase to a host of emotional processes (Buhle et al., 2014; Costafreda et al., 2008; Kober et al., 2008). However, there is also emerging evidence that the amygdala does not exclusively respond to aversive, or even affective stimuli (Cunningham and Brosch, 2012). As such, it is possible that developmental changes in amygdala and prefrontal function are related not only to emotional development, but also to a broader set of developmental processes (e.g., salience processing, social appraisals) (Pfeifer and Blakemore, 2012; van den Bulk et al., 2013). The present study sought to examine two non-competing possibilities for how amygdala and prefrontal function relate to general and affect-specific changes in development.
The first possibility was that age would predict general changes in the way individuals respond to both negative affective and neutral stimuli. Specifically, it was hypothesized that age would be associated with diminished engagement of subcortical systems like the amygdala which has been broadly implicated in responding to motivationally salient (Cunningham and Brosch, 2012), intense (Anderson et al., 2003), and emotion-eliciting – both positive and negative (Breiter et al., 1996) – stimuli (Costafreda et al., 2008). A sizeable body of neuroimaging work suggests that amygdala responses to aversive stimuli including fearful faces and emotionally evocative scenes are elevated in childhood (Gee et al., 2013; Silvers et al., 2015) and adolescence (Guyer et al., 2008; Hare et al., 2008; Monk et al., 2003; Passarotti et al., 2009) and decrease in adulthood. However, the evidence that age-related changes in amygdala responses are emotion-specific is more mixed (Helfinstein and Casey, 2014). Indeed, neuroimaging studies have revealed age-related decreases in amygdala responding for neutral (Forbes et al., 2011; Thomas et al., 2001), positive (Vasa et al., 2011), or a combination of different types of stimuli (Hare et al., 2008; Swartz et al., 2014; Vink et al., 2014). This suggest that perhaps children interpret a broader variety of affective and neutral stimuli as being salient or personally relevant than do adults and thus show elevated amygdala responses for both aversive and non-aversive stimuli. Among studies that have specifically examined age-related effects in the amygdala for aversive stimuli, most have focused on contrasts between aversive stimuli and fixation (Gee et al., 2013), or, in the case of our own work, on the effects of different regulatory conditions on responses to aversive stimuli (Silvers et al., in press; Silvers et al., 2015). While such approaches are useful for characterizing changes in amygdala function in affective contexts, they do not address whether or not such age-related changes are unique to affective contexts. As such, this prior research leaves open the possibility that the amygdala shows general, rather than negative affect-specific, age-related decreases in responding.

br Acknowledgements The authors would like to express

The authors would like to express their sincere thanks to DRDO (TBR-1251) for funding and awarding the Project. The authors are expressed their sincere thanks to Sh. C. Sarkar, Sh. N. Mukherjee, Dr. P. K. Soni and Dr. Manjit Singh, Distinguished Scientist/Director TBRL for their motivation, guidance and constant help provided during the execution of this work.

Pyrotechnic compositions have wide range of applications including gas generator, smoke, noise, heat, and colored flame [1–5]. The production of bright light with single wave length is the primary purpose of colored flame compositions [6–8]. Certain elements and compounds when heated to high temperature have the unique property of emitting lines or narrow bands of light in the visible region (380–780 nm) [9–13]. These elements are called the color source, for instance strontium (red), barium (green), copper (green or blue), and sodium (yellow) [14–17]. Strontium, barium, and copper emit color by forming their halides; this emission type is known as molecular emission which is characterized by broad band emission [18]. In the meantime, atomic emission is characterized by sharp discrete wave length [19,20]. The production of a vividly colored flame is a challenging problem which need a delicate balance between different factors including [21,22].
The combustion wave of colored flame was demonstrated to consist of five distinctive zones as demonstrated in Fig. 1[23–25].
The vapors of the atomic or the molecular emitting species are excited by the thermal energy of the secondary luminous combustion zone [26]. The excited levels of atoms, or molecules relaxed to the ground state with the emission of the visible light. Yellow flame presents no color problem considering the very strong atomic emission from excited sodium atoms [15,27]. The wavelength of sodium light actually consists of two wavelengths called D lines (D1 and D2) [28]. The sodium spectrum is dominated by the bright doublet known as the sodium D-lines at 584 ± 2 and 588 ± 1 nm [29]. The transition which gives rise to the doublet is from the 3P to the 3S level [30,31]. The 3P level is split into states with total angular momentum j = 3/2 and j = 1/2 by the magnetic energy of the atp gamma s spin in the presence of the internal magnetic field caused by the orbital motion; this effect is called the spin-orbit effect [32]. The difference in energy for the 3P3/2 and 3P1/2 is 0.0021 eV (Fig. 2).
Magnesium metal fuel is broadly used in many colored flame compositions. In an oxidizing flame, magnesium is converted to magnesium oxide (MgO), which is an excellent white light emitter by incandescence which may lower the color purity [10,33–36]. In yellow flares the emission intensity at D1 and D2 lines increases as the reaction temperature is raised; there is no molecular emitting species to decompose. However, there is an upper limit of temperature that must be avoided for maximum color quality (5000 K) as demonstrated in Fig. 3[14,37,38].
The chromaticity diagram describes colors in terms of rectangular x and y dimensionless coordinates, further details can be found in the following reference [39]. The pure colors are ranged along the upper edge of the diagram, their wavelengths indicated in nm. The colors displayed by sources of blackbody radiation at different temperatures (in kelvin) lie along a line that extends into the center of the diagram [38,40]. As the temperature increases the yellow color fades until 5000 K, above 5000 K the flame becomes white.

Experimental work

Results and discussion

Arabic gum was found to be a novel binder for the development of yellow flares with superior spectral performance; as it has a dual function as a binder and prevent the formation of NaCl in the flame zone. Upon combustion, arabic gum exhibited an effective rule to support the formation of Na atom (the main yellow color emitting specimen). Al fuel was found to eliminate any incandescent emotions from (MgO). Furthermore, Al provides a higher heat of combustion which has a substantial rule to excite the Na vapors. Consequently, yellow colored flame with high intensity and quality was developed. Thanks to the optimum ratio of color source (NaNO3) to novel binder (arabic gum) using Al fuel, this approach secured yellow tracer with superior spectral performance. It exhibited an increases the luminous intensity by 287. The yellow band spectrum (575–600 nm) was enhanced by 170% to the standard reference flare. Furthermore, yellow flare formulations based on aluminum fuel can exhibit extended service life without loss of reactivity in virtue of the protective oxide layer on aluminum.

Si bien es cierto que en los

Si bien es cierto que en los 80 se estabilizó en toda Latinoamérica un feminismo que se reconoce en las otras luchas sociales, el papel jugado localmente por atem fue, sin duda, mucho más molecular order Wortmannin la hora de delinear las agendas públicas o políticas que lo que su grado de inscripción política sugiere (invisibilidad política), o de lo que se ha escrito o se sabe sobre su historia (invisibilidad académica). Sin embargo, y por otra parte, es también necesario remarcar que este indiscutible proceso positivo conllevó una serie de efectos negativos para la historia del feminismo local. Más concretamente, el combate emprendido por las feministas de los 80 para con los rezagos —o las antiguallas— del feminismo anterior produjo un efecto de silenciamiento que tuvo las correspondientes secuelas de invisibilización, tergiversación y trivialización de los ensayos políticos y los escarceos intelectuales de los feminismos argentinos en los años 70. Estos ensayos, a pesar de sus limitaciones, fueron pioneros en varios de sus postulados que hoy día continúan siendo contribuciones fundamentales para el desarrollo del feminismo local.
A los silencios cocidos al calor de las rivalidades y los malentendidos entre agrupaciones —moneda viviente entre las diversas posiciones del feminismo local—, se sobreimprimió el silencio sobre la militancia peronista femenina y quien fuera su emblema, Eva Perón. De allí la inquietud suscitada por la presencia del nombre peronista entreverado en el nombre feminista. En el atroz 1976, María Elena Walsh, figura crucial de la cultura feminista argentina, publica su Cancionero para el mal de ojos. Uno de los textos que lo integran es “Eva”, e inevitable resulta no escuchar allí ese entrevero de los nombres y el despuntar de una más generosa revisión del pasado, como lo muestra este fragmento:
Se instala entonces la pregunta por las razones que estancaron y siguen aminorando la calidad y el alcance de los debates en el feminismo latinoamericano. Entre ellas, Lamas, siguiendo a Signal hypothesis Pereda, ubica la función de la arrogancia y su papel en la dificultad para el reconocimiento del otro. Para esta militante y académica, la arrogancia funge como “una estrategia que comparten dos inculturas: la académica y la antiacadémica” (Lamas 2006: 116). En ambas posiciones, opera una lógica sectaria que se nutre de sus propios blindajes teóricos y que produce el efecto fantasmático de inventar un contendiente que no hace más que impermeabilizar el ya ajustado terreno de las propias certezas. Teoría versus práctica, pensamiento versus acción y ciencia versus política son otras tantas parejas terminológicas que hacen al chantaje argumental, y no a la controversia.
La proliferación de esas oposiciones en la discusión es, para Lamas, en parte, consecuencia del clima antintelectual que se vivió en Latinoamérica entre fines de los años 80 y los comienzos del siglo en curso. Dice Lamas que, habida cuenta del estado de la discusión en el movimiento feminista latinoamericano, “la teoría no es un lujo sino que es una necesidad vital” (Lamas 2006: 116). En esa dirección, podemos decir que es vital, porque formaliza la escena del debate, y esa formalización hoy es un prerrequisito de cualquier interpretación política o epistemológica del mundo en que nos toca militar o conocer. Sólo mediante esa formalización será posible el desacuerdo, que no debe confundirse con el desconocimiento o el malentendido, sino que surge, entre otras cosas, de la claridad que guía el florecimiento del debate. La ausencia de ordenamiento simbólico es terreno fértil para desventuras imaginarias.
Los archivos y las escrituras de estos feminismos argentinos que hemos querido recobrar muestran que hicieron su esfuerzo militante e intelectual, y que lo hicieron a contrapelo de una historia nacional cruenta e inmersos en la larga noche del feminismo latinoamericano. Una noche atestada de silencios

Primera sesi n de mayo de

Primera sesión (21 de mayo de 2013)
Alumno Rojo: Tengo un compañero que es mi amigo. Una vez, platicando con él, nos mencionaba que le gustaría casarse con una mujer virgen. Él decía que no se casaría con una mujer que hubiera tenido muchas parejas sexuales, no porque según él le diera asco, pero nos dio a entender que para él es así como raro haber tenido relaciones sexuales con una mujer que ya ha estado con muchos hombres. Finalmente, es un prejuicio, pues creo que muchas mujeres tienen la idea de que deben ser vírgenes porque es lo que el hombre espera, no porque ellas lo quieran.
Debate: Pero ese muchacho, ¿era virgen? No, ¿verdad? [Risas.]
Debate: ¿Alguien conoce a un hombre que diga que su ideal es llegar virgen al matrimonio?
Alumna Azul: Yo sí conozco el caso de un chico. De hecho, tiene 24 años este amigo y es virgen. Pero creo que ahí sí influye mucho la religión, porque sus papás son pastores. Dice: “yo sí quiero llegar virgen al matrimonio, yo quiero tener mi familia, yo quiero hacer todo conforme a la ley de Dios”. Pero él no tiene ningún inconveniente en casarse con una mujer que no sea virgen. Aquí yo lo veo porque la educación que le da la mamá es como que la mujer es lo importante en la casa, y el hombre es lo importante afuera; pero que no importa si la mujer ya ha tenido dos, tres, cuatro parejas… que las mujeres no somos jabón para desgastarnos.
Alumno Negro: Depende mucho también de la sociedad en que nos desenvolvamos. Hay opiniones diversas. Es una distancia inmensa de mente a mente entre nosotros mismos. He estado en provincia, en pueblos de Oaxaca y Guerrero muy conservadores, muy tradicionales, y he SCR 7 estado en los lugares más liberales del Distrito Federal, por decirlo así. Son inmensas las diferencias de opiniones. En el pueblo, lo que importa es que una mujer sea virgen para que pueda consumarse algún matrimonio o tal vez la unión de dos familias. Lo importante es que la mujer sepa lavar, sepa planchar, sepa hacer todo lo que se supone hace una mujer. Y aparte que sea virgen para mantener y satisfacer sexualmente nada más a chlorophyll a su marido, o sea, al hijo de la familia que tiene más dinero. Ya en las sociedades más liberales, en el Distrito Federal, no interesa tanto porque, aun en familias católicas, la virginidad ya no es asunto de trascendencia.
Alumno Blanco: Estoy de acuerdo con Negro, porque México es muy complejo, pero creo que hay otro factor que importa mucho, tanto en las ciudades como en provincia, que es la globalización a través de los medios de comunicación. Muchos jóvenes, tanto de provincia como en la capital, ya tenemos acceso a series de televisión, a películas que nos muestran una forma de vida distinta de la tradicional católica mexicana; una forma de vida que es más gringa, más anglosajona, que se preocupa menos por las costumbres sexuales tradicionales. Entonces, creo que eso, si no determina directamente el comportamiento de los jóvenes, sí los pone a pensar en el sentido de, “por qué si estoy viendo una realidad en una serie de televisión donde ya no se preocupan por x y y valores, mi mamá y mi papá o la iglesia a la que yo pertenezco me está exigiendo tales valores”. Siento que entran en conflicto. También aquí en la ciudad hay lugares muy conservadores, no todos somos muy liberales.
Alumna Rosa: Desde el kínder hasta la prepa estuve en una misma escuela y era religiosa, entonces marcó mucho mi opinión al respecto de la sexualidad y cómo debía de llevarse, porque todo el tiempo estuve ceñida al principio religioso. Cuando salí de la prepa sí fue, no sé, una ruptura total con todo lo que ya tenía de cierto modo establecido como verdad, y pues me di cuenta de que hay otras posibilidades por descubrir, no solo el hecho de que te restrinjan o que tengas como principio rector de tu vida que la virginidad es lo mejor y lo único que le puedes dar al hombre como mujer. No sé, tienes muchísimas cosas más que una membrana para dar. Pero sí, mi formación siempre estuvo marcada por cuestiones religiosas y sí te limitan como ser humano.

br Results and discussion In Fig a and

Results and discussion
In Fig. 6a and b, four electrical impedance signals are shown, those were taken for each supporting substances (Black silicone, white gypsum, green gypsum, acrylic) with the BBPS device. Each specimen was mounted in a press to constraint each supporting substance, as depicted in Fig. 5. Each subfigure presents three curves that correspond to a pristine supporting substance, a supporting substance with a drilling A and a third one which correspond to a support with drillings A and B. Each drilling represents a structural modification since the volume is diminished by the drillings; this changes the stiffness of the support. In Fig. 6, there are observed similar trends in all materials, except the signal for green gypsum that does not have a resonant peak. A similar characteristic is given by each material since the electrical impedances are displaced among them when the drilling are done in the supporting material. However, we can see that the frequency intervals are different in each case. It means that the resonant peak correspond to BBPS and when the device is coupled to the supporting substance, the coupling affects the resonant value as explained by Ref. [36]. In each electrical impedance, there are seen different aspects when the supporting substance is drilled. For example, the impedance shifted backwards when the drilling A is done. This can be verified in all cases shown in Fig. 6. Other characteristics are considered in the level of impedance of the maximum and minimum values reached by the transition of the resonance in the impedance signal. However, these changes can be taken by the derivative of each signal by means of an index as proposed in subsection 2.4.
In the EMI technique, structural modification assessment is quantified using statistical indices, such as the root mean square deviation (RMSD), mean absolute percentage deviation (MAPD), correlation coefficient deviation (CCD) among others. In our case, we design an index based on a Gaussian function called and which was presented in section 2.4.
To calculate the index , first one; it purchase Phos-tag was necessary to approximate the derivative of the electrical impedance by means of a Gaussian function (see Eq. (5)). In Fig. 7a are shown three approximations done for the white gypsum; which represent the following cases; pristine, with hole A, with holes A and B. We can observe Oncogenes the approximated Gaussian functions present differences between them; for example the frequency peak value where the higher amplitude is located as well as the amplitude value of each approximation. These characteristics define the effects of the stiffness variation in each substance. In Table 2, there are shown the frequency values of each pristine supporting substance. The differences of the approximations are quantified characteristics calculating the index for all cases as shown in Fig. 7b. There is observed that is possible differentiate each stiffness stage in each supporting substance except in the black silicon for which the values of are very close. Whereas, in the other cases the differences in the index are notable. For the white gypsum is seen a comparable variation between 8 and 14% when the perforations were made. In the other cases, the variations find among 1 and 14% (green gypsum); 12.5 and 14.5% (Acrylic). It demonstrates that the proposed method was able to distinguish all different structural conditions (pristine, hole A, holes A and B). It is important to denote that the sensitivity is higher in the first stage (drilling A) than in the second stage (drilling A and B) since the variations are about 1 and 3%. However, the index values show a correspondence such that the means present the following values % (pristine, green gypsum is discarded), % (with drilling A) and % (with drilling A and B). For the data mentioned above, the standard deviations present close values in all cases, respectively. It indicates that the taken measurements shows a similar variability in each stiffness stage for each material. Then from Fig. 7b, we can conclude that the stiffness modification can be identified in all cases except in the black silicon.

IoT may be defined as A

IoT may be defined as “A global infrastructure for the information society enabling advanced services by interconnecting (physical and virtual) things based on, existing and evolving, interoperable information and communication technologies” [37]. The definition of “Cloud” is presented as prescribed by the NIST (National Institute of Standards and Technology) in its Special Publication of 7 pages (800-1457) in September, 2011. According to it, “Cloud Computing is a model for enabling ubiquitous, convenient, on-demand network access to a shared pool of configurable computing resources (e.g., networks, servers, storage, applications, and services) that can be rapidly provisioned and released with minimal management effort or service provider interaction”. Till date no definition of IoT cloud was present. Henceforth, the novel definition of IoT Cloud may be framed as “A model designed to facilitate the information society, enabling advanced services by interconnecting (physical and virtual) things based on, existing and evolving, interoperable information and communication technologies through ennoblement of ubiquitous, convenient, on-demand network access to a shared pool of configurable computing resources (e.g., networks, servers, storage, applications, and services) that can be rapidly provisioned and released with minimal management effort or service provider interaction that leverage the need and heterogeneous connectivity issues of the user centric things in well defined fashion”. Here, at this corticotropin releasing factor point we may integrate the recently proposed definition of IoT cloud with the cloud platform which is given as “a platform offered by a service provider as a hosted service which facilitates the deployment of software applications without the cost and complexity of acquiring and managing the underlying hardware and software layers [38].” Now finally, IoT cloud platform may be corticotropin releasing factor formulated by the novel definition as proposed as: “a platform offered by a service provider as a hosted service which facilitates the deployment of software applications without the cost and complexity of acquiring and managing the underlying hardware and software layers to hinder a model designed to facilitate the information society, enabling advanced services by interconnecting (physical and virtual) things based on, existing and evolving, interoperable information and communication technologies through ennoblement of ubiquitous, convenient, on-demand network access to a shared pool of configurable computing resources (e.g., networks, servers, storage, applications, and services) that can be rapidly provisioned and released with minimal management effort or service provider interaction that leverage the need and heterogeneous connectivity issues of the user centric things in well defined fashion”.
Methodologically, in tissues survey, 26 different genres of IoT cloud are selected as an arbitrary way to provide information to the readers regarding their technology, specificity, appropriateness, and convergence with existing knowledge of communication platforms. Moreover, these IoT cloud platforms are surveyed according to their appropriate deployment services including application development, device management, system management, heterogeneity management, data management, tools for analysis, deployment, monitoring, visualization, and research (see Fig. 1). While describing the cloud platforms following parameters such as real time data capture capability, data visualization, cloud model type, data analytics, device configuration, API protocols, and usage cost are chosen as the key selective features. The presented article shall pave the readers to gain an intrusive and overall idea about the stringent aspects of the IoT clouds towards solving multiple genres of service domains.
This paper is organized as follow. Section 2 presents acute problems associated with the presented IoT clouds which need to be solved by the researcher while incorporating the enterprises together. Section 3 concludes this paper.

buprenorphine hydrochloride The diagnosis of VPS induced bowel perforation is often difficult

The diagnosis of VPS-induced bowel perforation is often difficult and predominantly depends upon the clinical manifestations, abdominal X-ray, ultrasound, and CT results. Typically, bowel perforation is considered in shunted patients with unexplained fever or prominent abdominal symptoms. Additionally, gut buprenorphine hydrochloride meningitis, confirmed through CSF culture or pneumocephalus observed in the head CT, may be an indicator of intestinal perforation. However, many cases do not manifest shunt infection or peritonitis, and bowel perforation is recognized only during shunt revision for obstruction. By contrast, the diagnosis is easy if patients with prior VPS operation present with anal protrusion of the tube, as was the case in our patient. The plain abdominal roentgenogram revealed that the long peritoneal tube encircled the abdomen and progressed to the perineal region, and the CT scan revealed that the tube entered the ileum and progressed to the colon. Occasionally, a shuntogram can be used to demonstrate the mucosal pattern of the intestine, which was the case in the three patients with VPS-induced small-intestinal perforation reported in the literature.
The management of the VPS-induced small-intestinal perforation must be individualized according to the clinical conditions of the patients. Typically, removing the protruded shunt system and controling the infection, followed by CSF diversion, is the standard treatment protocol,; however, abdominal exploration for managing VPS-induced intestinal perforation is controversial. Several reports demonstrated that the peritoneal tube can be removed without abdominal exploration, because the opening into the bowel lumen is often small and self-sealing in the absence of peritonitis or abdominal abscess. Abdominal exploration for perforation repair might be required in cases accompanied by peritonitis, abdominal abscess, acute bowel perforation, failure of the closure of the fistulous tract following peritoneal tube removal, difficulty in removing the peritoneal tube, and knotting or twisting of the peritoneal tube. In a report reviewing 45 cases of VPS-induced intestinal perforation, the shunt tube was removed without abdominal exploration in 31 patients (68.9%), laparotomy for bowel repair was performed in eight patients (17.8%), and an unclear method of tube retrieval was used in six patients (13.3%). Concerning abdominal exploration, laparoscopic surgery can be performed as an alternative to laparotomy, however, only in one report was a patient with VPS-induced silent bowel perforation managed laparoscopically. Our patient had persistent intermittent abdominal pain and focal ileus; therefore, we performed laparoscopic surgery for diagnosis and definite repair. The resection of the involved ileum and anastomosis was performed extracorporeally through laparoscopy.
The prognosis for recovery in patients with VPS-induced bowel perforation is more accurate when bowel perforation is detected at the asymptomatic stage. However, if bowel perforation is undetected, patients are at a high risk of developing meningitis or ventriculitis, and the mortality rate may increase to 15%.

Ischemic bowel disease varies from full-thickness necrosis or gangrene to transient inflammation. The disease is caused by occlusion or stenosis either of the mesenteric artery or, less frequently, the vein. Some cases are idiopathic, whereas others may be due to decreased perfusion in the absence of a vascular lesion. Phlebosclerotic colitis is a rare chronic and gradually worsening ischemic colitis caused by phlebosclerosis of the mesenteric vein and its tributaries. Its symptoms are the gradual onset of right-side abdominal pain with or without diarrhea, and recurrent ileus. The most commonly affected site is the region from the terminal ileum to the sigmoid colon, particularly the cecum and ascending colon.
The characteristic radiologic findings of mesenteric phlebosclerosis are luminal narrowing, wall thickening of the affected colon (typically the proximal colon), and calcification of the mesenteric veins. Plain radiographs and computed tomography can easily detect the characteristic linear calcification of numerous branches of the mesenteric vein at the affected site.

Introduction Human embryonic stem cells HESCs can

Human embryonic stem alzheimer\’s association (HESCs) can differentiate into the three embryonic germ layers and have the potential to develop into every cell in the human body (Thomson et al., 1998). In order to enable the clinical practice of HESC cell therapy it is essential to understand their differentiation course into the various cell types, and to generate appropriate differentiation protocols. Differentiation into the endoderm lineage is of special interest since it gives rise to both pancreatic and hepatic cells that have high clinical value (Murry and Keller, 2008). Since the isolation of HESCs, multiple differentiation protocols into diverse endoderm derivatives have been published, including pancreatic beta cells (D\’Amour et al., 2006; Jiang et al., 2007a, 2007b; Shim et al., 2007), hepatic cells (Roelandt et al., 2010; Si-Tayeb et al., 2010), lung alveolar epithelial cells (Van Vranken et al., 2007; Wang et al., 2007) and intestinal tissue (Spence et al., 2010). These differentiation protocols were mostly based on developmental cues that were discovered in animal models. Despite the tremendous progress in studying endoderm differentiation, the intermediate progenitor cells that play a significant role in the differentiation into mature endoderm derivative and their interactions are still largely unknown.
During early stages of development the inner cell mass (ICM), from which HESCs are derived, differentiates into a limited set of cell types: the primitive endoderm that will contribute to extra embryonic tissues, and the three embryonic germ layers – the ectoderm, mesoderm and endoderm. The three embryonic germ layers are generated through the complex process of gastrulation. The study of these early stages of human development has been demonstrated by several groups (reviewed in Murry and Keller, 2008). Previously we demonstrated via an embryoid body (EB) differentiation protocol, that HESCs initially differentiate into three distinct cell populations (Kopper et al., 2010). These cell populations could be isolated by specific cell surface markers. Molecular characterization determined that these cell populations represent the extra embryonic endoderm, primitive ectoderm and the mesendoderm.

Previously, it was shown that three days after aggregation into embryoid bodies (EBs), HESCs differentiate into three major cell populations that correspond to the extra embryonic endoderm, primitive ectoderm and the mesendoderm (Kopper et al., 2010). The extra embryonic endoderm and mesendoderm cell lineages can be isolated using antibodies against erythropoietin receptor (EPOR) and N-CADHERIN (NCAD), respectively. In order to better characterize the mesendoderm cells we analyzed them using DNA micro-array, and screened the entire set of genes expressed in the NCAD+ cell population for additional uniquely expressed cell surface markers. We found that both CXCR4 and PDGFRA genes are exclusively expressed in NCAD+ cells (Fig. 1A), moreover, CXCR4 and PDGFRA are associated with early mouse endoderm and mesoderm cell lineages (respectively) (McGrath et al., 1999; Yusuf et al., 2005; Mizoguchi et al., 2008; Yang et al., 2008; Ataliotis et al., 1995; Mercola et al., 1990). Indeed, FACS analysis on 3-day old dissociated EBs with antibodies against CXCR4 or PDGFRA revealed the existence of both CXCR4+ and PDGFRA+ cell populations (Fig. 1B). When we double stained the EBs with antibodies against both CXCR4 and PDGFRA we could demonstrate that these cell surface markers segregate the EBs into four cell populations: CXCR4-/PDGFRA-; CXCR4+/PDGFRA-, CXCR4-/PDGFRA+ and a cell population which expresses both CXCR4 and PDGFRA (Fig. 1B). In order to further examine the identity of these cell populations we isolated them according to these surface markers using FACS. Following isolation, gene expression profile was performed for each of the populations. Correct sorting was verified by the expression levels of the marker genes PDGFRA and CXCR4 (Fig. 1C). Both the CXCR4+ cells and the CXCR4+/PDGFRA+ cells express endodermal genes such as KIT, HNF1B and HHEX (Gouon-Evans et al., 2006; Ott et al., 1991; Thomas et al., 1998). Interestingly, both the PDGFRA+ cells and the CXCR4+/PDGFRA+ cells express mesodermal genes such as RND3, EDNRB and HES1 (Goda et al., 2009; Masamizu et al., 2006; Welsh and O\’Brien, 2000) (Supplementary Table 1). These results support the hypothesis that the CXCR4+/PDGFRA+ cell population represent the mesendoderm lineage that is positive for both endodermal and mesodermal markers. In accordance with our hypothesis the mesendoderm cell population differentiates to endoderm (CXCR4+/PDGFRA-) or mesoderm (CXCR4-/PDGFRA+) that express only the endodermal or mesodermal markers, respectively. Moreover, we could demonstrate an up regulation of mesodermal markers such as T (Brachyury) and KDR (FLK-1) in the CXCR4-/PDGFRA+ cell population, suggesting that this cell population represents mesoderm progenitor cells (Supplementary Table 1).

As with many biological phenomena

As with many biological phenomena, immunomodulation is a double-edged sword, and many of these tolerogenic mechanisms appear to be manipulated by cancer Apremilast manufacturer to create an immunoprivileged niche to further their own growth (Rabinovich et al., 2007). One of the most prominent immunomodulatory leukocyte subpopulations in cancer consists of myeloid-derived suppressor cells (MDSCs) (Ostrand-Rosenberg and Sinha, 2009). Derived from myeloid precursors, MDSCs suppress immune response by a number of mechanisms, such as suppressing cytotoxic lymphocyte effector functions and targeting T cells by expressing the enzymes arginase 1 (ARG1) and inducible nitric oxide synthase (iNOS), both of which block the production of the T cell CD3-ζ chain by metabolizing L-arginine (Gabrilovich and Nagaraj, 2009; Gabrilovich et al., 2012). Human and mouse studies have revealed that chronic inflammation and proinflammatory mediators such granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1β, IL-6, and prostaglandin E2 (PGE2) are involved in the induction of these suppressor leukocytes (Bunt et al., 2007; Serafini et al., 2004; Sinha et al., 2007; Young and Wright, 1992). Although it is clear that the tumor microenvironment is maintained by diverse cell types, the role of secreted factors other than cytokines and proinflammatory factors in the expansion of MDSCs has largely been unexplored, with the exception of vascular endothelial growth factor (Fricke et al., 2007; Shojaei et al., 2007). We report that MDSCs can be expanded by MSC-secreted hepatocyte growth factor (HGF), a potent mitogenic growth factor.


Recent reports have highlighted MDSCs as a prominent leukocyte subpopulation involved not only in tumor-associated immune suppression but also in regulation of the immune system at large (Almand et al., 2001; Gabrilovich and Nagaraj, 2009; Rodríguez and Ochoa, 2008). Previous data have shown that a number of proinflammatory mediators are important inducers of these cells, but there has been no report regarding the involvement of tumor-associated mitogenic growth factors in the process. Our data link HGF secreted by MSCs to the expansion of MDSCs. Our findings can help to explain the strong association of MDSCs with tumors, since it is well established that in the tumor microenvironment, HGF is highly secreted by both the cancer cells themselves and the supporting stromal cells, promoting cell survival and tumor growth (Cecchi et al., 2010; Mueller and Fusenig, 2004). While HGF has been implicated in immunoregulatory responses (Benkhoucha et al., 2010; Di Nicola et al., 2002), and the liver, which naturally secretes high levels of HGF, was reported to have some immunological functions (Sheth and Bankey, 2001), the specific molecular mechanisms underlying these observations have been largely unexplored and the reported effects have not been consistently replicated (Le Blanc et al., 2003). Our finding that high numbers of hepatic MDSCs in mice can be significantly altered by disruption of the HGF/c-Met pathway sheds some mechanistic light on this issue, and, overall, our data demonstrate that HGF mediates the expansion of functional MDSCs by engaging c-Met, its receptor, and increasing the phosphorylation of STAT3, one of its downstream molecules.
The immunomodulatory properties of MSCs have been highlighted as being therapeutic for autoimmune diseases and other immune-related diseases such as graft-versus-host disease (Abdi et al., 2008; Djouad et al., 2009; Keating, 2012; Le Blanc et al., 2008). As exciting as these findings are, some researchers have noted that the same immunomodulatory effects of MSCs can allow for the growth of tumors (Djouad et al., 2003). However, whether MSCs definitively enhance or inhibit tumor growth and cancer progression is still unresolved, since differences in the experimental design, cancer histologic cell type, and MSC isolation technique used can all affect the experimental outcome (Klopp et al., 2011; Yen and Yen, 2008). Moreover, to date, studies on MSC and cancer interactions have largely focused on the homing of MSCs to tumors, rather than the immunological aspects of MSCs (Elzaouk et al., 2006; Studeny et al., 2002; Xin et al., 2007). Although a considerable amount of data support MSC expansion of Tregs (Uccelli et al., 2008), and these immunosuppressive T lymphocytes are also found in tumors, MDSCs appear to play a more crucial role in maintaining the profound immune suppression of the tumor niche (Almand et al., 2001; Ostrand-Rosenberg and Sinha, 2009; Sinha et al., 2005; Young and Wright, 1992). Our data suggest that through HGF and the consequent expansion of MDSCs, MSCs may play a role in maintaining tumor growth.

Cytoskeletal and rhythmic contraction and pulsatile laminar shear stress are

Cytoskeletal and rhythmic contraction, and pulsatile laminar shear stress, are mechanical forces that have been suggested to play a crucial role in heart development and growth (Taber, 2001; Zhu et al., 2014; Andrés-Delgado and Mercader, 2016). Cytoskeletal contraction is involved in several morphogenetic processes in the embryo (Taber, 2001). Rhythmic contraction is the exposure of CMs to regular cyclic stretch (Zhu et al., 2014). The heart is exposed to blood flow during most heart developmental stages and throughout adult life (Andrés-Delgado and Mercader, 2016). Pulsatile laminar shear stress generated by blood flow in healthy hearts influences heart chamber formation and maturation, trabeculation, CM proliferation, and valvulogenesis (Andrés-Delgado and Mercader, 2016). Employing physical signals to mimic cardiogenesis in vitro is a potential strategy to achieve PSC-CM maturation. Several groups have developed methods to apply uniaxial stress to PSCs (Tulloch et al., 2011; Wan et al., 2011; Mihic et al., 2014). Although uniaxial stress can promote PSC-CM maturation, using stretch alone does not mimic in vivo physical signals that act on CMs within the heart (Guan et al., 2011). Carrier et al. (2002) demonstrated that perfusion flow leads to a continuous medium change and therefore increases the spatial uniformity of CMs by improving the control of oxygen, pH, nutrients, and metabolites in the cellular microenvironment; however, the impact of pulsatile flow on PSC-CM maturation, or a possible synergistic effect of the combination of pulsatile flow and cyclic strain has not been investigated.
In the present study, we designed and evaluated a bioreactor system to expose mouse embryonic stem cell (mESC)- and human ESC (hESCs)-derived filipin to defined mechanical stimuli. We investigated the impact of pulsatile flow-induced shear stress and physiological stretch on murine and human ESC-CM maturation in vitro by extensively analyzing cardiac protein and gene expression patterns. We analyzed the calcium-handling properties and sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) activity in dynamically-cultured CMs. In addition, we characterized the phenotype of ESC-CMs employing filipin marker-free Raman microspectroscopy. Elucidating the effect of defined mechanical forces on the maturation of ESC-CMs is an essential step toward developing fully matured and functional cardiovascular tissues in vitro that can be used to study cardiovascular diseases and investigate potential drug candidates.


In our study, we revealed that d18 dyn mESC-CMs and d20 dyn hESC-CMs showed a functional improvement as the typical systolic calcium transient parameters, the rate of constant of Ca2+ decay (tau), slope, and amplitude improved with extended culture times, indicating rapid electromechanical coupling. This change could be the result of structural changes in the contractile apparatus, the better orientation of the myocyte network associated with enhanced expression of gap junctions, or alterations in the balance of cardiac ion channels (Zhu et al., 2014). In previous studies, most of the ESC-CMs did not respond to caffeine as they relied on calcium influx from sarcolemma instead of the SR as seen in adult CMs (Khan et al., 2013; Li et al., 2013). In a few studies, hESC-CMs cultured for more than 27 days showed a response to caffeine (Nunes et al., 2013; Kosmidis et al., 2015). Here, ESC-CMs responded to caffeine after 12 (mESC-CMs) or 10 days (hESC-CMs), as shown by an increased Ca2+ handling consistent with a functional SR. Furthermore, when compared with d12 dyn mESC-CMs and d10 hESC-CMs, d18 dyn mESC-CMs and d20 dyn hESC-CMs exhibited a higher store of Ca2+ and an improved SERCA function. We further performed concentration-response studies employing nifedipine and dofetilide. Although hESC-CMs exhibited a dose-dependent response to nifedipine and dofetilide, no significant differences were seen between stat and dyn hESC-CMs. The electrophysiology was stable throughout the recordings. This indicates that the calcium and hERG channels in all hESC-CMs were fully functional without any limitation.