br Sin recetas para el crecimiento econ

Sin recetas para el crecimiento económico
Dentro de la economía como disciplina se ha desarrollado un cuerpo analítico de teorías del crecimiento, mismas que parten de modelos y supuestos para explicar cómo y bajo qué mecanismos podría impulsarse el crecimiento del pib, el cual se interpreta como el principal detonante para salir del atraso y alcanzar el desarrollo. Ya en lo concreto todos los modelos son la amiodarone hcl para diseñar políticas, estrategias y acciones en materia educativa, tecnológica, fiscal, monetaria, laboral, etc., que se supone determinarán el rumbo de la dinámica nacional. Desde un punto de vista pragmático se afirma que cada país fija su propia ruta sin embargo, ya en la realidad pocos lo pueden lograr puesto que se imponen otras fuerzas que condicionan en buena medida la toma de decisiones y de cada proyecto de crecimiento nacional. Interviene como ya se mencionó: el contexto histórico y geográfico, la situación mundial vigente y la posición que se juega dentro del sistema político-económico mundial.
En su momento el desarrollo de países como Francia, Inglaterra, Estados Unidos o Alemania fueron la base de estudio para connotados economistas como Simon Kusnetz para explicar que su éxito consistió entre otros aspectos en una serie de factores fundamentales siendo estos: la consolidación de instituciones, el desarrollo tecnológico e industrial, el cambio de valores sociales, el control demográfico, la administración del espacio urbano y los cambios de la organización económica, (Kusnetz, 1970). Posterior a la caída del keynesianismo y con el modelo de libre mercado en todo su esplendor, en casi todas las economías del planeta se han seguido al pie de la letra los postulados del Consenso de Washington y una segunda serie de reformas denominadas de “segunda generación”, (Rodrik, 2011: 37). Sin embargo, los resultados en un periodo de 30 años distan mucho de lo que el discurso original pregonaba acerca de mejorar las condiciones de vida de millones de habitantes sobre todo en alc debido a que los resultados pueden catalogarse como negativos: tasas de crecimiento del producto bajas, pobreza creciente, etc.
Dentro de este contexto China viene a guard cells irrumpir con su propia interpretación y aplicación de políticas rompiendo con ello el mainstream económico de que el Estado debe limitar su participación en la actividad económica y social. El propio Rodrik de manera didáctica expone en su obra “Una economía, muchas recetas” (2007), que hasta un marciano estaría confundido por el hecho de que mientras China hizo todo lo contrario a dicho Consenso, su producto creció durante tres décadas en promedio 10% a diferencia de alc. Tal exposición sirve para explicar que China al igual que otros países del sudeste asiático se ha valido de mecanismos que controlan lo económico bajo el Estado aun con la presencia de capitales extranjeros, (Ibídem, 47). Arrighi cita al respecto:
Desde una perspectiva heterodoxa no se trata de explicar solamente el crecimiento del producto sino de todo el proceso de acumulación en su conjunto. Por esta razón para aquellos que buscan en el caso chino elementos que pudieran trasladarse a la realidad latinoamericana sin conocer el universo de medidas establecidas por el gobierno chino desde la era maoísta, están cometiendo un enorme error interpretativo. En este sentido, hay una serie de políticas que han trastocado significativamente a diversas generaciones de habitantes chinos en sus valores y reproducción social. De tal suerte que medidas de control demográfico y migratorio como el Hukou y la política del hijo único (hoy ya eliminada), serían impensables en alc. A ello se suma el férreo control de la información y de sus distintas formas de expresión, el cual es comúnmente denunciado desde occidente y por los propios disidentes chinos exiliados en el extranjero o por presos político al interior de China, (Li, 16/12/13). El ascenso de China a decir de Harvey, se debe a la construcción de un particular tipo de economía de mercado que combina elementos del neoliberalismo con control centralizado autoritario para aplicar todo lo establecido dentro de los planes quinquenales, es decir, un neoliberalismo con características chinas, (Harvey, 2005: 120).

Terra is one of the main references

Terra (2003) is one of the main references in the Brazilian literature. More recently, we can cite the work of Aldrighi and Bisinha (2010). The general conclusion of these authors is that Brazilian firms are indeed credit-constrained. However, at odds with the conventional literature, firms that should be more credit constrained when using some standard measure (size, for instance) do not appear to have a more significant coefficient in the investment — cash flow equation. In Terra (2003), the MK-8669 that the cash flow coefficient is equal for large and small firms cannot be rejected, unless in a limited period of time (1994–1997) when credit constraints were softer among large firms. In Aldrighi and Bisinha (2010), the cash flow coefficient is always significant, and indeed increases with firm size. The authors suggest that financial difficulties between firms with smaller size may explain their findings, as the desire to maintain a “financial slack”, avoiding in this way future liquidity problems, may weaken the investment – cash flow relationship.

Methodology
The model to investigate whether Brazilians firms are credit constrained is based on Carpenter and Guariglia (2008) and Guariglia (2008), as shown in (1).where i and t=1,…,T identify, respectively, firms and time, is the firms’ investment, Kit is the firms’ fixed asset, γt is the time-effect for controlling business-cycle effects, is the firms’ fixed-effect, and is the error-term. For robustness checks, the specification (1) may include covariates , given by investment opportunities variables, which also impact the dependent variable.
For eliminating time invariant unobservables firms’ characteristics, we estimate Eq. (1) by fixed-effect and first-difference. Time-effect is controlled by imposing dummies for instant t.
The OLS in first-difference may present problems of endogeneity associated to a reverse causality between firms’ investment and cash flow. Ideally, an exogenous instrument which can only affect investment through cash flow would be able to MK-8669 address this issue effectively. However, papers in this literature fail to provide a completely exogenous instrument to address the endogeneity. Due to this fact, we apply Generalized Method of Moments approach (GMM) based on the structure of instrumental variables of Arellano and Bover (1995) and Blundell and Bond (1998), as they represent most current strategy to address this shortcoming, since replication has been used in the recent literature, see Guariglia et al. (2011) as an example. This approach combines the standard set of equations in first-difference with lagged levels of regressors as instruments with the incorporation of equations in levels with lagged first-difference as instruments.
In this case, we assume that actual cash flow shocks do not influence future realization of the error term; therefore cash flow is considered an exogenous variable. The same assumption is considered for covariates. First-difference equation includes all regressors lagged twice as instruments. It means that we assume the moment restrictions where -2/Kit-3 is not correlated to (εit−εit-1).
Following Blundell and Bond (1998), we also incorporate an additional moment restriction to GMM estimations. As we have only instruments lagged twice for the level equation and given our limited number of years in the database (T=3), we also incorporate equations in levels with lagged first-difference instruments to the system. The estimation, which includes additional moment condition proposed by Blundell and Bond (1998), is called system-GMM or SYS-GMM. In this case, our assumption requires that εit is not correlated to (/Kit-2−-2/Kit-3).
The consistency of system GMM estimators depends on the validity of instruments, i.e., it is necessary that instruments satisfy the orthogonal condition. In the empirical literature of system GMM approach, papers evaluate this aspect by applying Sargan test of overidentifying restriction (j-test), which tests the validity of orthogonal conditions.

Introduction The application of minimally invasive

Introduction
The application of minimally invasive spine surgery (MIS) for treating thoracolumbar spine disorders and injuries has evolved rapidly, and the technical feasibility and safety of MIS has been well established. MIS can be defined as a spine operation based on the following basic principles: prevention of muscle crush injuries and preservation of the tendon attachment sites of crucial muscles using self-retaining retractors, using known anatomic neurovascular and muscle compartment planes, and minimizing collateral soft tissue injuries by limiting the width of the surgical corridor. The use of these basic principles in MIS has led to significant reductions in intraoperative blood loss, postoperative pain, and surgical morbidity compared with the traditional midline posterior approach. Thus, MIS has become an alternative to conventional open surgery for treating various spine diseases, particularly degenerative spine diseases. Recently, MIS has been used for treating nondegenerative diseases. In this review, we present evidence that supports the use of MIS for treating an increasingly wide range of spinal pathologies and elucidate the current role of MIS in nondegenerative spine diseases such as neoplasms, infections, and traumatic spine diseases.

Spine neoplasm

MIS has been used for treating spinal neoplasms and theoretically reduces postoperative instability. According to a finite THZ1 Hydrochloride analysis comparing traditional and minimally invasive intradural tumor exposures, minimally invasive hemilaminar exposure preserves the structural integrity of the lumbar spine and minimizes postoperative alterations to segmental motion. The feasibility of MIS for treating patients with intradural extramedullary tumors limited to one or two spinal segments has been thoroughly documented. In a retrospective case series of 10 patients with thoracolumbar neurofibromas, the authors used unilateral limited laminectomy for tumor removal, sparing the joint and ligamentum interspinosum. No complications, particularly new neurological deficits, were observed, and watertight dural closure was performed using 5-0 or 6-0 stitches in each case. However, this approach was limited to one or two levels. Therefore, in that series, one female patient with three neurofibromas required surgery twice. Another retrospective case series of six patients demonstrated that MIS was a feasible technique with an operative time of 247 minutes, estimated blood loss of 56 mL, and a hospital stay of 57 hours. All these intradural extramedullary tumors were limited to one or two levels. In a retrospective study of 15 patients with spinal schwannomas, the authors reported that gross total resection was achieved in all cases by using MIS, and none of the patients necessarily required a fusion procedure, although the tumor extensions caused problems for the surgeons in approach, tumor resectability, and spine stability. The authors suggested using laminectomy for removing intradural tumors, hemilaminectomy for removing extradural lesions, the paramedian route for removing the extraspinal part of the tumor, and costotransversectomy for removing tumors in the thoracic region. Furthermore, two retrospective case series of patients with intradural medullary or extradural tumors demonstrated that MIS was a feasible and safe procedure. All these studies suggest that MIS, when performed by an experienced surgeon, may serve as an alternative to traditional open tumor resection for treating intradural extramedullary tumors and potentially reduces blood loss, the hospital stay duration, and disruption to local tissues. However, the role of MIS in treating intramedullary tumors or complicated large intradural extramedullary tumors remains unclear. In a retrospective case series, the authors used MIS for treating one intramedullary tumor (inclusion tumor) without remarkable complications.
Percutaneous vertebroplasty (PVP) has been proven to effectively relieve pain associated with spinal metastasis. A randomized controlled trial comprising 100 patients compared the clinical efficacy and safety of PVP combined with 125I implantation with those of regular radiation therapy for treating spinal osteoblastic metastasis. The clinical efficacy of PVP combined with 125I seeds was more satisfactory than that of regular radiation therapy (p < 0.05) according to the visual analog scale (VAS) of pain and Karnofsky performance scores during the follow-up period of 6 months to 5 years. In a retrospective case series of eight patients with spinal metastasis of the spinal canals, all patients underwent percutaneous transpedicular coblation corpectomy that was immediately followed by balloon kyphoplasty and then radiation therapy for 2 weeks. PVP can effectively relieve pain, stabilize the spine, improve the quality of life, and reduce the occurrence of paraplegia in patients with spinal osteoplastic metastasis. In a retrospective case series of 26 patients with pathological compression fractures who underwent combined kyphoplasty and spinal radiosurgery treatment, axial pain improved in 24 (92%) patients during the follow-up period of 7–20 months. A retrospective three-case series showed that kyphoplasty was an effective, simple, and safe alternative for treating vertebral collapse consequent to multiple myeloma.

The higher rate of GSD

The higher rate of GSD-related surgery in the diabetic group compared with the control group may indicate a different presentation of pain symptoms between the two groups, which might be explained by diabetic neuropathy. Diabetic rats exhibited sluggish sensory nerve conduction and a high pain threshold. Evidence has indicated that hyperglycemia may result in changes to the gastric motor and sensory functions, suggesting that any impaired sensory functioning might be related to the dysfunctional control of blood glucose in diabetic patients. Therefore, diabetic patients are likely to be less sensitive to their pain symptoms, and this seems to delay GSD diagnosis until acute and severe cholecystitis develops. This eventually leads to a higher incidence of cholecystectomy in diabetic patients than in nondiabetic controls.

Conclusion

Introduction
Meningiomas are common in nonglial intracranial AN-2728 tumors and account for 13–26% of primary intracranial tumors, whereas cystic meningiomas are rare and account for only 1.6–10% of all meningiomas. Appropriate diagnosis of brain tumor is crucial not only for formulating an appropriate treatment plan, but also in prognosis and chemoradiotherapy. Differential diagnosis varies with astrocytoma, metastatic tumor, ganglioglioma, pleomorphic xanthoastrocytoma, and neuroblastoma. We report a case of a patient with left frontal cystic meningioma, and a mural nodule mimicking hemangioblastoma and lacking the typical characters of meningioma.

Case Report
A 37-year-old female, a hepatitis B carrier with no other systemic disease, visited the emergency department because of involuntary right-side limb movement, without loss of consciousness. The patient did not report other episodes of discomfort, such as headache, giddiness, nausea, or vomiting. The patient was suspected to have intracranial lesion; thus, brain computed tomography (CT) was conducted. The CT revealed a large (4.6 cm × 3.0 cm × 4.0 cm) left frontal mass lesion with a cystic component AN-2728 and perifocal edema. Brain magnetic resonance imaging (MRI) through gadolinium enhancement revealed cerebrospinal fluid enrichment within the septated cyst, a centrally located enhancing mural nodule measuring 1.27 cm × 0.73 cm, and perifocal edema (Figure 1). Suspecting supratentorial hemangioblastoma, the tumor was approached through the supine position. A cystic tumor with xanthochromic content was observed after a left frontal craniotomy and dura take-up suture (Figure 2). The grayish tumor was centrally located, away from the cystic component. A cytological study of the fluid within the cyst was conducted. Owing to the suspicion of hemangioblastoma and the lack of cystic wall thickening, gross removal of the tumor without the cystic component was performed with microscopic assistance. A cytology report showed no malignant cells, and a permanent pathology report showed a skull-invading meningothelial meningioma, World Health Organization Grade II (Figure 3A and B). The patient recovered uneventfully postoperation without subsequent neurological sequelae, and a subsequent follow-up was performed.

Discussion
Meningiomas are the most common intracranial nonglial brain neoplasms. Cystic meningiomas are rare and lack an appropriate diagnostic method.
According to the relationship between tumors, two classification systems, provided by Nauta et al and Rengachary et al, are applied for cystic meningioma. Based on the classification provided by Rengachary et al, cystic meningiomas can be classified as intratumoral and peritumoral cystic meningiomas. Nauta et al classified cystic meningiomas into four categories according to the relationship between the cystic cavity and the tumoral mass, as follows: Type I, centrally located intratumoral cyst; Type II, peripherally located intratumoral cyst; Type III, peritumoral cyst in the adjacent parenchyma; and Type IV, peritumoral cyst between the tumor and the adjacent parenchyma. The patient had Type III cystic meningioma, according to the classification provided by Nauta et al, and peritumoral cystic meningioma, according to the classification provided by Rengachary et al.

It has been previously demonstrated that hESCs are extremely

It has been previously demonstrated that hESCs are extremely vulnerable to apoptosis after single cell dissociation (Amit et al., 2000; Reubinoff et al., 2000; Thomson et al., 1998) and are therefore often manually passaged as mechanically fragmented colonies or as small cell clumps to increase cell survival rate and plating efficiency. Recently it was demonstrated that ROCK inhibitors significantly increase the survival of hESCs upon single cell dissociation (Harb et al., 2008; Watanabe et al., 2007), allowing the use of enzymatic passaging methods. Furthermore, in the presence of a ROCK inhibitor, A-1210477 Y-27632, single cell-dissociated hESCs can efficiently form cell A-1210477 and grow in suspension (Watanabe et al., 2007). Utilizing ROCK inhibitors, several recent studies showed that hESCs can be maintained, serial passaged, and expanded in an undifferentiated state in suspension culture (Amit et al., 2010; Amit et al., 2011; Krawetz et al., 2010; Olmer et al., 2010; Singh et al., 2010; Steiner et al., 2010; Zweigerdt et al., 2011). These studies described various types of suspension systems, including low-attachment static plates, rotated dishes or Erlenmeyer flasks, and spinner flasks. Although the studies using plate, Petri dish, or Erlenmeyer flask systems appeared promising systems, the scalability was limited. Those utilizing spinner flasks are preferred for their potential scalability as closed bioreactor systems. However, the long-term scalable expansion of hESC lines using spinner flasks has not been demonstrated.
Despite the success of hESC suspension culture with spinner flasks from previous studies, the cultures were reported to yield either low expansion rates or low overall cell yield (Krawetz et al., 2010; Singh et al., 2010). Using a spinner flask for hESC suspension culture, Singh et al. showed a 2-fold expansion over 7days when cells were seeded at 1×106cells/ml. In contrast, with a much lower cell seeding density, 1.8×104cells/ml, Krawetz et al. reported a significant expansion rate but a low cell yield, approximately 5×105cells/ml over 6days. To establish a scalable and efficient suspension culture system for large-scale hESC production, it will be necessary to further optimize culture conditions to achieve a high expansion rate with a high yield of hESCs.

Results

Discussion
Conventionally, expansion of hESC adherent culture requires passaging the cells in small cell clumps, as cells which have been dissociated to single cells show poor viability and seeding efficiency (Amit et al., 2000; Reubinoff et al., 2000; Thomson et al., 1998). Recently, several reports have demonstrated that single cell-dissociated hESCs can survive in suspension by forming cell aggregates. (Amit et al., 2010; Krawetz et al., 2010; Olmer et al., 2010; Singh et al., 2010; Steiner et al., 2010). Unlike mES cells, which can form cell aggregates from single cells in suspension (Cormier et al., 2006; Kehoe et al., 2008; zur Nieden et al., 2007), hESCs require a ROCK inhibitor, Y-27632, to form cell aggregates and propagate. Formation of cell aggregates appears to be a critical step for hESCs to survive and expand in suspension and the ROCK inhibitor is a key factor for this step.
We have found that when hESC aggregates are maintained in suspension culture, it is critical to control the size of the aggregates to ensure efficient expansion and quality of hESCs. It is a reasonable speculation that nutrients and cytokines will be difficult to penetrate into cell aggregates to maintain hESC growth as cell aggregates gain in size. We selected culture conditions which can generate a great number of cell aggregates in small sizes at the initial stage to achieve a better expandability. We found passaging cells every 3–4days provided the optimal expansion rate. In addition we found that cultures in StemPro media formed small and homogeneous aggregates and resulted in a better expansion rate than cultures in mTeSR media. At lower cell seeding density, 1.5×105cells/ml, initial sizes of cell aggregates appeared slightly smaller than those of seeding at 2.5×105cells/ml but we also noticed that aggregates appeared less at lower seeding density, resulting in a lower cell yield. Previous studies have shown great expansion rates of their hESC suspension cultures using much lower seeding density, while the cell yields were not comparable with adherent cell cultures (Krawetz et al., 2010; Olmer et al., 2010). In contrast, a higher seeding cell density results in higher cell yield but lower expansion rate (Singh et al., 2010). Therefore, it is crucial to optimize cell seeding density to ensure proper expansion rates and cell yields of hESC suspension culture. As the growth characteristics of hESC lines are varied, the passaging interval and cell seeding density may also need to be optimized for different lines.

Development of biosensors for mycotoxins detection is in great demand

Development of biosensors for mycotoxins detection is in great demand nowadays, with optical immuno-sensors leading the way [2]. There are many types of optical transduces used in optical bio-sensing with surface plasmon resonance (SPR) being the most common and widely used [2,3]. The method of Total Internal Reflection Ellipsometry (TIRE) combines the advantages of SPR and spectroscopic ellipsometry and offer 10 times higher sensitivity than SPR and therefore became particularly suitable for detection of low molecular weight molecules such as mycotoxins [4]. Recent advances in nanotechnology brought to practice some new methods which explore a physical phenomenon of localized surface plasmon resonance (LSPR) [5]. In this work we are trying to study LSPR phenomenon using spectroscopic ellipsometry (SE) and to explore for the first time the use TIRE method for LSPR bio-sensing applications, particularly for detection of Aflatoxin B1.

Sample preparation and experimental methodology
Gold nanostructured, were prepared by evaporation of gold in 10Tor vacuum onto standard microscopic glass slides using an intermediate 2nm thick layer of chromium to improve adhesion of gold. Thin gold films of different nominal thicknesses (4, 5, 6, 8, and 10nm) were deposited and then annealed at 480°C for 2h. For comparison, 5nm thick Au films (with no Cr under-layer) were annealed at higher temperature (550°C) for 10h in order to form Au nano-islands embedded into glass matrix, similar to those reported in [6].
The morphology of samples of nano-structured gold films was studied first with SEM (FEI-Nova, NanoSEM 200) and AFM (Nanoscope IIIa, Bruker). Optical properties of gold nano-structures were studied with UV-visible Cardiogenol C Supplier spectroscopy (Cary 50, Varian) and spectroscopic ellipsometry (M2000, J.A. Woollam). In order to evaluate the refractive index sensitivity of LSPR gold nanostructures structures produced, UV-vis absorption spectra and SE measurements were performed in media with different refractive indices: air (n=1), water (n=1.3325), ethanol (n=1.3616), chloroform (n=1.4441), and DMSO (n=1.4772). For SE measurements, a special 70o PTF cell was designed.
Some of the spectroscopic ellipsometry (SE) measurements were carried out using total internal reflection ellipsometry (TIRE) configuration described in detail in our early publications [4,7,8]. In this work, the detection of mycotoxin aflatoxin B1 was carried out in direct immunoassay with specific monoclonal antibodies to aflatoxin B1 immobilized electrostatically on the surface of gold. The electrostatic immobilization of proteins which was developed and routinely used in our work previously [4,7,8] requires the following adsorption/binding stages: (i) overnight treatment of gold-coated samples in 0.1M solution of sodium 3-mercapto-1-propanesulfonate in methanol which makes the surface of Au negatively charged, (ii) deposition of polycation layer of poly(allylamine) hydrochloride (PAH) from its 1mg/ml aqueous solution; (iii) deposition of protein A from its solution 0.02mg/ml in Trisma-HCl buffer, pH7.5; deposition of antibodies to aflatoxin B1 from its 1:1000 solution in the same buffer; (iv) and finally sequential biding of aflatoxin B1 of different concentrations 1ng/ml, 10ng/ml, 100ng/ml, and 1μg/ml in water starting from the smallest. Typical incubation time for all adsorption/biding stages was from 10 to15min. The use of protein A helps improving the orientation of IgG based antibodies immobilized on the surface [4]; occasionally, for testing purposed the deposition protein A was skipped as not essential.

Experimental results and discussion

Conclusions and suggestions for future work

Acknowledgements
This work was supported by NATO Science for Peace program through the project NUKR.SFPP 984637.

Introduction
Glancing to the scientific research in recent year is associated with optical fiber technology. It is exceedingly growing which dealing with photonic crystal fiber (PCF) sensor. It is vivid that, this research has a great impact to make the technology sustainable. PCF is a type of optical fiber where numerous air holes are arranged in longitudinal direction which arise some identical properties that does not lie in conventional optical fiber. These identical properties including endlessly single mode, high nonlinearity, large effective area, high birefringence and low confinement loss [1–4] are contributing a tremendous support to enriching optical communication as well as optical sensing.

br Conclusion br Future scope Irrespective of the scale up

Conclusion

Future scope
Irrespective of the scale up targets achieved by the discussed research works, each of such work had been a fruitful attempt to gain beneficial knowledge to carry out future upscaling attempts in the field of NCs. In a nut shell, it could be proposed that a successful scale up demands an adequate process characterization, proper choice of equipment, development of a robust formula and satisfactory Rimonabant study results (Srivalli and Mishra, 2014). It was understood that process characterization is required for filtering the processing parameters influencing the product quality; the design of equipment at different scales of study should ensure the consistency in product quality; a robust formulation incorporating proper choice of stabilizers and redispersants is a must to retain the stability of the product all through its shelf life; and stability studies are imperative to determine the stability of the product and to predict its shelf life. More studies based on the scale up of NCs are expected to be taken up by the researchers so as to take an advantage of the product line extension offered by FDA for these products. Future upscaling studies on NCs may incorporate the in vivo studies on animals as a definitive part of their formulation characterization.

Declaration of interest

Acknowledgment

Background and history
The concept of drug safety, also called “Medication Safety”, is not new, especially in the developed countries in the field of health. For instance, we find in the United States of America (USA) an experience for more than a century in the field of the safety of medications, and the use of these drugs led to creation of new acts or changes to the existing ones. For example, in October 1937, the use of the antibiotic sulfanilamide caused the death of more than 100 people in the USA. These deaths were not due to the active ingredient itself; rather, they were caused by the addition of diethylene glycol (DEG), the excipient used as a solvent for the active drug. DEG was supposed to be inert, with no therapeutic benefits; however, it was the toxic substance that led to those fatal side effects. The company claimed they did not foresee these side effects, which was true, as they did not commit animal studies before they marketed the drug. Because of this incident, the U.S. Food and Drug Administration (FDA) approved an act to ensure the safety of any drug by conducting non-clinical and clinical studies before the drugs are marketed for public use (Geiling and Cannon, 1938; Young, 1984; Wax, 1995).
Of course, the problems arising from drugs and their side effects did not stop occurring. A severe worldwide crisis was initiated by the use of the drug thalidomide, which was used as an antiemetic agent for pregnant women in many countries. In the early 1960s, the use of thalidomide during the first trimester of pregnancy led to teratogenic effects manifested by the birth of infants with severe deformities known as “Phocomelia”. Babies would be born lacking extremities (hands and legs) or with only very short ones. Many infants died because of this “medication” as well. Overall, more than 10,000 children in 46 countries were victims of thalidomide. It is important to mention that this drug was not authorized or approved for use in the United States because of some concerns that arose during non-clinical studies (animal studies) due to the existence of cases of deformities on animal embryos. Note that those animal studies were conducted according to the act that was initiated following the sulfanilamide incident in the USA; therefore the public was protected and avoided from this crisis (Ito et al., 2011; Kim and Scialli, 2011; Martinez-Frias, 2012).
Up until now, there are drugs that could be taken off the market or withdrawn due to safety issues concerning their relation with the emergence of serious side effects, such as the recent withdrawal of the anti-diabetic agent rosiglitazone (Avandia®) from the global market as a result of its relationship with the incidence of heart attacks. Therefore, we find the concept of drug safety a very important and comprehensive concept that is considered a priority with regard to the use of medications. Actually, this concept can be considered an integrated science in itself that involves many other scientific aspects, such as the side effects of drugs, the quality of medications, medical errors in the use of drugs, lack of efficacy of drugs, and counterfeit drugs (Psaty and Furberg, 2007a,b; Hiatt et al., 2013). In Saudi Arabia, there is a need to educate and enhance the knowledge of healthcare professionals regarding the concept of drug safety since many studies that have been conducted Rimonabant in Saudi Arabia found that there is a lack of culture of drug safety in Saudi Arabia among all levels of healthcare professionals (Aljadhey et al., 2014; Khan, 2013; Mahmoud et al., 2014).

br A partir de la observaci n

A partir de la observación del desarrollo de la fiesta, proponemos que es posible referirnos LY2606368 la Huamantlada como el acto ritual en el que los participantes desafían el peligro —representado por los toros— exponiéndose voluntariamente a él. Y que su participación, por supuesto, conlleva una actuación, no a partir de un guión cerrado sino abierto, que posibilita, en el marco de unos códigos de comportamiento, que el participante despliegue una serie de realizaciones corporales que finalmente constituyen esta actuación.
Desde el ámbito antropológico, entenderemos el concepto de performance, como ha sido definido por Turner (2002:116): LY2606368 “la presentación del sí mismo en la vida diaria”, y como lo concibe Wulf (2008: 200): “la imbricación de realizaciones culturales, actos de escenificación y presentación del cuerpo”.
Caracterizaremos pues a laperformance como la presentación de uno o diversos participantes (performers) ante un espectador — que tampoco lo es en el sentido clásico — y que llevan a la acción una trama situacional estrechamente relacionada con su sistema cultural. Esta trama además, articula la acción con las experiencias de los participantes y los espectadores.
En la fiesta taurina de Huamantla, es posible encontrar elementos tales como la contingencia de lo posible o la incapacidad de conocer el desenlace de una actuación, a pesar de que existe una especie de guión tácito que señala los tiempos y los momentos en que cada secuencia debe ocurrir. Existen por otra parte, participantes que interpretan sus propios papeles: representan el desafío ante la mirada de quienes observan las acciones, mientras los toros, condición sine qua non de esta representación, simbolizan el peligro. Los voluntarios no se limitan a interpretar un papel a partir de un guión aprendido, los performers de la Huamantlada pondrán en evidencia capacidades corporales que es posible desplegar en medio de esa libertad que la performance provee al participante. Quienes participan, orientan su actuación en función de la escena que se crea de manera particular en cada evento: en función del comportamiento de los toros, de las eventualidades que puedan surgir y de la actuación de los demás participantes.
En tanto muestra escénica o género teatral, la performance, aunque conlleva una importante dosis de improvisación, no se trata de un evento teatral sin trama. Como se ha señalado, en nuestro ejemplo, la trama versa en torno a herbaceous unos hombres que escenifican un desafío y que dependiendo de particulares circunstancias, desenlazarán favorablemente o no la contingencia.
La teoría desarrollada por Víctor Turner, entiende la performance como “la presentación del sí mismo en la vida diaria” y al hombre como un homo perfor-mans, cuyos performances son, en cierta manera, reflexivos. Siguiendo al mismo autor (2002:114), este tipo de presentaciones nunca son amorfas o completamente abiertas, sino que poseen una estructura diacrónica, un principio, una secuencia de fases sobrepuestas pero aislables, y un final; asimismo, pueden contener momentos o elementos de caos y espontaneidad, siendo éstos prescritos en tiempo y espacio, es decir, que se trata de eventos organizados.
Como espectadores, quienes acuden a presenciar la Huamantlada, tienen un carácter distinto al del espectador tradicional en el teatro, hosperformers traspasan constantemente los límites de la participación y la observación y se mueven libremente a través de ambos, convirtiéndose a ratos en espectadores, a ratos en protagonistas. Tanto la movilidad del actor, como la posibilidad de participación del público, expanden el campo de la performance sobre todo porque ambos tienen lugar, según Schechner, en el punto de quiebre donde el evento estético se convierte en evento social o ritual (en Turner, 2002: 169), es decir, en el punto en el cual la comunidad, compartiendo códigos experienciales se involucra con la acción llevada a cabo en los terrenos de la escenificación.

Related works There exists a large body of work

Related works: There exists a large body of work on DVS as an effective technique to reduce order GSK-J1 sodium salt dissipation during system operation  [10]. Since there is a quadratic relationship between voltage and energy in DVS  [13], lowering the supply voltage provides significant energy saving. However, it cannot perform well for fast growing popular dynamic systems, in which the workload varies significantly  [6]. Therefore, feedback control theory has been recently used in real-time scheduling to address workload variations  [5,6,14–17]. It should be noted that none of these works has considered fault-tolerance issues, while it has been observed that reliability and fault-tolerance are of great importance in DVS-enabled systems  [11]. Therefore, some research work has addressed this tradeoff in DVS-enabled systems and provided methods to achieve both objectives at the same time  [9,10,12,18–20]. However, none of these works has considered any feedback control method for DVS. Furthermore, they have not considered workload variations. The authors in  [21] have presented a control-theoretic method based on a proportional controller to address the tradeoff between energy consumption and reliability. However, this work has not considered workload variations and hard real-time systems. Furthermore, this work uses the deadline miss ratio as the controlled variable, while it has been shown in  [22] that the deadline miss ratio is not a proper controlled variable, as it has a negative impact on system performance.

In this paper, by targeting hard real-time embedded systems, we propose a Fault-Tolerant Feedback-based DVS (FTF-DVS) scheme to reduce energy consumption, without compromising overall system reliability. In the proposed method, static slack-time is exploited for recovery executions (re-executions) to achieve fault-tolerance, while dynamic slack-time (slack-time that is dynamically created during runtime) is exploited through feedback-controlled DVS to reduce energy consumption. In our feedback-controlled DVS, we have developed a discrete Proportional-Integral (PI) controller to control CPU utilization. The main objective of this discrete controller is to maximize CPU utilization by decreasing CPU voltage and frequency (which leads to a reduction in energy consumption). In this paper (Section  3.1), we have discussed that, compared to other options, like the PID controller, a PI controller is a preferable option for our purpose. We consider the systems with workload variations during runtime and our proposed control-theoretic DVS adapts the system to unpredictable workload variations while guaranteeing hard real-time requirements. The runtime task splitting scheme  [6] is used to guarantee hard real-time requirements in cases of unpredictable workload variation. Thus, each task is split into two subtasks, which are allowed to execute at different frequency and voltage levels. During runtime, the difference between the actual execution time of the first subtasks (without considering the frequency scaling) in the current and previous invocation intervals shows the variation in the task workload. In cases of an increase in the system workload, to satisfy all deadlines, the second subtask is executed at the maximum CPU frequency/voltage. In other cases, the second subtask is executed at the same CPU frequency as the first subtask. In addition, the time and energy overheads, caused by changing the system supply voltage and frequency, are also taken into account in our simulation experiments  [23]. The simulation results show that, compared with the traditional DVS method (which also does not have fault tolerance), our proposed approach not only provides up to 59% (51% on average, assuming that WCU is uniformly distributed) energy saving, but also satisfies hard real-time constraints in the presence of workload variations and faults.

In a new approach doxorubicin and cholesterol derivatives Fig

In a new approach, doxorubicin and cholesterol derivatives (50) (Fig. 11) were bound by pH-sensitive hydrazone bonds to N -(2-hydroxypropyl)methacrylamide (HPMA) copolymers. At pH 5.0, the hydrazone bond showed a hydrolysis rate strongly dependent on the microenvironment around the bond. This property led to the site-specific release of the doxorubicin and hydrophobic domains because of the decrease in pH in the endosomes or lysosomes of tumor cells. Doxorubicin would be released in the first stage, whereas the polymer macromolecule would be disintegrated very slowly into short fragments that are small enough to be eliminated by glomerular filtration (Chytil et al., 2012).

Cholesterol-based targeted delivery of anticancer compounds
One of the successful chemotherapeutic approaches is the boron neutron capture therapy (BNCT) that is currently used to treat order bupropion hydrochloride tumors such as glioblastoma multiforme (GBM) and anaplastic astrocytomas (AA) (Barth, 2003; Zamenhof et al., 2004; Barth et al., 2005). BNCT delivers boron-10 to the tumor tissue followed by external radiation of low energy (e.g., ∼0.025keV) thermal neutron that results in fission reactions which produce high linear energy transfer (LET) α-particles and recoiling 7Li nuclei (10B+1n→[11∗B] → 4He (α)+7Li+2.39MeV), which are highly lethal to surrounding cells. It is crucial for efficient BNCT to selectively deliver a sufficient amount of 10B (∼20μg/g tumor) to tumor cells (Vicente, 2006; Wu et al., 2006). Delivery of 10B containing agents via liposomes conjugated to the anti-EGFR monoclonal antibody (MAb) cetuximab (C225) and L8A4, which is directly against EGFRvIII is an attractive delivery approach for BNCT, because of their high payload capacity (Barth et al., 2002; Wu et al., 2006). These liposomes consist of cholesterol anchored folate (folate-PEG-Chol) (51) in EGFR-folate receptor targeted liposomes (Fig. 12) (Lee and Low, 1994; Guo et al., 2000) or consist of cholesterol anchored MAb (MAb-PEG-Chol) (53) in the preparation of immunoliposomes (55) (Figs. 13 and 14) (Pan et al., 2007).

Cholesterol-sugar conjugates as anticancer agents against peritoneal dissemination of tumor cells
Peritoneal dissemination of cancer cells is a major form of recurrence in patients with advanced stages of gastric, colorectal, ovarian, and pancreatic cancers after curative resection of tumors (Vogel and Kalthoff, 2001; Sugarbaker, 2005; Koppe et al., 2006; de Bree et al., 2006; Yan et order bupropion hydrochloride al., 2006). In this phenomenon, tumor cells exfoliate from the tumors to the abdominal cavity, adhere to the surface of the peritoneum to invade the basement membrane, and, in particular, adhere to the greater omentum and the mesenterium (Asao et al., 1994; Asao et al., 1995; Okamura et al., 2000). In this process cell surface glycoconjugates have an essential role. Chemically synthesized sugars have been developed as anti-adhesion molecules against the peritoneal dissemination of cancer cells (Asao et al., 1994; Asao et al., 1995; Okamura et al., 2000). Basically, chemically synthesized sugar-cholestanols with mono-, di-, and tri-saccharides attached to cholestanol (56) showed a strong inhibiting activity against the proliferation of colorectal and gastric cancer cells by inducing apoptotic cell death. Also, these sugar-cholestanols were suggested to have clinical potential as a novel anticancer agent based on their strong inhibiting activity against peritoneal dissemination in a mouse model. In contrast, cholestanol without sugar moieties was totally ineffective. Furthermore, when cancer cells were exposed to GlcNAcRβ-cholestanol (R=(−) or β1–3Gal; Fig. 15) (56), the compound was rapidly taken up via the lipid rafts/microdomains on the cell surface. The uptake of sugar-cholestanol in mitochondria increased gradually and was followed by the release of cytochrome c from mitochondria and the activation of apoptotic signals through the mitochondrial pathway and the caspase cascade, leading to apoptotic cell death, characterized by DNA ladder formation and nuclear fragmentation (Shinji et al., 2008).