Limonoids showing selective toxicity to DNA repair-deficient yeast and other constituents of Trichilia emetica

Bioactivity-directed fractionation of the MeCOEt extract of Trichilia emetica (Meliaceae) resulted in the isolation of the limonoids nymania 1 (1), drageana 4 (3), trichilin A (4), rohituka 3 (5),and Tr-B (7) and the novel seco-A protolimonoid 8. of these, nymania 1 and Tr-B showed selective inhibitory activity toward DNA repair-deficient yeast mutants. The isolation, structure elucidation, C-13 NMR spectral assignments, and biological activities of:these compounds are reported.

BIOACTIVE AND OTHER PIPERIDINE ALKALOIDS FROM CASSIA-LEPTOPHYLLA

Four new piperidine alkaloids, leptophyllin A (4), 3-acetylleptophyllin A (5), leptophyllin B (8), and (-)-spectaline (1), and 3 known piperidine alkaloids, (-)-spectalinine (2), canavaline (3), and iso-6-canavaline (7), were isolated by a bioassay-guided fractionation of a leaf extract of Cassia leptophylla. The alkaloids 1 - 3 were active in a mechanism-based DNA-modifying yeast assay and 2 was moderately active in Vero monkey and Chinese hamster ovary cell cytotoxicity assays.

A DNA-damaging sesquiterpene and other constituents from Frullania nisquallensis

Bioassay-guided fractionation of an MeCOEt extract of Frullania nisquallensis Sull. has furnished a DNA-damaging sesquiterpene, costunolide (1), and two inactive compounds, a sesquiterpene (-)-frullanolide (2) and a tridepside tenuiorin (3). C-13-NMR data of 3 are reported.

An analysis of the Hygiea asteroid family orbital region

(10) Hygiea is the fourth largest asteroid of the main belt, by volume and mass, and it is the largest member of its family, that is made mostly by low-albedo, C-type asteroids, typical of the outer main belt. Like many other large families, it is associated with a 'halo' of objects, that extends far beyond the boundary of the core family, as detected by traditional hierarchical clustering methods (HCM) in proper element domains. Numerical simulations of the orbital evolution of family members may help in estimating the family and halo family age, and the original ejection velocity field. But, in order to minimize the errors associated with including too many interlopers, it is important to have good estimates of family membership that include available data on local asteroid taxonomy, geometrical albedo and local dynamics. For this purpose, we obtained synthetic proper elements and frequencies of asteroids in the Hygiea orbital region, with their errors. We revised the current knowledge on asteroid taxonomy, including Sloan Digital Sky Survey-Moving Object Catalog 4th release (SDSS-MOC 4) data, and geometric albedo data from Wide-field Infrared Survey Explorer (WISE) and Near-Earth Object WISE (NEOWISE). We identified asteroid family members using HCM in the domain of proper elements (a, e, sin (i)) and in the domains of proper frequencies most appropriate to study diffusion in the local web of secular resonances, and eliminated possible interlopers based on taxonomic and geometrical albedo considerations. To identify the family halo, we devised a new hierarchical clustering method in an extended domain that includes proper elements, principal components PC1, PC2 obtained based on SDSS photometric data and, for the first time, WISE and NEOWISE geometric albedo. Data on asteroid size distribution, light curves and rotations were also revised for the Hygiea family. The Hygiea family is the largest group in its region, with two smaller families in proper element domain and 18 families in various frequencies domains identified in this work for the first time. Frequency groups tend to extend vertically in the (a, sin (i)) plane and cross not only the Hygiea family but also the near C-type families of Themis and Veritas, causing a mixture of objects all of relatively low albedo in the Hygiea family area. A few high-albedo asteroids, most likely associated with the Eos family, are also present in the region. Finally, the new multidomains hierarchical clustering method allowed us to obtain a good and robust estimate of the membership of the Hygiea family halo, quite separated from other asteroids families halo in the region, and with a very limited (about 3 per cent) presence of likely interlopers. © 2013 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society.

Anti-atherogenic and anti-angiogenic activities of polyphenols from propolis

Propolis is a polyphenol-rich resinous substance extensively used to improve health and prevent diseases. The effects of polyphenols from different sources of propolis on atherosclerotic lesions and inflammatory and angiogenic factors were investigated in LDL receptor gene (LDLr-/-) knockout mice. The animals received a cholesterol-enriched diet to induce the initial atherosclerotic lesions (IALs) or advanced atherosclerotic lesions (AALs). The IAL or AAL animals were divided into three groups, each receiving polyphenols from either the green, red or brown propolis (250 mg/kg per day) by gavage. After 4 weeks of polyphenol treatment, the animals were sacrificed and their blood was collected for lipid profile analysis. The atheromatous lesions at the aortic root were also analyzed for gene expression of inflammatory and angiogenic factors by quantitative real-time polymerase chain reaction and immunohistochemistry. All three polyphenol extracts improved the lipid profile and decreased the atherosclerotic lesion area in IAL animals. However, only polyphenols from the red propolis induced favorable changes in the lipid profiles and reduced the lesion areas in AAL mice. In IAL groups. VCAM, MCP-1, FGF, PDGF, VEGF, PECAM and MMP-9 gene expression was down-regulated, while the metalloproteinase inhibitor TIMP-1 gene was up-regulated by all polyphenol extracts. In contrast, for advanced lesions, only the polyphenols from red propolis induced the down-regulation of CD36 and the up-regulation of HO-1 and TIMP-1 when compared to polyphenols from the other two types of propolis. In conclusion, polyphenols from propolis, particularly red propolis, are able to reduce atherosclerotic lesions through mechanisms including the modulation of inflammatory and angiogenic factors. (C) 2012 Elsevier Inc. All rights reserved.

[Alternative sonographic determination of liver size by intercostal scans]

BACKGROUND: The evaluation of hepatic size is a daily question in abdominal ultrasound, especially to determine the presence of hepatomegaly. In the literature, different methods of measurement are described, mostly as a subcostal measured organ diameter in one direction. This method has its limits in patients with obesity, accumulation of abdominal gas or in uncooperative patients (lack of coordinative respiration) so that alternative measurements are necessary. METHODS: In 241 patients hepatic size was first measured in two conventional sections: midclavicular line (MCL) and anterior axillary line (AAL). Additionally, we measured the organs in midaxillary line craniocaudal (MAL) by determination of the cranio-caudal diameter. In 58 patients additional computed tomography was performed due to special diagnostical reasons so that liver size in MCL could be revealed and compared with ultrasonographical values. RESULTS: The mean value in MCL was 10.7 +/- 2.1 cm measured by ultrasound, 11.4 +/- 3.7 cm measured by computed tomography, 14.0 +/- 1.9 cm in AAL and 14.9 +/- 2.0 cm in MAL. In 5% of the cases the liver could not be measured in the conventional subcostal sections due to obesity or masking by gas, but this was possible in MAL. CONCLUSIONS: We revealed a good correlation of liver size in MCL between ultrasound and computed tomography, as well as in the measurement of AAL and MAL diameters. However, even in cases with difficult subcostal approach intercostal diameters allow for an accurate determination of hepatic size.

Metabolic inflexibility and insulin resistance in obese adolescents with non-alcoholic fatty liver disease.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a comorbidity of childhood obesity. OBJECTIVE We examined whole-body substrate metabolism and metabolic characteristics in obese adolescents with vs. without NAFLD. SUBJECTS Twelve obese (BMI ≥ 95th percentile) adolescents with and without NAFLD [intrahepatic triglyceride (IHTG) ≥5.0% vs. <5.0%] were pair-matched for race, gender, age and % body fat. METHODS Insulin sensitivity (IS) was assessed by a 3-h hyperinsulinemic-euglycemic clamp and whole-body substrate oxidation by indirect calorimetry during fasting and insulin-stimulated conditions. RESULTS Adolescents with NAFLD had increased (p < 0.05) abdominal fat, lipids, and liver enzymes compared with those without NAFLD. Fasting glucose concentration was not different between groups, but fasting insulin concentration was higher (p < 0.05) in the NAFLD group compared with those without. Fasting hepatic glucose production and hepatic IS did not differ (p > 0.1) between groups. Adolescents with NAFLD had higher (p < 0.05) fasting glucose oxidation and a tendency for lower fat oxidation. Adolescents with NAFLD had lower (p < 0.05) insulin-stimulated glucose disposal and lower peripheral IS compared with those without NAFLD. Although respiratory quotient (RQ) increased significantly from fasting to insulin-stimulated conditions in both groups (main effect, p < 0.001), the increase in RQ was lower in adolescents with NAFLD vs. those without (interaction, p = 0.037). CONCLUSION NAFLD in obese adolescents is associated with adverse cardiometabolic profile, peripheral insulin resistance and metabolic inflexibility.

AALUMO: a user model ontology for ambient assisted living services supported in next-generation networks

Ambient Assisted Living (AAL) services are emerging as context-awareness solutions to support elderly people?s autonomy. The context-aware paradigm makes applications more user-adaptive. In this way, context and user models expressed in ontologies are employed by applications to describe user and environment characteristics. The rapid advance of technology allows creating context server to relieve applications of context reasoning techniques. Specifically, the Next Generation Networks (NGN) provides by means of the presence service a framework to manage the current user's state as well as the user's profile information extracted from Internet and mobile context. This paper propose a user modeling ontology for AAL services which can be deployed in a NGN environment with the aim at adapting their functionalities to the elderly's context information and state.

Entornos de ayuda a la vida independiente de personas mayores sobre servicios de redes de próxima generación

El progresivo envejecimiento de la población está produciendo una elevada demanda de servicios socio‐asistenciales por parte de las personas mayores para mantener su vida independiente y el consiguiente “envejecimiento activo”. La iniciativa Ambient Assisted Living (AAL) promueve el “envejecimiento activo” a través de las Tecnologías de la Información y las Comunicaciones (TIC) y es en ella donde se centrará el trabajo de esta tesis doctoral. Una característica fundamental de los servicios AAL es su adaptación y personalización a las características y preferencias del usuario y su contexto. Así, el paradigma “context awareness” presenta una gran relevancia en la provisión de servicios AAL y en el soporte a la vida independiente de las personas mayores. Concretamente, la utilización de ontologías permite crear modelos de usuarios y contexto que pueden ser utilizadas para los mecanismos de razonamiento incluidos en los servicios context‐aware. Por otra parte, los usuarios actualmente precisan acceder a un conjunto de servicios desde cualquier red de acceso y desde cualquier dispositivo. Las redes de próxima generación (Next Generation Networks‐NGN) lo hacen posible pues ofrecen una convergencia dispositivo‐red‐servicio. La tecnología IMS (IP Multimedia Subsystem) es una arquitectura que implementa el paradigma NGN y ofrece una serie de servicios de red genéricos llamados servicios habilitadores o enablers que pueden ser reutilizados en cualquier aplicación, soportando mecanismos de interoperabilidad entre aplicaciones y permitiendo un desarrollo robusto, rápido y sencillo. Además, los servicios enablers permiten mecanismos de gestión de la información de usuario para realizar una provisión adaptada del servicio en función de la información del estado del usuario. El objetivo de esta tesis doctoral se centra en establecer un marco de convergencia entre estos dos campos diseñando y desarrollando un conjunto de servicios enablers soportados en una arquitectura IMS implementada para soportar la provisión de aplicaciones AAL bajo el paradigma context‐awareness y la triple convergencia reddispositivo‐ servicio cubriendo así las necesidades y requisitos de las personas mayores. Entre las aportaciones de la presente tesis se destaca la realización de un modelo de plataforma servicios AAL, denominado Residencia Virtual Asistiva, para su provisión en el domicilio de la persona mayor, así como la propuesta de implementación de sus servicios a través de servicios enablers. Por otra parte se define una ontología destinada a modelar servicios AAL así como sus usuarios (personas mayores) para lograr una provisión personalizada y adaptada de servicios AAL. Esta ontología se ha implementado a través del servicio de presencia de la arquitectura IMS para poder crear perfiles de usuario y así poder realizar dicha provisión personalizada. Además, se desarrolla una aplicación de teleconsulta, como ejemplo de servicio AAL, que utiliza una serie de servicios enablers desarrollados para ofrecer funcionalidades avanzadas a la aplicación. Bajo el paradigma contex‐awareness se ha desarrollado y evaluado técnicamente un servicio enabler para ofrecer soporte a la movilidad y a la independencia de las personas mayores con deterioro cognitivo que sufren episodios de desorientación espacial. ABSTRACT The progressive ageing of the population is making elderly people demand sociohealthcare services to maintain an independent living and therefore an “active ageing”. The initiative Ambient Assisted Living (AAL), on which the current PhD thesis is focused, promotes the “active ageing” by means of Information and Communication Technologies (ICT). Essential features of AAL services are the adaptation and personalization to the user’s characteristics and preferences as well as user’s context. Thus, the “context‐awareness” paradigm implies a great importance in the AAL service provision and the elderly independent living support. In particular, the usage of ontologies allows creating user and contexts models to be employed in the reasoning mechanism of context‐aware services. On the other hand, users currently require accessing to a set of services from anywhere and any device. Next‐Generation Networks (NGN) support this need by offering a service‐network‐device convergence. The IP Multimedia Subsystem (IMS) technology is an architecture that implements the NGN paradigm and offers a generic network services know as service enabler which can be reused by any application supporting application interoperability mechanism as well as allowing a simple, fast and robust application development. Furthermore, the service enablers offer user’s information management procedures to achieve and adapt service provision considering the user’s status. The objective of this PhD thesis is focused on establishing a convergence framework between these two previous fields by designing and developing a group of service enablers that will be deployed in an IMS architecture. The enablers developed will support the AAL applications provision from the context‐awareness paradigm and service‐network‐device convergence in order to cover the elderly people’s requirements and needs. Among the contributions achieved in this PhD thesis, the definition of an AAL platform service model, named as “Assited Virtual Nursing Home”, for being deployed in the older adult home is emphasised. In addition, a proposal of service enablers to support the AAL service defined in the model is made. Otherwise, an ontology is defined to model AAL services as well as their users with the aim at achieve a personalized and adapted AAL service. This ontology has been implemented by means of the IMS service presence in order to create users profiles to be used in the personalized AAL services. As an example of AAL service, a teleconsulting application has been developed to employ a group of service enablers developed using a set of advanced functionalities. Considering the context‐paradigm, a service enabler has been developed and technologically evaluated to support the mobility and independence of elderly people with mild cognitive impairment who suffers spatial disorientation episodes.

How network operators can enhance ambient assisted living applications through next generation networks

Within the technological framework of Information and Communication Technologies (ICT), consumers are currently requesting multimedia services with simplicity of use, reliability, security and service availability through mobile and fixed access. Network operators are proposing the Next Generation Networks (NGN) to address the challenges of providing both services and network convergence. Apart from these considerations, there is a need to provide social and healthcare assistance services in order to support the progressive aging in the elderly population. In order to achieve this objective, the Ambient Assisted Living (AAL) initiative proposes ICT systems and services to promote autonomy and an independent life among the elderly. This paper describes the design and implementation of a group of services, called “service enablers”, which helps AAL applications to be supported in NGN. The presented enablers are identified to support the teleconsulting applications requirements in an NGN environment, involving the implementation of a virtual waiting room, a virtual whiteboard, a multimedia multiconference and a vital-signs monitoring presence status. A use case is defined and implemented to evaluate the developed enablers' performance.

Fumonisins and Alternaria alternata lycopersici toxins: sphinganine analog mycotoxins induce apoptosis in monkey kidney cells.

Fusarium moniliforme toxins (fumonisins) and Alternaria alternata lycopersici (AAL) toxins are members of a new class of sphinganine analog mycotoxins that occur widely in the food chain. These mycotoxins represent a serious threat to human and animal health, inducing both cell death and neoplastic events in mammals. The mechanisms by which this family of chemical congeners induce changes in cell homeostasis were investigated in African green monkey kidney cells (CV-1) by assessing the appearance of apoptosis, cell cycle regulation, and putative components of signal transduction pathways involved in apoptosis. Structurally, these mycotoxins resemble the sphingoid bases, sphingosine and sphinganine, that are reported to play critical roles in cell communication and signal transduction. The addition of fumonisin B1 or AAL toxin, TA, to CV-1 cells induced the stereotypical hallmarks of apoptosis, including the formation of DNA ladders, compaction of nuclear DNA, and the subsequent appearance of apoptotic bodies. Neither mycotoxin induced cell death, DNA ladders, or apoptotic bodies in CV-1 cells expressing simian virus 40 large T antigen (COS-7) at toxin concentrations that readily killed CV-1 cells. Fumonisin B1 induced cell cycle arrest in the G1 phase in CV-1 cells but not in COS-7 cells. AAL toxin TA did not arrest cell cycle progression in either cell line. The induction of apoptosis combined with the widespread presence of these compounds in food crops and animal feed identifies a previously unrecognized health risk to humans and livestock. These molecules also represent a new class of natural toxicants that can be used as model compounds to further characterize the molecular and biochemical pathways leading to apoptosis.

The Impact of PL 480 Title I in Peru : food aid as an effective development resource /

"PN-AAL-021"--Cover.

AID assistance to local government : experience and issues /

"PN-AAL-026"--Cover.

The private sector, the public sector, and donor assistance in economic development : an interpretive essay /

"PN-AAL-007"--Cover.

A comparative analysis of policies and other factors which affect the role of the private sector in economic development /

"PN-AAL-031"--Cover.