A glucose-centric perspective of hyperglycemia

Digestion of food in the intestines converts the compacted storage carbohydrates, starch and glycogen, to glucose. After each meal, a flux of glucose (>200 g) passes through the blood pool (4-6 g) in a short period of 2 h, keeping its concentration ideally in the range of 80-120 mg/100 mL. Tissue-specific glucose transporters (GLUTs) aid in the distribution of glucose to all tissues. The balance glucose after meeting the immediate energy needs is converted into glycogen and stored in liver (up to 100 g) and skeletal muscle (up to 300 g) for later use. High blood glucose gives the signal for increased release of insulin from pancreas. Insulin binds to insulin receptor on the plasma membrane and activates its autophosphorylation. This initiates the post-insulin-receptor signal cascade that accelerates synthesis of glycogen and triglyceride. Parallel control by phos-dephos and redox regulation of proteins exists for some of these steps. A major action of insulin is to inhibit gluconeogensis in the liver decreasing glucose output into blood. Cases with failed control of blood glucose have alarmingly increased since 1960 coinciding with changed life-styles and large scale food processing. Many of these turned out to be resistant to insulin, usually accompanied by dysfunctional glycogen storage. Glucose has an extended stay in blood at 8 mM and above and then indiscriminately adds on to surface protein-amino groups. Fructose in common sugar is 10-fold more active. This random glycation process interferes with the functions of many proteins (e.g., hemoglobin, eye lens proteins) and causes progressive damage to heart, kidneys, eyes and nerves. Some compounds are known to act as insulin mimics. Vanadium-peroxide complexes act at post-receptor level but are toxic. The fungus-derived 2,5-dihydroxybenzoquinone derivative is the first one known to act on the insulin receptor. The safe herbal products in use for centuries for glucose control have multiple active principles and targets. Some are effective in slowing formation of glucose in intestines by inhibiting alpha-glucosidases (e.g., salacia/saptarangi). Knowledge gained from French lilac on active guanidine group helped developing Metformin (1,1-dimethylbiguanide) one of the popular drugs in use. One strategy of keeping sugar content in diets in check is to use artificial sweeteners with no calories, no glucose or fructose and no effect on blood glucose (e.g., steviol, erythrytol). However, the three commonly used non-caloric artificial sweetener's, saccharin, sucralose and aspartame later developed glucose intolerance, the very condition they are expected to evade. Ideal way of keeping blood glucose under 6 mM and HbAlc, the glycation marker of hemoglobin, under 7% in blood is to correct the defects in signals that allow glucose flow into glycogen, still a difficult task with drugs and diets.

Transgenic Drosophila model to study apolipoprotein E4-induced neurodegeneration

The epsilon 4 isoform of apolipoprotein E (ApoE4) that is involved in neuron-glial lipid metabolism has been demonstrated as the main genetic risk factor in late-onset of Alzheimer's disease. However, the mechanism underlying ApoE4-mediated neurodegeneration remains unclear. We created a transgenic model of neurodegenerative disorder by expressing epsilon 3 and epsilon 4 isoforms of human ApoE in the Drosophila melanogaster. The genetic models exhibited progressive neurodegeneration, shortened lifespan and memory impairment. Genetic interaction studies between amyloid precursor protein and ApoE in axon pathology of the disease revealed that over expression of hApoE in Appl-expressing neurons of Drosophila brain causes neurodegeneration. Moreover, acute oxidative damage in the hApoE transgenic flies triggered a neuroprotective response of hApoE3 while chronic induction of oxidative damage accelerated the rate of neurodegeneration. This Drosophila model may facilitate analysis of the molecular and cellular events implicated in hApoE4 neurotoxicity. (C) 2015 Elsevier B.V. All rights reserved.

Biochemical and Behavioral Evaluation of Human MAPT Mutations in Transgenic Drosophila melanogaster

Mutations in the human microtubule-associated protein tau (hMAPT) gene including R406W and V337M result in autosomal dominant neurodegenerative disorder. These mutations lead to hyperphosphorylation and aggregation of Tau protein which is a known genetic factor underlying development of Alzheimer's disease (AD). In the present study, transgenic Drosophila models of AD expressing wild-type and mutant forms of hMAPT exhibit a progressive neurodegeneration which was manifested in the form of early death and impairment of cognitive ability. Moreover, they were also found to have significantly decreased activity of neurotransmitter enzymes accompanied by decreased cellular endogenous antioxidant profile. The extent of neurodegeneration, memory impairment, and biochemical profiles was different in the tau transgenic strains which indicate multiple molecular and cellular responses underlie each particular form of hMAPT.

Three-dimensional plotted hydroxyapatite scaffolds with predefined architecture: comparison of stabilization by alginate cross-linking versus sintering

Scaffolds for bone tissue engineering are essentially characterized by porous three-dimensional structures with interconnected pores to facilitate the exchange of nutrients and removal of waste products from cells, thereby promoting cell proliferation in such engineered scaffolds. Although hydroxyapatite is widely being considered for bone tissue engineering applications due to its occurrence in the natural extracellular matrix of this tissue, limited reports are available on additive manufacturing of hydroxyapatite-based materials. In this perspective, hydroxyapatite-based three-dimensional porous scaffolds with two different binders (maltodextrin and sodium alginate) were fabricated using the extrusion method of three-dimensional plotting and the results were compared in reference to the structural properties of scaffolds processed via chemical stabilization and sintering routes, respectively. With the optimal processing conditions regarding to pH and viscosity of binder-loaded hydroxyapatite pastes, scaffolds with parallelepiped porous architecture having up to 74% porosity were fabricated. Interestingly, sintering of the as-plotted hydroxyapatite-sodium alginate (cross-linked with CaCl2 solution) scaffolds led to the formation of chlorapatite (Ca9.54P5.98O23.8Cl1.60(OH)(2.74)). Both the sintered scaffolds displayed progressive deformation and delayed fracture under compressive loading, with hydroxyapatite-alginate scaffolds exhibiting a higher compressive strength (9.5 +/- 0.5MPa) than hydroxyapatite-maltodextrin scaffolds (7.0 +/- 0.6MPa). The difference in properties is explained in terms of the phase assemblage and microstructure.

一类含裂隙岩质边坡的滑动弱化逐步破坏机理

含裂隙的岩土材料在剪切作用下,随着剪应变的增加,裂纹端部一定区域内的强度会表现出滑动弱化的现象.岩土材料这种性质的变化不同于粘性土结构性破坏,也不同于剪胀.在一定的载荷作用下,坡体内裂隙端部的滑动弱化使坡体内的应力重新分配,从而使得应力集中加剧,裂隙尖端进一步扩展,造成岩体结构性的破坏,乃至整个滑面的贯通直至发生滑坡.因此,滑动弱化是一类含裂隙岩质边坡滑坡的机理.

3D Anisotropic Elastoplastic-Damage Model and its Application in Simulating the Behavior of Rock Materials

A 3D anisotropic elastoplastic-damage model was presented based on continuum damage mechanics theory. In this model, the tensor decomposition technique is employed. Combined with the plastic yield rule and damage evolution, the stress tensor in incremental format is obtained. The derivate eigenmodes in the proposed model are assumed to be related with the uniaxial behavior of the rock material. Each eigenmode has a corresponding damage variable due to the fact that damage is a function of the magnitude of the eigenstrain. Within an eigenmodes, different damage evolution can be used for tensile and compressive loadings. This model was also developed into finite element code in explicit format, and the code was integrated into the well-known computational environment ABAQUS using the ABAQUS/Explicit Solver. Numerical simulation of an uniaxial compressive test for a rock sample is used to examine the performance of the proposed model, and the progressive failure process of the rock sample is unveiled.

A Dynamic Comprehensive Method for Landslide Control

A slope failure is developed due to progressive external loads and deteriorations of slope geomaterials, thus forming a progressive and dynamic development and occurrence of landslides. Site geological properties and other active factors such as hydrodynamic load and human activities are complex and usually unknown, thus this dynamic development and occurrence of landslides can only be understood through the progressive accumulation of knowledge on the landslides. For such a progressive process, this paper proposes a dynamic comprehensive control method for landslide control. This control method takes full advantage of updated monitoring data and site investigations of landslides, and emphasizes the implementation of possible measures for landslide control at reasonable stages and in different groups. These measures are to prevent the occurrence of a landslide disaster. As a case study, a landslide project at the Panluo open-pit iron mine is analyzed to illustrate this dynamic comprehensive control method.

On-line observation of interlaminar damage by ultrasonic inspection

This paper explores an on-line experimental method to highlight the process of internal damage development in composites by taking advantage of ultrasonic inspection. A loading device, which can work together with an ultrasonic inspection system, was designed, and the interlaminar shear damage of a double-sided grooved specimen of composite was examined on-line with the system. A full view of the progressive internal interlaminar damage, seen only with difficulty by common inspection methods, was successfully achieved.

An incremental micromechanical scheme for nonlinear particulate composites

A general incremental micromechanical scheme for the nonlinear behavior of particulate composites is presented in this paper. The advantage of this scheme is that it can reflect partly the effects of the third invariant of the stress on the overall mechanical behavior of nonlinear composites. The difficulty involved is the determination of the effective compliance tensors of the anisotropic multiphase composites. This is completed by making use of the generalized self-consistent Mori-Tanaka method which was recently developed by Dai et al. (Polymer Composites 19(1998) 506-513; Acta Mechanica Solida 18 (1998) 199-208). Comparison with existing theoretical and numerical results demonstrates that the present incremental scheme is quite satisfactory. Based on this incremental scheme, the overall mechanical behavior of a hard-particle reinforced metal matrix composite with progressive particle debonding damage is investigated.

Rendimiento y calidad de las interacciones sociocognitivas en díadas que trabajan colaborativamente en forma presencial y por chat

Resumen: En este trabajo se examina el rendimiento de estudiantes universitarios en razonamiento formal con y sin interacción social. La muestra N = 83 estuvo conformada por alumnos provenientes de dos universidades (UNMDP y UAA) quienes fueron asignados a dos condiciones: experimental con interacción (n = 40) y grupo control sin interacción (n = 43). El reactivo empleado consistió en una serie de pruebas del Test de Matrices Progresivas escala general y avanzada. Todos los participantes debieron resolver dichas tareas durante varias semanas: primero en forma individual (pretest), luego en forma colectiva presencial y por chat (díadas, condición experimental) y en forma individual (grupo control), y finalmente en forma individual (postest). Se registraron las interacciones que llevaron a cabo los participantes mediante videofilmación y logs del Chat. El rendimiento fue evaluado según la condición asignada: individual o grupal y en los últimos mediante una evaluación interjueces se estableció la calidad de las interacciones. Los resultados corroboran la superioridad de las díadas por sobre la performance individual; la reiteración en la fase de postest de aquellos ítems incorrectamente resueltos en el pretest más el agregado de nuevos ejercicios pusieron de relieve dos zonas de avance o de internalización de los progresos. En cuanto a la calidad de las interacciones, las mismas son coincidentes. Estos resultados abren nuevos interrogantes acerca del conflicto sociocognitivo y su papel para el avance grupal – individual.

La heráldica, el retrato y el fin de la Edad Media : un acercamiento antropológico a la iconografía

Resumen: Durante la Edad Media hizo su aparición la heráldica como forma de identificar ciertos aspectos de las personas, ya sea por su condición social o por su actividad específica. El uso de blasones y escudos de armas desde el siglo XI generó una importante cantidad de signos, colores y símbolos que edificaron todo un “patrón de lectura” del “rostro social” de la persona que portaba tal insignia, sin importar o no la veracidad de su rostro al confeccionarse un retrato pintado o esculpido. Paralelo a esto, la retratística que hubo durante todo el período medieval de personas reales, sagradas o ideales avanzó hacia un progresivo naturalismo que finalizó en el siglo XV con la reproducción del retratado tal cual era su fisonomía y abandonando el canon estereotipado que durante los siglos precedentes habían proliferado. Finalmente, con el creciente Humanismo, la aparición de la perspectiva y el progresivo abandono de la identificación de determinado personaje con sólo su escudo de armas, sirvió para que el retratado mirase a los ojos del observador y “dialogase”, develando aspectos espirituales antes ocultos. El objetivo de este trabajo es acercarse con una visión antropológica a la cuestión del retrato tardomedieval y renacentista en conjunción con los cambios operados en la heráldica y la iconografía, comprobando que la mirada tiene marcada intencionalidad, los rostros se frontalizan progresivamente y la heráldica pierde el espesor que tuvo en siglos precedentes

La excéntrica centralidad de las materias artúrica y caballeresca en la narrativa gallega y catalana de la década de 1950 (Merlín e familia de Cunqueiro y Llibre cavalleries de Perucho)

Integran este número de la revista ponencias presentadas en Studia Hispanica Medievalia VIII: Actas de las IX Jornadas Internacionales de Literatura Española Medieval, 2008, y de Homenaje al Quinto Centenario de Amadis de Gaula

¿Existe una gradualidad inherente a la ley moral?

La Familiaris consortio n.34 definió la “ley de la gradualidad”, como cumplimiento progresivo de la ley moral, contraponiéndola a la “gradualidad de la ley”, la cual es considerada como una expresión del rechazo al carácter vinculante de la misma. Pero no es éste el único modo posible de concebir la gradualidad de la ley. Santo Tomás presenta en la Suma Teológica un ejemplo de gradualidad de la ley (civil), a partir del cual este estudio se propone mostrar que existe una gradualidad inherente a la ley moral, que, sin privar a ésta de su fuerza obligatoria, le permite adaptarse dinámicamente al desarrollo moral del sujeto.

Cien años de la Facultad de Teología : la progresiva maduración de un estilo

Resumen: En su lectio inauguralis del año académico de la Facultad de Teología de la Universidad Católica Argentina, el autor toma la oportunidad de la celebración del Centenario de dicha Facultad y los cincuenta años de la clausura del Concilio Vaticano II, para reflexionar sobre la influencia de este último en el “estilo” de aquélla. Este estilo es, en efecto, fruto de la recepción del Concilio, que ha hecho prevalecer el tema del amor en el pensamiento y la vida cristiana, junto con una visión de la revelación como comunicación de Dios a los hombres en la historia, y una nueva atención a los “signos de los tiempos”, generando así una nueva actitud caracterizada por la apertura y el diálogo. El “estilo integrador” de nuestra Facultad, inspirado en el Concilio y en la figura de Pablo VI, encuentra un renovado impulso en el Papa Francisco, para quien la “auténtica” teología debe ser hecha “de rodillas” y desde el “corazón”, siendo a la vez saber humilde y amor comprometido

Energy Principle And Nonlinear Electric-Mechanical Behavior Of Ferroelectric Ceramics

Many experimental observations have shown that a single domain in a ferroelectric material switches by progressive movement of domain walls, driven by a combination of electric field and stress. The mechanism of the domain switch involves the following steps: initially, the domain has a uniform spontaneous polarization; new domains with the reverse polarization direction nucleate, mainly at the surface, and grow though the crystal thickness; the new domain expands sideways as a new domain continues to form; finally, the domain switch coalesces to complete the polarization reversal. According to this mechanism, the volume fraction of the domain switching is introduced in the constitutive law of the ferroelectric material and used to study the nonlinear constitutive behavior of a ferroelectric body in this paper. The principle of stationary total potential energy is put forward in which the basic unknown quantities are the displacement u(i), electric displacement D-i and volume fraction rho(I) of the domain switching for the variant I. The mechanical field equation and a new domain switching criterion are obtained from the principle of stationary total potential energy. The domain switching criterion proposed in this paper is an expansion and development of the energy criterion established by Hwang et al. [ 1]. Based on the domain switching criterion, a set of linear algebraic equations for determining the volume fraction rho(I) of domain switching is obtained, in which the coefficients of the linear algebraic equations only contain the unknown strain and electric fields. If the volume fraction rho(I) of domain switching for each domain is prescribed, the unknown displacement and electric potential can be obtained based on the conventional finite element procedure. It is assumed that a domain switches if the reduction in potential energy exceeds a critical energy barrier. According to the experimental results, the energy barrier will strengthen when the volume fraction of the domain switching increases. The external mechanical and electric loads are increased step by step. The volume fraction rho(I) of domain switching for each element obtained from the last loading step is used as input to the constitutive equations. Then the strain and electric fields are calculated based on the conventional finite element procedure. The finite element analysis is carried out on the specimens subjected to uniaxial coupling stress and electric field. Numerical results and available experimental data are compared and discussed. The present theoretic prediction agrees reasonably with the experimental results.