P450 oxidoreductase deficiency: a new disorder of steroidogenesis

Microsomal P450 enzymes, which metabolize drugs and catalyze steroid biosynthesis require electron donation from NADPH via P450 oxidoreductase (POR). POR knockout mice are embryonically lethal, but we found recessive human POR missense mutations causing disordered steroidogenesis and Antley-Bixler syndrome (ABS), a skeletal malformation syndrome featuring craniosynostosis. Dominant mutations in exons 8 and 10 of fibroblast growth factor receptor 2 (FGFR2) cause phenotypically related craniosynostosis syndromes and were reported in patients with ABS and normal steroidogenesis. Sequencing POR and FGFR2 exons in 32 patients with ABS and/or hormonal findings suggesting POR deficiency showed complete genetic segregation of POR and FGFR2 mutations. Fifteen patients carried POR mutations on both alleles, four carried POR mutations on 1 allele, nine carried FGFR2/3 mutations on one allele and no mutation was found in three patients. The 34 affected POR alleles included 10 with A287P, 7 with R457H, 9 other missense mutations and 7 frameshifts. These 11 missense mutations and 10 others identified by database mining were expressed in E. coli, purified to apparent homogeneity, and their catalytic capacities were measured in four assays: reduction of cytochrome c, oxidation of NADPH, and support of the 17alpha-hydroxylase and 17,20 lyase activities of human P450c17. As assessed by Vmax/Km, 17,20 lyase activity provided the best correlation with clinical findings. Modeling human POR on the X-ray crystal structure of rat POR shows that these mutant activities correlate well with their locations in the structure. POR deficiency is a new disease, distinct from the craniosynostosis syndromes caused by FGFR mutations.

Living Renal Allograft Transplantation: Diffusion-weighted MR Imaging in Longitudinal Follow-up of the Donated and the Remaining Kidney.

Purpose To determine whether diffusion-weighted (DW) magnetic resonance (MR) imaging in living renal allograft donation allows monitoring of potential changes in the nontransplanted remaining kidney of the donor because of unilateral nephrectomy and changes in the transplanted kidney before and after transplantation in donor and recipient, respectively, and whether DW MR parameters are correlated in the same kidney before and after transplantation. Materials and Methods The study protocol was approved by the local ethics committee; written informed consent was obtained. Thirteen healthy kidney donors and their corresponding recipients prospectively underwent DW MR imaging (multiple b values) in donors before donation and in donors and recipients at day 8 and months 3 and 12 after donation. Total apparent diffusion coefficient (ADCT) values were determined; contribution of microcirculation was quantified in perfusion fraction (FP). Longitudinal changes of diffusion parameters were compared (repeated-measures one-way analysis of variance with post hoc pairwise comparisons). Correlations were tested (linear regression). Results ADCT values in nontransplanted kidney of donors increased from a preexplantation value of (188 ± 9 [standard deviation]) to (202 ± 11) × 10(-5) mm(2)/sec in medulla and from (199 ± 11) to (210 ± 13) × 10(-5) mm(2)/sec in cortex 1 week after donation (P < .004). Medullary, but not cortical, ADCT values stayed increased up to 1 year. ADCT values in allografts in recipients were stable. Compared with values obtained before transplantation in donors, the corticomedullary difference was reduced in allografts (P < .03). Cortical ADCT values correlated with estimated glomerular filtration rate in recipients (R = 0.56, P < .001) but not donors. Cortical ADCT values in the same kidney before transplantation in donors correlated with those in recipients on day 8 after transplantation (R = 0.77, P = .006). FP did not show significant changes. Conclusion DW MR imaging depicts early adaptations in the remaining nontransplanted kidney of donors after nephrectomy. All diffusion parameters remained constant in allograft recipients after transplantation. This method has potential monitoring utility, although assessment of clinical relevance is needed. © RSNA, 2013 Online supplemental material is available for this article.

Liver Remnant Regeneration in Donors After Living Donor Liver Transplantation: Long-Term Follow-Up Using CT and MR Imaging

Purpose: To assess liver remnant volume regeneration and maintenance, and complications in the long-time follow-up of donors after living donor liver transplantation using CT and MRI. Materials and Methods: 47 donors with a mean age of 33.5 years who donated liver tissue for transplantation and who were available for follow-up imaging were included in this retrospective study. Contrast-enhanced CT and MR studies were acquired for routine follow-up. Two observers evaluated pre- and postoperative images regarding anatomy and pathological findings. Volumes were manually measured on contrast-enhanced images in the portal venous phase, and potential postoperative complications were documented. Pre- and postoperative liver volumes were compared for evaluating liver remnant regeneration. Results: 47 preoperative and 89 follow-up studies covered a period of 22.4 months (range: 1 - 84). After right liver lobe (RLL) donation, the mean liver remnant volume was 522.0 ml (± 144.0; 36.1 %; n = 18), after left lateral section (LLS) donation 1,121.7 ml (± 212.8; 79.9 %; n = 24), and after left liver lobe (LLL) donation 1,181.5 ml (± 279.5; 72.0 %; n = 5). Twelve months after donation, the liver remnant volume were 87.3 % (RLL; ± 11.8; n = 11), 95.0 % (LS; ± 11.6; n = 18), and 80.1 % (LLL; ± 2.0; n = 2 LLL) of the preoperative total liver volume. Rapid initial regeneration and maintenance at 80 % of the preoperative liver volume were observed over the total follow-up period. Minor postoperative complications were found early in 4 patients. No severe or late complications or mortality occurred. Conclusion: Rapid regeneration of liver remnant volumes in all donors and volume maintenance over the long-term follow-up period of up to 84 months without severe or late complications are important observations for assessing the safety of LDLT donors. Key Points: Liver remnant volumes of LDLT donors rapidly regenerated after donation and volumes were maintained over the long-term follow-up period of up to 84 months without severe or late complications.

Extended duration of torsional loading reduced the survival of the NP cells of the intervertebral disc

Introduction Previous studies on the influence of torsion and combined torsion-compression loading revealed a positive effect on the cell viability when a repetitive short-term torsion was applied at a physiological magnitude to intervertebral disc organ culture.1 However, after an extended period (8 hours) of combined torsion-compression loading, substantial cell death was detected in the nucleus pulposus (NP).2 In this follow-up study, we aimed to investigate the relationship, if any, between the duration of torsion applied to the intervertebral disc (IVD) and the level of NP cell viability. Materials and Methods Bovine caudal discs were harvested and cultured in a custom-built multiaxis dynamic loading bioreactor.2 Torsion (± 2 degrees) was applied to the samples at a frequency of 0.2 Hz. Torsion was applied for durations of 0, 1, 4, and 8 h/d, repeated over 7 days. After the last day of loading, disc tissue was dissected for analysis of cell viability and gene expression. Results Disc NP cell viability remained above 85% after torsional loading for 0, 1, or 4 h/d. Viability was statistical significantly reduced to below 70% when torsion was applied for 8 h/d (p = 0.03) (Table 1). The daily duration of torsional loading did not affect the AF cell viability (> 80% for all loading durations). The trend of collagen 2 gene upregulation and matrix metalloproteases 13 downregulation with an increasing duration of torsion was observed in both NP and AF (Fig. 1).Conclusion We have demonstrated that an extended duration of torsion could inhibit the survival of NP cells within the IVD in organ culture. Acknowledgments Funds from the Orthopedic Department of the Insel University Hospital of Bern and a private donation from Prof. Dr. Paul Heini, Spine Surgeon, Sonnenhof Clinic Bern were received to support this work. Disclosure of Interest None declared References References 1 Chan SC, Ferguson SJ, Wuertz K, Gantenbein-Ritter B. Biological response of the intervertebral disc to repetitive short-term cyclic torsion. Spine 2011;36(24):2021–2030 2 Chan SC, Walser J, Käppeli P, Shamsollahi MJ, Ferguson SJ, Gantenbein-Ritter B. Region specific response of intervertebral disc cells to complex dynamic loading: an organ culture study using a dynamic torsion-compression bioreactor. PLoS ONE 2013;8(8):e72489

Efficacy of mechanical postconditioning following warm, global ischaemia depends on circulating fatty acid levels in an isolated, working rat heart model†

OBJECTIVES The number of heart transplantations is limited by donor organ availability. Donation after circulatory determination of death (DCDD) could significantly improve graft availability; however, organs undergo warm ischaemia followed by reperfusion, leading to tissue damage. Laboratory studies suggest that mechanical postconditioning [(MPC); brief, intermittent periods of ischaemia at the onset of reperfusion] can limit reperfusion injury; however, clinical translation has been disappointing. We hypothesized that MPC-induced cardioprotection depends on fatty acid levels at reperfusion. METHODS Experiments were performed with an isolated rat heart model of DCDD. Hearts of male Wistar rats (n = 42) underwent working-mode perfusion for 20 min (baseline), 27 min of global ischaemia and 60 min reperfusion with or without MPC (two cycles of 30 s reperfusion/30 s ischaemia) in the presence or absence of high fat [(HF); 1.2 mM palmitate]. Haemodynamic parameters, necrosis factors and oxygen consumption (O2C) were assessed. Recovery rate was calculated as the value at 60 min reperfusion expressed as a percentage of the mean baseline value. The Kruskal-Wallis test was used to provide an overview of differences between experimental groups, and pairwise comparisons were performed to compare specific time points of interest for parameters with significant overall results. RESULTS Percent recovery of left ventricular (LV) work [developed pressure (DP)-heart rate product] at 60 min reperfusion was higher in hearts reperfused without fat versus with fat (58 ± 8 vs 23 ± 26%, P < 0.01) in the absence of MPC. In the absence of fat, MPC did not affect post-ischaemic haemodynamic recovery. Among the hearts reperfused with HF, two significantly different subgroups emerged according to recovery of LV work: low recovery (LoR) and high recovery (HiR) subgroups. At 60 min reperfusion, recovery was increased with MPC versus no MPC for LV work (79 ± 6 vs 55 ± 7, respectively; P < 0.05) in HiR subgroups and for DP (40 ± 27 vs 4 ± 2%), dP/dtmax (37 ± 24 vs 5 ± 3%) and dP/dtmin (33 ± 21 vs 5 ± 4%; P < 0.01 for all) in LoR subgroups. CONCLUSIONS Effects of MPC depend on energy substrate availability; MPC increased recovery of LV work in the presence, but not in the absence, of HF. Controlled reperfusion may be useful for therapeutic strategies aimed at improving post-ischaemic recovery of cardiac DCDD grafts, and ultimately in increasing donor heart availability.

Nierenersatzverfahren – gestern, heute und morgen

Die Nierenersatztherapie ist eine der erfolgreichsten Geschichten eines künstlichen Organersatzes. Der vorliegende Artikel beschreibt die wichtigsten Schritte in der Evolution zur modernen Therapie mit Peritonealdialyse und Hämodialyse. Aktuelle Fragen im Bereich der Nierenersatztherapie werden diskutiert und zukünftige Entwicklungen aufgezeigt. Dem Patienten stehen heute diverse Therapiemöglichkeiten offen. Allerdings nur, wenn er mindestens ein halbes Jahr vor der Notwendigkeit eines Therapiebeginns die für ihn ideale Therapieform auswählen kann. Verspätete Zuweisungen und die Notwendigkeit eines akuten Dialysebeginns führen nicht nur zu einer erhöhten Mortalität, sondern auch dazu, dass eine präemptive Lebendnierentransplantation verunmöglicht wird. Zudem bleiben diese Patienten in der Regel im Dialysezentrum und können für eine Heimbehandlung, sei es nun in Form einer Peritonealdialyse oder Heimhämodialyse, nicht mehr motiviert werden.

Efficacy of mechanical postconditioning following warm, global ischaemia depends on circulating fatty acid levels in an isolated, working rat heart model

Gebiet: Chirurgie Abstract: OBJECTIVES: – The number of heart transplantations is limited by donor organ availability. Donation after circulatory determination of death (DCDD) could significantly improve graft availability, however, organs undergo warm ischaemia followed by reperfusion, leading to tissue damage. Laboratory studies suggest that mechanical postconditioning [(MPC), brief, intermittent periods of ischaemia at the onset of reperfusion] can limit reperfusion injury, however, clinical translation has been disappointing. We hypothesized that MPC-induced cardioprotection depends on fatty acid levels at reperfusion. – – METHODS: – Experiments were performed with an isolated rat heart model of DCDD. Hearts of male Wistar rats (n = 42) underwent working-mode perfusion for 20 min (baseline), 27 min of global ischaemia and 60 min reperfusion with or without MPC (two cycles of 30 s reperfusion/30 s ischaemia) in the presence or absence of high fat [(HF), 1.2 mM palmitate]. Haemodynamic parameters, necrosis factors and oxygen consumption (O2C) were assessed. Recovery rate was calculated as the value at 60 min reperfusion expressed as a percentage of the mean baseline value. The Kruskal-Wallis test was used to provide an overview of differences between experimental groups, and pairwise comparisons were performed to compare specific time points of interest for parameters with significant overall results. – – RESULTS: – Percent recovery of left ventricular (LV) work [developed pressure (DP)-heart rate product] at 60 min reperfusion was higher in hearts reperfused without fat versus with fat (58 ± 8 vs 23 ± 26%, P < 0.01) in the absence of MPC. In the absence of fat, MPC did not affect post-ischaemic haemodynamic recovery. Among the hearts reperfused with HF, two significantly different subgroups emerged according to recovery of LV work: low recovery (LoR) and high recovery (HiR) subgroups. At 60 min reperfusion, recovery was increased with MPC versus no MPC for LV work (79 ± 6 vs 55 ± 7, respectively, P < 0.05) in HiR subgroups and for DP (40 ± 27 vs 4 ± 2%), dP/dtmax (37 ± 24 vs 5 ± 3%) and dP/dtmin (33 ± 21 vs 5 ± 4%, P < 0.01 for all) in LoR subgroups. – – CONCLUSIONS: – Effects of MPC depend on energy substrate availability, MPC increased recovery of LV work in the presence, but not in the absence, of HF. Controlled reperfusion may be useful for therapeutic strategies aimed at improving post-ischaemic recovery of cardiac DCDD grafts, and ultimately in increasing donor heart availability.

Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting plasma oxytocin and testosterone.

Gamma-hydroxybutyrate (GHB) is a GHB-/GABAB-receptor agonist. Reports from GHB abusers indicate euphoric, prosocial, and empathogenic effects of the drug. We measured the effects of GHB on mood, prosocial behavior, social and non-social cognition and assessed potential underlying neuroendocrine mechanisms. GHB (20mg/kg) was tested in 16 healthy males, using a randomized, placebo-controlled, cross-over design. Subjective effects on mood were assessed by visual-analogue-scales and the GHB-Specific-Questionnaire. Prosocial behavior was examined by the Charity Donation Task, the Social Value Orientation test, and the Reciprocity Task. Reaction time, memory, empathy, and theory-of-mind were also tested. Blood plasma levels of GHB, oxytocin, testosterone, progesterone, dehydroepiandrosterone (DHEA), cortisol, aldosterone, and adrenocorticotropic-hormone (ACTH) were determined. GHB showed stimulating and sedating effects, and elicited euphoria, disinhibition, and enhanced vitality. In participants with low prosociality, the drug increased donations and prosocial money distributions. In contrast, social cognitive abilities such as emotion recognition, empathy, and theory-of-mind, and basal cognitive functions were not affected. GHB increased plasma progesterone, while oxytocin and testosterone, cortisol, aldosterone, DHEA, and ACTH levels remained unaffected. GHB has mood-enhancing and prosocial effects without affecting social hormones such as oxytocin and testosterone. These data suggest a potential involvement of GHB-/GABAB-receptors and progesterone in mood and prosocial behavior.

Significant lethality following liver resection in A20 heterozygous knockout mice uncovers a key role for A20 in liver regeneration

Hepatic expression of A20, including in hepatocytes, increases in response to injury, inflammation and resection. This increase likely serves a hepatoprotective purpose. The characteristic unfettered liver inflammation and necrosis in A20 knockout mice established physiologic upregulation of A20 as integral to the anti-inflammatory and anti-apoptotic armamentarium of hepatocytes. However, the implication of physiologic upregulation of A20 in modulating hepatocytes' proliferative responses following liver resection remains controversial. To resolve the impact of A20 on hepatocyte proliferation and the liver's regenerative capacity, we examined whether decreased A20 expression, as in A20 heterozygous knockout mice, affects outcome following two-third partial hepatectomy. A20 heterozygous mice do not demonstrate a striking liver phenotype, indicating that their A20 expression levels are still sufficient to contain inflammation and cell death at baseline. However, usually benign partial hepatectomy provoked a staggering lethality (>40%) in these mice, uncovering an unsuspected phenotype. Heightened lethality in A20 heterozygous mice following partial hepatectomy resulted from impaired hepatocyte proliferation due to heightened levels of cyclin-dependent kinase inhibitor, p21, and deficient upregulation of cyclins D1, E and A, in the context of worsened liver steatosis. A20 heterozygous knockout minimally affected baseline liver transcriptome, mostly circadian rhythm genes. Nevertheless, this caused differential expression of >1000 genes post hepatectomy, hindering lipid metabolism, bile acid biosynthesis, insulin signaling and cell cycle, all critical cellular processes for liver regeneration. These results demonstrate that mere reduction of A20 levels causes worse outcome post hepatectomy than full knockout of bona fide liver pro-regenerative players such as IL-6, clearly ascertaining A20's primordial role in enabling liver regeneration. Clinical implications of these data are of utmost importance as they caution safety of extensive hepatectomy for donation or tumor in carriers of A20/TNFAIP3 single nucleotide polymorphisms alleles that decrease A20 expression or function, and prompt the development of A20-based liver pro-regenerative therapies.

Ser, hacer y decir

El artículo cuestiona la interacción y la comunicación en tanto fenómenos intencionales desde una perspectiva ontológica. Recorre críticamente el esencialismo que supone la teoría de la sustancia y las tesis básicas de las vertientes analíticas antimetafísicas, con el fin de descubrir la relación entre la palabra en cuanto signo y la palabra entendida como donación. Así, acentúa el carácter constituible de la persona y la función plenificadora de la coexistencia en su concreción pragmático-lingüística.

Del discurso poblador a la praxis latifundista: la distribución de la tierra pública en la Patagonia

Una de las tareas fundamentales cumplidas por el Estado nacional consolidado a partir de 1880 fue la de continuar con las prácticas de los anteriores gobiernos de aplicar una política sistemática de transferencia de tierras públicas a manos privadas a través de la donación, la venta o la recompensa por servicios prestados a la Nación. La concentración de la tierra en pocas manos y la expansión de las grandes propiedades fueron las consecuencias más conocidas de estas políticas, incrementadas a partir del avance de las fronteras internas por las campañas militares de ocupación de los espacios indígenas. En este trabajo se estudian las características del proceso de acumulación terrateniente en la Patagonia, mediante compras de tierras al Estado durante el proceso de expansión de las fronteras que desalojó a la sociedad preexistente y consolidó la propiedad terrateniente sin generar un proceso masivo de aparición de sectores de medianos y pequeños propietarios rurales, ni núcleos de población efectivos en las nuevas fronteras, tal y como el discurso oficial parecía sugerir.

Del discurso poblador a la praxis latifundista: la distribución de la tierra pública en la Patagonia

Una de las tareas fundamentales cumplidas por el Estado nacional consolidado a partir de 1880 fue la de continuar con las prácticas de los anteriores gobiernos de aplicar una política sistemática de transferencia de tierras públicas a manos privadas a través de la donación, la venta o la recompensa por servicios prestados a la Nación. La concentración de la tierra en pocas manos y la expansión de las grandes propiedades fueron las consecuencias más conocidas de estas políticas, incrementadas a partir del avance de las fronteras internas por las campañas militares de ocupación de los espacios indígenas. En este trabajo se estudian las características del proceso de acumulación terrateniente en la Patagonia, mediante compras de tierras al Estado durante el proceso de expansión de las fronteras que desalojó a la sociedad preexistente y consolidó la propiedad terrateniente sin generar un proceso masivo de aparición de sectores de medianos y pequeños propietarios rurales, ni núcleos de población efectivos en las nuevas fronteras, tal y como el discurso oficial parecía sugerir.

Del discurso poblador a la praxis latifundista: la distribución de la tierra pública en la Patagonia

Una de las tareas fundamentales cumplidas por el Estado nacional consolidado a partir de 1880 fue la de continuar con las prácticas de los anteriores gobiernos de aplicar una política sistemática de transferencia de tierras públicas a manos privadas a través de la donación, la venta o la recompensa por servicios prestados a la Nación. La concentración de la tierra en pocas manos y la expansión de las grandes propiedades fueron las consecuencias más conocidas de estas políticas, incrementadas a partir del avance de las fronteras internas por las campañas militares de ocupación de los espacios indígenas. En este trabajo se estudian las características del proceso de acumulación terrateniente en la Patagonia, mediante compras de tierras al Estado durante el proceso de expansión de las fronteras que desalojó a la sociedad preexistente y consolidó la propiedad terrateniente sin generar un proceso masivo de aparición de sectores de medianos y pequeños propietarios rurales, ni núcleos de población efectivos en las nuevas fronteras, tal y como el discurso oficial parecía sugerir.

Modelo de diseño orientado a marcos para sistemas basados en el conocimiento

El objetivo de esta Tesis es crear un Modelo de Diseño Orientado a Marcos que, intermedio entre el Mundo Externo y el Modelo Interno del Mundo que supone el sistema ímplementado, disminuya la pérdida de conocimiento que se produce al formalizar la realidad en Bases de Conocimientos. El modelo disminuye la pérdida de conocimiento al formalizar Bases de Conocimiento, acercando el formalismo de Marcos al Mundo Externo, porque: 1. Crea una base teórica que uniformiza el concepto de Marco en el plano de la Formalización, estableciendo un conjunto de restricciones sintácticas y semánticas que impedirán, al Ingeniero del Conocimiento (IC) cuando formaliza, definir elementos no permitidos o el uso indebido de ellos. 2. Se incrementa la expresividad del formalismo al asociar a cada una de las propiedades de un marco clase un parámetro adicional que simboliza la representatividad de la propiedad en el concepto. Este parámetro, y las técnicas de inferencia que trabajan con él, permitirán al IC introducir en el Modelo Formalizado conocimiento que antes no introducía al construir la base de conocimientos y que, sin embargo, sí existía en la realidad. 3. Se propone una técnica de equiparación que trabaja con el conocimiento incierto presente en el dominio. Esta técnica de equiparación, utiliza la representatividad de las propiedades en los marcos clase y el grado de certeza de las propiedades de las entidades para calcular el valor de equiparación y, así, determinar en qué medida los marcos clase seleccionados son consistentes con la descripción de la situación actual dada por una entidad. 4. Proporciona nuevas técnicas de inferencia basadas en la transferencia de propiedades y modifica las ya existentes. Las transferencias de propiedades realizadas sobre relaciones "ad hoc" definidas por el IC al construir el sistema, es una nueva técnica de inferencia independiente y complementaria a la transferencia de propiedades llamada tradicionalmente Herencia (cesión de propiedades entre padres e hijos). A esta nueva técnica, se le ha llamado Donación, es decir, cesión de propiedades entre marcos sin parentesco. Como aportación práctica, se ha construido un entorno de construcción de Sistemas Basados en el Conocimiento formalizados en Marcos, donde se han introducido todos los nuevos conceptos del Modelo Teórico de la Tesis. Se trata de una cierta anidación. Es decir, son marcos que permiten formalizar cualquier SBC en marcos. El entorno permitirá al IC formalizar bases de conocimientos automáticamente y éste podrá validar el conocimiento del dominio en la fase de formalización en lugar de tener que esperar a que la BC esté implementada. Todo ello lleva a describir el Modelo de Diseño Orientado a Marcos como un puente que aproxima y comunica el Mundo Externo con el Modelo Interno asociado a la realidad e implementado en una computadora, disminuyendo así las diversas pérdidas de conocimiento que si bien no ocurren simultáneamente al construir Sistemas Basados en el Conocimiento, sí coexisten en él.---ABSTRACT---The goal of this thesis is to créate a Frame-Orlented Deslgn Model that, bridging the Outside World and the implemented system's Internal Model of the World, reduces the amount of knowledge lost when reality is formalized in Knowledge Bases (KB). The model diminishes the loss of knowledge when formalizing a KB and brings the Frame-formalized Model closer to the Outside World because: 1. It creates a theory that standardizes the concept of trame at the formalization level to establish a set of syntactic and semantic constraints that will prevent the Knowledge Engineer (KE) from defining forbidden elements or their undue use in the formalization process. 2. The formalism's expressiveness is increased by associating an additional parameter to each of the properties of a class frame to symbolize the representativeness of the concept property. This parameter and the related inference techniques will allow the KE to enter knowledge into the Formalized Model that actually existed but that was not used previously when building the KB. 3. The proposed technique involves matching and works with uncertain knowledge present in the domain. This matching technique takes the representativeness of the properties in the class frame and the degree of certainty of the properties of the entities to calcúlate the matching valué and thus determine to what extent the class frames selected are consistent with the description of the present situation given by an entity. 4. It offers new inference techniques based on property transfer and alters existing ones. Property transfer on ad hoc relations defined by the KE when building a system is a new inference technique independent of and complementary to property transfer traditionally termed Inheritance (transfer of properties between parents and children). This new technique has been callad Donation (transfer of properties between trames without relationships). 5. It improves control of the procedural knowledge defined in the trames by introducing OO concepta. A frame-formalized KBS building environment has been constructed, incorporating all the new concepts of the theoretical model set out in the thesis. There is some embedding, that is, they are trames that provide for any KBS to be formalizad in trames. The environment will enable the KE to formaliza KB automatically, and he will be able to valídate the domain knowledge in the formalization stage instead of havíng to wait until the KB has been implemented. This is a description of the Frame-oriented Design Model, a bridge that brings closer and communicates the Outside World with the Interna! Model associated to reality and implemented on a computar, thus reducing the different losses in knowledge that, though they do not occur simultaneosly when building a Knowledge-based System, coexist within it.

Technology transfer of renewable energy for rural development: historical evolution and lessons of experience from the model WWP

Technology transfer (TT) in the area of renewable energy (RE) throughout history has been an important tool for rural development (RD). Initially, the TT has been conceptualized as the purchase or donation of machinery from first world countries - without any consideration of staff training and contextual conditions for the adaptation of technology to the needs of the country. Various researches have revealed the existence of different approaches to planning the TT of RE, demonstrating the high complexity of projects from the social and contextual dimension. This paper addresses the conceptual evolution of the TT of RE for RD, examining its different periods considered for three criteria: historical events occurred, the role of stakeholders and changing objectives for the TT of RE for RD. For the conceptual analysis of changes the model Working With People (WWP) is used for planning and project management of high social complexity in RD. The analysis defines the existence of four historical periods in the TT of RE and synthesizes the lessons of experience from the three dimensions (ethical-social, technical-entrepreneurial, and political-contextual) of the WWP model.