Virtopsy: postmortem imaging of the human heart in situ using MSCT and MRI.

The rapid further development of computed tomography (CT) and magnetic resonance imaging (MRI) induced the idea to use these techniques for postmortem documentation of forensic findings. Until now, only a few institutes of forensic medicine have acquired experience in postmortem cross-sectional imaging. Protocols, image interpretation and visualization have to be adapted to the postmortem conditions. Especially, postmortem alterations, such as putrefaction and livores, different temperature of the corpse and the loss of the circulation are a challenge for the imaging process and interpretation. Advantages of postmortem imaging are the higher exposure and resolution available in CT when there is no concern for biologic effects of ionizing radiation, and the lack of cardiac motion artifacts during scanning. CT and MRI may become useful tools for postmortem documentation in forensic medicine. In Bern, 80 human corpses underwent postmortem imaging by CT and MRI prior to traditional autopsy until the month of August 2003. Here, we describe the imaging appearance of postmortem alterations--internal livores, putrefaction, postmortem clotting--and distinguish them from the forensic findings of the heart, such as calcification, endocarditis, myocardial infarction, myocardial scarring, injury and other morphological alterations.

Can stable isotope analysis and tooth histology assist in detecting stillbirth? An approach using neonatal remains from the Roman settlement Studen Petinesca

Infant burials in Roman settlements are a common observation. Even though ancient authors provide information many questions remain uncertain. For instance, the burial ritual for stillbirth and infanticide neonates is not specifically mentioned. This study therefore aimed to investigate the application of stable nitrogen (δ15N) and carbon (δ13C) isotopes from neonatal bone collagen in differentiating between a breastfeeding signal and stillbirth or a short survival of less than ten days. For this purpose collagen of 11 human and 14 non-human bones from the Roman settlement Petinesca (1st - 3rd century AD, Switzerland) was extracted and analysed for δ15N and δ13C. Tooth histology was performed for the central incisor and canine of the right mandible in order to investigate the presence of a neonatal line. According to the length of the long bones the age varied between 8.5 lunar months to 2 months ex utero. The stable isotope results provided a breastfeeding signal for all except one individual where the breastfeeding signal was absent. The tooth histological analysis of this individual exhibited no neonatal line. It is concluded that stable isotope analysis could indicate stillbirth or a short survival after birth. The tooth histology confirmed the stable isotope results. Furthermore, this might indicate that the burial ritual did not differentiate between stillbirth and neonates, who died within the time span stated by ancient authors of up to 40 days of age or the appearance of teeth. However, for further justifications additional research is going to be conducted.

Rapamycin impairs endothelial cell function in human internal thoracic arteries.

BACKGROUND Definitive fate of the coronary endothelium after implantation of a drug-eluting stent remains unclear, but evidence has accumulated that treatment with rapamycin-eluting stents impairs endothelial function in human coronary arteries. The aim of our study was to demonstrate this phenomenon on functional, morphological and biochemical level in human internal thoracic arteries (ITA) serving as coronary artery model. METHODS After exposure to rapamycin for 20 h, functional activity of ITA rings was investigated using the organ bath technique. Morphological analysis was performed by scanning electron microscopy and evaluated by two independent observers in blinded fashion. For measurement of endothelial nitric oxide synthase (eNOS) release, mammalian target of rapamycin (mTOR) and protein kinase B (PKB) (Akt) activation, Western blotting on human mammary epithelial cells-1 and on ITA homogenates was performed. RESULTS Comparison of the acetylcholine-induced relaxation revealed a significant concentration-dependent decrease to 66 ± 7 % and 36 ± 7 % (mean ± SEM) after 20-h incubation with 1 and 10 μM rapamycin. Electron microscopic evaluation of the endothelial layer showed no differences between controls and samples exposed to 10 μM rapamycin. Western blots after 20-h incubation with rapamycin (10 nM-1 μM) revealed a significant and concentration-dependent reduction of p (Ser 1177)-eNOS (down to 38 ± 8 %) in human mammary epithelial cells (Hmec)-1. Furthermore, 1 μM rapamycin significantly reduced activation of p (Ser2481)-mTOR (58 ± 11 %), p (Ser2481)-mTOR (23 ± 4 %) and p (Ser473)-Akt (38 ± 6 %) in ITA homogenates leaving Akt protein levels unchanged. CONCLUSIONS The present data suggests that 20-h exposure of ITA rings to rapamycin reduces endothelium-mediated relaxation through down-regulation of Akt-phosphorylation via the mTOR signalling axis within the ITA tissue without injuring the endothelial cell layer.

Effect of boundary conditions on yield properties of human femoral trabecular bone

Trabecular bone plays an important mechanical role in bone fractures and implant stability. Homogenized nonlinear finite element (FE) analysis of whole bones can deliver improved fracture risk and implant loosening assessment. Such simulations require the knowledge of mechanical properties such as an appropriate yield behavior and criterion for trabecular bone. Identification of a complete yield surface is extremely difficult experimentally but can be achieved in silico by using micro-FE analysis on cubical trabecular volume elements. Nevertheless, the influence of the boundary conditions (BCs), which are applied to such volume elements, on the obtained yield properties remains unknown. Therefore, this study compared homogenized yield properties along 17 load cases of 126 human femoral trabecular cubic specimens computed with classical kinematic uniform BCs (KUBCs) and a new set of mixed uniform BCs, namely periodicity-compatible mixed uniform BCs (PMUBCs). In stress space, PMUBCs lead to 7–72 % lower yield stresses compared to KUBCs. The yield surfaces obtained with both KUBCs and PMUBCs demonstrate a pressure-sensitive ellipsoidal shape. A volume fraction and fabric-based quadric yield function successfully fitted the yield surfaces of both BCs with a correlation coefficient R2≥0.93. As expected, yield strains show only a weak dependency on bone volume fraction and fabric. The role of the two BCs in homogenized FE analysis of whole bones will need to be investigated and validated with experimental results at the whole bone level in future studies.

Mechanisms of Ad-p53 induced apoptosis in human malignant glioma

Malignant brain tumors are one of the most challenging cancers affecting society today. In a recent survey, an estimated 17,000 annual cases were recorded with a staggering total of 13,300 deaths. A unique degree of heterogeneity typifies glial tumors and presents a challenge for solitary anti-neoplastic treatments. Tumors subsist as heterogeneous masses that progress through dysplasia to astrocytomas, mixed glioma and glioblastoma multiforme. Although traditional therapeutic approaches have provided increments of success, the median survival time remains 12 months. The urgency to improve upon current clinical protocols has encouraged alternative experimental strategies such as p53 adenoviral gene therapy (Ad-p53). This study addresses the efficacy of Ad-p53 for the treatment of glioma. Our model presents a tumor response that is unique among human cancers. Ad-p53 effectively induces apoptosis in mutant p53 expressing cells yet fails to do so in those with wildtype p53. In order to adopt Adp53 as a standard anti-cancer modality, we characterized the role of the tumor suppressor gene p53 in mediating apoptosis. We demonstrate that altering cellular p53 status through the introduction of a dominant negative mutant p53 (175H, 248W, 273H) sensitized cells to Ad-p53. We discovered that wild-type p53 expressing glioma cells retain the apoptotic machinery necessary to accomplish cell death, but have developed mechanisms that interfere with p53 signaling. Earlier studies have not addressed the mechanisms of Ad-p53 apoptosis nor the resistance exhibited by wild-type p53 glioma. To explain the divergent phenotypes, we identified apoptotic pathways activated and effectors of the response. We illustrated that modulation of the death receptor Fas/APO-1 is a principal means of Ad-p53 signaling that is impaired in wild-type p53 glioma. Moreover, the apoptotic response was found to be a multi-faceted process that engaged several caspases, most notably caspases -1, -3 and -8. Lastly, we assessed the ability of anti-apoptotic molecules Bcl-2 and CrmA to inhibit Ad-p53 apoptosis. These studies revealed that Ad-p53 is a powerful tool for inducing apoptosis that can be delayed but not inhibited by anti-apoptotic means. This work is critical for understanding the development of glioma and the phenotypic and genotypic alterations that account for tumor resistance. ^

Pharmacogenetics of the human glutathione S-transferase P1 gene in the metabolism and therapeutic efficacy of cis-diamminedichloroplatinum

The human GSTP1 gene has been shown, conclusively, to be polymorphic. The three main GSTP1 alleles, GSTP1*A, GSTP1*B, and GSTP1*C, encode proteins which differ in the 3-dimensional structure of their active sites and in their function in phase II metabolism of carcinogens, mutagens, and anticancer agents. Although, it is well established that GSTP1 is over expressed in many human tumors and that the levels of GSTP1 expression correlate directly with tumor resistance to chemotherapy and inversely with patient survival, the significance of the polymorphic GSTP1 gene locus on tumor response to chemotherapy remains unclear. The goal of this project was to define the role and significance of the polymorphic GSTP1 gene locus in GSTP1-based tumor drug resistance and as a determinant of patient response to chemotherapy. The hypothesis to be tested was that the polymorphic GSTP1 gene locus will confer to tumors a differential ability to metabolize cisplatin resulting in a GSTP1 genotype-based sensitivity to cisplatin. The study examined: (a) whether the different GSTP 1 alleles confer different levels of cellular protection against cisplatin-induced cytotoxicity, (b) whether the allelic GSTP1 proteins metabolize cisplatin with different efficiencies, and (c) whether the GSTP1 genotype is a determinant of tumor response to cisplatin therapy. The results demonstrate that the GSTP1 alleles differentially protect tumors against cisplatin-induced apoptosis and clonogenic cell kill in the rank order: GSTP1*C > GSTP1*B > GSTP1*A. The same rank order was observed for the kinetics of GSTP1-catalyzed cisplatin metabolism, both in cell-free and cellular systems, to the rate-limiting monoglutathionyl-platinum metabolite, which was characterized, for the first time, by mass spectral analysis. Finally, this study demonstrates that both GSTP1 genotype and the level of GSTP1 expression significantly contribute to tumor sensitivity to cisplatin treatment. Overall, the results of this project show that the polymorphic GSTP1 gene locus plays a significant role in tumor sensitivity to cisplatin treatment. Furthermore, these studies have contributed to the overall understanding of the significance of the polymorphic GSTP1 gene locus in tumor resistance to cancer chemotherapy and have provided the basis for further investigations into how this can be utilized to optimize and individualize cancer chemotherapy for cancer patients. ^

Perpetual Conflict or Compromise? The Cost of Domestic Legitimacy in the Realm of Women's Human Rights: A Case Study on the Right to an Abortion

With its turbulent and volatile legal evolution, the right to an abortion in the United States still remains a highly contested issue and has developed into one of the most divisive topics within modern legal discourse. By deconstructing the political underpinnings and legal rationale of the right to an abortion through a systematic case law analysis, I will demonstrate that this right has been incrementally destabilized. This instability embedded in abortion jurisprudence has been primarily produced by a combination of textual ambiguity in the case law and judicial ambivalence regarding this complex area of law. In addition, I argue that the use of the largely discredited substantive due process doctrine to ground this contentious right has also contributed to the lack of legal stability. I assert that when these elements culminate in the realm of reproductive privacy the right to terminate a pregnancy becomes increasingly unstable and contested.

The transcription factor nuclear factor kappa B (NFkappaB) maintains TRAIL resistance in human pancreatic cancer cells

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) is a member of the TNF family of cytokines that induces apoptosis in a variety of tumor cells while sparing normal cells. However, many human cancer cell lines display resistance to TRAIL-induced apoptosis and the mechanisms contributing to resistance remain controversial. Previous studies have demonstrated that the dimeric transcription factor Nuclear Factor kappa B (NFκB) is constitutively active in a majority of human pancreatic cancer cell lines and primary tumors, and although its role in tumor progression remains unclear it has been suggested that NFκB contributes to TRAIL resistance. Based on this, I examined the effects of NFκB inhibitors on TRAIL sensitivity in a panel of nine pancreatic cancer cell lines. I show here that inhibitors of NFκB, including two inhibitors of the proteasome (bortezomib (Velcade™, PS-341) and NPI-0052), a small molecule inhibitor of IKK (PS1145), and a novel synthetic diterpene NIK inhibitor (NPI-1342) reverse TRAIL resistance in pancreatic cancer cell lines. Further analysis revealed that the expression of the anti-apoptosic proteins BclXL and XIAP was significantly decreased following exposure to these inhibitors alone and in combination with TRAIL. Additionally, treatment with NPI0052 and TRAIL significantly reduced tumor burden relative to the control tumors in an L3.6pl orthotopic pancreatic xenograft model. This was associated with a significant decrease in proliferation and an increase in caspase 3 and 8 cleavage. Combination therapy employing PS1145 or NPI-1342 in combination with TRAIL also resulted in a significant reduction in tumor burden compared to either agent alone in a Panc1 orthotopic xenograft model. My studies show that combination therapy with inhibitors of NFκB alone and TRAIL is effective in pre-clinical models of pancreatic cancer and suggests that the approach should be evaluated in patients. ^

CHARACTERIZATION OF TCL1-Tg:P53-/- MICE THAT RESEMBLE HUMAN CHRONIC LYMPHOCYTIC LEUKEMIA WITH 17P-DELETION

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the United Statesand Europe. CLL patients with deletion of chromosome 17p, where the tumor suppressor p53 gene is located, often develop a more aggressive disease with poor clinical outcomes. However, the underlying mechanism remains unclear. In order to understand the underneath mechanism in vivo, I have recently generated mice with Eu-TCL1-Tg:p53-/- genotype and showed that these mice develop aggressive leukemia that resembles human CLL with 17p deletion. The Eu-TCL1-Tg:p53-/- mice developed CLL disease at 3-4 months, significantly earlier than the parental Eu-TCL1-Tg mice that developed CLL disease at 8-12 months. Flow cytometry analysis showed that the CD5+/ IgM+ cell population appeared in the peritoneal cavity, bone marrow, and the spleens of Eu-TCL1-Tg:p53-/- mice significantly earlier than that of the parental Eu-TCL1-Tg mice. Massive infiltration and accumulation of leukemia cells were found in the spleen and peritoneal cavity. In vitro study showed that the leukemia cells isolated from the Eu-TCL1-Tg:p53-/- mice were more resistant to fludarabine treatment than the leukemia cells isolated from spleens of Eu-TCL1-Tg mice. Interestingly, TUNEL assay revealed that there was higher apoptotic cell death found in the Eu-TCL1-Tg spleen tissue compared to the spleens of the Eu-TCL1-Tg:p53-/- mice, suggesting that the loss of p53 compromises the apoptotic process in vivo, and this might in part explain the drug resistant phenotype of CLL cells with 17p-deletion. In the present study, we further demonstrated that the p53 deficiency in the TCL1 transgenic mice resulted in significant down-regulation of microRNAs miR-15a and miR16-1, associated with a substantial up-regulation of Mcl-1, suggesting that the p53-miR15a/16-Mcl-1 axis may play an important role in CLL pathogenesis. Interestingly, we also found that loss of p53 resulted in a significant decrease in expression of the miR-30 family especially miR-30d in leukemia lymphocytes from the Eu-TCL1-Tg:p53-/- mice. Such down-regulation of those microRNAs and up-regulation of Mcl-1 were also found in primary leukemia cells from CLL patients with 17p deletion. To further exam the biological significance of decrease in the miR-30 family in CLL, we investigated the potential involvement of EZH2 (enhancer of zeste homolog 2), a component of the Polycomb repressive complex known to be a downstream target of miR-30d and plays a role in disease progression in several solid cancers. RT-PCR and western blot analyses showed that both EZH2 mRNA transcript and protein levels were significantly increased in the lymphocytes of Eu-TCL1-Tg:p53-/- mice relative to Eu-TCL1-Tg mice. Exposure of leukemia cells isolated from Eu-TCL1-Tg:p53-/- mice to the EZH2 inhibitor 3-deazaneplanocin (DZNep) led to induction of apoptosis, suggesting EZH2 may play a role in promoting CLL cell survival and this may contribute to the aggressive phenotype of CLL with loss of p53. Our study has created a novel CLL mouse model, and suggests that the p53/miR15a/16-Mcl-1 axis & p53/miR30d-EZH2 may contribute to the aggressive phenotype and drug resistance in CLL cells with loss of p53.

Structure-function analysis of human Integrator subunit-4

Structure-function analysis of human Integrator subunit 4 Anupama Sataluri Advisor: Eric. J. Wagner, Ph.D. Uridine-rich small nuclear RNAs (U snRNA) are RNA Polymerase-II (RNAPII) transcripts that are ubiquitously expressed and are known to be essential for gene expression. snRNAs play a key role in mRNA splicing and in histone mRNA expression. Inaccurate snRNA biosynthesis can lead to diseases related to defective splicing and histone mRNA expression. Although the 3′ end formation mechanism and processing machinery of other RNAPII transcripts such as mRNA has been well studied, the mechanism of snRNA 3′ end processing has remained a mystery until the recent discovery of the machinery that mediates this process. In 2005, a complex of 14 subunits (the Integrator complex) associated with RNA Polymerase-II was discovered. The 14subunits were annotated Integrator 1-14 based on their size. The subunits of this complex together were found to facilitate 3′ end processing of snRNA. Identification of the Integrator complex propelled research in the direction of understanding the events of snRNA 3’end processing. Recent studies from our lab confirmed that Integrator subunit (IntS) 9 and 11 together perform the endonucleolytic cleavage of the nascent snRNA 3′ end to generate mature snRNA. However, the role of other members of the Integrator complex remains elusive. Current research in our lab is focused on deciphering the role of each subunit within the Integrator complex This work specifically focuses on elucidating the role of human Integrator subunit 4 (IntS4) and understanding how it facilitates the overall function of the complex. IntS4 has structural similarity with a protein called “Symplekin”, which is part of the mRNA 3’end processing machinery. Symplekin has been thoroughly researched in recent years and structure-function correlation studies in the context of mRNA 3’end processing have reported a scaffold function for Symplekin due to the presence of HEAT repeat motifs in its N-terminus. Based upon the structural similarity between IntS4 and Symplekin, we hypothesized that Integrator subunit 4 may be behaving as a Symplekin-like scaffold molecule that facilitates the interaction between other members of the Integrator Complex. To answer this question, the two important goals of this study were to: 1) identify the region of IntS4, which is important for snRNA 3′ end processing and 2) determine binding partners of IntS4 which promote its function as a scaffold. IntS4 structurally consists of a highly conserved N-terminus with 8 HEAT repeats, followed by a nonconserved C- terminus. A series of siRNA resistant N and C-terminus deletion constructs as well as specific point mutants within its N-terminal HEAT repeats were generated for human IntS4 and, utilizing a snRNA transcriptional readthrough GFP-reporter assay, we tested their ability to rescue misprocessing. This assay revealed a possible scaffold like property of IntS4. To probe IntS4 for interaction partners, we performed co-immunoprecipitation on nuclear extracts of IntS4 expressing stable cell lines and identified IntS3 and IntS5 among other Integrator subunits to be binding partners which facilitate the scaffold like function of hIntS4. These findings have established a critical role for IntS4 in snRNA 3′ end processing, identified that both its N and C termini are essential for its function, and mapped putative interaction domains with other Integrator subunits.

Human-robot interaction for telemanipulation in large workspaces

Independientemente de la existencia de técnicas altamente sofisticadas y capacidades de cómputo cada vez más elevadas, los problemas asociados a los robots que interactúan con entornos no estructurados siguen siendo un desafío abierto en robótica. A pesar de los grandes avances de los sistemas robóticos autónomos, hay algunas situaciones en las que una persona en el bucle sigue siendo necesaria. Ejemplos de esto son, tareas en entornos de fusión nuclear, misiones espaciales, operaciones submarinas y cirugía robótica. Esta necesidad se debe a que las tecnologías actuales no pueden realizar de forma fiable y autónoma cualquier tipo de tarea. Esta tesis presenta métodos para la teleoperación de robots abarcando distintos niveles de abstracción que van desde el control supervisado, en el que un operador da instrucciones de alto nivel en la forma de acciones, hasta el control bilateral, donde los comandos toman la forma de señales de control de bajo nivel. En primer lugar, se presenta un enfoque para llevar a cabo la teleoperación supervisada de robots humanoides. El objetivo es controlar robots terrestres capaces de ejecutar tareas complejas en entornos de búsqueda y rescate utilizando enlaces de comunicación limitados. Esta propuesta incorpora comportamientos autónomos que el operador puede utilizar para realizar tareas de navegación y manipulación mientras se permite cubrir grandes áreas de entornos remotos diseñados para el acceso de personas. Los resultados experimentales demuestran la eficacia de los métodos propuestos. En segundo lugar, se investiga el uso de dispositivos rentables para telemanipulación guiada. Se presenta una aplicación que involucra un robot humanoide bimanual y un traje de captura de movimiento basado en sensores inerciales. En esta aplicación, se estudian las capacidades de adaptación introducidas por el factor humano y cómo estas pueden compensar la falta de sistemas robóticos de alta precisión. Este trabajo es el resultado de una colaboración entre investigadores del Biorobotics Laboratory de la Universidad de Harvard y el Centro de Automática y Robótica UPM-CSIC. En tercer lugar, se presenta un nuevo controlador háptico que combina velocidad y posición. Este controlador bilateral híbrido hace frente a los problemas relacionados con la teleoperación de un robot esclavo con un gran espacio de trabajo usando un dispositivo háptico pequeño como maestro. Se pueden cubrir amplias áreas de trabajo al cambiar automáticamente entre los modos de control de velocidad y posición. Este controlador háptico es ideal para sistemas maestro-esclavo con cinemáticas diferentes, donde los comandos se transmiten en el espacio de la tarea del entorno remoto. El método es validado para realizar telemanipulación hábil de objetos con un robot industrial. Por último, se introducen dos contribuciones en el campo de la manipulación robótica. Por un lado, se presenta un nuevo algoritmo de cinemática inversa, llamado método iterativo de desacoplamiento cinemático. Este método se ha desarrollado para resolver el problema cinemático inverso de un tipo de robot de seis grados de libertad donde una solución cerrada no está disponible. La eficacia del método se compara con métodos numéricos convencionales. Además, se ha diseñado una taxonomía robusta de agarres que permite controlar diferentes manos robóticas utilizando una correspondencia, basada en gestos, entre los espacios de trabajo de la mano humana y de la mano robótica. El gesto de la mano humana se identifica mediante la lectura de los movimientos relativos del índice, el pulgar y el dedo medio del usuario durante las primeras etapas del agarre. ABSTRACT Regardless of the availability of highly sophisticated techniques and ever increasing computing capabilities, the problems associated with robots interacting with unstructured environments remains an open challenge. Despite great advances in autonomous robotics, there are some situations where a humanin- the-loop is still required, such as, nuclear, space, subsea and robotic surgery operations. This is because the current technologies cannot reliably perform all kinds of task autonomously. This thesis presents methods for robot teleoperation strategies at different levels of abstraction ranging from supervisory control, where the operator gives high-level task actions, to bilateral teleoperation, where the commands take the form of low-level control inputs. These strategies contribute to improve the current human-robot interfaces specially in the case of slave robots deployed at large workspaces. First, an approach to perform supervisory teleoperation of humanoid robots is presented. The goal is to control ground robots capable of executing complex tasks in disaster relief environments under constrained communication links. This proposal incorporates autonomous behaviors that the operator can use to perform navigation and manipulation tasks which allow covering large human engineered areas of the remote environment. The experimental results demonstrate the efficiency of the proposed methods. Second, the use of cost-effective devices for guided telemanipulation is investigated. A case study involving a bimanual humanoid robot and an Inertial Measurement Unit (IMU) Motion Capture (MoCap) suit is introduced. Herein, it is corroborated how the adaptation capabilities offered by the human-in-the-loop factor can compensate for the lack of high-precision robotic systems. This work is the result of collaboration between researchers from the Harvard Biorobotics Laboratory and the Centre for Automation and Robotics UPM-CSIC. Thirdly, a new haptic rate-position controller is presented. This hybrid bilateral controller copes with the problems related to the teleoperation of a slave robot with large workspace using a small haptic device as master. Large workspaces can be covered by automatically switching between rate and position control modes. This haptic controller is ideal to couple kinematic dissimilar master-slave systems where the commands are transmitted in the task space of the remote environment. The method is validated to perform dexterous telemanipulation of objects with a robotic manipulator. Finally, two contributions for robotic manipulation are introduced. First, a new algorithm, the Iterative Kinematic Decoupling method, is presented. It is a numeric method developed to solve the Inverse Kinematics (IK) problem of a type of six-DoF robotic arms where a close-form solution is not available. The effectiveness of this IK method is compared against conventional numerical methods. Second, a robust grasp mapping has been conceived. It allows to control a wide range of different robotic hands using a gesture based correspondence between the human hand space and the robotic hand space. The human hand gesture is identified by reading the relative movements of the index, thumb and middle fingers of the user during the early stages of grasping.

Sobre la Arquitectura en la definición del Paisaje

Comúnmente la Arquitectura se manifiesta en los edificios como un hecho de la realidad que tiene siempre carácter contemporáneo y ése debe ser el valor supremo de un arte que no distingue entre antiguo y moderno, por afectar al presente y ser contemporáneo como experiencia. Los objetos se insertan irremediablemente en su medio e incluso llegan a definirlo en ocasiones: así, arquitectura y paisaje, aparecerán a veces confundidos con diferencias difíciles de determinar. El término “paisaje” es relativamente moderno y se deriva de ciertas representaciones gráficas o pictóricas producidas en Occidente en época algo posterior al Renacimiento. No obstante, el hecho de que una palabra se pueda escribir o se cite no quiere decir que la realidad a la que responde no pueda existir, pues lo escrito es solamente un medio de expresión, y es obvio que existen otros quizá más antiguos y de idéntica importancia, pues la propia escritura no es más que el reflejo de un fenómeno que ya se ha producido con anterioridad. Parece así que el testimonio de la realidad viene dado por distintos contextos en lo que suele llamarse “cultura” de modo que las culturas pueden tener aspectos de gran interés mediante diferentes sistemas de expresión variados sin que eso tenga que pasar forzosamente por el filtro de un alfabeto y una escritura. A tenor de los primeros descubrimientos, parece que la cuestión de escribir tuvo originalmente un carácter de constatación de apunte contable y tampoco se puede establecer con certeza si algunos utilizaron la escritura como el so-porte adecuado para referir mitos o historias, pues la Arqueología no ha proporcionado sino testimonios fragmentarios; de lo que si está repleta sin duda la historia es de apuntes contables. Otra cuestión que suscita dudas es la propia definición de escritura, pues parece que los más antiguos modos de expresión escrita se reducen a pictogramas que resultan aún indescifrables. Lenguas y toponimia son también herramientas muy útiles para bucear en el pasado, pero aún así persisten dudas en las escrituras que pro-vienen de las representaciones primordiales: la propia escritura en sus orígenes parece alimentarse de las propias intuiciones inmediatas de la representación, algo que evolucionaría representando esa realidad urgente e inmediata del control o el abastecimiento que luego se convertirían en los fragmentos de texto que han podido conservarse. Es notorio, sin embargo, que ese conjunto enorme de convenios gráficos estaba sujeto a la palabra y la desaparición de las culturas determinó también la desaparición consecuente de sus lenguas, y esos signos - fueran o no escritura - han pasado definitivamente a las zonas oscuras del conocimiento. Escribir supone también disponer de capacidad de abstracción gráfica que diferencie la palabra y la cosa, y es posible que la razón que llevara a ese descubrimiento fuera simplemente el de una economía de signos, pues escritura y lenguaje son limitados por definición, mientras que las cosas del mundo son innumerables: ningún idioma contiene todas las palabras para describir todo lo que puede aparecer. Aparentemente, ese el motivo por el cual existe un localismo – un término específico que refiere algo que existe en un lugar y no en otros - en lo que se refiere a dar el nombre a la cosa y también fuente de paradigma entre los pueblos que se consideran primitivos y los que se consideran civilizados. Debe tenerse en cuenta también que esa transposición se da en ambos sentidos, de modo que las culturas más aisladas también incorporan conceptos que carecen de una explicación racional consistente. Las mitologías son así eternas, pues sirven para explicar realidades que carecen de un entendimiento alcanzable y está también bastante claro que los lenguajes resultan ser un enigma, como realidad autónoma que queda en-cerrada y se explica en sí misma. Parece también que los primeros en escribir las consonantes aisladas fueron los pueblos semíticos occidentales de las orillas del Mediterráneo, pueblos que crearon un alfabeto silábico que llegó a ser utilizado incluso por los tartesios en el sur de la península ibérica como el primer alfabeto de toda Europa occidental. Resulta patente que el término “paisaje” se ha nutrido siempre de representaciones, bien escritas o artísticas, pero queda también claro que esas representaciones se suponen derivadas de la creencia en una idea de paisaje como algo que se ve representado en sí mismo, es decir, como la imagen de una realidad externa situada fuera del individuo. Eso es un hecho trascendente, pues el paisaje requiere lejanía de la cosa, de modo que el actor – aún sabiéndose inserto en su paisaje – es incapaz de percibirlo desde dentro. En el paisaje ocurre igual que en un teatro o en una representación: los actores son conscientes de su papel y su posible cometido, pero no son los que realmente pueden disfrutar de la eficacia o de la propia presencia de la obra, pues forman parte de ella. La idea de paisaje proviene de una lectura externa a la de los propios protagonistas del drama, de modo que si quieren ser un crítico del paisaje se debe abandonar la representación para mirar el espectáculo desde una distancia adecuada, al fin y a cabo externa. De ese modo, aparece la primera constatación del hecho del paisaje como una realidad construida por objetos y personajes, pero, sobre todo, es una realidad construida por miradas. Llama también la atención otorgada en las lecturas de los especialistas hacia esa referencia externa - artística si se quiere - sobre el término “paisaje”, de modo que la bibliografía no especializada sobre el particular siempre acaba en tratados de pintura o poesía. Parece sin embargo que el hombre y sus paisajes son realidades indisolubles desde la propia aparición de la especie, de modo que llevar la cuestión hacia términos exclusivamente esteticistas parece una posición parcial. Hombre y medio han formado siempre una sola unidad, aunque esa unidad se haya convertido en determinados casos en sinónimo de depredación y destrozo. Sin embargo, esa destrucción crea igualmente un paisaje como desolación que es resultado del propio quehacer del hombre: elementos que también poseen un contenido sustancial de memoria en los paisajes industriales como un momento de la Historia previo a la automatización y a la globalización de la vida actuales. Quizá el concepto más interesante desde el punto de vista teórico sea precisamente el de esa cualidad del paisaje como mirada, algo externo producido por el contemplador en un momento ajeno a la pertenencia, una mirada que no es tan sólo estética sino comprensiva, gozosa, activa o analítica - pues existen tantas maneras de mirar como sujetos - sin que pueda definirse con precisión esa contemplación más que en términos que alcanzan la propia individualidad. En términos poéticos, también podría establecerse como ese conjunto de miradas individuales crean también una estructura que hace que ese paisaje se valore y se comprenda, de modo que desde ese punto de vista ese paisaje supone una creación colectiva. Con respeto o como depredador, el hombre se ha instalado en su medio, y al hacerlo, ha dejado huellas dentro del propio paisaje que hacen que tome una determinada significación. Naturalmente, existe una teoría que distingue entre “país” y “paisaje”, asumiendo para el primero la noción exclusiva de territorio en la cual el hombre no tiene papel estético alguno. He intentado muchas veces comprender esa posición, sin acabar de entender el planteamiento que la sustenta: parece que la visión de la cosa estará siempre humanizada, aún en las zonas “vírgenes” o intactas, pues la propia visión hace que el objeto se modifique en su propia unidad perceptiva, creando una curiosa indeterminación que lleva a los conocidos equívocos entre imagen real y representación. Efectivamente, la visión de la cosa requiere de una cultura y unos medios que la informan, de modo que un texto, una pintura, una descripción o una fotografía quedarán ya humanizadas por el propio hecho de ser informadas, pues ello otorga una forma a priori. De ese modo, el paisaje figura inscrito en una función que establece tanto aspectos de un paisaje posible como aspectos del paisaje descrito y solamente podrá hablarse sobre la potencialidad del estado final de ese paisaje y nada del propio paisaje en sí, mientras ese paisaje no quede humanizado por el propio observador. Esta cuestión obliga a elegir una definición de paisaje alejada de presupuestos esteticistas para acercarla a los puramente culturales, de modo que no existe otra vía para la investigación que contemplar esa realidad física en función de las coordenadas del hombre que la habita, dotada del contenido correspondiente a esa revelación. Lejos de las posiciones de la geomorfología, el término “paisaje” implicará así unas condiciones determinadas de contemplación por parte de un sujeto por el cual el espectáculo queda humanizado en dicho acto.Cabe pensar también si no es cierto que todos los paisajes requieren de esa condición humanizada, pues aunque no estén habitados están siempre ocupados por esa mirada que los habita, al igual que un escenario sin público que carece de vigencia. A partir de ahí se sitúan las coordenadas en donde este trabajo configura la presencia de la arquitectura en la definición del paisaje, una premisa que parece ya venir otorgada desde el principio, pues esa misma mirada del espectador ya está dotando de un sentido de orden y jerarquía a la contemplación, unas cualidades que están en la base de toda actividad arquitectónica, De hecho la propia definición de “monumento natural” - en si misma una contradicción – expresa ese conflicto, dotado de un fenómeno de admiración y solape entre cultura y naturaleza, como conceptos enfrentados desde su origen. La conclusión sobre el dilema propuesta en la tesis no ha sido otra que suponer que esas dos realidades que son la cultura y el paisaje se han solapado desde el principio de los tiempos del hombre formando un binomio indeslindable. Se ha dicho antes que el proceso de invasión del territorio por el hombre es significativo, y esa significación es la que origina una creación autónoma que se aísla como un concepto abstracto de los entes naturales, tomándolos como material de trabajo, y estableciendo una oposición conceptual en la realidad perforada e interpretada por el hombre que viene a oponerse a lo que supone la caja cerrada e ignota del enigma del mundo. La cuestión de la significación del hombre sobre el territorio se subsume en la creación de unos productos que permanecen y que son testimonio de la propia cultura, de forma que la cantidad de rastro que el hombre deja sobre el territorio contribuye en mayor medida a la cualificación del paisaje como concepto. Eso lleva a establecer que cualquier paisaje - por el mero hecho de serlo y ser definido así – es ya cultural, puesto que está configurado por los productos de la cultura. Las palabras que puedan quedar encerradas en las piedras de los monumentos o de las ciudades son las de los hombres que trabajaron allí, y también las de los que las habitaron: más aún, el propio sentido del paisaje y su conservación vienen determinados por la presencia del hombre como único interprete de conceptos como ecología o conservación, algo que se pone de manifiesto también en la espantosa devastación que producen los fenómenos propios de la naturaleza. La historia natural, al igual que la vida, están conformadas por éxito y devastación, sin que uno y otra tengan especial preferencia, pues la preferencia se alimenta de otra clase de conceptos. La cuestión de atribuir valores morales al mundo natural es algo muy antiguo, y quizá sea la fuente o el manantial de las primeras religiones, una cuestión que se une a la indefectible noción de mortalidad que define la existencia del hombre frente a la inmanencia de la naturaleza. Esa propia naturaleza está dotada intuitivamente de un carácter “inocente” suponiendo que la inocencia es lo opuesto a la sabiduría. La cuestión es bien otra, ya que la naturaleza no posee ni siquiera algo que pueda definirse como “carácter”, en el sentido personal del término. La cuestión no cae, evidentemente, del lado de las definiciones o de las cualidades, sino del propio análisis de la realidad que el hombre va construyendo, destruyendo, embelleciendo o perjudicando para definir el territorio que habita, interponiendo a su manera recursos, instalaciones y en definitiva todos los testimonios posibles como principal manifestación de su esencia. Entre los artefactos que el hombre produce, uno de los más persistentes y más conspicuamente descritos es el de la arquitectura - entendida aquí en un sentido amplio - es decir, como el conjunto de modificaciones del espacio y del territorio. El espacio se puede modificar de muchos modos, pero en cualquiera de los casos constituye una de las huellas más características que el hombre establece como manifestación física de su propio ser discursivo. También la arquitectura ha demostrado ser una de los fenómenos más persistentes, incluso más que la propia lengua que la origina en su discurso primero antes que pueda ac-cederse a una idea sobre la conformación del material. Es paradigmático que el episodio descrito sobre la Torre de Babel en la Biblia la cuestión de la ambición de los hombres frente a Dios, representada precisamente en una arquitectura, se asimile a la discusión sobre el lenguaje primordial. La cuestión no es baladí, pues el fenómeno de la creación es algo que se concede exclusivamente a los dioses, que por esa razón habitan los territorios a los que los hombres no pueden llegar; territorios de albergue en los que las mitologías sitúan a dioses y demonios, con amplios espacios intermedios donde situar a las divinidades menores, héroes o seres híbridos en los que la coyunda de los dioses con los humanos produce sujetos que alivian el sentido de la mortalidad. El comentario del Génesis también concede un valor a la técnica, al mito de Prometeo y al fuego como creador de excelencia. Frente al progreso prometeico, se postula el valor divino, y la única forma posible de paliar ese progreso es la confusión del lenguaje, pues eso será lo que produzca la dispersión y la falta de acuerdo. La cuestión también puede explicar esa afición tan común por lo canónico en arquitectura que se mantiene a lo largo de grandes períodos, al igual que una gran máquina de inercia. Parece que los conceptos primordiales de la arquitectura basados en elementos simples como el hito, el dintel, lo recto y lo curvo, la rampa o la escalera, y el uso distinto o cualificado que se otorga a la piedra, el ladrillo, la madera o el metal como componentes primordiales del material arquitectónico se haya mantenido a lo largo de muchos milenios sin apenas cambios, al igual que ocurre con las costumbres alimenticias que siguen una progresión ascendente a través de lo crudo, lo asado y lo cocido, hasta obtener distintos grados de refina-miento, pero que siempre se sustentan en la sensación primigenia. El descubrimiento de la arquitectura proviene de un cierto manejo de las dimensiones, y consiguientemente de la geometría. Pero la geometría es cosa abstracta al igual que el lenguaje, de modo que para poder realizar arquitectura se hace necesaria esa capacidad de abstracción primera que luego permite la realización de un dispositivo. La realidad y su número exhiben un divorcio, al igual que las cosas y sus nombres exhiben el suyo, y el análisis numérico es solamente una forma de ver la realidad, una forma rigurosa y exacta – aunque parcial - que solamente representa el modelo ideal al cual la realidad se aproxima en mayor o menor medida: esa aproximación matemática hace que el universo pueda condensarse parcialmente en números, al igual que la realidad puede condensarse en nombres, pero ni el nombre ni el número reflejarán el mundo en toda su complejidad. El número es quizá solamente un medio de describir las cosas, como lo serían las formas puras que responden a una configuración matemática que pueda producirse en teoría en cualquier parte del Universo. Sin embargo, para el ejercicio de la arquitectura es preciso acudir a esa simplificación que exige la visión abstracta del plano como una sección cierta realidad como un corte abstracto del elemento considerado. Con su traza o sin ella, con la propia expresión matemática que lo describa o sin precisarla, esa intuición del plano como elemento generador del espacio es anterior a aquella expresión, al igual que el habla fue anterior a la escritura, pues solamente se produjo a través de ella y como refuerzo y sustituto de la memoria. Existen así abstracciones de la memoria que aparecen derivadas de los signos de la naturaleza aparecidos solamente de forma eventual y fragmentaría: así ocurre con la línea, el cuadrado y el círculo, formas iniciales y abstractas sonsacadas en cierta medida de la observación que dan origen a los primeros signos de la arquitectura primordial, de modo que cuadrados y círculos, elevados a prismas y superficies esféricas o esferoides aparecen en tumbas y edificios elementales de los primeros tiempos mediante una geometría primordial que se superpone al paisaje en el que se inserta. Es cierto también que esas formas se encuentran ya aproximadas en objetos que se encuentran en el medio físico, líneas en extremidades, ramas y miembros; ángulos rectos en algunos cristales que se observan mediante corte o formas circulares en astros y cráteres, pero esa realidad solamente presenta su forma aproximada y no su abstracción pura, de igual modo que el jeroglífico propondrá al ave rapaz para representar la idea de vigilancia y la buena vista, o incluso que la imagen del propio ojo sustituya la idea del Dios que todo lo ve en las culturas anti-guas. La elección fue resuelta, después de muchos intentos y aproximaciones, con la adopción del ángulo recto como un artificio fácil para el replanteo a través del triángulo sagrado 3:4:5 que ya se utilizó para construir las pirámides de Egipto, y que dio origen también a la mayor parte del urbanismo antiguo, coexistiendo con la forma circular primordial en el tipo denominado “tholo”. Aquella trama cuadrangular era uno de los patrones de relleno del espacio más comunes y compactos, y esa fue probablemente la razón por la que en tiempos muy posteriores fuera adoptada como una forma eficaz permanente de organización frente al desorden topológico que procura el conjunto de asociación de plantas circulares. Otra cuestión paradigmática es que esos conceptos primordiales e ignotos - que convergen en el mismo origen de las civilizaciones - se conviertan luego en algo canónico, a través del uso. El canon en sí mismo es algo ideal, como una norma aplicable a objetos de una realidad que ha sido creada solamente como indicio del ca-non, algo abstracto que tiene proporciones estrictas que son siempre las mismas y no obedece a criterios racionales: será absurdo sin embargo buscar el canon griego entre los templos de época como algunos lo hicieron, pues los edificios solamente se aproximan a los ejemplos canónicos y por esa razón se habla del “dórico del Partenón” que es diferente del de Egina o del de Paestum, siendo todos ellos evidentemente dóricos. Sin embargo, esa idea resulta útil al tratadista, al teórico de la arquitectura y al historiador, aun-que solamente refleje una vaga idea de lo que sucede más allá del tratado. Otra cuestión es la sutileza de los ejemplos de arquitectura, y del mismo modo que los cuerpos de los seres vivos jamás son simétricos, aunque respondan a un diseño simétrico general derivado de las condiciones de la división celular, los edificios supuestamente canónicos en los que los especialistas se inspiraron para definir los órdenes clásicos no disponen de esa simetría modular exacta, sino que adaptan un modelo general al lugar siempre cambiante del emplazamiento, es decir, se adaptan con habilidad a la vez que configuran el paisaje en el que se insertan. La luz de los distintos intercolumnios del Partenón es ligeramente distinta, aunque guarde un evidente sentido de simetría axial, de manera que aquellos “órdenes” que formaron la Teoría de la Arquitectura no son más que una bella interpretación sectorial de la arquitectura antigua elaborada por los tratadistas del Renacimiento y, posteriormente, por los neoclásicos. Parece, sin embargo, que ese ansia por el canon como claridad de lenguaje es algo consustancial al desarrollo de la arquitectura, una lingua franca que tiende a evitar la dispersión producida entre los mortales por los dioses antiguos, de modo que si no era posible llegar al cielo de los dioses se procuró que el lenguaje de la Tierra fuera al menos inteligible para poder entenderse entre los hombres. Parece que la estructura del poder siempre requirió de un determinado nivel de organización, y también que las instrucciones se entendieran con claridad: parece que en nuestros tiempos esos antiguos cánones se han sustituido por la obediencia a normas abstractas, dictadas por instituciones también algo abstractas y que tienen nombres divertidos compuestos por siglas, aunque no se conozca bien su virtud. El canon actual está constituido por “normas” que dejan tranquilos a algunos, aunque parece quizá que todo ese entramado formal que sirve como anestesia para el cuerpo social procura también la destrucción de los bosques en formas de montañas ingentes de papel burocrático. Durante muchos siglos las normas fueron otras, en la forma de un canon del cual nadie podía escapar: aún así, mediante la utilización de cánones o sin ellos, la arquitectura prosperó en la civilización desde los primeros refugios cavernarios o los abrigos primigenios y de ese modo fue configurando la realidad, es decir, el paisaje. Como antes se dijo, ese es un viaje de ida y vuelta en el cual ambos se confundían y subsumían: el manejo de las formas y lenguajes de la arquitectura posibilitaría con el tiempo la distinción entre el campo en donde reina el caos y la ciudad, en donde reina teóricamente el orden, creando un divorcio que duraría milenios y que aún persiste. Esa oposición generaría también una forma de paisaje y una serie de usos simbólicos y sagrados de los elementos de la arquitectura - como son puertas y murallas - que se han mantenido conceptualmente aunque hoy las ciudades ya no posean murallas físicas, ni puertas que se cierran con la llegada de la noche. En ese sentido, la arquitectura ha podido definir el paisaje, entendiendo la arquitectura no solamente como los edificios en sí, sino como el hecho de la manifestación del hombre sobre el territorio, de modo que no podrá hablarse de paisaje sin su arquitectura, del mismo modo que no puede hablarse de paisaje sin hombres. Por esta razón, la Tesis habla sobre Arquitectura y Paisaje, pero más particularmente sobre el hecho de la arquitectura en la definición del paisaje, es decir, de como los hechos arquitectónicos van a determinar o no la cualidad y la calificación de un paisaje. Deberá partirse en primer lugar de una definición de lo que se entiende y se ha entendido comúnmente por paisaje: igualmente, y habida cuenta del contexto en el que sitúa el propio trabajo de tesis, la cuestión solamente se circunscribirá a lo que se entiende como cultura occidental, pues el desarrollo de la civilización presenta siempre un color local que hace que el análisis de un fenómeno de esta envergadura tenga distintas connotaciones en las distintas áreas de civilización. De igual modo, y habida cuenta también que el paisaje se construye a través de todas las manifestaciones culturales, se hará a veces necesario indagar en otras disciplinas no arquitectónicas para comprender el alcance de algunos casos en los cuales los restos arquitectónicos han desaparecido, o en los que subsisten escasas trazas. Una definición tan amplia de la Arquitectura llevaría a escribir un relato sobre toda la cultura occidental y por ese motivo solamente se han esbozado ideas sobre la aparición de esos signos sobre el paisaje basados en elementos antiguos y primigenios que se repiten con insistencia y van dando lugar al variado repertorio de la arquitectura occidental cómo conformación de ideas sobre el me-dio y sobre el mundo que se percibe y se habita. ABSTRACT About Architecture in defining Landscape. Abstract Architecture is commonly manifested in buildings as a fact of reality that has always a contemporary character and that should be the highest value of an art that does not distinguish between ancient and modern, to affect the present and be contemporary as experience. Objects are inserted irremediably in their midst and even sometimes come to define it: thus, architecture and landscape, appear sometimes confused with differences difficult to determine. However, the term "landscape" is relatively modern and is derived from certain graphical or pictorial representations produced in the West in some subsequent period to the Renaissance. The fact that a word can be written or quoting does not mean that the reality that can not be answered, because the writing is only a mean of expression, and it is obvious that there are other and perhaps older equally important, because the writing itself is nothing more than the reflection of a phenomenon that has occurred before. It thus appears that the testimony of reality is given by different contexts in what is called "culture", so that cultures can have aspects of great interest by many different expression systems without this necessarily have to pass through the filter of alphabet and writing. Under the initial findings, it appears that the question of writing originally had a character and finding accounting entries, and it can not be established with certainty whether some used writing as the support appropriate to refer myths or stories, because archaeology has provided only fragmentary evidence. Another issue that raises questions is what can properly be defined as writing, it seems that the oldest modes are reduced to writing pictograms are still indecipherable. Languages and place names are also very useful tools for diving in the past, but still questions remain in the scriptures that come from the primordial representations: either it is very well defined what the own writing in its origins: the beginnings seem to feed on immediate intuitions of representation, which would evolve representing reality that urgent and immediate control or supply which is then inherited into fragments. It is noteworthy, however, that this huge set of graphics agreements was subject to the word and the disappearance of cultures determined also the consequent disappearance of their languages, and those signs - whether or not they write - have passed definitively to dark areas of knowledge. Writings supposed also the capacity of abstraction graph differentiates the word and the thing, and it is possible that the reason to carry this discovery was simply that of an economy of signs, for writing and language are limited by definition, while the things of the world are innumerable: no language contains all words to describe all that may appear. Apparently, that's why there is a localism - a specific term that refers to something that exists in one place and not in others - in regards to name the thing and also the source of paradigm among peoples are considered primitive and civilized. It should be noted also that transposition occurs in both directions, so that the most isolated cultures also incorporate concepts that lack a consistent rational explanation. Mythologies are eternal and therefore serve to explain realities that lack an understanding achievable and also pretty clear that languages happen to be an enigma, as an autonomous reality that is enclosed and explains itself. It also seems that the first to write consonants were isolated western Semitic peoples from the shores of the Mediterranean, peoples who created a syllabic alphabet came to be used even by tartesios in southern Iberia as the first alphabet in Western Europe. It is clear that the term "landscape" has always nurtured representations, either written or artis-tic, but it is also clear that these representations are assumed arising from belief in an idea of landscape as something that is represented in itself, as the image of a reality external located outside the individual. That is an important fact because the landscape requires remoteness of the thing, so that the actor - even knowing insert in landscape - is unable to perceive from within. The landscape is just as in a theatre or a performance: the actors are aware of their role and their possible role, but they are not the ones who can really enjoy the efficiency or the presence of the work itself, as part of it. The idea comes from an external landscape reading the principles of players in the drama, so if you want to be a critic of the landscape should leave the actual representation to watch the spectacle from a safe distance, finally external. Thus, the first finding of fact of the landscape appears as a reality constructed by objects and characters, but above all, a reality constructed by looks. Also noteworthy given the readings of specialists to the external reference - art if it could be - on the term "landscape", so no specialized literature on the subject always ends in treatises on painting or poetry. It seems however that the man and his landscapes are inseparable realities from the very onset of the species, so bring the issue into terms exclusively aesthetics seems a partial position. Man and environment have always been a single unit, but that unit has become synonymous with certain cases predation and destruction. Nevertheless, this destruction also creates a landscape as desolation that results from proper task of man elements that also have substantial contents of memory in industrial landscapes as a time of pre-automation history and globalization of current life. Perhaps the most interesting from a theoretical point of view is precisely that quality of landscape as something external produced by the viewer in a strange time of membership, a look that is not only aesthetic but sympathetic, joyful, active concept or analytical - because there are so many ways to look as subjects - it may not be precisely defined that contemplation rather than in terms that reach one's individuality. In poetic terms, it could also be set as the set of individual gazes also create a structure that makes this landscape is valued and understood, so from that point of view that landscape is a collective creation. With respect or as a predator, man has settled in his environment and in doing so has left traces in the landscape itself that make take a certain significance. Naturally, there is a theory that distinguishes what is "home" and what is "nature" providing for the first notion of the exclusive territory in which man has no aesthetic role. I tried many times to understand this position, without understanding the approach that supports: it seems that the vision of the thing is always humane, even in the "virgin" or untouched areas, as the vision itself makes the object modified in its own perceptual unit, creating a curious indeterminacy leading to the known misunderstandings between real image and representation. Indeed, the vision of the thing requires a culture and means that the report, so that a text, a picture, a description or photograph will be humanized by the very fact of being informed, as this provides a way a priori. Thus, the landscape provides a function that sets both aspects of a potential landscape as described aspects of the landscape and can only talk about the potential of the final state of the landscape, while the landscape remains humanized by the observer himself. This question forces to choose a definition of remote landscape budgets purely cultural, so there is another way for research to contemplate that physical reality in terms of the coordinates of the man who inhabits gifted content corresponding to that revelation. Far from the positions of the geomorphology, the term "landscape" and involve a certain condition by contemplation of a subject for which the show is humanized in the act. It should also consider, in the light of the above, if it is not true that all landscapes require that humanized condition, because although they are not inhabited they are always occupied by the look that dwells, like a stage without audience produces no consistent effect. From there the coordinates where this work sets the presence of architecture in defining landscape, a premise which seems to come from the beginning given lie, because that same look is already giving the viewer a sense of order and hierarchy to contemplation, qualities that are at the basis of all architectural activity, in fact the very definition of "natural monument" - in itself a contradiction - expresses this conflict, which has a phenomenon of admiration and overlap between culture and nature as concepts faced since its inception. The conclusion on the dilemma proposed in the thesis has not been another to assume that these two realities are the culture and landscape have overlapped since the beginning of man time forming a pair. It has been said before that the process of invasion of the territory by man is significant, and that meaning is the originating autonomous creation that is isolated as an abstract concept of nature, taking them as working material, and establishing a conceptual opposition in reality and punched by the man who comes to oppose representing the closed and unknown to the enigma of the world interpreted. The question of the significance of the man on the land is subsumed in the creation of products that remain and are testimony of their own culture, so that the trace amount that the man leaves the territory contributes most to the qualification landscape as a concept. That brought into any landscape - by the mere fact of being and being well defined - is already cultural, as it is configured by culture products. The words that can be locked in the stones of the monuments or cities are those of the men who worked there, and also of those who inhabited: even more, the sense of the landscape itself and its conservation are determined by the presence of man as the sole interpreter of concepts such as ecology or conservation, something which becomes manifest also in the awful devastation that produce the phenomena of nature. The natural history, like life, are shaped by success and devastation without special preference, the preference is used for feeding on other kinds of concepts. The question of moral values attributed to the natural world is very ancient, and may be the source or the source of the first religions, an issue that joins the unfailing notion of mortality that defines the existence of man against immanence of nature. That nature is endowed intuitively an "innocent" character assuming that innocence is the opposite of wisdom. The other issue is well, since nature does not even have what is defined as "character" because that is something that serves to qualify beings, but not objects. The question does not fall clearly on the side of the definitions or qualities, but from the analysis of the reality that man is building, destroying or damaging to define the territory, interposing his way resources facilities and possible witness as the main manifestation of its essence. Among the artifacts that man produces one of the most persistent and most conspicuously disclosed is architecture as a way of modification of space and territory. The space can be modified in many ways, but in either case is one of the most characteristic traces that man establishes as a physical manifestation of his own discourse being. Architecture has also proven to be one of the most persistent phenomena, even more than their own language that originates in his speech first. The paradigm wrote in the episode described on the Tower of Babel in the Bible shows the question of ambition of men before God - represented precisely in architecture - is assimilated to the discussion about the primary language. The issue is not trivial, since the phenomenon of creation is something that is granted exclusively to the gods, for that reason inhabit the territories to which men can not reach; territories where the hostel located mythologies gods and demons, with large gaps where to place the minor deities, heroes or hybrid beings where the yoke of the gods with human subjects produces relieving sense of mortality. The commentary on Genesis also gives a value to the art, the myth of Prometheus and fire as creator of excellence. In front of promethean progress, divine value is postulated, and the only possible way to alleviate this progress is the confusion of language, because that is what will produce the dispersion and lack of agreement. The issue may also explain such a common passion for the canonical architecture maintained throughout long periods, like a great machine inertia. It seems that the main concepts of architecture based on simple elements like milestone, lintels, straight and curved stairs or ramps, or other qualified and used are granted to the stone, brick, wood or metal as the primary components of the architectural material maintained throughout many millennia are almost unchanged, as is the case with the eating habits that follow a progression through the raw, the cooked and roasted or fried until obtain different degrees of refinement, but always are based on the primal feeling. The discovery of the architecture comes from a management dimensions, and consequently the geometry. But the geometry is abstract thing like the language so that to make architecture that first absorption capacity which then allows the realization of a device is necessary. Reality and its number exhibit a divorce, like things and their names displayed his; numerical analysis is just one way of seeing reality, rigorous and accurate - though partial - only represents the ideal model to which reality is coming to a greater or lesser extent: the mathematical approach makes the universe can condense on numbers, like reality may condense on names, but neither the name nor the number will reflect in all its complexity. The number is only a means of describing things, such as the pure forms that match setup a mathematical theory that occurs anywhere in the universe. However, for the practice of architecture is necessary to go to the simplification that requires abstract view of a section plane of reality, as an abstract element considered cutting. With its trace or not, with the mathematical expression that describes what or without clarify, this intuition of the plane as a generator of space predates his own expression, like speech preceded the writing, which only occurred through it and as reinforcement and replacement of memory. There are abstractions of memory displayed on the signs of nature only on casual and fragmentary, such as line, square and circle: those initials and abstract forms located in abstraction give rise to the first signs of primordial architecture, so that squares and circles, lifting two prisms and spheroids or spherical surfaces appear in tombs and elementary buildings the first few times, and that primordial geometry overlaps the landscape in which it is inserted. It is also true that these forms are approximate objects found in the physical environment, limb lines, branches and limbs; straight in some crystals angles observed by cutting or circular in stars and craters forms, but only the approximate shape and not its abstraction, just as the hieroglyphic of a falcon to represent the idea of surveillance presents the good view, or even the image of the eye itself replace the idea of the all-seeing God. The election was resolved, after many attempts and approaches, with the adoption of the right angle as an easy trick for stake through the sacred triangle 3:4:5 already used to build the pyramids of Egypt, and also gave rise to most of the old urbanism tend coexist with the primary circular form type called "Tholo". That frame homer was one of the fill patterns of common and compact space, and that was probably the reason why in much later times was adopted as a permanent effective form of organization against the topological disorder that seeks the set of association circular plants. Another issue is that these paradigmatic and unknown primary concepts - that converge at the origin of civilizations - then become something canon, through use. The canon itself is something ideal, as a rule for objects of a reality that has been created only as an indication of the ca-non, something abstract that has strict proportions are always the same and not due to rational criteria: be absurd however seek the Greek canon among the temples of time as some did, because the buildings only approximate the canonical examples and for that reason we speak of "doric from Parthenon" which is different from Aegina or Paestum, being all clearly doric. However, this idea is useful to scholar, the architectural theorist and historian, although it reflects only a vague idea of what happens beyond the book. Another issue is the subtlety of the examples of architecture, just as the bodies of living beings are never symmetrical, even if they involve a general symmetrical design derived from the conditions of cell division, the supposedly canonical buildings where specialists were inspired to define the classical orders do not have that exact modular symmetry, but a general model adapted to the ever changing location of the site shaping the landscape in which they are inserted. The light of the various bays of the Parthenon is slightly different, but keep a clear sense of axial symmetry, so that those "orders" that formed the theory of architecture are just a beautiful sectoral interpretation of ancient architecture developed by writers of the Renaissance and later by neoclassical. It seems, however, that craving for clarity of language canon as is inherent to the development of architecture, a lingua franca that tends to avoid scattering among mortals by the ancient gods, so if it was not possible the heaven of the gods sought the language of the Earth was at least intelligible to be understood. Power structure has always required a certain level of organization, and the instructions are clearly understood: it seems that in our times these ancient canons were replaced by obedience to abstract rules, issued by institutions also somewhat abstract and have funny names made up acronym, although not well known virtue. The current canon consists of "rules" that leave some quiet, although it seems that maybe all that interweaves-do formally serving as anaesthesia for the social body also seeks the destruction of forests in forms of huge mountains of bureaucratic paper. For many centuries were other rules, in the form of a canon which no one could escape: still using royalties or without them, civilization flourished in architecture from the earliest cave shelters or shelters and the primordial reality was setting mode in landscape. As noted above, this is a return trip in which both confused and subsumed: the management of forms and languages of architecture over time would allow the distinction between the field where chaos reigns and city, where order reigns theoretically creating a divorce that lasted millennia and still persists. This opposition also generate a form of landscape and a series of symbolic and sacred uses of architectural elements - such as doors and walls - which have remained conceptually although today the cities no longer having physical walls or doors close during the night. In this sense, the architecture could define the landscape, architecture is not only understood as the buildings themselves, but the fact of the manifestation of the man on the premises, so you can not speak without his landscape architecture, the same so we can not speak of landscape without men. For this reason, the thesis discusses architecture and landscape, but more particularly to the fact of architecture in defining landscape, as the facts of architectural or not will determine the quality and qualification of a landscape. One should begin first a definition of what is understood and has been commonly understood by landscape: equally, and given the context in which it places the own thesis work, the issue only be limited to what is understood as western culture, for the development of civilization always has a local colour that makes the analysis of a phenomenon of this magnitude have different connotations in different areas of civilization. Similarly, and given also that the landscape is constructed through all cultural manifestations, will sometimes necessary to investigate other non-architectural disciplines to understand the scope of some cases in which the architectural remains have disappeared, or the remaining few traces. Such a broad definition of architecture take to write a story about all of Western culture and for this reason only been sketched ideas about the appearance of these signs on the landscape based on ancient and primitive elements are repeated insistently and leading the varied repertoire of Western architecture shaping ideas about how the media and the world is perceived and inhabited.

Distribution of haplotypes from a chromosome 21 region distinguishes multiple prehistoric human migrations

Despite mounting genetic evidence implicating a recent origin of modern humans, the elucidation of early migratory gene-flow episodes remains incomplete. Geographic distribution of haplotypes may show traces of ancestral migrations. However, such evolutionary signatures can be erased easily by recombination and mutational perturbations. A 565-bp chromosome 21 region near the MX1 gene, which contains nine sites frequently polymorphic in human populations, has been found. It is unaffected by recombination and recurrent mutation and thus reflects only migratory history, genetic drift, and possibly selection. Geographic distribution of contemporary haplotypes implies distinctive prehistoric human migrations: one to Oceania, one to Asia and subsequently to America, and a third one predominantly to Europe. The findings with chromosome 21 are confirmed by independent evidence from a Y chromosome phylogeny. Loci of this type will help to decipher the evolutionary history of modern humans.

Segregating the functions of human hippocampus

It is now accepted that hippocampal lesions impair episodic memory. However, the precise functional role of the hippocampus in episodic memory remains elusive. Recent functional imaging data implicate the hippocampus in processing novelty, a finding supported by human in vivo recordings and event-related potential studies. Here we measure hippocampal responses to novelty, using functional MRI (fMRI), during an item-learning paradigm generated from an artificial grammar system. During learning, two distinct types of novelty were periodically introduced: perceptual novelty, pertaining to the physical characteristics of stimuli (in this case visual characteristics), and exemplar novelty, reflecting semantic characteristics of stimuli (in this case grammatical status within a rule system). We demonstrate a left anterior hippocampal response to both types of novelty and adaptation of these responses with stimulus familiarity. By contrast to these novelty effects, we also show bilateral posterior hippocampal responses with increasing exemplar familiarity. These results suggest a functional dissociation within the hippocampus with respect to the relative familiarity of study items. Neural responses in anterior hippocampus index generic novelty, whereas posterior hippocampal responses index familiarity to stimuli that have behavioral relevance (i.e., only exemplar familiarity). These findings add to recent evidence for functional segregation within the human hippocampus during learning.