Fragment-based Discovery Aiming at a Novel Modulation of Malate Dehydrogenase and Beyond

Malaria is a disease caused by the parasite Plasmodium falciparum, which causes thousands of deaths among children. In this dissertation Atilio Reyes Romero researched the role of malate dehydrogenase protein at the biochemical level in the metabolism of the parasite and identified small molecules that bind at the oligomeric interface with an allosteric an inhibiting mechanism. This result paves the way for chemical optimisation to a new class of anti-malarial drugs with better selectivity than for the human isoforms. However, tackling protein interfaces, such as oligomeric interfaces, is an challenge in the discovery of medicines because they are flat with a dependency on a local network of molecular interactions spread over the surfaces. Natural and artificial macrocycles are a class of heterogeneous compounds that bind these interfaces. In This thesis will be Moloc, one of the first and most complete molecular modelling packages, presented. We have the accuracy, the diversity, the the speed, completeness and efficiency of sampling in the production of macro-cyclicals. We have quantified the results in accordance with four commercial software and four open access. The result is that Moloc is equivalent to or better than the proprietary products relating to the above metrics. These results imply that not only that Moloc can be used as an alternative to the design of macrocycles on the interface of proteins, but also the bioavailability of biologically relevant predict conformations (i.e. cell membranes that penetrate)

Memantine for prevention of migraine: a retrospective study of 60 cases.

The objective was to retrospectively characterise the efficacy of memantine as preventive therapy in a series of patients with frequent migraine. Patients in a university headache clinic completed a survey regarding their experience with memantine, and medical records were reviewed. All patients who received memantine as preventive therapy for migraine over a 15-month period were mailed surveys and consent forms for record review. Patients were treated with memantine beginning at a dose of 5 mg/day, increasing if needed by 5 mg/week up to 10 mg twice a day. The majority of patients (36 out of 54) treated with memantine for at least 2 months reported a significant reduction in estimated headache frequency, and improved function. Side effects were uncommon and generally mild. This limited retrospective case review suggests that memantine may be an effective preventive therapy for patients with frequent migraine. A prospective trial is warranted

Bioclimatic Design Guidelines: A Valuable Tool for Landscape Architects

This research project aims to create awareness, among landscape architects, on the importance of ecological design. Bioclimatic knowledge contributes to enhance the coexistence between natural and built environments, resulting in healthy places with high quality of life. The study examines ways of graphically representing climate information, to facilitate the understanding and application of bioclimatic design strategies for human comfort. Cache Valley, Utah is used as an example to demonstrate how extensive data can be represented graphically in a more readable and useful manner for practicing professionals. Temperature, humidity, wind and solar information were analyzed and converted into graphics through methods of bioclimatic analysis. The outcome is a recollection of graphic design guidelines to specific climate conditions, in this case Cache Valley, Utah. The resulting design guidelines will aid professionals to design sensitive spaces that minimize energy consumption while maximizing human comfort

Assessment of heritage rammed-earth buildings. The Alcázar of King Don Pedro I (Spain).

The conservation and maintenance of earthen buildings is crucial, especially when dealing with heritage sites. This normally involves considerable effort in preliminary studies, which must be well planned in order to efficiently manage any restoration. This case study proposes a methodology to briefly assess the current state of a historical rammed-earth wall, to bring to light specific information regarding approaches for subsequent studies or decisions. This methodology is based on the study of damage and risk as a tool to swiftly discern critical areas or issues needing immediate attention. The procedure is illustrated on an outstanding heritage building: the Alcázar of King Don Pedro I in Carmona (Seville, Spain). Our conclusions confirm that this methodology constitutes an efficient and straightforward means to obtain not only a preliminary assessment of rammed-earth walls, but also objective and useful criteria for decision-makers

Geografía e historia cultural del maíz palomero toluqueño (Zea mays everta)

Se identifican los lugares donde existió el maíz palomero toluqueño, así como sus usos culturales a través de fuentes históricas y trabajo de campo

Tránsito hacia un nuevo panorama de reconocimiento de los derechos pensionales de las madres comunitarias en Colombia

Artículo de reflexiónEn el marco de la pretensión de universalidad que se establece en el reconocimiento del derecho a la seguridad social, el Estado debe crear los mecanismos suficientes para que dicha prerrogativa sea en la mayor medida posible, efectiva a todos los habitantes del territorio. Este es el argumento de fondo que descansa en prolongada jurisprudencial en materia pensional, sobre todo para los casos en los que se abordan temáticas de sujetos poblacionales como las madres comunitarias. La Corte en lo más reciente ha señalado que, las madres comunitarias son personas trabajadoras sobre una relación laboral, que merecen la asignación de derechos prestacionales en materia pensional, situación que conduce a una discusión, sobre el alcance de esta lectura del Alto Tribunal. En vista de esta realidad, el actual documento propone hacer un ejercicio reflexivo sobre el tema, que ponga de relieve los elementos relevantes de la discusión jurídica que se debe dar con relación a la temática propuesta.30 p.INTRODUCCIÓN 1. EL SISTEMA PENSIONAL COLOMBIANO EN EL MARCO DEL PRINCIPIO DE SOLIDARIDAD 2. MADRES COMUNITARIAS EN COLOMBIA Y SU RECONOCIMIENTO DEL DERECHO PENSIONAL CONCLUSIONES REFERENCIASPregradoAbogad

Cancer and orofacial pain

Cancer pain is a devastating condition. Pain in the orofacial region, may be present as the single symptom of cancer or as a symptom of cancer in its later stages. This manuscript revises in a comprehensive manner the content of the conference entitled ?Orofacial Pain and Cancer? (Dolor Orofacial y Cancer) given at the VI Simposio International ?Advances in Oral Cancer? on the 22 July, 2016 in Donostia. We have reviewed (pubmed-medline) from the most relevant literature including reviews, systematic reviews and clinical cases, the significant and evidence-based mechanisms and mediators of cancer-associated facial pain, the diverse types of cancers that can be present in the craniofacial region locally or from distant sites that can refer to the orofacial region, cancer therapy that may induce pain in the orofacial region as well as discussed some of the new advancements in cancer pain therapy. There is still a lack of understanding of cancer pain pathophysiology since depends of the intrinsic heterogeneity, type and anatomic location that the cancer may present, making more challenging the creation of better therapeutic options. Orofacial pain can arise from regional or distant tumor effects or as a consequence of cancer therapy. The clinician needs to be aware that the pain may present the characteristics of any other orofacial pain disorder so a careful differential diagnosis needs to be given. Cancer pain diagnosis is made by exclusion and only can be reached after a thorough medical history, and all the common etiologies have been carefully investigated and ruled out. The current management tools are not optimal but there is hope for new, safer and effective therapies coming in the next years

GUÍA PEDAGÓGICA INGLÉS 6

GUÍA PEDAGÓGIC