Notícia de dues tesis doctorals llegides en 2016 sobre Curial e Güelfa, els lectors i els contextos de lectura del segle xv

Notícia de dues tesis doctorals llegides en 2016 sobre Curial e Güelfa, els lectors i els contextos de lectura del segle x

NON-HEPATIC HYPERAMMONEMIC COMA: A CASE REPORT

ABSTRACTWhile the most common cause of hyperammonemic (HA) coma is hepatic disorder, other rare etiologies to be considered include congenital causes,drug induced states, portosystemic shunts, and urinary tract infections with urea-splitting organisms. HA usually results from one of the followingthree mechanisms: A relative excessive nitrogen load on a normal functioning liver via the portal circulation (e.g., parenteral nutrition in a patientwith urea cycle defect); ammonia bypassing liver (e.g., congenital vascular malformations, portal hypertension in cirrhotic patients); or from impairedammonia metabolism. Herein, we describe a case of HA coma secondary to an interplay of multiple psychiatric drugs mainly sodium valproate andprobably an added effect by the lithium-induced hypothyroidism/myxedema.Keywords: Drug-induced, Hyperammonemia, Lithium, Myxedema, Valproic acid

Groundwater flow modelling in the upper Anga’a river watershed, Yaounde, Cameroon

The Anga’a River watershed is located within the Yaounde IV district, South-east of Yaounde City, Cameroon. The groundwater flow and particle tracking modelling was carried out to determine in detail the groundwater flow and particle migration in the shallow unconfined aquifer of the Upper Anga’a river watershed. The watershed was modelled with a grid of 106 columns x 68 rows with two layers viz., unconfined and semi-confined aquifers extending up to 50 m depth. The Anga’a river traverses in the central part of the watershed and generally flows North-South. Lateral inflows and outflows were simulated with constant head. The Anga’a river heads and the Lake levels were simulated using a river package. Natural recharge due to rainfall formed the main input to the aquifer system and the output was made of abstraction from pumping wells, base flow to Anga’a River, lake, springs and Evapotranspiration. A steady state groundwater flow simulation was carried out using Visual MODFLOW software and calibrated for the February, 2008 groundwater levels at 18 observation wells. The model computation has converged after 170 iterations with a convergence criterion of 0.01 m. The computed groundwater level contours have been following the trend of observed ones. The computed groundwater balance indicated that the Anga’a river base flows come from the groundwater regime. Groundwater Flow model results indicated that the topography controls groundwater flow in the watershed and that base flow to river is an important factor moderating groundwater movement in the Anga’a river watershed

Genetic diversity in Indian isolates of Fusarium oxysporum f. sp. ciceris, chickpea wilt pathogen

Forty-eight isolates of FOC collected from different chickpea growing regions in India were evaluated for genetic variations using amplified fragment length polymorphism (AFLP). Out of 48 isolates, 41 werefound pathogenic and seven non-pathogenic. Pathogenic isolates differ in their virulence however; there was no apparent correlation between geographical origin and virulence of the isolates. The genetic variation was evaluated by the AFLP analysis. A total 339 fragments were scored following selective amplification with five EcoR1 and Mse1 primer combinations E-TC/M-CAT, E-TC/M-CAC, EAC/ M-CAG, E-TA/MCAG, E-TA/M-CAG, out of which 331 fragments were polymorphic. UPGMA cluster analysis and principle coordinate analysis distinctly classified 48 isolates into two major groups; pathogenic and non-pathogenic. The pathogenic isolates could be further clustered into six majorgroups at 0.77 genetic similarities. Region specific grouping was observed with in few isolates. The results of the present study provide evidence of the high discriminatory power of AFLP analysis,suggesting the applicability of this method to the molecular characterization of Fusarium oxysporum f.sp. ciceris

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies

Exploring the Free Energy Landscape: From Dynamics to Networks and Back

The knowledge of the Free Energy Landscape topology is the essential key to understand many biochemical processes. The determination of the conformers of a protein and their basins of attraction takes a central role for studying molecular isomerization reactions. In this work, we present a novel framework to unveil the features of a Free Energy Landscape answering questions such as how many meta-stable conformers are, how the hierarchical relationship among them is, or what the structure and kinetics of the transition paths are. Exploring the landscape by molecular dynamics simulations, the microscopic data of the trajectory are encoded into a Conformational Markov Network. The structure of this graph reveals the regions of the conformational space corresponding to the basins of attraction. In addition, handling the Conformational Markov Network, relevant kinetic magnitudes as dwell times or rate constants, and the hierarchical relationship among basins, complete the global picture of the landscape. We show the power of the analysis studying a toy model of a funnel-like potential and computing efficiently the conformers of a short peptide, the dialanine, paving the way to a systematic study of the Free Energy Landscape in large peptides.Comment: PLoS Computational Biology (in press

The statistical neuroanatomy of frontal networks in the macaque

We were interested in gaining insight into the functional properties of frontal networks based upon their anatomical inputs. We took a neuroinformatics approach, carrying out maximum likelihood hierarchical cluster analysis on 25 frontal cortical areas based upon their anatomical connections, with 68 input areas representing exterosensory, chemosensory, motor, limbic, and other frontal inputs. The analysis revealed a set of statistically robust clusters. We used these clusters to divide the frontal areas into 5 groups, including ventral-lateral, ventral-medial, dorsal-medial, dorsal-lateral, and caudal-orbital groups. Each of these groups was defined by a unique set of inputs. This organization provides insight into the differential roles of each group of areas and suggests a gradient by which orbital and ventral-medial areas may be responsible for decision-making processes based on emotion and primary reinforcers, and lateral frontal areas are more involved in integrating affective and rational information into a common framework

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Evaluation of a web-based ECG-interpretation programme for undergraduate medical students

<p>Abstract</p> <p>Background</p> <p>Most clinicians and teachers agree that knowledge about ECG is of importance in the medical curriculum. Students at Karolinska Institutet have asked for more training in ECG-interpretation during their undergraduate studies. Clinical tutors, however, have difficulties in meeting these demands due to shortage of time. Thus, alternative ways to learn and practice ECG-interpretation are needed. Education offered via the Internet is readily available, geographically independent and flexible. Furthermore, the quality of education may increase and become more effective through a superior educational approach, improved visualization and interactivity.</p> <p>Methods</p> <p>A Web-based comprehensive ECG-interpretation programme has been evaluated. Medical students from the sixth semester were given an optional opportunity to access the programme from the start of their course. Usage logs and an initial evaluation survey were obtained from each student. A diagnostic test was performed in order to assess the effect on skills in ECG interpretation. Students from the corresponding course, at another teaching hospital and without access to the ECG-programme but with conventional teaching of ECG served as a control group.</p> <p>Results</p> <p>20 of the 32 students in the intervention group had tested the programme after 2 months. On a five-graded scale (1- bad to 5 – very good) they ranked the utility of a web-based programme for this purpose as 4.1 and the quality of the programme software as 3.9. At the diagnostic test (maximal points 16) by the end of the 5-month course at the 6th semester the mean result for the students in the intervention group was 9.7 compared with 8.1 for the control group (p = 0.03).</p> <p>Conclusion</p> <p>Students ranked the Web-based ECG-interpretation programme as a useful instrument to learn ECG. Furthermore, Internet-delivered education may be more effective than traditional teaching methods due to greater immediacy, improved visualisation and interactivity.</p