14 resultados para McNeil, Legs: Please kill me
em Consorci de Serveis Universitaris de Catalunya (CSUC), Spain
Resumo:
What abortion laws a liberal political community ought to have? Much has been said about the moral problem of abortion, but there has not been yet (to my knowledge) a fully articulate account of the bearing of the competing answers to this ethical problem on liberal public reason. The first part of my project consists in a critical review of the different attempts to solve the various philosophical puzzles, both metaphysical and moral, posed by the abortion problem. Why is it wrong to kill beings like you and me? By answering this question we shall gain a better insight into those properties we have that give us such strong reasons against killing beings like us. Here we face a tremendous philosophical diffuculty, for it is not possible to determine what the robustest account of the wrongness of killing is without dealing with deeper metaethical and metaphysical problems. Indeed, consequentialist and nonconsequentialist moral theories differ in what it is that makes an action morally wrong -is it just the outcome of the action as compared with the outcomes of its alternatives? Or is it something else? Also, what are we essentially? Is the foetus merely our precursor? Then killing a foetus is relevantly similar to contraception. Or is the foetus one of us? If so, when we kill it, are we depriving it of a future as valuable as ours? Perhaps the relation of identity (the fact that it is its future as opposed to someone else's) doesn't matter. That may be because the foetus is an aggregate of biological and psychological facts and perhaps aggregates are not substances. Or maybe it is a substance but only psychological realtions matter, not personal identity. The second part of my project has to do with the different status these metaphisical and ethical positions ought to have in liberal public reason. Though this is the part in which most research is still needed, my own intuition is that, given the depth of the philosphical views in competition, restrictive abortion laws ought to be considered unrespectful to citizens' autonomy.
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L'objectiu principal d'aquest treball de final de carrera és estudiar la usabilitat en el programari en general i específicament quina relació té amb el programari mèdic.
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La meva incorporació al grup de recerca del Prof. McCammon (University of California San Diego) en qualitat d’investigador post doctoral amb una beca Beatriu de Pinós, va tenir lloc el passat 1 de desembre de 2010; on vaig dur a terme les meves tasques de recerca fins al darrer 1 d’abril de 2012. El Prof. McCammon és un referent mundial en l’aplicació de simulacions de dinàmica molecular (MD) en sistemes biològics d’interès humà. La contribució més important del Prof. McCammon en la simulació de sistemes biològics és el desenvolupament del mètode de dinàmiques moleculars accelerades (AMD). Les simulacions MD convencionals, les quals estan limitades a l’escala de temps del nanosegon (~10-9s), no son adients per l’estudi de sistemes biològics rellevants a escales de temps mes llargues (μs, ms...). AMD permet explorar fenòmens moleculars poc freqüents però que son clau per l’enteniment de molts sistemes biològics; fenòmens que no podrien ser observats d’un altre manera. Durant la meva estada a la “University of California San Diego”, vaig treballar en diferent aplicacions de les simulacions AMD, incloent fotoquímica i disseny de fàrmacs per ordinador. Concretament, primer vaig desenvolupar amb èxit una combinació dels mètodes AMD i simulacions Car-Parrinello per millorar l’exploració de camins de desactivació (interseccions còniques) en reaccions químiques fotoactivades. En segon lloc, vaig aplicar tècniques estadístiques (Replica Exchange) amb AMD en la descripció d’interaccions proteïna-lligand. Finalment, vaig dur a terme un estudi de disseny de fàrmacs per ordinador en la proteïna-G Rho (involucrada en el desenvolupament de càncer humà) combinant anàlisis estructurals i simulacions AMD. Els projectes en els quals he participat han estat publicats (o estan encara en procés de revisió) en diferents revistes científiques, i han estat presentats en diferents congressos internacionals. La memòria inclosa a continuació conté més detalls de cada projecte esmentat.
Resumo:
The recent availability of the chicken genome sequence poses the question of whether there are human protein-coding genes conserved in chicken that are currently not included in the human gene catalog. Here, we show, using comparative gene finding followed by experimental verification of exon pairs by RT–PCR, that the addition to the multi-exonic subset of this catalog could be as little as 0.2%, suggesting that we may be closing in on the human gene set. Our protocol, however, has two shortcomings: (i) the bioinformatic screening of the predicted genes, applied to filter out false positives, cannot handle intronless genes; and (ii) the experimental verification could fail to identify expression at a specific developmental time. This highlights the importance of developing methods that could provide a reliable estimate of the number of these two types of genes.
Resumo:
Selenocysteine (Sec) is co-translationally inserted into selenoproteins in response to codon UGA with the help of the selenocysteine insertion sequence (SECIS) element. The number of selenoproteins in animals varies, with humans having 25 and mice having 24 selenoproteins. To date, however, only one selenoprotein, thioredoxin reductase, has been detected in Caenorhabditis elegans, and this enzyme contains only one Sec. Here, we characterize the selenoproteomes of C.elegans and Caenorhabditis briggsae with three independent algorithms, one searching for pairs of homologous nematode SECIS elements, another searching for Cys- or Sec-containing homologs of potential nematode selenoprotein genes and the third identifying Sec-containing homologs of annotated nematode proteins. These methods suggest that thioredoxin reductase is the only Sec-containing protein in the C.elegans and C.briggsae genomes. In contrast, we identified additional selenoproteins in other nematodes. Assuming that Sec insertion mechanisms are conserved between nematodes and other eukaryotes, the data suggest that nematode selenoproteomes were reduced during evolution, and that in an extreme reduction case Sec insertion systems probably decode only a single UGA codon in C.elegans and C.briggsae genomes. In addition, all detected genes had a rare form of SECIS element containing a guanosine in place of a conserved adenosine present in most other SECIS structures, suggesting that in organisms with small selenoproteomes SECIS elements may change rapidly.
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Working Paper no longer available. Please contact the author.
Resumo:
Classical transport theory is employed to analyze the hot quark-gluon plasma at the leading order in the coupling constant. A condition on the (covariantly conserved) color current is obtained. From this condition, the generating functional of hard thermal loops with an arbitrary number of soft external bosonic legs can be derived. Our approach, besides being more direct than alternative ones, shows that hard thermal loops are essentially classical.
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This paper describes a mesurement system designed to register the displacement of the legs using a two-dimensional laser range sensor with a scanning plane parallel to the ground and extract gait parameters. In the proposed methodology, the position of the legs is estimated by fitting two circles with the laser points that define their contour and the gait parameters are extracted applying a step-line model to the estimated displacement of the legs to reduce uncertainty in the determination of the stand and swing phase of the gait. Results obtained in a range up to 8 m shows that the systematic error in the location of one static leg is lower than 10 mm with and standard deviation lower than 8 mm; this deviation increases to 11 mm in the case of a moving leg. The proposed measurement system has been applied to estimate the gait parameters of six volunteers in a preliminary walking experiment.
Resumo:
This work describes the analysis of different walking paths registered using a Light Detection And Ranging (LIDAR) laser range sensor in order to measure oscillating trajectories during unsupervised walking. The estimate of the gait and trajectory parameters were obtained with a terrestrial LIDAR placed 100 mm above the ground with the scanning plane parallel to the floor to measure the trajectory of the legs without attaching any markers or modifying the floor. Three different large walking experiments were performed to test the proposed measurement system with straight and oscillating trajectories. The main advantages of the proposed system are the possibility to measure several steps and obtain average gait parameters and the minimum infrastructure required. This measurement system enables the development of new ambulatory applications based on the analysis of the gait and the trajectory during a walk.
Resumo:
Nucleoside transporters (NTs) mediate the uptake of nucleosides and nucleobases across the plasma membrane, mostly for salvage purposes. The canonical NTs belong to two gene families, SLC29 and SLC28. The former encode equilibrative nucleoside transporter proteins (ENTs), which mediate the facilitative diffusion of natural nucleosides with broad selectivity, whereas the latter encode concentrative nucleoside transporters (CNTs), which are sodium-coupled and show high affinity for substrates with variable selectivity. These proteins are expressed in most cell types, exhibiting apparent functional redundancy. This might indicate that CNTs play specific roles in the physiology of the cell beyond nucleoside salvage. Here, we addressed this possibility using adenoviral vectors to restore tumor cell expression of hCNT1 or a polymorphic variant (hCNT1S546P) lacking nucleoside translocation ability. We found that hCNT1 restoration in pancreatic cancer cells significantly altered cell-cycle progression and phosphorylation status of key signal-transducing kinases, promoted poly-(ADP ribose) polymerase hyperactivation and cell death, and reduced tumor growth and cell migration. Importantly, the translocation-defective transporter triggered these same effects on cell physiology. These data predict a novel and totally unexpected biological role for the nucleoside transporter protein hCNT1 that appears to be independent of its role as mediator of nucleoside uptake by cells, thereby suggesting a transceptor function. Cell Death & Disease Anastasis Stephanou Receiving Editor Cell Death & Disease 19th Apr 2013 Dr Perez-Torras Av/ Diagonal 643. Edif. Prevosti, Pl -1 Barcelona 08028 Spain RE: Manuscript CDDIS-13-0136R, 'CDDIS-13-0136R' Dear Dr Perez-Torras, It is a pleasure to inform you that your manuscript has been evaluated at the editorial level and has now been officially accepted for publication in Cell Death & Disease, pending you meet the following editorial requirements: 1) the list of the abbreviations is missing please include Could you send us the revised text as word file via e-mail and we will proceed and transfer the paper onto our typesetters. Please download, print, sign, and return the Licence to Publish Form using the link below. This must be returned via FAX to ++ 39 06 7259 6977 before your manuscript can be published:
Resumo:
Objectius: Analitzar la utilització d’una o altra cama com a cama d’atac predominant en atletes de 400 metres tanques d’alt nivell. Mètode: L’estudi és descriptiu de tall transversal. Es van estudiar totes les curses de 400 metres tanques dels 72 participants (34 homes i 38 dones) en els XIII Campionats del Món d’Atletisme Daegu 2011 mitjançant la gravació en vídeo des de la tribuna principal del Daegu Stadium de les 18 curses de 400 metres tanques disputades i la posterior anàlisi mitjançant l’aplicació informàtica Kinovea 0.8.4. Resultats: Per atletes, en el total de les curses masculines, la cama d’atac predominant va ser l’esquerra, amb el 63,6 % (42 atletes), i amb la cama dreta va haver-hi el 34,8 % (23 atletes). Només en un cas hi havia un equilibri entre esquerra i dreta. A la final va haver-hi el 75 % (6 atletes) la cama predominant d’atac dels quals va ser l’esquerra. Quant a les dones, la cama d’atac predominant va ser l’esquerra, amb el 48,6 %, seguida de la cama dreta, amb el 41,4 %, i per al 10 % hi havia un equilibri de les dues. A la final, en canvi, la cama predominant d’atac va ser la dreta, amb el 87,5 % (7 atletes), pel 12,5 % de l’esquerra (1 sola atleta). Es van trobar diferències significatives (p = 0,018) en la mitjana de temps finals dels atletes masculins segons quina fos la seva cama d’atac. Conclusions: La majoria dels atletes ataquen les tanques amb dreta i esquerra en algun moment de la cursa, la qual cosa obliga al domini tècnic bilateral. La cama d’atac més utilitzada és l’esquerra, encara que en menor mesura en el cas de les dones. Per primera vegada en una gran competició, 7 de les 8 finalistes tenen la cama dreta com a cama predominant.
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Membrane active peptides can perturb the lipid bilayer in several ways, such as poration and fusion of the target cell membrane, and thereby efficiently kill bacterial cells. We probe here the mechanistic basis of membrane poration and fusion caused by membrane-active, antimicrobial peptides. We show that the cyclic antimicrobial peptide, BPC194, inhibits growth of Gram-negative bacteria and ruptures the outer and inner membrane at the onset of killing, suggesting that not just poration is taking place at the cell envelope. To simplify the system and to better understand the mechanism of action, we performed Förster resonance energy transfer and cryogenic transmission electron microscopy studies in model membranes and show that the BPC194 causes fusion of vesicles. The fusogenic action is accompanied by leakage as probed by dual-color fluorescence burst analysis at a single liposome level. Atomistic molecular dynamics simulations reveal how the peptides are able to simultaneously perturb the membrane towards porated and fused states. We show that the cyclic antimicrobial peptides trigger both fusion and pore formation and that such large membrane perturbations have a similar mechanistic basis
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Cyclin-dependent kinases CDK4 and CDK6 are essential for the control of the cell cycle through the G1 phase. Aberrant expression of CDK4 and CDK6 is a hall- mark of cancer, which would suggest that CDK4 and CDK6 are attractive targets for cancer therapy. Herein, we report that calcein AM is a potent specific inhibitor of CDK4 and CDK6 in HCT116 human colon adenocarcinoma cells, inhibiting retinoblastoma protein (pRb) phosphorylation and inducing cell cycle arrest in the G1 phase. The metabolic effects of calcein AM (the calcein acetoxymethyl-ester) on HCT116 cells were also evaluated and the flux between the oxidative and non-oxidative branches of the pentose phos-phate pathway was significantly altered. To elucidate whe-ther these metabolic changes were due to the inhibition of CDK4 and CDK6, we also characterized the metabolic profile of a CDK4, CDK6 and CDK2 triple knockout of mouse embryonic fibroblasts. The results show that the metabolic profile associated with the depletion of CDK4, CDK6 and CDK2 coincides with the metabolic changes induced by calcein AM on HCT116 cells, thus confirming that the inhibition of CDK4 and CDK6 disrupts the balance between the oxidative and non-oxidative branches of the pentose phosphate pathway. Taken together, these results indicate that low doses of calcein can halt cell division and kill tumor cells. Thus, selective inhibition of CDK4 and CDK6 may be of greater pharmacological interest, since inhibitors of these kinases affect both cell cycle progression and the robust metabolic profile of tumors.