44,424 research outputs found
Formālisms kā reālās matemātikas filozofija: 14 argumenti
Referāts Latvijas Universitātes 73.zinātniskajā konferencē 2015.gada 13.februārī.Dāvids Hilberts: Matemātika ir tas, ko ar to saprot kompetenti cilvēki. Pirmajā brīdī skan pat it kā drosmīgi un nekaunīgi. Bet īstenībā ar tādu pozīciju nav ko lepoties: sakarīgāk pateikt neprotam, un tāpēc “nostājamies pozā”! Bet tie, kuri par matemātiku mēģina izdomāt kaut ko līdz galam un “pateikt sakarīgi”, parasti nonāk vienā no galējām pozīcijām – platonismā vai formālismā. Gēdela nepilnības teorēmas: kā aiziet pa maldu ceļu, un kā ir īstenībā. Par kontinuuma problēmu
Erythrocytes from GGTA1/CMAH knockout pigs: implications for xenotransfusion and testing in non-human primates
Background
Pig erythrocytes are potentially useful to solve the worldwide shortage of human blood for transfusion. Domestic pig erythrocytes, however, express antigens that are bound by human preformed antibodies. Advances in genetic engineering have made it possible to rapidly knock out the genes of multiple xenoantigens, namely galactose α1,3 galactose (aGal) and N-glycolylneuraminic acid (Neu5Gc). We have recently targeted the GGTA1 and CMAH genes with zinc finger endonucleases resulting in double knockout pigs that no longer express aGal or Neu5Gc and attract significantly fewer human antibodies. In this study, we characterized erythrocytes from domestic and genetically modified pigs, baboons, chimpanzees, and humans for binding of human and baboon natural antibody, and complement mediated lysis.
Methods
Distribution of anti Neu5Gc IgG and IgM in pooled human AB serum was analyzed by ELISA. Erythrocytes from domestic pigs (Dom), aGal knockout pigs (GGTA1 KO), aGal and Neu5Gc double knockout pigs (GGTA1/CMAH KO), baboons, chimpanzees, and humans were analyzed by flow cytometry for aGal and Neu5Gc expression. In vitro comparative analysis of erythrocytes was conducted with pooled human AB serum and baboon serum. Total antibody binding was accessed by hemagglutination; complement-dependent lysis was measured by hemolytic assay; IgG or IgM binding to erythrocytes was characterized by flow cytometry.
Results
The pooled human AB serum contained 0.38 μg/ml anti Neu5Gc IgG and 0.085 μg/ml anti Neu5Gc IgM. Both Gal and Neu5Gc were not detectable on GGTA1/CMAH KO erythrocytes. Hemagglutinaion of GGTA1/CMAH KO erythrocytes with human serum was 3.5-fold lower compared to GGTA1 KO erythrocytes, but 1.6-fold greater when agglutinated with baboon serum. Hemolysis of GGTA1/CMAH KO erythrocytes by human serum (25%) was reduced 9-fold compared to GGTA1 KO erythrocytes, but increased 1.64-fold by baboon serum. Human IgG binding was reduced 27-fold on GGTA1/CMAH KO erythrocytes compared to GGTA1 KO erythrocytes, but markedly increased 3-fold by baboon serum IgG. Human IgM binding was decreased 227-fold on GGTA1/CMAH KO erythrocytes compared to GGTA1 KO erythrocytes, but enhanced 5-fold by baboon serum IgM.
Conclusions
Removal of aGal and Neu5Gc antigens from pig erythrocytes significantly reduced human preformed antibody-mediated cytotoxicity but may have complicated future in vivo analysis by enhancing reactivity from baboons. The creation of the GGTA1/CMAH KO pig has provided the xenotransplantion researcher with organs and cells that attract fewer human antibodies than baboon and our closest primate relative, chimpanzee. These finding suggest that while GGTA1/CMAH KO erythrocytes may be useful for human transfusions, in vivo testing in the baboon may not provide a direct transplation to the clinic
Nave industrial para ganado equino y desarrollo de actividades ecuestres
Este proyecto trata el cálculo de una nave industrial cuya aplicación estará destinada al ganado equino y desarrollo de actividades ecuestres. Se ubica en El Cabrio, Valle de Mena (Burgos). La nave está compuesta por una nave principal a dos aguas de 24m y una partición adosada a un agua al lado izquierdo de 6m, dando un total de 30m de ancho. Se compone de 7 pórticos (6 huecos) cada 7m, dando como resultado una nave de 42m de largo, haciendo un total de 1260m2 de superficie construida. En el último vano, tiene una entreplanta, destinada a vestuarios, baños, comedor y una oficina, proporcionándole así a la nave de 168m2 más.Proiektu hau zaldientzako aterpe gisa eta zalditan ibiltzeko ekintzak egitera bideratutako egitura industrial bat kalkulatzen du. El Cabrio herrian dago kokatuta, Mena Haranean (Burgos). 24m-ko bi isurialdeko egitura printzipal batek eta 6m-ko isurialde bakarreko beste batek osatzen dute 30m-ko egitura totala. Egitura, 7 portikok osatzen dute 7m-ro kokatuak, 6 tarte osatuz, beraz 42m-ko luzera lortzen da. Honela, 1260m2-ko azalera da eraikuntzak izango duena. Gainera, azkeneko tartean beste solairu bat egongo da, 168m2-ko azalerakoa, eta bertan aldagelak, komunak, jantokia eta bulego bat egongo dira.The present project goes about the required calculations to build an industrial unit destined to give shelter to horses and to be a place to do horse riding activities. It is located in El Cabrio, in Valle de Mena (Burgos). The industrial unit is made up of a 24m principal gable roof unit and a secondary 6m single water deck unit, which make a total of 30m width. It is based on 7 porticos every 7m, providing the industrial unit with 42m length. That way, the built surface is 1260m2. What is more, in the last hole of the structure, there is a 168m2 mezzanine that will be used for toilets, changing rooms, a dining room and an office
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